title: Effect of non-pharmaceutical interventions to contain COVID-19 in China.

text: On March 11, 2020, the World Health Organization declared COVID-19 a pandemic1. The outbreak containment strategies in China based on non-pharmaceutical interventions (NPIs) appear to be effective2, but quantitative research is still needed to assess the efficacy of NPIs and their timings3. Using epidemiological and anonymised human movement data4,5, here we develop a modelling framework that uses daily travel networks to simulate different outbreak and intervention scenarios across China. We estimated that there were a total of 114,325 COVID-19 cases (interquartile range 76,776 - 164,576) in mainland China as of February 29, 2020. Without NPIs, the COVID-19 cases would likely have shown a 67-fold increase (interquartile range 44 - 94) by February 29, 2020, with the effectiveness of different interventions varying. The early detection and isolation of cases was estimated to have prevented more infections than travel restrictions and contact reductions, but combined NPIs achieved the strongest and most rapid effect. The lifting of travel restrictions since February 17, 2020 does not appear to lead to an increase in cases across China if the social distancing interventions can be maintained, even at a limited level of 25% reduction on average through late April. Our findings contribute to an improved understanding of NPIs on COVID-19 and to inform response efforts across the World.


title: Development of the designed ankyrin repeat protein (DARPin) G3 for HER2 molecular imaging.

text: PURPOSE Human epidermal growth factor receptor-2 (HER2) overexpression is a predictor of response to anti-HER2 therapy in breast and gastric cancer. Currently, HER2 status is assessed by tumour biopsy, but this may not be representative of the larger tumour mass or other metastatic sites, risking misclassification and selection of suboptimal therapy. The designed ankyrin repeat protein (DARPin) G3 binds HER2 with high affinity at an epitope that does not overlap with trastuzumab and is biologically inert. We hypothesized that radiolabelled DARPin G3 would be capable of selectively imaging HER2-positive tumours, and aimed to identify a suitable format for clinical application. METHODS G3 DARPins tagged with hexahistidine (His6) or with histidine glutamate (HE)3 and untagged G3 DARPins were manufactured using a GMP-compatible Pichia pastoris protocol and radiolabelled with (125)I, or with (111)In via DOTA linked to a C-terminal cysteine. BALB/c mice were injected with radiolabelled G3 and tissue biodistribution was evaluated by gamma counting. The lead construct ((HE)3-G3) was assessed in mice bearing HER2-positive human breast tumour (BT474) xenografts. RESULTS For both isotopes, (HE)3-G3 had significantly lower liver uptake than His6-G3 and untagged G3 counterparts in non-tumour-bearing mice, and there was no significantly different liver uptake between His6-G3 and untagged G3. (HE)3-G3 was taken forward for evaluation in mice bearing HER2-positive tumour xenografts. The results demonstrated that radioactivity from (111)In-(HE)3-G3 was better maintained in tumours and cleared faster from serum than radioactivity from (125)I-(HE)3-G3, achieving superior tumour-to-blood ratios (343.7 ± 161.3 vs. 22.0 ± 11.3 at 24 h, respectively). On microSPECT/CT, (111)In-labelled and (125)I-labelled (HE)3-G3 could image HER2-positive tumours at 4 h after administration, but there was less normal tissue uptake of radioactivity with (111)In-(HE)3-G3. Preadministration of trastuzumab did not affect the uptake of (HE)3-G3 by HER2-positive tumours. CONCLUSION Radiolabelled DARPin (HE)3-G3 is a versatile radioligand with potential to allow the acquisition of whole-body HER2 scans on the day of administration.


Detection of equine coronavirus in horses in the United Kingdom.


title: Design and biocompatibility of endovascular aneurysm filling devices.

text: The rupture of an intracranial aneurysm, which can result in severe mental disabilities or death, affects approximately 30,000 people in the United States annually. The traditional surgical method of treating these arterial malformations involves a full craniotomy procedure, wherein a clip is placed around the aneurysm neck. In recent decades, research and device development have focused on new endovascular treatment methods to occlude the aneurysm void space. These methods, some of which are currently in clinical use, utilize metal, polymeric, or hybrid devices delivered via catheter to the aneurysm site. In this review, we present several such devices, including those that have been approved for clinical use, and some that are currently in development. We present several design requirements for a successful aneurysm filling device and discuss the success or failure of current and past technologies. We also present novel polymeric-based aneurysm filling methods that are currently being tested in animal models that could result in superior healing.


title: Reduced port laparoscopic splenectomy using a newly developed multichannel port: a pilot study.

text: BACKGROUND The authors introduce the dual-incision laparoscopic splenectomy (DILS) technique using a specially designed multichannel trocar and report on the surgical outcomes and operative cost of DILS compared with conventional laparoscopic splenectomy (CLS). MATERIAL AND METHODS The medical records of 53 patients who underwent a laparoscopic splenectomy using CLS with four trocars and DILS at our institution were analyzed. RESULTS There was no statistical difference in operative time between the two groups and the intraoperative transfusion rate of red blood cell substitution was not different between the two groups. In terms of postoperative pain score, hospital stay, and overall complication rate, there were no differences between the two groups. Operative cost was significantly lower in the DILS group compared with the CLS group. CONCLUSIONS DILS is a feasible and cost-effective modality of reduced port surgery in laparoscopic splenectomy.


title: SMA Syndrome Treated by Single Incision Laparoscopic Duodenojejunostomy.

text: Superior mesenteric artery (SMA) syndrome is a mechanical duodenal obstruction by the SMA. The traditional approach to SMA syndrome was open bypass surgery. Nowadays, a conventional approach has been replaced by laparoscopic surgery. But single incision laparoscopic approach for SMA syndrome is rare. Herein, we report the first case of SMA syndrome patient who was treated by single incision laparoscopic duodenojejunostomy.


title: Human Vγ9Vδ2-T cells efficiently kill influenza virus-infected lung alveolar epithelial cells.

text: γδ-T cells play an indispensable role in host defense against different viruses, including influenza A virus. However, whether these cells have cytotoxic activity against influenza virus-infected lung alveolar epithelial cells and subsequently contribute to virus clearance remains unknown. Using influenza virus-infected A549 cells, human lung alveolar epithelial cells, we investigated the cytotoxic activity of aminobisphosphonate pamidronate (PAM)-expanded human Vγ9Vδ2-T cells and their underlying mechanisms. We found that PAM could selectively activate and expand human Vγ9Vδ2-T cells. PAM-expanded human Vγ9Vδ2-T cells efficiently killed influenza virus-infected lung alveolar epithelial cells and inhibited virus replication. The cytotoxic activity of PAM-expanded Vγ9Vδ2-T cells was dependent on cell-to-cell contact and required NKG2D activation. Perforin-granzyme B, tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas-Fas ligand (FasL) pathways were involved in their cytotoxicity. Our study suggests that targeting γδ-T cells by PAM can potentially offer an alternative option for the treatment of influenza virus.


The COVID-19 Pandemic: Challenges for the Neurosurgeons and Neurologists.


title: Rare complication of anterior communicating artery aneurysm coiling: Transient retrograde amnesia.

text: Amnesia is an unusual and rare complication following endovascular coiling of intracranial aneurysms. We present a case of anterior communicating artery (ACOM) aneurysm in which the patient developed retrograde amnesia following endovascular coiling of the aneurysm. On imaging there was infarct involving bilateral fornices. The patient showed significant clinical improvement on follow up.


title: Protective effect of recombinant human brain natriuretic peptide on acute renal injury induced by endotoxin in canines.

text: The objective of this study was to evaluate the protective effect of recombinant human brain natriuretic peptide (rhBNP) on endotoxin-induced acute kidney injury (AKI) in canine model of septic shock and its potential mechanisms. Dogs with endotoxin-induced septic shock were subjected to intravenous infusion of saline solution or rhBNP at the concentrations of 5 μg/kg (low-dose intervention group) or 10 μg/kg (high-dose intervention group). At 0, 2, 4, 8, and 12 h, the systemic vascular resistance index (SVRI) as well as serum levels of high mobility group box 1 protein (HMGB-1) and creatinine were measured, and kidney tissue samples were taken for histological examination. We have found that low and high doses of rhBNP could significantly reduce kidney tissue damage, such as tubular epithelial swelling and atrophy, and interstitial cell swelling in response to LPS injection in the dog sepsis models. rhBNP administration significantly reduced SVRI and serum levels of creatinine in dogs with LPS-induced sepsis in a dose-dependent manner, and attenuated the rise in the circulating HMGB-1. In conclusion, these findings suggest that rhBNP may exert dose-dependent protective effect on kidney tissue with endotoxin-induced injury, and this effect may be associated with the changes in blood levels of HMGB-1. rhBNP may be considered as therapeutic agents for treating sepsis-induced AKI.


Investigation on cognition of covid-19 and safety during the pandemic among hospital pharmacy staff.


title: An experimental study in six fresh human cadavers using a novel approach to avoid abdominal wall incisions in total colectomy: totally transanal laparoendoscopic single-site pull-through colectomy with J-pouch creation.

text: BACKGROUND The use of transanal laparoscopic access to completely avoid abdominal wall incisions represents the most current evolution in minimally invasive surgery. The combination of single-site surgery and natural orifice transluminal endoscopic surgery (NOTES™) can be used for totally transanal laparoendoscopic pull-through colectomy with J-pouch creation (TLPC-J). The aim of the present study was to provide evidence for the feasibility of TLPC-J in adult human cadavers. METHODS TLPC-J was performed in six fresh adult human cadavers. The procedure involved endorectal submucosal dissection from 1 cm above the dentate line to a point above the peritoneal reflection, where the rectal muscle was divided circumferentially. The edge of the mucosal cuff was closed distally in order to prevent fecal contamination and the endorectal tube was placed back into the abdomen. A Triport+™ or QuadPort+™ system was introduced transanally, and it served as a multiport device (MD). Resection of the entire colon, mobilization of the distal ileal segment, and extracorporeal suture of the ileal J-loop were performed via the transanal approach. The J-pouch was created using Endo GIA™. After removal of the MD, the J-pouch was sutured to the rectal wall. RESULTS TLPC-J was performed in all cadavers, with a mean operation duration of 236 ± 22 min. Conversion to either transabdominal laparoscopy or laparotomy was not required in any of the cadavers. No bowel perforation or damage to other organs was observed. The use of a curved endoscope greatly facilitated visualization during transanal laparoscopic dissection for partial and total colectomy, making the procedure feasible. All specimens were retrieved through the anus, eliminating the need for additional transabdominal incisions. CONCLUSIONS TLPC-J was technically feasible in adult human cadavers, and abdominal wall incisions were not required. However, clinical studies are needed to determine its feasibility in living adults.


title: Superior mesenteric artery syndrome: a single centre experience of laparoscopic duodenojejunostomy as the operation of choice.

text: INTRODUCTION The superior mesenteric artery (SMA) syndrome, or Wilkie's syndrome, is a rare cause of postprandial epigastric pain, vomiting and weight loss caused by compression of the third part of the duodenum as it passes beneath the proximal superior mesenteric artery. The syndrome may be precipitated by sudden weight loss secondary to other pathologies, such as trauma, malignancy or eating disorders. Diagnosis is confirmed by angiography, which reveals a reduced aorto-SMA angle and distance, and contrast studies showing duodenal obstruction. Conservative management aims to increase intra-abdominal fat by dietary manipulation and thereby increase the angle between the SMA and aorta. Where surgery is indicated, division of the ligament of Treitz, anterior transposition of the third part of the duodenum and duodenojejunostomy have been described. METHODS We present four cases of SMA syndrome where the intention of treatment was laparoscopic duodenojejunostomy. The procedure was completed successfully in three patients, who recovered quickly with no short-term complications. A fourth patient underwent open gastrojejunostomy (complicated by an anastomotic bleed) when dense adhesions prevented duodenojejunostomy. CONCLUSIONS The superior mesenteric artery syndrome should be considered in patients with epigastric pain, prolonged vomiting and weight loss. Laparoscopic duodenojejunostomy is a safe and effective operation for management of the syndrome. A multi-speciality team approach including gastrointestinal, vascular and radiological specialists should be invoked in the management of these patients.


title: Coxiella burnetii antibody dynamics in heifers born to vaccinated versus non-vaccinated dams in a chronically infected dairy herd.

text: This study was designed to compare Coxiella burnetii antibody dynamics in heifers born to vaccinated or non-vaccinated dams in a single high-producing dairy herd chronically infected with the bacterium. Antibody dynamics were examined from birth to the postpartum period in replacement heifers (n = 14) born to non-vaccinated dams (n = 7) or to dams that had been vaccinated on gestation days 171-177 (n = 7) and 192-198. Samples of blood, milk, faeces, vaginal fluid, colostrum and cotyledons (the latter two only at parturition) were obtained in the dams over the period from gestation days 171-177 to postpartum days 91-97. Blood samples were used to detect antibodies against C. burnetii and remaining samples for PCR identification of the bacterium. In their calves/heifers, blood samples for antibody determinations were collected from birth to postpartum at the time points 1-7 and 22-28 days and 3, 6 and 12 months of age; 90-96 and 210-216 days of gestation; and 22-28 days postpartum. All calves were born seronegative for C. burnetii. Irrespective of the shedding status of their mothers (7 were C. burnetii shedders), seroconversion occurred after colostrum intake in all calves born to seropositive cows (n = 9) and in two of three vaccinated seronegative dams. Thereafter antibody titres gradually declined and by 6 months of age all calves were seronegative. Seronegativity persisted until their first postpartum period. These findings indicate that cows vaccinated during advanced pregnancy transfer immunity to their calves via the colostrum. Maternal C. burnetii antibodies in calves persisted for three months in calves born both to seronegative vaccinated and seropositive dams.


title: Impact of the COVID-19 Pandemic on Neurosurgical Practice in India: Results of an Anonymized National Survey.

text: Background The COVID-19 pandemic has created an unprecedented challenge for medical professionals throughout the world to tackle the rapidly changing scenario. The objective of this survey was to analyze the change in neurosurgical practice in India following the COVID-19 outbreak and assess its impact on practising neurosurgeons. Materials and Methods Between May 7th and 23rd, 2020, a validated questionnaire was circulated amongst practising neurosurgeons across the country by social media and e-mails, regarding changes in the patterns of patients seen, adaptations made in their practice, effect on surgeries performed, financial burden, and impact on their personal lives. The responses were kept anonymous and were analyzed for correlations between the changes observed and independent factors such as hospital affiliations, teaching professions, and neurosurgical experience. Results Our survey showed a drastic fall in the number of neurosurgical patients seen in the outpatient department (OPD) as well as the number of surgeries performed. A drop of 76.25% was seen in OPD patients (P = 0.000) and that of 70.59% in surgeries performed (P = 0.000). There was no uniformity among the neurosurgeons in the number of COVID-19 tests being done before elective/emergency surgery and in the use of protective gear while examining patients. Private practitioners were more affected financially as compared to those in the government sector. The pandemic has affected the research work of 53.23% of all respondents, with those in the teaching profession (70.96%) more affected than those in the non-teaching profession (24.67%). Conclusions Evidence-based policies, screening COVID-19 tests with better sensitivity, and better-quality personal protective equipment kits in adequate numbers are required to protect our medical professionals from COVID-19. Mental health issues among neurosurgeons may also be an issue, this being a high risk speciality and should be closely watched for.


title: Effects of Sprint-Interval and Endurance Respiratory Muscle Training Regimens.

text: INTRODUCTION Recently a novel, time-saving respiratory muscle sprint-interval training (RMSIT) was developed. To test the extent to which RMSIT improves respiratory muscle performance compared with a conventional respiratory muscle endurance training (RMET), a novel incremental respiratory muscle test (IncRMT), loading inspiratory and expiratory muscles, was designed to assess performance changes associated with respiratory muscle training (RMT). METHODS Healthy, moderately trained males and females (age: 26 ± 5 yr, V˙O2peak: 47 ± 12 mL·min·kg) were randomized and balanced to three groups (RMSIT 5m/5f; RMET 6m/6f; PLAT 5m/6f). Lung function, respiratory muscle strength, and IncRMT performance were tested before and after 1 month of RMT. During the IncRMT, muscle activity and muscle deoxygenation were assessed via surface EMG and near-infrared spectroscopy of sternocleidomastoid (STERNO), intercostal (INTER), and abdominal (ABDO) muscles. RESULTS Two-way ANOVA revealed a main effect of training for increased maximal voluntary ventilation (P = 0.001) and maximal inspiratory pressure (P = 0.017). Both RMT groups increased work of breathing during training sessions to the same extent (RMSIT: +17.4 ± 8.9 kJ; RMET: +26.2 ± 16.1 kJ; P = 0.143) with a larger increase in average mouth pressure in RMSIT (RMSIT: +20.0 ± 15.0 cm H2O; RMET: +3.3 ± 1.5 cm H2O; P = 0.001). After training, IncRMT duration increased in both RMT groups compared with PLAT (RMSIT: +5.6 ± 2.1 min, P = 0.0006 vs PLAT; RMET: +3.8 ± 4.2 min, P = 0.020 vs PLAT). At similar work, only INTER activity during inspiration increased after RMET. Higher performance after RMSIT was associated with higher activity in STERNO and ABDO, but after RMET, STERNO, INTER, and ABDO showed higher activity. CONCLUSION One month of RMSIT and RMET shows similar improvements in respiratory muscle performance despite different duration of training sessions. Also, muscular adaptations might differ.


title: Hand-sewn cystogastrostomy using the novel single-incision laparoscopy with flexible-tip laparoscope.

text: Laparoscopy performed through a single incision has been increasingly reported as a novel technique implemented in a wide variety of surgical procedures. We report what we believe to be the first case of cystogastrostomy for treatment of a pancreatic pseudocyst using this technique. Patient developed pancreatic pseudocyst after severe biliary pancreatitis. The cyst was noted to increase in size on follow-up computed tomography scans. In addition, patient developed symptoms requiring intervention.


title: Direct thrombus aspiration using the Penumbra system for the treatment of pediatric intracranial dissection.

text: We describe a case of a 15-year-old girl who developed a spontaneous intracranial arterial dissection with distal middle cerebral artery (MCA) occlusions. From the digital subtraction angiography provided, the dissection flap appeared to originate at the internal carotid artery terminus with extension into the right M1 segment and occluding the right anterior cerebral artery, A1 segment. CT perfusion study showed salvageable tissue in the posterior MCA territory, including the motor cortex. In order to avoid further injury to the dissection, clot retrieval systems were not a treatment option. We therefore performed selective thrombus aspiration with the Penumbra system for the occluded central and precentral arteries distal to the non-occlusive dissecting lesion. Sufficient recanalization was achieved and the patient made a marked recovery. Although mechanical thrombectomy with the use of retrieval intracranial stent systems has demonstrated satisfactory recanalization rates, the aspiration methodology remains useful for patients with an accompanying proximal vascular lesion.


title: AYUSH, modern medicine and the Covid-19 pandemic.

text: The COVID-19 pandemic has posed several challenges to the Indian healthcare system. Here, we examine the situation in India considering the moral and ethical imperatives of decision making for public health. Currently, in the absence of proven therapies, empirical evidence is being used for treatment of Covid-19 disease. We find a dual standard of practice. Currently, only modern medicine therapies are used on an empirical basis, however, the same principle is not considered for the use of AYUSH systems. Appropriate use of evidence is required. In the ethics context and in the interest of the larger public good, we suggest the inclusion of simple and safe measures from AYUSH systems in the integrative protocols for prophylaxis and treatment of Covid-19. Keywords: AYUSH systems, Covid-19, pandemic, prophylaxis, evidence, empirical evidence, priority setting, public health decision making, global health emergencies,complementary medicine, integrative healthcare.


title: Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative cognitive dysfunction.

text: BACKGROUND Postoperative delirium in elderly patients is a frequent complication and associated with poor outcome. The aim of this parallel group study was to determine whether monitoring depth of anaesthesia influences the incidence of postoperative delirium. METHODS Patients who were planned for surgery in general anaesthesia expected to last at least 60 min and who were older than 60 yr were included between March 2009 and May 2010. A total of 1277 patients of a consecutive sample were randomized (n=638 open, n=639 blinded) and the data of 1155 patients were analysed (n=575 open, n=580 blinded). In one group, the anaesthesiologists were allowed to use the bispectral index (BIS) data to guide anaesthesia, while in the other group, BIS monitoring was blinded. Cognitive function was evaluated at baseline, 1 week, and 3 months after operation. RESULTS Delirium incidence was lower in patients guided with BIS. Postoperative delirium was detected in 95 patients (16.7%) in the intervention group compared with 124 patients (21.4%) in the control group (P=0.036). In a multivariate analysis, the percentage of episodes of deep anaesthesia (BIS values <20) were independently predictive for postoperative delirium (P=0.006; odds ratio 1.027). BIS monitoring did not alter the incidence of postoperative cognitive dysfunction (7th day P=0.062; 90th day P=0.372). CONCLUSIONS Intraoperative neuromonitoring is associated with a lower incidence of delirium, possibly by reducing extreme low BIS values. Therefore, in high-risk surgical patients, this may give the anaesthesiologist a possibility to influence one precipitating factor in the complex genesis of delirium. Clinical trial registration ISRCTN Register: 36437985. http://www.controlled-trials.com/ISRCTN36437985/.


title: Kinetics of the formation of a protein corona around nanoparticles.

text: Interaction of metal or oxide nanoparticles (NPs) with biological soft matter is one of the central phenomena in basic and applied biology-oriented nanoscience. Often, this interaction includes adsorption of suspended proteins on the NP surface, resulting in the formation of the protein corona around NPs. Structurally, the corona contains a "hard" monolayer shell directly contacting a NP and a more distant weakly associated "soft" shell. Chemically, the corona is typically composed of a mixture of distinct proteins. The corresponding experimental and theoretical studies have already clarified many aspects of the corona formation. The process is, however, complex, and its understanding is still incomplete. Herein, we present a kinetic mean-field model of the formation of the "hard" corona with emphasis on the role of (i) protein-diffusion limitations and (ii) interplay between competitive adsorption of distinct proteins and irreversible reconfiguration of their native structure. The former factor is demonstrated to be significant only in the very beginning of the corona formation. The latter factor is predicted to be more important. It may determine the composition of the corona on the time scales comparable or longer than a few hours.


title: Time series analysis of California's prescription monitoring program: impact on prescribing and multiple provider episodes.

text: UNLABELLED Prescription monitoring programs (PMPs) are designed to reduce medication diversion by identifying individuals obtaining the same medication from multiple providers (termed multiple provider episodes [MPEs]). This study determined whether recent changes to California's PMP influenced: 1) the extent that practitioners issue prescriptions for a variety of Schedule II opioids; and 2) the incidence of MPEs involving these opioids. Intervention time series of California's PMP data was used to determine the effect of requiring practitioners to transition from using triplicate prescription forms for Schedule II medications to security forms for all controlled substances. Outcome measures included changes in number of prescriptions issued for Schedule II long-acting or short-acting (SA) opioids and the MPEs involving these medications. Requiring a security form was associated with a sustained prescribing increase for SA hydromorphone, meperidine, and SA oxycodone; no prescribing changes were found for SA fentanyl, methadone, and SA morphine, or for any long-acting opioids. The same policy change, however, increased MPEs involving all opioids. Further effort is required to determine how California's PMP can continue to ensure availability of prescription opioids for medical use while better mitigating their diversion. PERSPECTIVE Statistical model-building was used to evaluate the influence of changes to California's prescription monitoring program. The extent that practitioners prescribe Schedule II opioids and the incidence of people receiving prescriptions from multiple providers were measured. Such research illustrates the viability of evaluating drug control program impact on prescribing practice and potential diversion behaviors.


The 2019 Novel Coronavirus (2019-nCoV): Novel Virus, Old Challenges.


title: Different radiolabelling methods alter the pharmacokinetic and biodistribution properties of plasminogen activator inhibitor type 2 (PAI-2) forms.

text: INTRODUCTION Tumour-associated urokinase plasminogen activator (uPA) is a critical marker of invasion and metastasis, and it is recognised as having strong prognostic relevance as well as being a therapeutic target. The specific uPA inhibitor plasminogen activator inhibitor type-2 (PAI-2, SerpinB2) specifically targets cell bound uPA and is internalised. Furthermore, preclinical studies have established the "proof-of-principle" of uPA-targeting by PAI-2-cytotoxin conjugates in human carcinoma models. However, these studies also suggest that PAI-2 is rapidly cleared via the renal system with low total dose reaching the tumour. In this study, a comparative single photon emission computed tomography (SPECT) and biodistribution (BD) analysis of different forms of PAI-2 labelled with the radioisotopes iodine-123 ((123)I) and technetium-99m ((99m)Tc) was undertaken. METHODS The pharmacokinetic (PK) properties and BD of wild-type, ΔCD-loop and PEGylated ΔCD-loop PAI-2 labelled with the commonly used diagnostic SPECT radioisotopes (99m)Tc or (123)I were compared in mouse models of human prostate carcinoma. Whole body SPECT imaging was also performed. RESULTS Both wild-type and the shorter but active ΔCD-loop form of PAI-2 (123)I-labelled indirectly via conjugation to free amine groups (termed (123)I-Bn-PAI-2) exhibited low tumour uptake, rapid excretion and similar PK profiles. Preliminary studies with a short branched-chain PEGylated (123)I-Bn-PAI-2 ΔCD-loop indicated an increase in blood retention time and tumour uptake. All (123)I-Bn-labelled radiotracers were largely excreted through the kidneys. By comparison, both wild-type (123)I-PAI-2 (labelled directly via tyrosine residues) and (99m)Tc-PAI-2 displayed different PK/BD patterns compared to (123)I-Bn-PAI-2, suggesting greater liver based catabolism and thus slower elimination. SPECT imaging mimicked the BD results of all radiotracers. CONCLUSION The different labelling methods gave distinct PAI-2 BD and tumour uptake profiles, with radioiodination resulting in the best non-tumour organ clearance profiles. Preliminary analyses with short branched-chain PEGylated (123)I-Bn-PAI-2 ΔCD-loop suggest that further investigations with other PEGylation reagents are required to optimise this approach for tumour imaging. These findings impact on the use of PAI-2 for drug delivery and/or diagnostic development.


title: Clinical review: Update on neurally adjusted ventilatory assist--report of a round-table conference.

text: Conventional mechanical ventilators rely on pneumatic pressure and flow sensors and controllers to detect breaths. New modes of mechanical ventilation have been developed to better match the assistance delivered by the ventilator to the patient's needs. Among these modes, neurally adjusted ventilatory assist (NAVA) delivers a pressure that is directly proportional to the integral of the electrical activity of the diaphragm recorded continuously through an esophageal probe. In clinical settings, NAVA has been chiefly compared with pressure-support ventilation, one of the most popular modes used during the weaning phase, which delivers a constant pressure from breath to breath. Comparisons with proportional-assist ventilation, which has numerous similarities, are lacking. Because of the constant level of assistance, pressure-support ventilation reduces the natural variability of the breathing pattern and can be associated with asynchrony and/or overinflation. The ability of NAVA to circumvent these limitations has been addressed in clinical studies and is discussed in this report. Although the underlying concept is fascinating, several important questions regarding the clinical applications of NAVA remain unanswered. Among these questions, determining the optimal NAVA settings according to the patient's ventilatory needs and/or acceptable level of work of breathing is a key issue. In this report, based on an investigator-initiated round table, we review the most recent literature on this topic and discuss the theoretical advantages and disadvantages of NAVA compared with other modes, as well as the risks and limitations of NAVA.


title: Subclinical pulmonary pathogenic infection in camels slaughtered in Cairo, Egypt.

text: INTRODUCTION Camels migrate between the open boundaries of Sudan and Egypt either for grazing or for slaughtering. Bad hygiene and stress is often related to pulmonary diseases in camels. This study investigated whether camels slaughtered in Cairo carried pulmonary infections. METHODOLOGY Five hundred lung tissues of slaughtered camels were examined and 100 samples suspected for pulmonary infection were subjected to microbial identification and histopathology. RESULTS A total of 70 lung tissues revealed 97 bacterial isolates of 8 species, including Staphylococcus aureus (37.14%), Escherichia coli (27.14%), Klebsiella pneumoniae (26.71%), Bacillus spp. (25.72%), Streptococcus pyogenes (10%), Corynebacterium spp. (8.85 %), Pasteurella spp. (2.85%), and Arcanobacterium pyogenes (1.4%). Some of these species were earlier reported to be associated with pulmonary infection. Histopathology revealed different types of pneumonia in 50% of the investigated lungs. CONCLUSIONS A considerable number of apparently healthy camels carry pathogenic agents in their lower respiratory tracts. Immunosuppression and stressful conditions might influence these pathogens to induce respiratory diseases in camels. Thus, the infected camels might act as reservoir of these infections agents. If adequate care is not taken, this might be a threat to abattoir workers and may spread infections to humans.


title: Viral and host factors related to the clinical outcome of COVID-19.

text: In December 2019, the Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus SARS-CoV-2, emerged in Wuhan, Hubei province, China1 and soon spread across the world. In this ongoing pandemic, public health concerns and the urgent need for effective therapeutic measures require a deep understanding of its epidemiology, transmissibility and pathogenesis. Here we analyzed the clinical, molecular and immunological data from 326 confirmed cases of COVID-19 in Shanghai. Genomic sequences of SARS-CoV-2 assembled from 112 quality samples together with sequences in the Global Initiative on Sharing All Influenza Data (GISAID) showed a stable evolution and suggested two major lineages with differential exposure history during the early phase of the outbreak in Wuhan. Nevertheless, they exhibited similar virulence and clinical outcomes. Lymphocytopenia, especially the reduced CD4+ and CD8+ T cell counts upon admission, was predictive of disease progression. High levels of IL-6 and IL-8 during treatment were observed in patients with severe or critical disease and correlated with decreased lymphocyte count. The determinants of disease severity seemed to stem mostly from host factors such as age, lymphocytopenia, and its associated cytokine storm, whereas viral genetic variation did not significantly affect the outcomes.


title: Comprehensive pollution monitoring of the Egyptian Red Sea coast by using the environmental indicators.

text: The environmental pollution indicators and multivariate statistical analysis were used to evaluate the potential ecological risk and the contamination of Fe, Mn, Zn, Ni, Pb, Cu, Cd, and Co in surface sediments of the Egyptian Red Sea coast. The results revealed that the studied area suffers from high contamination of certain metals such as the Hurghada area (Pb, Cd, Zn, Ni, and Cu), Quseir City area (Cd, Co, Pb, and Ni), and Safaga and Marsa Alam areas (Cd and Pb). Enrichment factor and principal components analysis reported that the pollution sources of Fe, Mn, and Co are related to natural weathering process while Cu, Zn, Ni, and Pb are related to anthropogenic sources as landfill, plastic rubbish, fishing boats, phosphate operations, and tourist activities. Moreover, Co and Cd metals can come from both of natural and anthropogenic sources. The average concentrations of Cd, Cu, Zn, Pb, Ni, and Co in sediments of the Egyptian Red Sea coast are higher than those in the coasts of the Red Sea (Saudi Arabia), Mediterranean Sea (Egypt and Libya), Bengal bay (India), and the Caspian Sea (Russia). However, the studied metal content is lower than the sediment quality guideline values except for Cd.


title: Middle East Respiratory Syndrome Coronavirus-Encoded Accessory Proteins Impair MDA5-and TBK1-Mediated Activation of NF-κB.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging coronavirus which is zoonotic from bats and camels. Its infection in humans can be fatal especially in patients with preexisting conditions due to smoking and chronic obstructive pulmonary disease (COPD). Among the 25 proteins encoded by MERS-CoV, 5 accessory proteins seem to be involved in viral evasion of the host immune responses. Here we report that ORF4a, ORF4b, and ORF8b proteins, alone or in combination, effectively antagonize nuclear factor kappa B (NF-κB) activation. Interestingly, the inhibition of NF-κB by MERS-CoV accessory proteins was mostly at the level of a pattern recognition receptor: melanoma differentiationassociated gene 5 (MDA5). ORF4a and ORF4b additively inhibit MDA5-mediated activation of NF-κB while that of retinoic acid-inducible gene 1 (RIG-I) is largely not perturbed. Of note, ORF8b was found to be a novel antagonist of MDA5-mediated NF-κB activation. In addition, ORF8b also strongly inhibits Tank-binding kinase 1 (TBK1)-mediated induction of NF-κB signaling. Taken together, MERS-CoV accessory proteins are involved in viral escape of NF-κB-mediated antiviral immune responses.


title: Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial.

text: BACKGROUND There is insufficient research into the use of mechanical ventilation with increased inspiratory oxygen concentration (FiO2) and fluid resuscitation with hypertonic saline solution in patients with septic shock. We tested whether these interventions are associated with reduced mortality. METHODS This two-by-two factorial, multicentre, randomised, clinical trial (HYPERS2S) recruited patients aged 18 years and older with septic shock who were on mechanical ventilation from 22 centres in France. Patients were randomly assigned 1:1:1:1 to four groups by a computer generated randomisation list stratified by site and presence or absence of acute respiratory distress syndrome by use of permuted blocks of random sizes. Patients received, in an open-labelled manner, mechanical ventilation either with FiO2 at 1·0 (hyperoxia) or FiO2 set to target an arterial haemoglobin oxygen saturation of 88-95% (normoxia) during the first 24 h; patients also received, in a double-blind manner, either 280 mL boluses of 3·0% (hypertonic) saline or 0·9% (isotonic) saline for fluid resuscitation during the first 72 h. The primary endpoint was mortality at day 28 after randomisation in the intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT01722422. FINDINGS Between Nov 3, 2012, and June 13, 2014, 442 patients were recruited and assigned to a treatment group (normoxia [n=223] or hyperoxia [n=219]; isotonic [n=224] or hypertonic [n=218]). The trial was stopped prematurely for safety reasons. 28 day mortality was recorded for 434 patients; 93 (43%) of 217 patients had died in the hyperoxia group versus 77 (35%) of 217 patients in the normoxia group (hazard ratio [HR] 1·27, 95% CI 0·94-1·72; p=0·12). 89 (42%) of 214 patients had died in the hypertonic group versus 81 (37%) of 220 patients in the isotonic group (HR 1·19, 0·88-1·61; p=0·25). We found a significant difference in the overall incidence of serious adverse events between the hyperoxia (185 [85%]) and normoxia groups (165 [76%]; p=0·02), with a clinically relevant doubling in the hyperoxia group of the number of patients with intensive care unit-acquired weakness (24 [11%] vs 13 [6%]; p=0·06) and atelectasis (26 [12%] vs 13 [6%]; p=0·04) compared with the normoxia group. We found no statistical difference for serious adverse events between the two saline groups (p=0·23). INTERPRETATION In patients with septic shock, setting FiO2 to 1·0 to induce arterial hyperoxia might increase the risk of mortality. Hypertonic (3%) saline did not improve survival. FUNDING The French Ministry of Health.


title: Porcine reproductive and respiratory syndrome virus nsp1-beta protein interacts with nucleoporin 62 (Nup62) to promote viral replication and immune evasion.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) blocks host mRNA nuclear export to the cytoplasm, and nonstructural protein (nsp) 1-beta of PRRSV has been identified as the protein disintegrating the nuclear pore complex. In the present study, the molecular basis for the inhibition of host mRNA nuclear export was investigated. Nucleoporin 62 (Nup62) was found to bind to nsp1-beta, and the region representing the C-terminal 328-522 residues of Nup62 was determined as the binding domain to nsp1-beta. The nsp1-beta L126A mutant in the SAP domain did not bind to Nup62, and in L126A-expressing cells, the host mRNA nuclear export occurred normally. The vL126A mutant PRRSV generated by reverse genetics replicated at a slower rate, and the titer was lower than wild-type virus. In nsp1-beta overexpressing cells or siRNA-mediated Nup62 knock-down cells, the viral protein synthesis increased. Notably, the production of type I interferons (IFNs-α/β), IFN-stimulated genes (PKR, OAS, Mx1, ISG15), IFN-induced proteins with tetratricopeptide repeats (IFITs) 1 and 2, and IFN regulatory factor 3 decreased in these cells. As consequence, the growth of vL126A mutant PRRSV was rescued to the level of wild-type PRRSV. These findings are attributed to the NPC disintegration by nsp1-beta, resulting in increased viral protein production and decreased host protein production including antiviral proteins in the cytoplasm. Our study reveals a new strategy of PRRSV for immune evasion and enhanced replication during infection.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) causes PRRS and is known to effectively suppress host innate immunity. The PRRSV nsp1-beta protein blocks host mRNA nuclear export, which has been shown as one of the viral mechanisms for inhibition of antiviral protein production. The nsp1-beta binds to the cellular protein nucleoporin 62 (Nup62), and as consequence, the nuclear pore complex (NPC) is disintegrated and the nucleocytoplasmic trafficking of host mRNAs and host proteins are blocked. We show the dual benefits of Nup62 and nsp1-beta binding for PRRSV replication; the inhibition of host antiviral protein expression and the exclusive usage of host translation machinery by the virus. Our study unveils a novel strategy of PRRSV for immune evasion and enhanced replication during infection.


title: A Survey of Labor and Delivery Practices in New York City during the COVID-19 Pandemic.

text: Recently, a novel coronavirus, precisely severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), that causes the disease novel coronavirus disease 2019 (COVID-19) has been declared a worldwide pandemic. Over a million cases have been confirmed in the United States. As of May 5, 2020, New York State has had over 300,000 cases and 24,000 deaths with more than half of the cases and deaths occurring in New York City (NYC). Little is known, however, of how this virus impacts pregnancy. Given this lack of data and the risk for severe disease in this relatively immunocompromised population, further understanding of the obstetrical management of COVID-19, as well as hospital level preparation for its control, is crucial. Guidance has come from expert opinion, professional societies and public health agencies, but to date, there is no report on how obstetrical practices have adapted these recommendations to their local situations. We therefore developed an internet-based survey to elucidate the practices put into place to guide the care of obstetrical patients during the COVID-19 pandemic. We surveyed obstetrical leaders in four academic medical centers in NYC who were implementing and testing protocols at the height of the pandemic. We found that all sites made changes to their practices, and that there appeared to be agreement with screening and testing for COVID-19, as well as labor and delivery protocols, for SARS-CoV-2-positive patients. We found less consensus with respect to inpatient antepartum fetal surveillance. We hope that this experience is useful to other centers as they formulate their plans to face this pandemic. KEY POINTS: · Practices changed to accommodate public health needs.. · Most practices are screened for novel coronavirus disease 2019 (COVID-19) on admission.. · Fetal testing in COVID-19 patients varied..


title: Laparoscopic Hysterectomy for Uterine Fibroids: Is it Safe?

text: As more complex cases and larger uterine specimens are able to be managed with minimally invasive surgery, the limitations of tissue retrieval with these methods are of increasing concern. Risks of morcellator-related injury, tissue dissemination, or fragmentation must be weighed against increased morbidity of abdominal approach to hysterectomy. In an effort to mitigate the risks of tissue morcellation, containment system use must be considered when fragmenting a specimen, either with power morcellation or a manual technique via the vagina or minilaparotomy.


title: Does Previous Surgical Training Impact the Learning Curve in Video-Assisted Thoracic Surgery Lobectomy for Trainees?

text: Background To analyze if the number of open lung resections performed by trainees before starting video-assisted thoracic surgery (VATS) lobectomy training program has any impact on intraoperative and postoperative outcomes. Materials and Methods Retrospective analysis of 46 consecutive patients who underwent VATS lobectomies between December 2011 and September 2012 by two trainees (A.B. and L.O.). The previous surgical experience of the two trainees was evaluated to assess for any difference in terms of learning curve. Group A comprised 25 VATS lobectomies performed by one trainee (A.B.) and group B comprised 21 VATS lobectomies performed by the other trainee (L.O.). Results There was no statistical difference in terms of operating time and intraoperative bleeding between the two groups (p = 0.16 and p = 0.6). The conversion rate was 8% (2 out of 25 cases) in group A and 23.8% (5 out of 21 cases) in group B (p = 0.002). Evaluation of vascular injury showed no difference in the conversion rate (p = 0.56). The median length of the drainage and of hospital stay were 4 days and 7 days in group A and 4 days and 8 days in group B, respectively (p = 0.36 and p = 0.24). The complication rate was 44% in group A and 47.6% in group B (p = 0.52). A.B. had performed 139 and L.O. 70 operations as first operator before starting their VATS lobectomy training; the surgical experience had an impact only on the conversion rate. Conclusion Our study showed that a training program in VATS lobectomy is feasible, and previous surgical training has a minimal impact on intraoperative and postoperative outcomes.


title: Applying the 15 Public Health Emergency Preparedness Capabilities to Support Large-Scale Tuberculosis Investigations in Complex Congregate Settings.

text: Public Health-Seattle and King County, a metropolitan health department in western Washington, experiences rates of tuberculosis (TB) that are 1.6 times higher than are state and national averages. The department's TB Control Program uses public health emergency management tools and capabilities sustained with Centers for Disease Control and Prevention grant funding to manage large-scale complex case investigations. We have described 3 contact investigations in large congregate settings that the TB Control Program conducted in 2015 and 2016. The program managed the investigations using public health emergency management tools, with support from the Preparedness Program. The 3 investigations encompassed medical evaluation of more than 1600 people, used more than 100 workers, identified nearly 30 individuals with latent TB infection, and prevented an estimated 3 cases of active disease. These incidents exemplify how investments in public health emergency preparedness can enhance health outcomes in traditional areas of public health.


title: Surgical outcome of laparoscopic surgery, including laparoendoscopic single-site surgery, for retroperitoneal paraganglioma compared with adrenal pheochromocytoma.

text: OBJECTIVE Paraganglioma (PGL) is a rare type of tumor that arises from the extra-adrenal paraganglia. A PGL tumor hypersecretes catecholamines and causes symptoms identical to those in patients with hyper-functioning adrenal pheochromocytoma (PCC). In this study, we compared the surgical outcome of laparoscopic surgery, including laparoendoscopic single-site (LESS) surgery, in patients with PCC and patients with retroperitoneal solitary PGL. METHODS The records of 49 patients with PCC and 9 patients with unilateral retroperitoneal PGL at our institution from January 2001 to March 2013 were retrospectively reviewed. Multiple tumors, tumors suspected of being malignant preoperatively, and tumors operated on using a retroperitoneal approach were excluded from the study. RESULTS Each group was equivalent with respect to patient background, hemodynamic variables, and preoperative biochemical assessments, including plasma catecholamine levels and catecholamine levels in 24-hour urine samples. The mean operative time was significantly longer in the PGL group (149.4 ± 56.5 minutes v 189.8 ± 44.9 minutes, P=0.019). In univariate and multivariate analyses, tumor size ≥ 50 mm and PGL were statistically significant factors that predicted prolonged operative time. Intraoperative hypotension occurred in 15 patients in the PCC group and in 8 patients in the PGL group, and the difference was statistically significant (P=0.002). One postoperative complication in the PCC group and two postoperative complications (Clavien-Dindo grade II or higher) in the PGL group were observed, and the difference was statistically significant (P=0.012). Twenty-two patients in this series underwent LESS surgery (PCC: n=19; PGL: n=3), and there was no statistically significant difference in the perioperative outcomes between the two groups. CONCLUSIONS The present results demonstrate that the operation for solitary extraperitoneal PGL required a longer operative time and had more hypotensive episodes and higher postoperative morbidity than the PCC group. Though the perioperative outcome of LESS surgery for PGL is comparable to that of PCC, we should treat the patients with PGL accordingly.


title: Vaginal Myomectomy for Prolapsed Submucous Fibroid: It is Not Only About Size.

text: Leiomyoma of the uterus, also called fibroids, are common in women. In this case report, we describe the case of a nulliparous woman with a large, prolapsed submucous uterine leiomyoma of 10 × 11 cm was vaginally impacted. The aim is to highlight the challenges in managing such uncommon clinical scenario focusing on the factors predicting the success of vaginal myomectomy including the size of the myoma but also the role of vaginal laxity to allow the steps of devascularization, detachment, and removal of the myoma. We also describe the preoperative and intraoperative methods that can be used to minimize intraoperative blood loss and enhance the safety and feasibility of the surgical procedure. Gonadotropin therapy was not applicable in our patient, and other treatments were also unavailable such as temporary ligation of uterine arteries, while others were unsuccessful like devascularization by hysteroscopy, twisting, and ligation of the pedicle. The final resort used in our case was morcellation of the myoma with intact pedicle, which should be attempted by experienced gynecologic surgeons only.


title: Flavivirus RNA methylation.

text: The 5' end of eukaryotic mRNA contains the type-1 (m7GpppNm) or type-2 (m7GpppNmNm) cap structure. Many viruses have evolved various mechanisms to develop their own capping enzymes (e.g. flavivirus and coronavirus) or to 'steal' caps from host mRNAs (e.g. influenza virus). Other viruses have developed 'cap-mimicking' mechanisms by attaching a peptide to the 5' end of viral RNA (e.g. picornavirus and calicivirus) or by having a complex 5' RNA structure (internal ribosome entry site) for translation initiation (e.g. picornavirus, pestivirus and hepacivirus). Here we review the diverse viral RNA capping mechanisms. Using flavivirus as a model, we summarize how a single methyltransferase catalyses two distinct N-7 and 2'-O methylations of viral RNA cap in a sequential manner. For antiviral development, a structural feature unique to the flavivirus methyltransferase was successfully used to design selective inhibitors that block viral methyltransferase without affecting host methyltransferases. Functionally, capping is essential for prevention of triphosphate-triggered innate immune activation; N-7 methylation is critical for enhancement of viral translation; and 2'-O methylation is important for subversion of innate immune response during viral infection. Flaviviruses defective in 2'-O methyltransferase are replicative, but their viral RNAs lack 2'-O methylation and are recognized and eliminated by the host immune response. Such mutant viruses could be rationally designed as live attenuated vaccines. This concept has recently been proved with Japanese encephalitis virus and dengue virus. The findings obtained with flavivirus should be applicable to other RNA viruses.


title: Advance care planning for patients with chronic respiratory diseases: a systematic review of preferences and practices.

text: BACKGROUND Advance care planning (ACP) supports patients in identifying and documenting their preferences and timely discussing them with their relatives and healthcare professionals (HCPs). Since the British Thoracic Society encourages ACP in chronic respiratory disease, the objective was to systematically review ACP practice in chronic respiratory disease, attitudes of patients and HCPs and barriers and facilitators related to engagement in ACP. METHODS We systematically searched 12 electronic databases for empirical studies on ACP in adults with chronic respiratory diseases. Identified studies underwent full review and data extraction. RESULTS Of 2509 studies, 21 were eligible: 10 were quantitative studies. Although a majority of patients was interested in engaging in ACP, ACP was rarely carried out. Many HCPs acknowledged the importance of ACP but were hesitant to initiate it. Barriers to engagement in ACP were the complex disease course of patients with chronic respiratory diseases, HCPs' concern of taking away patients' hopes and lack of continuity of care. The identification of trigger points and training of HCPs on how to communicate sensitive topics were identified as facilitators to engagement in ACP. CONCLUSIONS In conclusion, ACP is surprisingly uncommon in chronic respiratory disease, possibly due to the complex disease course of chronic respiratory diseases and ambivalence of both patients and HCPs to engage in ACP. Providing patients with information about their disease can help meeting their needs. Additionally, support of HCPs through identification of trigger points, training and system-related changes can facilitate engagement in ACP. SYSTEMATIC REVIEW REGISTRATION NUMBER CRD42016039787.


Implications for Telehealth in a Postpandemic Future: Regulatory and Privacy Issues.


title: Analysis of the interaction between tropomyosin allergens and antibodies using a biosensor based on imaging ellipsometry.

text: A biosensor based on high spatial resolution imaging ellipsometry has been studied to examine its role in the rapid detection and analysis of the tropomyosin allergen existing in crustaceans. This methodology has been established for detection of the tropomyosin allergen and includes ligand screening, the determination of sensitivity, and a comparison with traditional detection methods. Three kinds of monoclonal antibodies (2F9, 4C7, and 2H6) known to have a high bioactivity against the tropomyosin allergen were screened and separately immobilized as ligands on a silicon wafer surface, thus allowing them to capture the tropomyosin allergen. Resulting changes on the wafer surface were visualized in gray scale variation on an ellipsometry image. Images showed that these antibodies are able to recognize the presence of the tropomyosin allergen in shrimp and crab with sensitivity of 1 mg L(-1), and at a detecting time of approximately 30 min for an extracted sample. This preliminary study has shown that the detection of the tropomyosin allergen is rapid and specific when using this type of assay on products containing shrimp and crab. When compared with the enzyme-linked immunosorbent assay, the biosensor based on imaging ellipsometry is able to perform a fast label-free analysis.


title: RadioGraphics Update: Medical 3D Printing for the Radiologist.

text: Editor's Note.-Articles in the RadioGraphics Update section provide current knowledge to supplement or update information found in full-length articles previously published in RadioGraphics. Authors of the previously published article provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes. Articles in this section are published solely online and are linked to the original article.


title: Liposomal bupivacaine for the management of postsurgical donor site pain in patients with burn injuries: a case series from two institutions.

text: Donor site pain associated with skin graft procedures is frequently intense and difficult to treat. Liposomal bupivacaine, a prolonged-release local anesthetic indicated for single-dose administration to produce postsurgical analgesia, may be a viable option in managing donor site pain.


title: Donor site healing dynamics: molecular, histological, and noninvasive imaging assessment in a porcine model.

text: Understanding the physiology of donor site healing will lead to advances in how these wounds are treated and may ultimately allow faster healing, more frequent autografting, and more effective care of the burn-injured patient. Unfortunately, a paucity of data exists regarding perfusion metrics over the course of donor site healing. Furthermore, there are no studies that interrelate indices of perfusion with the molecular and cellular processes of donor site healing. Male Duroc pigs were anesthetized and donor site wounds were created using a Zimmer dermatome at a depth of 0.060 inch (1.52 mm). Digital photographs, laser Doppler images, and punch biopsies were obtained before and after excision and on days 2, 4, 7, 9, 11, 14, and 16 until wounds were healed. RNA isolation was performed and quantitative polymerase chain reaction was used to examine differential gene expression over the time course. Formalin-fixed biopsies were embedded in paraffin, sectioned, stained, and examined. Wound surfaces were 83% re-epithelialized by day 16. Perfusion peaked on day 2 then declined, but it remained significantly elevated compared to before excision (P < .05). From day 9 onward, mean perfusion units were not significantly different from baseline (P < .05). Twenty-two representative genes were selected for examination. RNA expression of collagen, tenascin-cytoactin, inflammatory cytokines, remodeling enzymes, growth factors, and Wnt was increased. Inflammatory cells and cytokines were demonstrated histologically. Nuclei per high powered field peaked at day 7 and neodermal thickness increased daily to day 14. A novel porcine model for donor site wound healing that interrelates re-epithelilaizationand perfusion with molecular and cellular indices has been demonstrated.


title: Cystic duct closure by sealing with bipolar electrocoagulation.

text: BACKGROUND Cystic duct leakage after cholecystectomy is not uncommon and is a potentially serious complication. The aim of this study was to assess a bipolar sealing system (LigaSure) for closure of the cystic duct. METHODS The records from consecutive laparoscopic cholecystectomies performed in 2 hospitals with closure of the cystic duct with LigaSure after informed consent were recorded and complications and morbidity registered. The records were compared with those of patients undergoing laparoscopic cholecystectomy with closure of the cystic duct with clips during the same period. RESULTS During the study period, 218 laparoscopic cholecystectomies were performed; 102 of these were performed with the LigaSure. One patient was excluded due to violation of the protocol. We experienced no cases of cystic duct leakage, but in one patient, bile leakage from the gallbladder bed was observed probably due to a small aberrant duct. CONCLUSION The LigaSure system was safe and effective for closure and division of the cystic duct in laparoscopic cholecystectomy.


Chest CT Findings and Clinical Conditions of Coronavirus Disease (COVID-19).


title: Structural and Molecular Evidence Suggesting Coronavirus-driven Evolution of Mouse Receptor.

text: Hosts and pathogens are locked in an evolutionary arms race. To infect mice, mouse hepatitis coronavirus (MHV) has evolved to recognize mouse CEACAM1a (mCEACAM1a) as its receptor. To elude MHV infections, mice may have evolved a variant allele from the Ceacam1a gene, called Ceacam1b, producing mCEACAM1b, which is a much poorer MHV receptor than mCEACAM1a. Previous studies showed that sequence differences between mCEACAM1a and mCEACAM1b in a critical MHV-binding CC' loop partially account for the low receptor activity of mCEACAM1b, but detailed structural and molecular mechanisms for the differential MHV receptor activities of mCEACAM1a and mCEACAM1b remained elusive. Here we have determined the crystal structure of mCEACAM1b and identified the structural differences and additional residue differences between mCEACAM1a and mCEACAM1b that affect MHV binding and entry. These differences include conformational alterations of the CC' loop as well as residue variations in other MHV-binding regions, including β-strands C' and C'' and loop C'C''. Using pseudovirus entry and protein-protein binding assays, we show that substituting the structural and residue features from mCEACAM1b into mCEACAM1a reduced the viral receptor activity of mCEACAM1a, whereas substituting the reverse changes from mCEACAM1a into mCEACAM1b increased the viral receptor activity of mCEACAM1b. These results elucidate the detailed molecular mechanism for how mice may have kept pace in the evolutionary arms race with MHV by undergoing structural and residue changes in the MHV receptor, providing insight into this possible example of pathogen-driven evolution of a host receptor protein.


Impact of COVID-19 on Traditional Healthcare Associated Infection Prevention Efforts - CORRIGENDUM.


title: Opportunists and opportunities: the 2010 SHEA Lecture.

text: My experience as a hospital epidemiologist at the National Institutes of Health Clinical Center has underscored the importance of aggressively managing infection with opportunistic pathogens and of taking advantage of opportunities as they arise (most often as crises). I review selected aspects of my career and use these as examples of the opportunists and opportunities now facing healthcare epidemiology.


title: Breath detection by transcutaneous electromyography of the diaphragm and the Graseby capsule in preterm infants.

text: OBJECTIVE To compare triggering, breath detection and delay time of the Graseby capsule (GC) and transcutaneous electromyography of the diaphragm (dEMG) in spontaneous breathing preterm infants. METHODS In this observational study, a 30 minutes respiration measurement was conducted by respiratory inductance plethysmography (RIP), the GC, and dEMG in stable preterm infants. Triggering was investigated with an in vitro set-up using the Infant Flow® SiPAPTM system. The possibility to optimize breath detection was tested by developing new algorithms with the abdominal RIP band (RIPAB ) as gold standard. In a subset of breaths, the delay time was calculated between the inspiratory onset in the RIPAB signal and in the GC and dEMG signal. RESULTS Fifteen preterm infants with a mean gestational age of 28 ± 2 weeks and a mean birth weight of 1086 ± 317 g were included. In total, 14 773 breaths were analyzed. Based on the GC and dEMG signal, the Infant Flow® SiPAP™ system, respectively, triggered 67.8% and 62.6% of the breaths. Breath detection was improved to 99.9% for the GC and 113.4% for dEMG in new algorithms. In 1492 stable breaths, the median delay time of inspiratory onset detection was +154 ms (IQR +118 to +164) in the GC and -50 ms (IQR -90 to -22) in the dEMG signal. CONCLUSION Breath detection using the GC can be improved by optimizing the algorithm. Transcutaneous dEMG provides similar breath detection but with the advantage of detecting the onset of inspiration earlier than the GC.


title: Mandibular Reconstruction by Using a Liquid Nitrogen-Treated Autograft in a Dog with an Oral Tumor.

text: A 10 yr old intact female German shepherd dog presented with a large peripheral odontogenic fibroma and malignant melanoma on her lower jaw. The tumor was resected with a unilateral subtotal rostral hemimandibulectomy. After the mandible was removed, it was devitalized intraoperatively by freezing it in liquid nitrogen. It was subsequently reimplanted. New bone tissue formed in the gap between the frozen bone and the host bone. The regenerated bone contained osteocytes, osteoblasts, and blood vessels. The cosmetic appearance of the dog was preserved. The dog had normal mastication. The malignant melanoma recurred rostral of the left canine tooth at 159 days after the reconstruction surgery. A subtotal hemimandibulectomy was consequently performed. This is the first reported case of mandibular reconstruction using a liquid nitrogen-treated autograft in a dog with oral tumors.


title: Pulmonary embolism in acute medicine: a case-based review incorporating latest guidelines in the COVID-19 era.

text: Pulmonary embolism remains an important cause of morbidity and mortality in the UK, particularly following the outbreak of the novel coronavirus 2019 (COVID-19), where those infected have an increased prevalence of venous thromboembolic events. The pathophysiology in COVID-19 patients is thought to relate to a thromboinflammatory state within the pulmonary vasculature, triggered by the infection, but other risk factors such as reduced mobility, prolonged immobilisation and dehydration are likely to contribute. Several societies have released comprehensive guidelines emphasising the importance of risk stratification in patients with acute pulmonary embolism. They advocate the use of clinically validated risk scores in conjunction with biochemical and imaging results. Patients with mild disease can now be managed in the outpatient setting and with newly developed therapies, such as catheter-directed thrombolysis, becoming available in more centres, treatment options for those with more severe disease are also expanding. This article presents four theoretical but realistic cases, each diagnosed with acute pulmonary embolism, but differing in levels of severity. These demonstrate how the guidelines can be applied in a clinical setting, with particular focus on risk stratification and management.


title: Dendritic cell targeted chitosan nanoparticles for nasal DNA immunization against SARS CoV nucleocapsid protein.

text: This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for noninvasive receptor mediated gene delivery to nasal resident DCs. The pDNA loaded biotinylated chitosan nanoparticles were prepared using a complex coacervation process and characterized for size, shape, surface charge, plasmid DNA loading and protection against nuclease digestion. The pDNA loaded biotinylated chitosan nanoparticles were targeted with bifunctional fusion protein (bfFp) vector for achieving DC selective targeting. The bfFp is a recombinant fusion protein consisting of truncated core-streptavidin fused with anti-DEC-205 single chain antibody (scFv). The core-streptavidin arm of fusion protein binds with biotinylated nanoparticles, while anti-DEC-205 scFv imparts targeting specificity to DC DEC-205 receptor. We demonstrate that intranasal administration of bfFp targeted formulations along with anti-CD40 DC maturation stimuli enhanced magnitude of mucosal IgA as well as systemic IgG against N protein. The strategy led to the detection of augmented levels of N protein specific systemic IgG and nasal IgA antibodies. However, following intranasal delivery of naked pDNA no mucosal and systemic immune responses were detected. A parallel comparison of targeted formulations using intramuscular and intranasal routes showed that the intramuscular route is superior for induction of systemic IgG responses compared with the intranasal route. Our results suggest that targeted pDNA delivery through a noninvasive intranasal route can be a strategy for designing low-dose vaccines.


title: One-year safety and efficacy study of arformoterol tartrate in patients with moderate to severe COPD.

text: BACKGROUND Arformoterol tartrate (arformoterol, 15 μg bid) is a nebulized long-acting β2-agonist approved for maintenance treatment of COPD. METHODS This was a multicenter, double-blind, randomized, placebo-controlled study. Patients (aged ≥ 40 years with baseline FEV1 ≤ 65% predicted, FEV1 > 0.50 L, FEV1/FVC ≤ 70%, and ≥ 15 pack-year smoking history) received arformoterol (n = 420) or placebo (n = 421) for 1 year. The primary assessment was time from randomization to respiratory death or first COPD exacerbation-related hospitalization. RESULTS Among 841 patients randomized, 103 had ≥ 1 primary event (9.5% vs 15.0%, for arformoterol vs placebo, respectively). Patients who discontinued treatment for any reason (39.3% vs 49.9%, for arformoterol vs placebo, respectively) were followed for up to 1 year postrandomization to assess for primary events. Fewer patients receiving arformoterol than placebo experienced COPD exacerbation-related hospitalizations (9.0% vs 14.3%, respectively). Twelve patients (2.9%) receiving arformoterol and 10 patients (2.4%) receiving placebo died during the study. Risk for first respiratory serious adverse event was 50% lower with arformoterol than placebo (P = .003). Numerically more patients on arformoterol (13; 3.1%) than placebo (10; 2.4%) experienced cardiac serious adverse events; however, time-to-first cardiac serious adverse event was not significantly different. Improvements in trough FEV1 and FVC were greater with arformoterol (least-squares mean change from baseline vs placebo: 0.051 L, P = .030 and 0.075 L, P = .018, respectively). Significant improvements in quality of life (overall St. George's Hospital Respiratory Questionnaire and Clinical COPD Questionnaire) were observed with arformoterol vs placebo (P < .05). CONCLUSIONS Arformoterol demonstrated an approximately 40% lower risk of respiratory death or COPD exacerbation-related hospitalization over 1 year vs placebo. Arformoterol was well-tolerated and improved lung function vs placebo. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00909779; URL: www.clinicaltrials.gov.


title: All India Ophthalmological Society - Eye Bank Association of India consensus statement on guidelines for cornea and eyebanking during COVID-19 era.

text: The COVID-19 pandemic has brought with it the huge burden of mortality and morbidity across the world and the added effects of the mandatory lockdown measures to try and control the spread. A number of aspects of healthcare including eye donation and eye collection require adequate safety precautions in place to keep both the involved healthcare workers and patients safe. This paper highlights the consensus-based guidelines by an expert panel on how to restart eye banking and eye collection services and carry out emergency corneal surgeries during this COVID-19 time. These guidelines will be applicable to all eye banks across the country and should help ophthalmologists and eye banking staff to restart eye banking while safeguarding themselves and their patients.


title: Posterior circulation CT angiography collaterals predict outcome of endovascular acute ischemic stroke therapy for basilar artery occlusion.

text: INTRODUCTION The natural history of acute ischemic stroke (AIS) due to basilar artery occlusion (BAO) is poor. Endovascular reperfusion therapy (EVT) improves recanalization rates in patients with emergent large vessel intracranial occlusion. OBJECTIVE To examine the hypothesis that good collateral patterns identified by pretreatment CT angiography (CTA) might be associated with favorable outcomes after EVT. METHODS We conducted a retrospective chart review of patients presenting with AIS due to BAO in a tertiary care stroke center during a 4-year period. BAO was diagnosed by CTA in all cases. Admission stroke severity was documented using the National Institute of Health Stroke Scale (NIHSS) score. Pretreatment collateral score for posterior circulation was defined as follows: 0, no posterior communicating artery (PCOM); 1, unilateral PCOM; 2, bilateral PCOM. Favorable outcome was defined as modified Rankin Scale score of 0-2 at 3 months. RESULTS A total of 21 patients with AIS due to BAO (age range 31-84 years, median admission NIHSS score: 18 points, range 2-38) underwent EVT. Eleven of 21 patients (52.4%) had bilateral PCOMs, while unilateral PCOM was seen in 3 patients (14.3%). Patients with bilateral PCOMs tended (p=0.261) to have less severe stroke at admission than those with absent/unilateral PCOM (median NIHSS score 18 vs 27 points). Neurological improvement during hospitalization (quantified by the median decrease in NIHSS score) and the rate of 3-month functional independence were greater in patients with good collaterals (16 vs 0 points (p=0.016) and 72.7% vs 0% (p=0.001)). CONCLUSIONS The presence of bilateral PCOMs on pretreatment CTA appears to be associated with more favorable outcomes in BAO treated with EVT.


Community engagement in times of COVID-19: Lessons from neo-Vaishnavite practices.


title: External fixation of proximal tracheal airway stents: a modified technique.

text: Treatment of subglottic and proximal tracheal stenosis for nonsurgical candidates includes tracheostomy, Montgomery T tubes, and silicone stents. When used in lesions with concomitant malacia, silicone stents have a high incidence of migration. We describe a simple and effective technique of securing endoluminal stents using an Endo Close suturing device (Coviden, Boston, MA) and an external silicone button in 9 consecutive patients.


title: Hesitance towards voluntary medical male circumcision in Lesotho: reconfiguring global health governance.

text: Drawing on work examining HIV prevention initiatives in Lesotho, this paper considers the hesitation of national state actors towards the new strategy for HIV prevention - voluntary medical male circumcision (VMMC). Lesotho offers a representative case study on global health governance, given the country's high HIV burden and heavy dependence on foreign donor nations to implement local HIV prevention initiatives. In this paper, I use the case of VMMC opposition in Lesotho to examine how the new era of 'partnerships' has shifted the architecture of contemporary global health, specifically considering how global agreements are translated or negotiated into local practice. I argue that Lesotho's domestic policy-makers, in employing national statistics to assess if VMMC is an effective approach to addressing the local epidemic, are asserting a claim of expertise. In doing so, they challenge the traditional structures of global health politics, which have largely been managed by experts and funders from and in the global North. I explore the development of global VMMC policy, what drives Lesotho's resistance to comply, and consider the impact renegotiation efforts may have on future global health architecture.


title: Visualization of somatostatin receptors in prostate cancer and its bone metastases with Ga-68-DOTATOC PET/CT.

text: PURPOSE To assess DOTATOC-affine somatostatin receptor expression in advanced prostate cancer and its bone metastases with regard to DOTATOC-mediated receptor therapies, using a Ga-68-DOTATOC PET/CT. PROCEDURES Twenty consecutive patients with advanced prostate cancer underwent bone scintigraphy, followed by Ga-68-DOTATOC PET/CT within 3 weeks. Through side-by-side comparison with bone scintigraphy, the number of visible bone metastases on PET was determined. In addition, in cases of visible metastases, the maximum standard uptake value (SUV(max)) of Ga-68-DOTATOC was measured in the metastases and in normal bone. In patients who did not undergo a prostatectomy (n = 12), the SUV(max) was additionally measured in the prostate and in adjacent tissue. For focal lesions, the difference in SUV(max) (Delta SUV(max)) between the metastases and normal bone was calculated. For patients still having their prostate, a Delta SUV(max) between the prostate and its adjacent tissue was calculated. RESULTS Sixty four of 216 metastases (30%) were visible in 13 patients with focal metastases. Of six patients with diffuse metastases (superscan), one showed diffuse metastases, three showed a total of ten focal metastases, and two showed no correlate on PET. One patient with a neuroendocrine prostate cancer showed no correlate on PET. The maximum Delta SUV(max) between metastases and normal bone was 4.9 (mean = 1.6 +/- 0.9) and between the prostate and adjacent tissue 5.9 (mean = 2.8 +/- 1.6). CONCLUSIONS In prostate cancer and its bone metastases, DOTATOC-affine somatostatin receptors (subtype 2 and 5) can be visualized with Ga-68-DOTATOC PET/CT. But their expression is so weak that other conjugates should be tested for receptor-mediated therapies which are better at addressing the prostate cancer-specific somatostatin receptor subtypes 1 and 4-or even other receptors.


title: Prognostic factors of functional outcome after hip fracture surgery: a systematic review.

text: Objective this systematic review aimed to identify immutable and modifiable prognostic factors of functional outcomes and their proposed mechanism after hip fracture surgery. Design systematic search of MEDLINE, Embase, CINAHL, PEDRO, OpenGrey and ClinicalTrials.gov for observational studies of prognostic factors of functional outcome after hip fracture among surgically treated adults with mean age of 65 years and older. Study selection, quality assessment, and data extraction were completed independently by two reviewers. The Quality in Prognosis Studies Tool was used for quality assessment and assigning a level of evidence to factors. Proposed mechanisms for reported associations were extracted from discussion sections. Results from 33 studies of 9,552 patients, we identified 25 prognostic factors of functional outcome after hip fracture surgery. We organised factors into groups: demographics, injury and comorbidities, body composition, complications, and acute care. We assigned two factors a weak evidence level-anaemia and cognition. We assigned Parkinson's disease an inconclusive evidence level. We could not assign an evidence level to the remaining 22 factors due to the high risk of bias across studies. Frailty was the proposed mechanism for the association between anaemia and functional outcome. Medication management, perceived potential, complications and time to mobility were proposed as mechanisms for the association between cognition and functional outcome. Conclusion we identified one modifiable and one immutable prognostic factor for functional outcomes after hip fracture surgery. Future research may target patients with anaemia or cognitive impairment by intervening on the prognostic factor or the underlying mechanisms.


Chronic non-communicable diseases: a sacrifice on the altar of COVID-19?


title: 111In-bevacizumab imaging of renal cell cancer and evaluation of neoadjuvant treatment with the vascular endothelial growth factor receptor inhibitor sorafenib.

text: UNLABELLED Clear cell renal cell cancer (ccRCC) prominently expresses vascular endothelial growth factor-A (VEGF-A), and new treatment strategies for renal cell cancer (RCC) aim at the inhibition of VEGF-VEGF receptor signaling. This study explores the ability of (111)In-bevacizumab scintigraphy to depict RCC and to evaluate response to neoadjuvant treatment with sorafenib, a VEGF receptor inhibitor. METHODS The ability to depict RCC with (111)In-bevacizumab scintigraphy was tested in 14 patients scheduled to undergo a tumor nephrectomy; of these, 9 RCC patients were treated in a neoadjuvant setting with sorafenib (400 mg orally twice a day). In the latter group, baseline and posttreatment (111)In-bevacizumab scans were compared. The intratumoral distribution of (111)In-bevacizumab was determined scintigraphically ex vivo in a 1-cm lamella of the resected tumorous kidney. Expression of VEGF-A, glucose transporter-1, carbonic anhydrase IX, α-smooth-muscle actin, and Ki67 was determined by immunohistochemistry and compared with the local concentration of (111)In-bevacizumab. Additionally, the VEGF-A content in tumor samples was determined quantitatively by enzyme-linked immunosorbent assay. RESULTS In all 5 non-neoadjuvant-treated patients, preferential accumulation of (111)In-bevacizumab was observed in the tumors. All ccRCC lesions with enhanced (111)In-bevacizumab targeting expressed high levels of VEGF-A. Treatment with sorafenib resulted in a significant decrease of (111)In-bevacizumab uptake in the tumor in the patients with ccRCC (mean change, -60.5%; range, +1.5% to -90.1%). The decrease in uptake was due to destruction of the tumor neovasculature, whereas the VEGF-A expression remained intact. In the patient with papillary RCC, limited uptake without change after sorafenib was observed. CONCLUSION RCC lesions were clearly delineated with (111)In-bevacizumab scintigraphy. Neoadjuvant treatment with sorafenib resulted in a significant decrease of (111)In-bevacizumab uptake in RCC. (111)In-bevacizumab scintigraphy can be an attractive biomarker for response and needs further study.


Evolving a pathogen to be protective.


SAGES guidelines for laparoscopic ventral hernia repair.


This information provided by the Thoracic Imaging Section of the German Radiological Society is intended to give physicians recommendations on the use of thoracic imaging procedures in the context of the current COVID-19 pandemic. It represents the consensus of the authors based on the previous scientific knowledge and is intended to provide guidance for unified, structured CT reporting if COVID-19 pneumonia is suspected. The recommendations presented correspond to state of knowledge at the time of print and will be updated according to the results of ongoing and future scientific studies. KEY POINTS:: · COVID-19. · chest imaging. · German Radiological Society. CITATION FORMAT: · Vogel-Claussen J, Ley-Zaporozhan J, Agarwal P et al. Recommendations of the Thoracic Imaging Section of the German Radiological Society for clinical application of chest imaging and structured CT reporting in the COVID-19 pandemic. Fortschr Röntgenstr 2020; DOI: 10.1055/a-1174-8378.


title: [Improvement of operative conditions during a laparoscopic prosthetic sacral colpopexy for pelvic organ prolapse repair].

text: Actually, the choice of surgical approach for pelvic organ prolapse repair depends more on surgeon experience rather than patients characteristics. Laparoscopic sacral colpopexy seems to offer complete repair, low morbidity and satisfactory anatomic and functional results. This technique requires specially trained and experienced surgeons and optimal operative conditions. To improve feasibility of laparoscopic sacral colpopexy, we propose a simplified operative strategy to optimise this complex procedure.


title: Basics of continuous renal replacement therapy in pediatrics.

text: In the last three decades, significant advances have been made in the care of children requiring renal replacement therapy (RRT). The move from the use of only hemodialysis and peritoneal dialysis to continuous venovenous hemofiltration with or without dialysis (continuous renal replacement therapy, CRRT) has become a mainstay in many intensive care units. The move to CRRT is the result of greater clinical experience as well as advances in equipment, solutions, vascular access, and anticoagulation. CRRT is the mainstay of dialysis in pediatric intensive care unit (PICU) for critically ill children who often have hemodynamic compromise. The advantages of this modality include the ability to promote both solute and fluid clearance in a slow continuous manner. Though data exist suggesting that approximately 25% of children in any PICU may have some degree of renal insufficiency, the true need for RRT is approximately 4% of PICU admissions. This article will review the history as well as the progress being made in the provision of this care in children.


title: Categorization in Mechanically Ventilated Pediatric Subjects: A Proposed Method to Improve Quality.

text: BACKGROUND Thousands of children require mechanical ventilation each year. Although mechanical ventilation is lifesaving, it is also associated with adverse events if not properly managed. The systematic implementation of evidence-based practice through the use of guidelines and protocols has been shown to mitigate risk, yet variation in care remains prevalent. Advances in health-care technology provided the ability to stream data about mechanical ventilation and therapeutic response. Through these advances, a computer system was developed to enable the coupling of physiologic and ventilation data for real-time interpretation. Our aim was to assess the feasibility and utility of a newly developed patient categorization and scoring system to objectively measure compliance with standards of care. METHODS We retrospectively categorized the ventilation and oxygenation statuses of subjects within our pediatric ICU utilizing 15 rules-based algorithms. Targets were predetermined based on generally accepted practices. All patient categories were calculated and presented as a percent score (0-100%) of acceptable ventilation, acceptable oxygenation, barotrauma-free, and volutrauma-free states. RESULTS Two hundred twenty-two subjects were identified and analyzed encompassing 1,578 d of mechanical ventilation. Median age was 3 y, median ideal body weight was 14.7 kg, and 63% were male. The median acceptable ventilation score was 84.6%, and the median acceptable oxygenation score was 70.1% (100% being maximally acceptable). Potential for ventilator-induced lung injury was broken into 2 components: barotrauma and volutrauma. There was very little potential for barotrauma, with a median barotrauma-free state of 100%. Median potential for a volutrauma-free state was 56.1%. CONCLUSIONS We demonstrate the first patient categorization system utilizing a coordinated data-banking system and analytics to determine patient status and a surveillance of mechanical ventilation quality. Further research is needed to determine whether interventions such as visual display of variance from goal and patient categorization summaries can improve outcomes. (ClinicalTrials.gov registration NCT02184208.).


title: [Analysis of myocardial injury in patients with COVID-19 and association between concomitant cardiovascular diseases and severity of COVID-19].

text: Objective: To evaluate the cardiovascular damage of patients with COVID-19, and determine the correlation of serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (cTnI) with the severity of COVID-19, and the impact of concomitant cardiovascular disease on severity of COVID-19 was also evaluated. Methods: A cross-sectional study was designed on 150 consecutive patients with COVID-19 in the fever clinic of Tongji Hospital in Wuhan from January to February in 2020, including 126 mild cases and 24 cases in critical care. Both univariate and multivariate logistic regression were used to analyze the correlation of past medical history including hypertension, diabetes and coronary heart disease (CHD) , as well as the levels of serum NT-proBNP and cTnI to the disease severity of COVID-19 patients. Results: Age, hypersensitive C-reactive protein(hs-CRP) and serum creatinine levels of the patients were higher in critical care cases than in mild cases(all P<0.05). Prevalence of male, elevated NT-proBNP and cTnI, hypertension and coronary heart disease were significantly higher in critical cases care patients than in the mild cases(all P<0.05). Univariate logistic regression analysis showed that age, male, elevated NT-proBNP, elevated cTnI, elevated hs-CRP, elevated serum creatinine, hypertension, and CHD were significantly correlated with critical disease status(all P<0.05). Multivariate logistic regression analysis showed that elevated cTnI(OR=26.909, 95%CI 4.086-177.226, P=0.001) and CHD (OR=16.609, 95%CI 2.288-120.577, P=0.005) were the independent risk factors of critical disease status. Conclusions: COVID-19 can significantly affect the heart function and lead to myocardial injury. The past medical history of CHD and increased level of cTnI are two independent determinants of clinical disease status in patients with COVID-19.


title: CDC Recommendations for Hepatitis C Screening Among Adults - United States, 2020.

text: Hepatitis C virus (HCV) infection is a major source of morbidity and mortality in the United States. HCV is transmitted primarily through parenteral exposures to infectious blood or body fluids that contain blood, most commonly through injection drug use. No vaccine against hepatitis C exists and no effective pre- or postexposure prophylaxis is available. More than half of persons who become infected with HCV will develop chronic infection. Direct-acting antiviral treatment can result in a virologic cure in most persons with 8-12 weeks of all-oral medication regimens. This report augments (i.e., updates and summarizes) previously published recommendations from CDC regarding testing for HCV infection in the United States (Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rec 2012;61[No. RR-4]). CDC is augmenting previous guidance with two new recommendations: 1) hepatitis C screening at least once in a lifetime for all adults aged ≥18 years, except in settings where the prevalence of HCV infection is <0.1% and 2) hepatitis C screening for all pregnant women during each pregnancy, except in settings where the prevalence of HCV infection is <0.1%. The recommendation for HCV testing that remains unchanged is regardless of age or setting prevalence, all persons with risk factors should be tested for hepatitis C, with periodic testing while risk factors persist. Any person who requests hepatitis C testing should receive it, regardless of disclosure of risk, because many persons might be reluctant to disclose stigmatizing risks.


title: Formation of bovine viral diarrhea virus E1-E2 heterodimers is essential for virus entry and depends on charged residues in the transmembrane domains.

text: The envelope of bovine viral diarrhea virus (BVDV) contains the glycoproteins Erns, E1 and E2. Complementation of a recombinant vesicular stomatitis virus (VSV) with BVDV glycoproteins resulted in infectious pseudotyped viruses. To elucidate the specific role of each of the single envelope glycoproteins during viral entry, pseudotypes were generated bearing the BVDV envelope proteins in different combinations. Pseudoviruses that contained E1 and E2 but not Erns were infectious, indicating that Erns is dispensable for virus entry. VSV/BVDV pseudotypes with chimeric proteins (the ectodomain of the BVDV glycoprotein and the transmembrane domain of the VSV-G protein) were not infectious. The fact that E1-E2 heterodimers were not detected if one of the proteins was chimeric indicated that the heterodimers are crucial for BVDV entry. It was shown by site-directed mutagenesis that the charged amino acids in the transmembrane domains of BVDV E1 (lysine and arginine) and the charged amino acid in the transmembrane domain of E2 (arginine) play a key role in heterodimer formation. Pseudoviruses bearing the mutation E2-R/A, where the charged amino acid was substituted by alanine, were not infectious, supporting the hypothesis that E1-E2 heterodimers are essential for BVDV entry.


title: Perioperative goal directed therapy using automated closed-loop fluid management: the future?

text: Although surgery has become much safer, it has also becoming increasingly more complex and perioperative complications continue to impact millions of patients worldwide each year. Perioperative hemodynamic optimization utilizing Goal Directed Therapy (GDT) has attracted considerable interest within the last decade due to its ability to improve postoperative short and long-term outcomes in patients undergoing higher risk surgeries. The concept of GDT in this context can be loosely defined as collecting data from minimally invasive hemodynamic monitors with the intention of using such data (flow-related parameters and/or dynamic parameters of fluid responsiveness) to titrate therapeutic interventions (intravenous fluids and/or inotropic therapy administration) with the ultimate aim of optimizing end organ tissue perfusion. Recently, the increasing amount of evidence supporting the implementation of GDT strategies has been considered so robust as to allow for the creation of national recommendations in the United Kingdom (UK), France, and Europe. These recommendations from such influential scientific societies and the potential clinical and economic benefits of GDT protocols need to also be examined within the current shift from a "pay for service" to a "pay for performance" health care system. This shift is strongly encouraged within emerging systems such as the Perioperative Surgical Home (PSH) paradigm from the United States. As a result, hospitals and clinicians around the world have become increasingly incentivized to implement perioperative hemodynamic optimization using GDT strategies within their departments. Unfortunately, its adoption continues to be quite limited and a lack of standardized criteria for perioperative fluid administrations has resulted in significant clinical variability among practitioners. This current review will provide a brief up-to-date overview of GDT, discuss current clinical practice, analyze why implementation has been limited and finally, describe the newer closed-loop GDT concept along with its potential risks and benefits.


title: Quality of life in patients undergoing hemodialysis or peritoneal dialysis treatment.

text: BACKGROUND Does the type of dialysis treatment make a difference to the quality of life (QoL) and mental health of renal patients in Athens? The study investigated the differences in 84 in-center hemodialysis (HD) and 60 continuous ambulatory peritoneal dialysis (CAPD/PD) patients. METHODS Patient-reported assessments included: WHOQOL-BREF inventory of World Health Organization, General Health Questionnaire (GHQ-28) of Goldberg, State-Trait Anxiety Inνentory, Center for Epidemiologic Studies Depression Scale (CES-D) and Multidimensional Health Locus of Control (MHLC). RESULTS Results indicated that HD patients reported lower QoL in the environment and social relationships domains. More symptoms were also reported in the GHQ-28 subscales of anxiety/insomnia and severe depression. This measurement includes sleep problems and suicidal thoughts. CONCLUSIONS The findings confirm the differences between the two treatment modalities, indicating that HD patients have poorer QoL in several aspects of their environment and their social relationships. Both groups reported elevated depression. However, HD patients reported more suicidal thoughts and sleep problems compared to PD patients.


A blueprint for robotic navigation: pre-clinical simulation for transanal total mesorectal excision (taTME).


title: Preoperative nutritional status is an important predictor of survival in patients undergoing surgery for renal cell carcinoma.

text: BACKGROUND The role of malnutrition has not been well studied in patients undergoing surgery for renal cell carcinoma (RCC). OBJECTIVE Our aim was to evaluate whether nutritional deficiency (ND) is an important determinant of survival following surgery for RCC. DESIGN, SETTING, AND PARTICIPANTS A total of 369 consecutive patients underwent surgery for locoregional RCC from 2003 to 2008. ND was defined as meeting one of the following criteria: body mass index <18.5 kg/m(2), albumin <3.5 g/dl, or preoperative weight loss ≥ 5% of body weight. INTERVENTION All patients underwent radical or partial nephrectomy. MEASUREMENTS Primary outcomes were overall and disease-specific mortality. Covariates included age, Charlson comorbidity index (CCI), preoperative anemia, tumor stage, Fuhrman grade, and lymph node status. Multivariate analysis was performed using a Cox proportional hazards model. Mortality rates were estimated using the Kaplan-Meier product-limit method. RESULTS AND LIMITATIONS Eighty-five patients (23%) were categorized as ND. Three-year overall and disease-specific survival were 58.5% and 80.4% in the ND cohort compared with 85.4% and 94.7% in controls, respectively (p<0.001). ND remained a significant predictor of overall mortality (hazard ratio [HR]: 2.41, 95% confidence interval [CI], 1.40-4.18) and disease-specific mortality (HR: 2.76; 95% CI, 1.17-6.50) after correcting for age, CCI, preoperative anemia, stage, grade, and nodal status. This study is limited by its retrospective nature. CONCLUSIONS ND is associated with higher mortality in patients undergoing surgery for locoregional RCC, independent of key clinical and pathologic factors. Given this mortality risk, it may be important to address nutritional status preoperatively and counsel patients appropriately.