title: Laparoscopic resection of a residual retroperitoneal tumor mass of nonseminomatous testicular germ cell tumors.

text: BACKGROUND Resection of a residual retroperitoneal tumor mass (RRRTM) is standard procedure after combination chemotherapy for metastatic nonseminomatous testicular germ cell tumors (NSTGCT). METHODS At the University Medical Center Groningen, 79 consecutive patients with disseminated NSTGCT were treated with cisplatin combination chemotherapy between 2005 and 2007. Laparoscopic RRRTM was performed for patients with RRTM located less than 5 cm ventrally or laterally from the aorta or the vena cava. The 29 patients who fulfilled the criteria had a median age of 25 years (range, 16-59 years). The stages of disease before chemotherapy treatment according to the Royal Marsden classification were 2A (n = 6, 21%), 2B (n = 14, 48%), 2C (n = 3, 10%), and 4 with a lymph node status of N2 (n = 6, 21%). RESULTS The median duration of laparoscopy was 198 min (range, 122-325 min). The median diameter of the RRTM was 21 mm (range, 11-47 mm). Laparoscopic resection was successful for 25 patients (86%). Conversion was necessary for three patients (10%): two due to bleeding and one because of obesity. One nonplanned hand-assisted procedure (3%) also had to be performed. Histologic examination of the specimens showed fibrosis or necrosis in 12 patients (41%), mature teratoma in 16 patients (55%), and viable tumor in 1 patient (3%). The median hospital stay was 1 day (range, 1-6 days). During a median follow-up period of 47 months (29-70 months), one patient experienced an early relapse (1 month after the end of treatment) (4%). CONCLUSION For properly selected patients, laparoscopic resection of RRTM is an improvement in the combined treatment of disseminated NSTGCT and associated with a short hospital stay, minimal morbidity, rapid recovery, and a neat cosmetic result. Long-term data to prove oncologic efficacy are awaited.


title: A systematic review exploring the content and outcomes of interventions to improve psychological safety, speaking up and voice behaviour.

text: BACKGROUND Having psychologically safe teams can improve learning, creativity and performance within organisations. Within a healthcare context, psychological safety supports patient safety by enabling engagement in quality improvement and encouraging staff to speak up about errors. Despite the low levels of psychological safety in healthcare teams and the important role it plays in supporting patient safety, there is a dearth of research on interventions that can be used to improve psychological safety or its related constructs. This review synthesises the content, theoretical underpinnings and outcomes of interventions which have targeted psychological safety, speaking up, and voice behaviour within a healthcare setting. It aims to identify successful interventions and inform the development of more effective interventions. METHODS A key word search strategy was developed and used to search electronic databases (PsycINFO, ABI/Inform, Academic search complete and PubMed) and grey literature databases (OpenGrey, OCLC WorldCat, Espace). Covidence, an online specialised systematic review website, was used to screen records. Data extraction, quality appraisal and narrative synthesis were conducted on identified papers. RESULTS Fourteen interventions were reviewed. These interventions fell into five categories. Educational interventions used simulation, video presentations, case studies and workshops while interventions which did not include an educational component used holistic facilitation, forum play and action research meetings. Mixed results were found for the efficacy or effectiveness of these interventions. While some interventions showed improvement in outcomes related to psychological safety, speaking up and voice, this was not consistently demonstrated across interventions. Included interventions' ability to demonstrate improvements in these outcomes were limited by a lack of objective outcome measures and the ability of educational interventions alone to change deeply rooted speaking up behaviours. CONCLUSION To improve our understanding of the efficacy or effectiveness of interventions targeting psychological safety, speaking up and voice behaviour, longitudinal and multifaceted interventions are needed. In order to understand whether these interventions are successful, more objective measures should be developed. It is recommended that future research involves end users in the design phase of interventions, target both group and organisational levels, ensure visible leader support and work across and within interdisciplinary teams. PROSPERO REGISTRATION NUMBER CRD42018100659.


title: The SAVE Technique : Large-Scale Experience for Treatment of Intracranial Large Vessel Occlusions.

text: BACKGROUND The stent retriever assisted vacuum-locked extraction (SAVE) technique was introduced as an effective thrombectomy method in stroke patients suffering from intracranial large vessel occlusion (LVO). This article presents our multicenter, large-scale experience with SAVE. METHODS The study involved a retrospective core team analysis of 200 patients undergoing mechanical thrombectomy using the SAVE technique due to intracranial LVO at 4 German centers. Primary endpoints were first-pass and overall complete/near complete reperfusion, defined as a modified thrombolysis in cerebral infarction (mTICI) score of 2c and 3. Secondary endpoints were the number of passes, time from groin puncture to reperfusion, embolization to new territories (ENT), postinterventional symptomatic intracranial hemorrhage (sICH), and favorable outcome at discharge, defined as a modified Rankin Scale (mRS) score ≤ 2. RESULTS The median age was 78 years (interquartile range IQR 68-85). Median National Institutes of Health stroke scale (NIHSS) at admission was 16 (IQR 12-20). Occlusions sites were: internal carotid artery (ICA-T) in 39/200 (19.5%), M1 in 126/200 (63%), M2 in 30/200 (15%), and others in 5/200 (2.5%) cases. The primary endpoints were documented in 114/200 (57% first pass mTICI 2c or 3) and 154/200 (77% overall mTICI 2c or 3) patients, respectively. The overall median time from groin puncture to reperfusion was 34 min (IQR 25-52) with a median of 1 (IQR 1-2) attempts. An ENT was observed in 3 patients (1.5%) and the rate of sICH was 2.6%. The rate of successful reperfusion (mTICI ≥ 2b) on final angiograms was 95%. At discharge, 73/200 (36.5%) patients revealed a favorable outcome. CONCLUSION Mechanical thrombectomy using the SAVE technique seems to be effective, fast and safe. First-line use of SAVE leads to high rates of complete and near complete reperfusion.


title: N-Myc-induced metabolic rewiring creates novel therapeutic vulnerabilities in neuroblastoma.

text: N-Myc is a transcription factor that is aberrantly expressed in many tumor types and is often correlated with poor patient prognosis. Recently, several lines of evidence pointed to the fact that oncogenic activation of Myc family proteins is concomitant with reprogramming of tumor cells to cope with an enhanced need for metabolites during cell growth. These adaptions are driven by the ability of Myc proteins to act as transcriptional amplifiers in a tissue-of-origin specific manner. Here, we describe the effects of N-Myc overexpression on metabolic reprogramming in neuroblastoma cells. Ectopic expression of N-Myc induced a glycolytic switch that was concomitant with enhanced sensitivity towards 2-deoxyglucose, an inhibitor of glycolysis. Moreover, global metabolic profiling revealed extensive alterations in the cellular metabolome resulting from overexpression of N-Myc. Limited supply with either of the two main carbon sources, glucose or glutamine, resulted in distinct shifts in steady-state metabolite levels and significant changes in glutathione metabolism. Interestingly, interference with glutamine-glutamate conversion preferentially blocked proliferation of N-Myc overexpressing cells, when glutamine levels were reduced. Thus, our study uncovered N-Myc induction and nutrient levels as important metabolic master switches in neuroblastoma cells and identified critical nodes that restrict tumor cell proliferation.


title: Neurocognitive Correlates of Internet Search Skills for eHealth Fact and Symptom Information in a Young Adult Sample.

text: As the Covid 19 crisis has revealed, the internet is a first-line tool for learning critical health-related information. However, internet searches are a complex and dynamic process that can be fraught with subtleties and potential error. The mechanics of searching for and using electronic health (eHealth) information is ostensibly cognitively demanding; yet we know little about the role of neurocognitive abilities in this regard. Fifty-six young adults completed two naturalistic eHealth search tasks: fact-finding (eHealth Fact) and symptom-diagnosis (eHealth Search). Participants also completed neurocognitive tests of attention, psychomotor speed, learning/memory, and executive functions. Shorter eHealth symptom-diagnosis search time was related to better executive functions, while better eHealth symptom-diagnosis search accuracy was related to better episodic and prospective memory. In contrast, neither eHealth Fact search time nor its accuracy were related to any of the neurocognitive measures. Our findings suggest a differential relationship between neurocognitive abilities and eHealth search behaviors among young adults such that higher-order abilities may be implicated in eHealth searches requiring greater synthesis of information. Future work should examine the cognitive architecture of eHealth search in persons with neurocognitive disorders, as well as that of other aspects of eHealth search behaviors (e.g., search term generation, website reliability, and decision-making).


title: Laparoscopic resection of adrenal neuroblastoma without image-defined risk factors: a prospective study on 21 consecutive pediatric patients.

text: BACKGROUND Over the last 20 years MIS has progressively gained popularity in children with cancer. We therefore aimed at evaluating the safety of Minimally Invasive Surgery (MIS) resection in a series of children affected by adrenal neuroblastoma (NB) presenting without Image-Defined Risk Factors (IDRFs). METHODS An Institutional protocol for MIS resection of adrenal NB in pediatric patients without IDRFs has been applied since 2008. Absence of IDRFs represented the main indication for MIS in NB, regardless of tumor size. All pediatric patients who underwent MIS for NB between January 2008 and May 2013 were included. Specific technical considerations, demographic data, and outcome have been recorded. RESULTS Twenty-one patients underwent MIS resection for IDRFs-negative adrenal NB. Nine of these patients experienced preoperative downgrading of IDRFs after chemotherapy. Radiological median diameter of the mass was 30 mm (range 10-83 mm). Median operative time was 90 min. Median hospital stay was 4 days. All patients were treated successfully, without serious intraoperative complications. One mild intraoperative hemorrhage occurred and was treated without the need for conversion to open surgery nor blood transfusion was required. No postoperative complications, including port-site or peritoneal metastases were experienced. CONCLUSIONS This study demonstrated the safety and effectiveness of MIS for the resection of adrenal NB without IDRFs in children. Pediatric surgeons dedicated to oncology should be aware of this alternative approach to open resection.


title: Azacitidine-associated pleuropericardial effusion in myelodysplastic syndrome: A case report.

text: Azacitidine, a deoxyribonucleic acid hypomethylating agent, is used in the treatment of myelodysplastic syndrome. Common adverse effects of azacitidine include bone marrow suppression, injection site reactions, nausea, vomiting, diarrhea, and fatigue. This report focuses on pleuropericardial effusions, an infrequently reported and potentially reversible adverse effect of azacitidine. In this case report, pleuropericardial effusion manifested as the sole radiographic finding in the evaluation of cough occurring during the eighth cycle of treatment with azacitidine. Symptoms and radiographic abnormalities resolved with corticosteroids and diuretics, and the patient could continue with therapy.


title: VATS Plication of the Diaphragm: A Descriptive Observational 10-Year Southampton Experience.

text: OBJECTIVE The aim of the study was to report the safety and efficacy of video-assisted thoracoscopic (VATS) plication of the diaphragm at our institution between 2006 and 2016. METHODS Adult patients selected on etiology and combination of investigations including plain chest x-ray, computed tomography of chest and abdomen, lung functions in supine and sitting positions, radiological/ultrasonic screening for diaphragmatic movement, and phrenic nerve conduction studies. We incorporated a triportal VATS and Endostitch device for plication, using CO2 insufflation to maximum 12 mm Hg. Bilateral simultaneous plication and high-risk patients were electively admitted to intensive therapy unit postoperatively. RESULTS Thirty-five patients (24 males) had their diaphragm plicated. The mean age was 56.6 years (range = 23-76 years). The mean body mass index was 32.1 (range = 22.2-45.4). Twenty one were right, 13 left, 2 patients had VATS simultaneous bilateral plication, and 1 had sequential VATS bilateral plication. Paralysis was idiopathic in 17, posttraumatic in 5, postremoval of mediastinal tumor in 4, and postcardiac surgery in 3. All patients presented with lifestyle-limiting dyspnea and orthopnea, three were on nocturnal noninvasive ventilation. Five were diabetic and 16 were smokers. The mean supine forced expiratory volume in the first second was 62.5% of predicted. Twenty two were performed by VATS (63%), three converted to thoracotomy, and 13 were open limited thoracotomy (historic). The mean hospital stay was 4.5 days (range = 1-18, mode 2 days). Intensive therapy unit admission was required in six patients for mechanical ventilation 0 to 3 days. Five patients (14%) had no improvement in symptoms. There were no deaths, no 30-day readmissions, and no long-term neuralgia in this series. CONCLUSIONS We found minimal access VATS plication of the diaphragm to be feasible and safe, but no firm conclusions should be drawn from our limited resources. We report the feasibility of concomitant bilateral VATS plication of the diaphragm in two adults, and this was not previously reported in the adult population. There is a need for further good quality, prospective studies, and randomized controlled studies evaluating efficacy of VATS diaphragmatic plication.


COVID-19 and the Financial Health of US Hospitals.


title: Single incision thoracoscopic sympathectomy for hyperhidrosis.

text: Thoracal sympatectomy for hyperhidrosis and vasospastic vascular diseases is a rare method of surgical treatment. Three patients (1 male, 2 female; mean age 27.6; between 25 and 30) with palmar hyperhidrosis and/or axillary and dorsal hyperhidrosis who underwent single port thoracoscopic sympatectomy were analysed for age, sex, time of operation room, intraoperative and postoperative complications and length of hospital stay. Mean operating room time was 70 min (between 30 and 120 min). Mean length of hospital stay was 1 day. No postoperative complications were noted. Single incision laparoscopic surgery for hyperhidrosis is a safe method of treatment and an alternative to laparoscopy.


title: Combined radiofrequency ablation and high-dose rate brachytherapy for early-stage non-small-cell lung cancer.

text: PURPOSE This retrospective analysis reports the results of patients with early-stage inoperable non-small-cell lung cancer treated with radiofrequency ablation (RFA) followed by adjuvant high-dose rate (HDR) brachytherapy. METHODS AND MATERIALS Seventeen medically inoperable patients with biopsy-proven Stage I non-small-cell lung cancer were treated with RFA followed by single fraction HDR brachytherapy. Brachytherapy catheters were inserted immediately after RFA, and one fraction of HDR brachytherapy was delivered on the same day. Doses of brachytherapy ranged from 14.4 to 20 Gy (median, 18 Gy). Patients were followed clinically and radiographically to determine tumor control and toxicity profile. RESULTS Median followup time was 22 months. Of the 17 patients, 3 patients have recurred locally. Each of the patients with local recurrences was originally treated for T2 disease. In total, three of seven cases with T2N0 disease experienced local recurrences, whereas all 9 patients with T1 disease were controlled locally. Five of the 17 patients required a chest tube posttreatment, and 1 patient developed an empyema. There were no deaths within 1 month of treatment. CONCLUSIONS RFA followed by HDR brachytherapy yields excellent local control with an acceptable toxicity profile for patients with otherwise inoperable early-stage lung cancer.


title: Uncovering the hidden villain within the human respiratory microbiome.

text: Respiratory tract infection increases the risk of secondary bacterial infection and causes mortality. Despite advances in the field of targeted molecular diagnostics, there are still failed attempts in identifying a valid causative etiological agent in a large proportion of respiratory tract infections. To date, a comprehensive list of human respiratory infection-associated eukaryotic viruses has been identified. However, there has been little progress towards the characterisation of the viruses that infect bacteria (phages), which are capable of mediating the transfer of virulence genes into non-pathogenic bacterial species to cause respiratory tract infections. With the advent of next-generation-sequencing, the application of an unbiased comparative metagenomic survey on the viral communities within the human respiratory tract may reveal to us how the phage virome changes between healthy individuals and respiratory tract infection patients. With this useful information, it will be feasible to develop an alternative phage-based diagnostic panel for respiratory tract infections. The review herein presents the current status of human airway microbiome research and highlights potential gaps which can be translated into research possibilities for future work on respiratory tract infection diagnosis.


title: Limb and back muscle activity adaptations to tripedal locomotion in dogs.

text: Alterations in muscle recruitment are key to the functional plasticity of the mammalian locomotor system. One particularly challenging situation quadrupeds may face is when the functionality of a limb is reduced or lost. To better understand how mammals manage in such situations and which muscular adaptations they exhibit when locomoting on three legs, we recorded the activity patterns of two limb and one back extensor muscle in nine dogs using surface electromyography. We compared the timing and the level of recruitment before and after the loss of a hindlimb was simulated. Both the intensity and the timing of the activity changed significantly in the m. vastus lateralis of the remaining hindlimb, consistent with this limb bearing a greater proportion of the body weight as well as with previously reported kinematic changes. In accordance with the greater body weight supported by the forelimbs, the m. triceps brachii showed first and foremost an increased level of excitation. The very asymmetrical changes in the timing and the level of activity in the m. longissimus dorsi reflects the highly asymmetrical functional requirements imposed on the trunk and the pelvis when one hindlimb is no longer involved in the production of locomotor work while the other hindlimb partially compensates the loss. Integration of our electromyographical findings with kinetic and kinematic results illustrates that dogs exhibited a well-coordinated response to the functional requirements of tripedalism and underlines the importance of moment-to-moment modulation in muscular recruitment for the functional plasticity of the mammalian locomotor system.


Laparoscopic gastric band slippage diagnosed with esophagogastroduodenoscopy in a 12-week gestation nulliparous patient.


title: Autophagy/virophagy: a "disposal strategy" to combat COVID-19.

text: Given the devastating consequences of the current COVID-19 pandemic and its impact on all of us, the question arises as to whether manipulating the cellular degradation (recycling, waste disposal) mechanism known as macroautophagy/autophagy (in particular, the selective degradation of virus particles, termed virophagy) might be a beneficial approach to fight the novel coronavirus, SARS-CoV-2. Knowing that "autophagy can reprocess everything", it seems almost inevitable that, sooner rather than later, a further hypothesis-driven work will detail the role of virophagy as a fundamental "disposal strategy" against COVID-19, yielding most needed therapeutic interventions. ABBREVIATIONS ATG, autophagy-related; CoV/CoVs coronavirus/coronaviruses; COVID-19, coronavirus disease 2019; MERS-CoV, Middle East respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.


US ventilator crisis brings patients and doctors face-to-face with life-or-death choices.


title: Utilization of sialylated glycans as coreceptors enhances the neurovirulence of serotype 3 reovirus.

text: Mammalian reoviruses display serotype-specific patterns of tropism and disease in the murine central nervous system (CNS) attributable to polymorphisms in viral attachment protein σ1. While all reovirus serotypes use junctional adhesion molecule-A as a cellular receptor, they differ in their utilization of carbohydrate coreceptors. This observation raises the possibility that carbohydrate binding by σ1 influences reovirus pathology in the CNS. In this study, we sought to define the function of carbohydrate binding in reovirus neuropathogenesis. Newborn mice were inoculated intramuscularly with wild-type strain type 3 Dearing (T3D) and T3D-σ1R202W, a point mutant T3D derivative that does not bind sialic acid (SA). Infected mice were monitored for survival, and viral loads at the sites of primary and secondary replication were quantified. Fewer mice inoculated with the wild-type virus survived in comparison to those inoculated with the mutant virus. The wild-type virus also produced higher titers in the spinal cord and brain at late times postinoculation but lower titers in the liver in comparison to those produced by the mutant virus. In addition, the wild-type virus was more virulent and produced higher titers in the brain than the mutant following intracranial inoculation. These animal infectivity studies suggest that T3D-σ1R202W harbors a defect in neural growth. Concordantly, compared with the wild-type virus, the mutant virus displayed a decreased capacity to infect and replicate in primary cultures of cortical neurons, a property dependent on cell surface SA. These results suggest that SA binding enhances the kinetics of reovirus replication in neural tissues and highlight a functional role for sialylated glycans as reovirus coreceptors in the CNS.


title: Esophageal tissue engineering.

text: Esophageal tissue engineering is still in an early state, and ideal methods have not been developed. Since the beginning of the 20th century, advances have been made in the materials that can be used to produce an esophageal substitute. Three approaches to scaffold-based tissue engineering have yielded good results. The first development concerned non-absorbable constructs based on silicone and collagen. The need to remove the silicone tube is the main disadvantage of this material. Polymeric absorbable scaffolds have been used since the 1990s. The main polymeric material used is poly (glycolic) acid combined with collagen. The problem of stenosis remains prevalent in most studies using an absorbable construct. Finally, decellularized scaffolds have been used since 2000. The promises of this new approach are unfulfilled. Indeed, stenosis occurs when the esophageal defect is circumferential regardless of the scaffold materials. Cell supplementation can decrease the rate of stenosis, but the type(s) of cells and their roles have not been defined. Finally, esophageal tissue engineering cannot provide a functional esophageal substitute, and further development is necessary prior to conducting human clinical studies.


From the Editor: At the heart of the mission of general practice.


COVID-19 infections are also affected by human ACE1 D/I polymorphism.


title: The temporoparietal fascia flap: a versatile tool for the dermatologic surgeon.

text: BACKGROUND Dermatologic surgeons may encounter challenging defects of the head and neck that are not amenable to repair with local flaps or grafts. OBJECTIVE We offer a comprehensive review of the temporoparietal fascia flap (TPFF) and provide a step-by-step illustration of its application performed under local anesthesia for a challenging reconstructive scenario. MATERIALS AND METHODS A 66-year-old male initially underwent Mohs micrographic surgery resulting in a large full-thickness defect at the postauricular scalp contiguous with a through-and-through defect of the upper right ear. A TPFF was performed under local anesthesia to reconstruct the surgical defect. RESULTS Complete healing in our patient was noted at 10 weeks after completion of the TPFF. However, granulation caused adherence of the ear to the postauricular scalp, which was corrected by a dividing incision to release the ear. At 4 weeks after the division, lateral projection of the ears was symmetric and readherence of the ear did not recur. CONCLUSION The TPFF is a highly versatile pedicled flap that can be performed under local anesthesia to reconstruct a variety of complex defects on the head and neck. This case reveals that the TPFF adds a powerful tool to the armamentarium of dermatologic surgeons.


title: Evaluation of three unchannelled videolaryngoscopes and the Macintosh laryngoscope in patients with a simulated difficult airway: a randomised, controlled trial.

text: This prospective randomised, controlled trial compares the performance of three unchannelled videolaryngoscopes (KingVision™ , Airtraq™ , A.P. Advance™ MAC) and the standard Macintosh laryngoscope. With ethics committee approval and written informed consent, 480 patients were included. A difficult airway was created with a cervical collar, limiting mouth opening and neck movement. Primary outcome was first-attempt orotracheal intubation success. Overall success, laryngeal view, intubation difficulty scale, handling, intubation times and side-effects were secondary outcomes. First-attempt success rates were: KingVision 90% (95% CI 83-94%), Airtraq 82% (74-88%), A.P. Advance MAC 49% (40-58%), Macintosh 44% (35-53%; p < 0.001). The 95% confidence interval of first-attempt success rate was thus below 90% for all devices, but the KingVision and the Airtraq performed better than the A.P. Advance MAC and the Macintosh laryngoscope. Also, performance was better with the KingVision and the Airtraq in terms of overall success, laryngeal view, intubation difficulty scale and quality of view. Problems with tube advancement were a frequent cause of intubation failure. In summary, the KingVision and the Airtraq performed better than the A.P. Advance MAC and the Macintosh laryngoscope. Success rates of the unchannelled KingVision and Airtraq were similar to those of their channelled versions reported previously, indicating that performance largely depends on blade design rather than the presence of a channel for tube advancement.


Quality improvement guidelines for percutaneous management of acute lower-extremity ischemia.


title: Structural architecture of an RNA that competitively inhibits RNase L.

text: Activation of RNase L endonuclease activity is part of the mammalian innate immune response to viral infection. The poliovirus RNA genome contains a sequence in its protein-coding region that can act as a competitive inhibitor of RNase L. Mutation, sequence, and functional analysis of this competitive inhibitor RNA (ciRNA) revealed that its activity depends on specific sequences, showed that a loop-loop hairpin interaction forms in the ciRNA, and suggested the presence of a loop E motif. These features lead to the hypothesis that the ciRNA's function is conferred in part by a specific three-dimensional folded RNA architecture. By using a combination of biophysical, mutational, and functional studies, we have mapped features of the three-dimensional architecture of the ciRNA in its unbound form. We show that the loop-loop interaction forms in the free ciRNA and affects the overall structure, perhaps forming long-range tertiary interactions with the loop E motif. Local tight RNA-RNA backbone packing occurs in parts of the structure, but the fold appears to be less stable than many other tightly packed RNAs. This feature may allow the ciRNA to accommodate the translocation of ribosomes and polymerase across this multifunctional region of the viral RNA but also to function as an RNase L inhibitor.


title: Poly-4-hydroxybutyrate (Phasix™) mesh onlay in complex abdominal wall repair.

text: BACKGROUND Poly-4-hydroxybutyric acid (P4HB, Phasix™) is a biosynthetic polymer that degrades by hydrolysis that can be woven into a mesh for use in soft tissue reinforcement. Herein, we describe our initial experience performing complex abdominal wall repair (CAWR) utilizing component separation and P4HB mesh as onlay reinforcement. METHODS All patients undergoing CAWR between June 2014 and May 2017 were followed prospectively for postoperative outcomes. Only those patients who underwent components separation with primary repair of the fascial edges followed by onlay of P4HB mesh were included in this study. RESULTS 105 patients (52 male, 53 female; mean age 59.2 years, range 22-84) met inclusion criteria. Mean BMI was 29.1 (range 16-48); 52% patients had prior attempted hernia repair, most with multiple medical comorbidities (71% of patients with ASA 3 or greater). 30% of cases were not clean at the time of repair (CDC class 2 or greater). Median follow-up was 36 months (range 9-63). Eighteen patients (17%) developed a hernia recurrence ranging from 2 to 36 months postoperatively. Five (5%) patients developed a localized superficial infection treated with antibiotics, three (2.8%) required re-operation for non-healing wounds, and six (6%) patients developed seroma. CONCLUSIONS These data demonstrate a relatively low rate of hernia recurrence, seroma, and other common complications of CAWR in a highly morbid patient population. Importantly, the rate of mesh infection was low and no patients required complete mesh removal, even when placed into a contaminated or infected surgical field.


title: Pan-intestinal capsule endoscopy in patients with postoperative Crohn's disease: a pilot study.

text: BACKGROUND Patients are at increased risk of disease recurrence after surgical treatment of Crohn's disease. Endoscopic detection of postoperative, ileo-colonic inflammation is well established, but the potential of pan-intestinal endoscopy is yet unknown. METHODS This prospective multicenter pilot study assessed the value of pan-intestinal capsule endoscopy using a colon capsule endoscope for the detection of inflammatory recurrence of Crohn´s disease. Patients who had been operatively treated for Crohn´s disease were included. Colon capsule endoscopy was performed 4-8 weeks (d1) and 4-8 months (d2) postoperatively together with ileo-colonoscopy at d2 using a modified Ruttgeerts index for evaluating disease activity. RESULTS Twenty-two patients were included into this study. At d1, significant disease activity (Ruttgeerts index ≥2) was detected in 3/16 (19%) of the patients. At d2, half of the patients (6/12) showed active disease, whereas ileo-colonoscopy revealed significant inflammation in 5/15 (33%). All patients rated as having active disease by ileo-colonoscopy had been revealed by PICE as well. These findings influenced the medical treatment in every case. CONCLUSION Pan-intestinal capsule endoscopy seems to be feasible in the postoperative surveillance of Crohn's disease. Disease activity is reliably detected. Especially, the findings in the small bowl might be a significant advantage in comparison to ileo-colonoscopy, as they can have significant impact on clinical management. Further studies with a larger number of patients are needed to confirm these findings and might lead to a replacement of the flexible ileo-colonoscopy with pan-intestinal capsule endoscopy in this indication in the future.


title: Surgical training in robotic surgery: surgical experience of robotic-assisted transabdominal preperitoneal inguinal herniorrhaphy with and without resident participation.

text: Robotic-assisted surgery is becoming more popular in general surgery. Implementation of a robotic curriculum is necessary and will influence surgical training. The aim of this study is to compare surgical experience and outcomes with and without resident participation in robotic inguinal herniorrhaphy. A retrospective review of patients who underwent either unilateral or bilateral robotic-assisted transabdominal preperitoneal (TAPP) inguinal herniorrhaphy, with and without resident participation as console surgeons from January through December 2015, was performed. Patient demographics, procedure-related data, postoperative variables, and follow-up data were analyzed. A total of 104 patients were included. Patients were significantly older in the Resident group (57.5 ± 14.1 vs 50.6 ± 13.5 years, p = 0.01). Gender, BMI, and ASA classification were similar between groups. There were similar mean operative times for unilateral (89.9 ± 19.5 vs 84.8 ± 22.2 min, p = 0.42) and bilateral (128.4 ± 21.9 vs 129.8 ± 50.9 min, p = 0.90) inguinal herniorrhaphy as well as mean robot console times for unilateral (73.2 ± 18.4 vs 67.3 ± 29.9 min, p = 0.44) and bilateral (115.5 ± 24.6 vs 109.3 ± 55.4 min, p = 0.67) inguinal herniorrhaphy with and without resident participation, respectively. Postoperative complications included urinary retention (11.1 vs 2.0%, p = 0.11), conversion to open repair (0 vs 2%, p = 0.48), and delayed reoperation (0 vs 4%, p = 0.22) with and without resident participation, respectively. Patients' symptoms/signs at follow-up were similar among groups. Robotic-assisted TAPP inguinal herniorrhaphy with resident participation as console surgeons did not affect the hospital operative experience or patient outcomes. This procedure can be implemented as part of the resident robotic curriculum with rates of morbidity equivalent to those of published studies.Level of evidence 2b.


title: Complete protection against severe acute respiratory syndrome coronavirus-mediated lethal respiratory disease in aged mice by immunization with a mouse-adapted virus lacking E protein.

text: Zoonotic coronaviruses, including the one that caused severe acute respiratory syndrome (SARS), cause significant morbidity and mortality in humans. No specific therapy for any human coronavirus is available, making vaccine development critical for protection against these viruses. We previously showed that recombinant SARS coronavirus (SARS-CoV) (Urbani strain based) lacking envelope (E) protein expression (rU-ΔE) provided good but not perfect protection in young mice against challenge with virulent mouse-adapted SARS-CoV (MA15). To improve vaccine efficacy, we developed a second set of E-deleted vaccine candidates on an MA15 background (rMA15-ΔE). rMA15-ΔE is safe, causing no disease in 6-week-, 12-month-, or 18-month-old BALB/c mice. Immunization with this virus completely protected mice of three ages from lethal disease and effected more-rapid virus clearance. Compared to rU-ΔE, rMA15-ΔE immunization resulted in significantly greater neutralizing antibody and SARS-CoV-specific CD4 and CD8 T cell responses. After challenge, inflammatory cell infiltration, edema, and lung destruction were decreased in the lungs of rMA15-ΔE-immunized mice compared to those in rU-ΔE-immunized 12-month-old mice. Collectively, these results show that immunization with a species-adapted attenuated coronavirus lacking E protein expression is safe and provides optimal immunogenicity and long-term protection against challenge with lethal virus. This approach will be generally useful for development of vaccines protective against human coronaviruses as well as against coronaviruses that cause disease in domestic and companion animals.


title: Frailty in patients undergoing transcatheter aortic valve implantation: a protocol for a systematic review.

text: INTRODUCTION Aortic stenosis is a significant cause of morbidity and mortality in older patients. The advent of transcatheter aortic valve implantation (TAVI) offers an alternative to surgical aortic valve replacement for patients with severe symptomatic aortic stenosis who are at high or intermediate risk of adverse events. Existing evidence highlights the importance of frailty as a predictor of poor outcomes post-TAVI. The objective of this study is to review the operationalisation of frailty instruments for TAVI recipients and determine clinical outcomes and the change in quality of life in frail patients undergoing TAVI. METHODS AND ANALYSIS Methods are reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 checklist. We will search relevant databases to identify published, completed but unpublished and ongoing studies. We will include studies of patients with aortic stenosis, diagnosed as frail and who underwent a TAVI procedure that report mortality, clinical outcomes or health-related quality of life. Retrospective or prospective cohort studies, randomised controlled trials and non-randomised controlled trials will be eligible for inclusion. Two researchers will independently screen articles for inclusion, with disagreements resolved by a third reviewer. One researcher will extract data with audit by a second researcher. The risk of bias in studies will be evaluated using the Quality in Prognosis Studies tool. Meta-analysis of mortality, survival curve and the change in quality of life will be performed if appropriate. Subgroup analysis, sensitivity analysis and meta-regression will be performed if necessary. ETHICS AND DISSEMINATION Due to the nature of this study, no ethical issues are foreseen. We will disseminate the results of our systematic review through a peer-reviewed journal. TRIAL REGISTRATION NUMBER CRD42018090597.


title: Oseltamivir compared with the Chinese traditional therapy maxingshigan-yinqiaosan in the treatment of H1N1 influenza: a randomized trial.

text: BACKGROUND Observational studies from Asia suggest that maxingshigan-yinqiaosan may be effective in the treatment of acute H1N1 influenza. OBJECTIVE To compare the efficacy and safety of oseltamivir and maxingshigan-yinqiaosan in treating uncomplicated H1N1 influenza. DESIGN Prospective, nonblinded, randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00935194) SETTING Eleven hospitals from 4 provinces in China. PATIENTS 410 persons [corrected] aged 15 to 69 [corrected] years with laboratory-confirmed H1N1 influenza. INTERVENTION Oseltamivir, 75 mg twice daily; maxingshigan-yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan-yinqiaosan; or no intervention (control). Interventions and control were given for 5 days. MEASUREMENTS Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction. RESULTS Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20% to 46%]; P < 0.001), maxingshigan-yinqiaosan (37% [CI, 23% to 49%]; P < 0.001), and oseltamivir plus maxingshigan-yinqiaosan (47% [CI, 35% to 56%]; P < 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with oseltamivir plus maxingshigan-yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores (P = 0.38). Two patients who received maxingshigan-yinqiaosan reported nausea and vomiting. LIMITATIONS Participants were young and had mild H1N1 influenza virus infection. Missing viral data precluded definitive conclusions about viral shedding. CONCLUSION Oseltamivir and maxingshigan-yinqiaosan, alone and in combination, reduced time to fever resolution in patients with H1N1 influenza virus infection. These data suggest that maxingshigan-yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection. PRIMARY FUNDING SOURCE Beijing Science and Technology Project and Beijing Nova Program.


title: Chronic peritoneal dialysis in children.

text: The incidence of end-stage renal disease in children is increasing. Peritoneal dialysis (PD) is the modality of choice in many European countries and is increasingly applied worldwide. PD enables children of all ages to be successfully treated while awaiting the ultimate goal of renal transplantation. The advantages of PD over other forms of renal replacement therapy are numerous, in particular the potential for the child to lead a relatively normal life. Indications for commencing PD, the rationale, preparation of family, technical aspects, and management of complications are discussed.


title: Association of Presence of Band Cells and Toxic Neutrophils with Systemic Inflammatory Response Syndrome and Outcome in Horses with Acute Disease.

text: BACKGROUND Band cells and toxic neutrophils are thought to indicate acute and severe systemic illness but no studies have investigated their importance in adult equine emergency admissions. OBJECTIVES The objective of this study was to evaluate the association of band cells and toxic neutrophils with systemic inflammatory response syndrome (SIRS) and outcome in horses. ANIMALS One hundred and five adult horses admitted on emergency basis to a private primary referral practice. METHODS Prospective observational study with sample collection. All horses admitted on emergency basis over the study period were included in the study if they had a CBC and a blood smear collected on admission. RESULTS The detection of band neutrophils on admission was associated with the SIRS status of the horse (RR = 2.80; 95% CI = 1.57-4.99; P < .001) and with poor outcome (RR = 1.88; 95% CI: 1.05-3.37; P = .038). Similarly, the presence of a neutrophil toxic grade higher than 3 was associated with SIRS (RR = 1.71; 95% CI: 1.03-2.82; P = .034) and death (RR = 2.34; 95% CI: 1.22-4.50, P = .007). The information gained from the blood smear review could not be captured by looking at only the WBC or neutrophil count. CONCLUSIONS AND CLINICAL IMPORTANCE The microscopic review of blood smears from critically ill horses to detect band cells or neutrophil toxic change is valuable and could help in assessing disease severity and prognosis in adult equine emergency admissions.


title: COVID-19 and Brazilian Indigenous Populations.

text: The newly discovered SARS-CoV-2 is the cause of COVID-19, including severe respiratory symptoms with an important lethality rate and high dissemination capacity. Considering the indigenous people of Brazil, it is feared that COVID-19 will spread to these communities, causing another stage of decimation. Despite advances in indigenous health care in the country, there are still many challenges due to the social vulnerability of this population, whose lands continue to be illegally exploited. Based on these considerations, this article discusses challenges in caring for the indigenous population in the context of the COVID-19 pandemic in Brazil.


title: Cerebral autoregulation in pregnancies complicated by diabetes and overweight.

text: AIM The aim of this study was to estimate the impact of diabetes and obesity on cerebral autoregulation in pregnancy. METHODS Cerebral autoregulation was evaluated in women with gestational diabetes, type 2 diabetes mellitus and/or overweight (body mass index ⩾ 25 kg m(-2)) and compared to a cohort of euglycaemic pregnant women. The autoregulation index was calculated using simultaneously recorded cerebral blood flow velocity in the middle cerebral artery and blood pressure. Autoregulation index values of 0 and 9 indicate absent and perfect autoregulation, respectively. RESULTS Autoregulation index in women with either diabetes (n = 33, 6.6 ± 1.1) or overweight (n = 21, 6.7 ± 0.6) was not significantly different to that in control patients (n = 23, 6.6 ± 0.8, p = 0.96). CONCLUSION Cerebral autoregulation is not impaired in pregnant women who have non-vasculopathic diabetes or overweight. This suggests that the increased risk of pre-eclampsia in diabetic and overweight women is not associated with early impaired cerebral autoregulation.


Response to: 'Incidence of severe COVID-19 in a Spanish cohort of 1037 patients with rheumatic diseases treated with biologics and JAK-inhibitors' by Jovani et al.


Covid-19: NHS outlines services to be prioritised to restart in next six weeks.


title: The Interference Phenomenon of Microcatheters in the Jailing Treatment for Internal Carotid Artery Side Wall Aneurysms with an Open Cell Stent System.

text: OBJECTIVE Excelsior XT-27 (Stryker Neurovascular, Fremont, CA, USA) or Rebar 27 (eV3 Covidien, Irvine, CA, USA) microcatheters have recently been used to overcome the limitations of the Renegade Hi-Flo microcatheter such as interference between two microcatheters (one for stent delivery and the other for cerebral aneurysm coiling) during the jailing technique. We evaluated differences and influential factors related to the interference phenomenon according to these two microcatheters group. MATERIALS AND METHODS Between June 2011 and September 2013, the jailing technique was applied to 94 internal cerebral artery (ICA) aneurysms. The jailing technique with the Neuroform EZ stent system was performed using Renegade (n = 22), Rebar (n = 35), and XT-27 microcatheters (n = 37). In the Renegade Hi-Flo microcatheter group, the jailing technique was successful in 19/22 patients (86.4%) and interference between the two microcatheters occurred in 6/21 patients (28.6%). In the Rebar and XT-27 microcatheter group, the jailing technique was successful in 71/72 patients (98.6%) and interference between the two microcatheters occurred in 1/72 patients (1.4%). RESULTS There was a significant difference in the interference between the two delivered microcatheters group (p-value < 0.000) and the carotid siphon angle (p-value: 0.004) in the univariate analysis. In the multiple logistic regression analysis, the Rebar and XT-27 microcatheter group (odds ratio [OD] [95% confidence interval (CI)]; 31.277 [3.138-311.729], p-value: 0.003) and the carotid siphon angle (OD [95%CI]; 0.959 [0.922-0.997], p-value: 0.035) were found to be influential factors in the interference phenomenon. CONCLUSION The Rebar 27 and XT-27 microcatheters were more successful and exhibited less interference between the two microcatheters than the Renegade Hi-Flo microcatheter.


title: The effect of mini-PEG-based spacer length on binding and pharmacokinetic properties of a 68Ga-labeled NOTA-conjugated antagonistic analog of bombesin.

text: The overexpression of gastrin-releasing peptide receptor (GRPR) in cancer can be used for peptide-receptor mediated radionuclide imaging and therapy. We have previously shown that an antagonist analog of bombesin RM26 conjugated to 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) via a diethyleneglycol (PEG2) spacer (NOTA-PEG2-RM26) and labeled with 68Ga can be used for imaging of GRPR-expressing tumors. In this study, we evaluated if a variation of mini-PEG spacer length can be used for optimization of targeting properties of the NOTA-conjugated RM26. A series of analogs with different PEG-length (n = 2, 3, 4, 6) was synthesized, radiolabeled and evaluated in vitro and in vivo. The IC50 values of natGa-NOTA-PEGn-RM26 (n = 2, 3, 4, 6) were 3.1 ± 0.2, 3.9 ± 0.3, 5.4 ± 0.4 and 5.8 ± 0.3 nM, respectively. In normal mice all conjugates demonstrated similar biodistribution pattern, however 68Ga-NOTA-PEG3-RM26 showed lower liver uptake. Biodistribution of 68Ga-NOTA-PEG3-RM26 was evaluated in nude mice bearing PC-3 (prostate cancer) and BT-474 (breast cancer) xenografts. High uptake in tumors (4.6 ± 0.6%ID/g and 2.8 ± 0.4%ID/g for PC-3 and BT-474 xenografts, respectively) and high tumor-to-background ratios (tumor/blood of 44 ± 12 and 42 ± 5 for PC-3 and BT-474 xenografts, respectively) were found already at 2 h p.i. of 68Ga-NOTA-PEG3-RM26. Results of this study suggest that variation in the length of the PEG spacer can be used for optimization of targeting properties of peptide-chelator conjugates. However, the influence of the mini-PEG length on biodistribution is minor when di-, tri-, tetra- and hexaethylene glycol are compared.


title: Single-incision laparoscopic trans-abdominal pre-peritoneal mesh hernia repair: a feasible approach.

text: BACKGROUND Single-incision laparoscopic surgery (SILS) is aimed at improving the cosmetic outcome following surgery. If the incision is made through the umbilicus, the surgery is almost 'scarless.' This is increasingly being used for laparoscopic cholecystectomy with good cosmetic results without compromising the safety of the operation. The challenge of this surgery lies in manipulating instruments within the limitations of the closely inserted ports. METHODS We describe the first case of SILS hernia repair via the trans-abdominal pre-peritoneal approach (TAPP) in a 39-year-old male as a day-case procedure. RESULTS The patient was discharged without any complications. CONCLUSIONS This novel surgical technique is feasible and improves cosmetic outcome without additional risk. The advantage of such an approach above and beyond cosmesis remains to be evaluated.


COVID-19 cumulative mortality rates for frontline healthcare staff in England.


title: Magnetic resonance imaging with gadoxetic acid for local tumour progression after radiofrequency ablation in patients with hepatocellular carcinoma.

text: OBJECTIVES To develop and validate a prediction model using magnetic resonance imaging (MRI) for local tumour progression (LTP) after radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) patients. METHODS Two hundred and eleven patients who had received RFA as first-line treatment for HCC were retrospectively analyzed. They had undergone gadoxetic acid-enhanced MRI before treatment, and parameters including tumour size; margins; signal intensities on T1-, T2-, and diffusion-weighted images, and hepatobiliary phase images (HBPI); intratumoral fat or tumoral capsules; and peritumoural hypointensity in the HBPI were used to develop a prediction model for LTP after treatment. This model to discriminate low-risk from high-risk LTP groups was constructed based on Cox regression analysis. RESULTS Our analyses produced the following model: 'risk score = 0.617 × tumour size + 0.965 × tumour margin + 0.867 × peritumoural hypointensity on HBPI'. This was able to predict which patients were at high risk for LTP after RFA (p < 0.001). Patients in the low-risk group had a significantly better 5-year LTP-free survival rate compared to the high-risk group (89.6 % vs. 65.1 %; hazard ratio, 3.60; p < 0.001). CONCLUSION A predictive model based on MRI before RFA could robustly identify HCC patients at high risk for LTP after treatment. KEY POINTS • Tumour size, margin, and peritumoural hypointensity on HBPI were risk factors for LTP. • The risk score model can predict which patients are at high risk for LTP. • This prediction model could be helpful for risk stratification of HCC patients.


title: Inhibition of sphingosine-1-phosphate-induced Th17 cells ameliorates alcoholic steatohepatitis in mice.

text: Chronic alcohol consumption is accompanied by intestinal inflammation. However, little is known about how alterations to the intestinal immune system and sphingolipids contribute to pathogenesis of alcoholic liver disease (ALD). We used WT mice, RORγt-deficient mice, sphingosine kinase-deficient mice and local gut anti-inflammatory, 5-aminosalicyclic acid (5-ASA)-treated mice in a chronic-binge ethanol feeding model. Targeted lipidomics assessed the sphingolipids in gut and liver samples. Gut immune cell populations, the amounts of sphingolipids, and the level of liver injury were examined. Results: Alcohol intake induces a pro-inflammatory shift in immune cell populations in the gut, including an increase in Th17 cells. Using RORγt-deficient mice, we found that Th17 cells are required for alcohol-associated gut inflammation and the development of ALD. Treatment with 5-ASA decreases alcohol-induced liver injury and reverses gut inflammation by the suppression of CD4+ /RORγt+ /IL-17A+ cells. Increased Th17 cells were due to upregulation of SK1 activity and RORγt activation. We found that S1P/S1PR1 signaling are required for the development of Th17 cell-mediated ALD. Importantly, in vivo intervention blocking of S1P/S1PR1 signaling markedly attenuated alcohol-induced liver inflammation, steatosis, and damage. Conclusion: Gut inflammation is a functional alteration of immune cells in ALD. Reducing gut Th17 cells leads to reduced liver damage. S1P signaling was crucial in the pathogenesis of ALD in a Th17 cell dependent manner. Furthermore, our findings suggest that compounds that reduce gut inflammation locally may represent a unique targeted approach in the treatment of ALD.


title: Transarterial chemoembolization using drug eluting beads and subsequent percutaneous MR-guided radiofrequency ablation in the therapy of intermediate sized hepatocellular carcinoma.

text: OBJECTIVE To evaluate safety, efficacy, survival and recurrence-free survival of transarterial chemoembolization (TACE) with drug eluting (DC) beads combined with MR-guided radiofrequency (RF) ablation for the treatment of hepatocellular carcinomas (HCC) larger than 3 cm. MATERIALS AND METHODS This retrospective study was approved by the institutional review board. 20 patients (69.6 years ± SD 8.8) with HCC underwent DC Bead TACE and subsequent MR-guided RF ablation. Treatment interval varied between 5 and 15 days. Mean HCC diameter was 39 mm ± SD 7 mm (range 31-50mm). Rates of recurrence-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS Technical success rate, primary and secondary technical effectiveness rate were 100%, 90% and 95%, respectively. Local tumour progression developed in one patient. Cumulative survival rates at 1, 3 and 5 years were 90% (Confidence Interval [CI]: 67%-97%), 50% (CI: 29%-70%), 27% (CI: 11%-51%) respectively. Median survival time was 37.4 months. During follow up (mean: 39.1 months ± SD 22.4; range 5-84 months), tumour progression in untreated liver developed in 14 cases. Cumulative recurrence-free survival rates at 1, 3 and 5 years were 48% (CI: 27-69%), 16% (5-39%), 16% (5-39%) respectively. Median recurrence-free survival time was 10.7 months. One major complication occurred due to misdiagnosed local recurrence. CONCLUSION In conclusion, we demonstrated that MR-guided RF ablation with subsequent DC Bead TACE is safe and effective in local tumour control in patients with intermediate sized HCC.


title: Ultrasound-guided transversus abdominis plane injection with computed tomography correlation: a cadaveric study.

text: BACKGROUND Ultrasound-guided transversus abdominis plane (TAP) injections are increasingly being used as an alternative to traditional perioperative analgesia in the abdominal region. With the use of a "blind" TAP block technique, these procedures have had variable success in cadaver and in vivo studies. For more accurate injection with the intended medication, ultrasound guidance allows visualization of the correct layer of the abdominal wall planes in which the thoracolumbar nerves reside. OBJECTIVE To assess the spread of various volumes of contrast placed under live ultrasound guidance into the TAP using computed tomography (CT). METHODS Four TAP blocks were performed on 2 fresh frozen cadaver torsos with predetermined contrast volumes of 5, 10, 15, or 20 mL. A CT scan of the cadaver was then performed and interpreted by a musculoskeletal radiologist. This cadaver study was carried out at a tertiary care academic medical center. RESULTS Cranial-caudal spread of injected contrast correlated with increasing injectate volume and was roughly 1 vertebral level (end plate to end plate) for the 5 mL injection and 2 vertebral levels for the 10, 15, and 20 mL injections. However, the degree of injectate spread may be different for live patients than for cadavers. CONCLUSION This study helps further the understanding of injectate spread following ultrasound-guided TAP injections. Specifically, it suggests that 15 mL provides additional cranial-caudal spread and may be an optimal volume of anesthesia.


title: Quarantined.

text: As an emergency medicine physician, I am used to working when most people are not working. At the end of February, the first patient in the U.S. to be diagnosed with COVID-19 without a travel history occurred in Sacramento, CA. Over 120 healthcare professionals who had contact with the patient were quarantined. Beginning of March, I worked in the emergency department and treated a patient with viral symptoms without a travel history who was admitted to the hospital.


title: Mechanical circulatory support for right ventricular failure.

text: OBJECTIVES The aim of this study was to explore the clinical utility of a commercially available centrifugal flow pump as a centrifugal flow-right ventricular support device (CF-RVSD) in patients with right ventricular failure (RVF). BACKGROUND RVF is associated with high in-hospital mortality. Limited data regarding efficacy of the CF-RVSD for RVF exist. METHODS We retrospectively reviewed data from 46 patients receiving a CF-RVSD for RVF from a registry comprising data from 8 tertiary-care hospitals in the United States. CF-RVSD use was recorded in the setting of acute myocardial infarction; myocarditis; chronic left heart failure; after valve surgery, orthotopic heart transplantation, left ventricular assist device surgery, coronary bypass grafting. Devices were implanted via the percutaneous (n = 22) or surgical (n = 24) route. RESULTS No intraprocedural mortality was observed. Mean time from admission to CF-RVSD implantation was 5.7 ± 8.5 days, with a mean of 6,769 ± 789 rotations/min, providing 4.2 ± 1.3 l/min of flow. Mean duration of support was 5.4 ± 5.1 days. Mean arterial pressure (65 ± 12 mm Hg vs. 73 ± 14 mm Hg; p < 0.05), right atrial pressure (21 ± 8 mm Hg vs. 16 ± 7 mm Hg; p = 0.05), pulmonary artery systolic pressure (43 ± 15 mm Hg vs. 33 ± 15 mm Hg; p = 0.01), and cardiac index (1.7 ± 0.7 vs. 2.2 ± 0.6; p = 0.01) were improved within 48 h of CF-RVSD implantation. Total in-hospital mortality was 57% and was lowest in the setting of left ventricular assist device implantation, chronic left heart failure, and acute myocardial infarction. Increased age, biventricular failure, and Thrombolysis In Myocardial Infarction-defined major bleeding were associated with increased in-hospital mortality. CONCLUSIONS Use of the CF-RVSD for RVF is clinically feasible and associated with improved hemodynamic status. Observations from the registry of patients who have received this device may support the development of prospective studies that will examine the role of percutaneous circulatory support for RVF.


title: Population pharmacokinetics of lamotrigine in Indian epileptic patients.

text: PURPOSE The aim of this analysis was to describe the pharmacokinetics of oral lamotrigine (LTG) in Indian epileptic patients using a population pharmacokinetic (PPK) modeling approach to confirm that the PK is similar to that of the Caucasian population, and to evaluate and confirm the impact of covariates predictive of inter-individual variability using a simulation platform. METHODS Blood samples were obtained from 95 patients, and LTG plasma concentrations were determined. Population PK modeling was performed using NONMEM. A one-compartment PK model with first-order absorption and elimination was used to describe the LTG PK. Log-likelihood profiling and normalized prediction distribution errors (NPDE) were used for model evaluation. A simulation study was performed to investigate dose regimens. RESULTS Clearance (CL) was estimated to be 2.27 L/h with inter-individual variability (IIV) of 29 CV%. Volume of distribution (V) was estimated to be 53.6 L (31 CV% IIV). Body weight and concurrent use of carbamazepine and valproate were identified as significant covariates on clearance. Log-likelihood profiling indicated that parameters could be estimated with adequate precision, and NPDE indicated that the model adequately described the data observed. The simulation study illustrated the impact of carbamazepine and valproate on LTG PK, and negligible differences in PK between Indian and Caucasian patients. CONCLUSIONS This is the first PK analysis of LTG in Indian patients. The population PK model developed adequately described the data observed. Comparison of identified PK parameters with previous PK analyses in Caucasian patients indicates that CL of LTG is similar, while V is somewhat lower compared with Caucasian patients, but this is not expected to lead to relevant differences in PK profiles during steady state.


Beyond the Respiratory System: A Case Report Highlighting the Impact of COVID-19 in Mental Illness and Its Physical Consequences.


title: The Effect of Carotid Chemoreceptor Inhibition on Exercise Tolerance in Chronic Heart Failure.

text: Purpose Chronic heart failure (CHF) is characterized by heightened sympathetic nervous activity, carotid chemoreceptor (CC) sensitivity, marked exercise intolerance and an exaggerated ventilatory response to exercise. The purpose of this study was to determine the effect of CC inhibition on exercise cardiovascular and ventilatory function, and exercise tolerance in health and CHF. Methods Twelve clinically stable, optimally treated patients with CHF (mean ejection fraction: 43 ± 2.5%) and 12 age- and sex-matched healthy controls were recruited. Participants completed two time-to-symptom-limitation (TLIM) constant load cycling exercise tests at 75% peak power output with either intravenous saline or low-dose dopamine (2 μg⋅kg-1⋅min-1; order randomized). Ventilation was measured using expired gas data and operating lung volume data were determined during exercise by inspiratory capacity maneuvers. Cardiac output was estimated using impedance cardiography, and vascular conductance was calculated as cardiac output/mean arterial pressure. Results There was no change in TLIM in either group with dopamine (CHF: saline 13.1 ± 2.4 vs. dopamine 13.5 ± 1.6 min, p = 0.78; Control: saline 10.3 ± 1.2 vs. dopamine 11.5 ± 1.3 min, p = 0.16). In CHF patients, dopamine increased cardiac output (p = 0.03), vascular conductance (p = 0.01) and oxygen delivery (p = 0.04) at TLIM, while ventilatory parameters were unaffected (p = 0.76). In controls, dopamine improved vascular conductance at TLIM (p = 0.03), but no other effects were observed. Conclusion Our findings suggest that the CC contributes to cardiovascular regulation during full-body exercise in patients with CHF, however, CC inhibition does not improve exercise tolerance.


title: Short-term outcomes of typical versus atypical lung segmentectomy by minimally invasive surgeries.

text: BACKGROUND Segmentectomy is increasingly used to resect lung nodules. Robotic-assisted thoracic surgery (RATS) is considered a safe and practical method for segmentectomy. Few studies have compared robotic surgery and video-assisted thoracic surgery (VATS) for lung segmentectomy. METHOD We retrospectively examined 215 consecutive patients who underwent typical (88 patients) or atypical (128 patients) segmentectomy by either robotic surgery or VATS. The postoperative characteristics including operation time, blood loss, pneumonia, tumor size, lymph nodes harvested, chest tube duration, prolonged air leak, atrial fibrillation, and postoperative hospital stay were recorded. RESULTS A total of 88 patients underwent typical segmentectomy, while 127 patients underwent atypical segmentectomy. A greater number of lymph nodes were resected via RATS than by VATS (13.24 ± 4.84 vs. 11.71 ± 3.89; P = 0.018). The operation time for typical segmentectomy was shorter than that for atypical segmentectomy (115.69 ± 22.32 vs. 131.68 ± 22.52; P = 0). No significant differences were found between RATS and VATS in terms of chest drainage duration and postoperative hospital stay. The incidence of postoperative complications including prolonged air leak and atrial fibrillation was not significantly different between typical segmentectomy and atypical segmentectomy. CONCLUSION Atypical segmentectomy is more complicated than typical segmentectomy, which may lead to increases in complications and operation time. Robotic surgery was safe and practical for segmentectomy compared to VATS and more lymph nodes could be dissected by RATS without increasing the risk of postoperative complications.


title: Endovascular treatment of cerebral mycotic aneurysm: a review of the literature and single center experience.

text: The management of mycotic aneurysm has always been subject to controversy. The aim of this paper is to review the literature on the intracranial infected aneurysm from pathogenesis till management while focusing mainly on the endovascular interventions. This novel solution seems to provide additional benefits and long-term favorable outcomes.


title: Hunting coronavirus severe acute respiratory syndrome coronavirus 2 (2019 novel coronavirus): From laboratory testing back to basic research

text: The rapid spread of coronavirus disease 2019 (COVID-19) in many countries causes citizens of daily inconvenience and even life-threat for elderly population. The invasion of the main pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; 2019 novel coronavirus [2019-nCoV]), into human body causes different levels of impact to various patients. One of the most important issues for COVID-19 is how to defend this virus with the ability to foresee the infected targets. Thus, we maintain the quarantined essentially as for as others saved from COVID-19. So far, the routine laboratory test to confirm whether infected by SARS-CoV-2/2019-nCoV or not is through real-time reverse transcription polymerase chain reaction (rRT-PCR; quantitative polymerase chain reaction [qPCR]) with certain sequence regions that recognize SARS-CoV-2/2019-nCoV RNA genome. The heavy loading of rRT-PCR (qPCR) machine and handling labor have tight-packed the instruments as well as the manpower almost in every country. Therefore, the alternative approaches are eagerly waiting to be developed. In this review article, we sort out some state-of-the-art novel approaches that might be applied for a fast, sensitive, and precise detection of SARS-CoV-2/2019-nCoV not only to help the routine laboratory testing but also to improve effective quarantine.


title: Potential of NO donor furoxan as SARS-CoV-2 main protease (Mpro) inhibitors: in silico analysis.

text: The sharp spurt in positive cases of novel coronavirus-19 (SARS-CoV-2) worldwide has created a big threat to human. In view to expedite new drug leads for COVID-19, Main Proteases (Mpro) of novel Coronavirus (SARS-CoV-2) has emerged as a crucial target for this virus. Nitric oxide (NO) inhibits the replication cycle of SARS-CoV. Inhalation of nitric oxide is used in the treatment of severe acute respiratory syndrome. Herein, we evaluated the phenyl furoxan, a well-known exogenous NO donor to identify the possible potent inhibitors through in silico studies such as molecular docking as per target analysis for candidates bound to substrate binding pocket of SARS-COV-2 Mpro. Molecular dynamics (MD) simulations of most stable docked complexes (Mpro-22 and Mpro-26) helped to confirm the notable conformational stability of these docked complexes under dynamic state. Furthermore, Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations revealed energetic contributions of key residues of Mpro in binding with potent furoxan derivatives 22, 26. In the present study to validate the molecular docking, MD simulation and MM-PBSA results, crystal structure of Mpro bound to experimentally known inhibitor X77 was used as control and the obtained results are presented herein. We envisaged that spiro-isoquinolino-piperidine-furoxan moieties can be used as effective ligand for SARS-CoV-2 Mpro inhibition due to the presence of key isoquinolino-piperidine skeleton with additional NO effect. Communicated by Ramaswamy H. Sarma.


title: Importance of controlling nanotube density for highly sensitive and reliable biosensors functional in physiological conditions.

text: Biosensors utilizing carbon nanotube field-effect transistors have a tremendous potential to serve as the basis for the next generation of diagnostic systems. While nanotubes have been employed in the fabrication of multiple sensors, little attention has previously been paid to how the nanotube density affects the biosensor performance. We conducted a systematic study of the effect of density on the performance of nanotube biosensors and discovered that this parameter is crucial to achieving consistently high performance. We found that devices with lower density offer higher sensitivity in terms of both detection limit and magnitude of response. The low density nanotube devices resulted in a detection limit of 1 pM in an electrolyte buffer containing high levels of electrolytes (ionic concentration ∼140 mM, matching the ionic strength of serum and plasma). Further investigation suggested that the enhanced sensitivity arises from the semiconductor-like behavior-strong gate dependence and lower capacitance-of the nanotube network at low density. Finally, we used the density-optimized nanotube biosensors to detect the nucleocapsid (N) protein of the SARS virus and demonstrated improved detection limits under physiological conditions. Our results show that it is critical to carefully tune the nanotube density in order to fabricate sensitive and reliable devices.


David Oliver: Let's not forget care homes when covid-19 is over.


title: Hemodynamic monitoring and management of patients undergoing high-risk surgery: a survey among Chinese anesthesiologists.

text: Hemodynamic monitoring and optimization improve postoperative outcome during high-risk surgery. However, hemodynamic management practices among Chinese anesthesiologists are largely unknown. This study sought to evaluate the current intraoperative hemodynamic management practices for high-risk surgery patients in China. From September 2010 to November 2011, we surveyed anesthesiologists working in the operating rooms of 265 hospitals representing 28 Chinese provinces. All questionnaires were distributed to department chairs of anesthesiology or practicing anesthesiologists. Once completed, the 29-item questionnaires were collected and analyzed. Two hundred and 10 questionnaires from 265 hospitals in China were collected. We found that 91.4% of anesthesiologists monitored invasive arterial pressure, 82.9% monitored central venous pressure (CVP), 13.3% monitored cardiac output (CO), 10.5% monitored mixed venous saturation, and less than 2% monitored pulse pressure variation (PPV) or systolic pressure variation (SPV) during high-risk surgery. The majority (88%) of anesthesiologists relied on clinical experience as an indicator for volume expansion and more than 80% relied on blood pressure, CVP and urine output. Anesthesiologists in China do not own enough attention on hemodynamic parameters such as PPV, SPV and CO during fluid management in high-risk surgical patients. The lack of CO monitoring may be attributed largely to the limited access to technologies, the cost of the devices and the lack of education on how to use them. There is a need for improving access to these technologies as well as an opportunity to create guidelines and education for hemodynamic optimization in China.


title: Histopathological Response and Adhesion Formation After Omentectomy with Ultrasonic Energy, Bipolar Sealing, and Suture Ligation.

text: This study was designed to evaluate the histopathological response and intra-abdominal adhesion formation after an omentectomy in rats using the bipolar vessel-sealing device, ultrasonic coagulator, and suture ligation techniques. Forty Wistar albino rats were used, divided into four random groups. The rats underwent a midline laparotomy, and a partial omentectomy was performed using a 3-0 silk suture with suture ligation in group 1, bipolar device in group 2, and ultrasonic coagulator in group 3; only a laparotomy was performed on the control group. Lateral thermal damage was examined the same day, and a piece of the omentum was left in the animals to be examined on postoperative day 15. A relaparotomy was performed to assess adhesion formation and histopathological response. In pairwise comparisons, there was no statistically significant difference among the ultrasonic device, bipolar device, and suture ligation groups in terms of microscopic adhesion scoring; however, the scores of the bipolar device and suture ligation groups were significantly higher compared with those of the control group (p < 0.01). Furthermore, the macroscopic adhesion scores were significantly lower for the ultrasonic device group when compared with those of the bipolar device and suture ligation groups (p < 0.05 and p < 0.01). The ultrasonic device seems to be superior to the bipolar device and suture ligation in terms of macroscopic adhesion formation, but no significant difference was found in terms of the histopathological response in rats following an omentectomy. Further research may be required.


title: Colonic Foreign Body Retrieval Using a Modified TAMIS Technique with Standard Instruments and Trocars.

text: Background. Reports of retained colorectal foreign bodies (CFBs) are no longer considered uncommon. We present a case where a retained CFB was retrieved using a modified TAMIS technique using standard instruments and trocars. Case Report. A 52-year-old man presented with a CFB. We report our technique of extraction with standard laparoscopic instruments without specialized access platforms. Conclusions. This modified TAMIS technique is well suited for resource poor environments because it requires no specialized equipment, platforms, or additional skill sets compared to conventional laparoscopy.


title: A combinatorial library of lipid-like materials for delivery of RNAi therapeutics.

text: The safe and effective delivery of RNA interference (RNAi) therapeutics remains an important challenge for clinical development. The diversity of current delivery materials remains limited, in part because of their slow, multi-step syntheses. Here we describe a new class of lipid-like delivery molecules, termed lipidoids, as delivery agents for RNAi therapeutics. Chemical methods were developed to allow the rapid synthesis of a large library of over 1,200 structurally diverse lipidoids. From this library, we identified lipidoids that facilitate high levels of specific silencing of endogenous gene transcripts when formulated with either double-stranded small interfering RNA (siRNA) or single-stranded antisense 2'-O-methyl (2'-OMe) oligoribonucleotides targeting microRNA (miRNA). The safety and efficacy of lipidoids were evaluated in three animal models: mice, rats and nonhuman primates. The studies reported here suggest that these materials may have broad utility for both local and systemic delivery of RNA therapeutics.


title: The Interferon-induced Transmembrane Proteins, IFITM1, IFITM2, and IFITM3 Inhibit Hepatitis C Virus Entry.

text: The interferon-induced transmembrane (IFITM) family of proteins have recently been identified as important host effector molecules of the type I interferon response against viruses. IFITM1 has been identified as a potent antiviral effector against hepatitis C virus (HCV), whereas the related family members IFITM2 and IFITM3 have been described to have antiviral effects against a broad range of RNA viruses. Here, we demonstrate that IFITM2 and IFITM3 play an integral role in the interferon response against HCV and act at the level of late entry stages of HCV infection. We have established that in hepatocytes, IFITM2 and IFITM3 localize to the late and early endosomes, respectively, as well as the lysosome. Furthermore, we have demonstrated that S-palmitoylation of all three IFITM proteins is essential for anti-HCV activity, whereas the conserved tyrosine residue in the N-terminal domain of IFITM2 and IFITM3 plays a significant role in protein localization. However, this tyrosine was found to be dispensable for anti-HCV activity, with mutation of the tyrosine resulting in an IFITM1-like phenotype with the retention of anti-HCV activity and co-localization of IFITM2 and IFITM3 with CD81. In conclusion, we propose that the IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation and demonstrate that the actions of the IFITM proteins are indeed virus and cell-type specific.


title: Hematology and oncology clinical care during the coronavirus disease 2019 pandemic.

text: New York City has been at the epicenter of the coronavirus disease 2019 (COVID-19) pandemic that has already infected over a million people and resulted in more than 70,000 deaths as of early May 2020 in the United States alone. This rapid and enormous influx of patients into the health care system has had profound effects on all aspects of health care, including the care of patients with cancer. In this report, the authors highlight the transformation they underwent within the Division of Hematology and Medical Oncology as they prepared for the COVID-19 crisis in New York City. Under stressful and uncertain conditions, some of the many changes they enacted within their division included developing a regular line of communication among division leaders to ensure the development and implementation of a restructuring strategy, completely reconfiguring the inpatient and outpatient units, rapidly developing the ability to perform telemedicine video visits, and creating new COVID-rule-out and COVID-positive clinics for their patients. These changes allowed them to manage the storm while minimizing the disruption of important continuity of care to their patients with cancer. The authors hope that their experiences will be helpful to other oncology practices about to experience their own individual COVID-19 crises.


title: Complete and Partial Aortic Occlusion for the Treatment of Hemorrhagic Shock in Swine.

text: Hemorrhage remains the leading cause of preventable deaths in trauma. Endovascular management of non-compressible torso hemorrhage has been at the forefront of trauma care in recent years. Since complete aortic occlusion presents serious concerns, the concept of partial aortic occlusion has gained a growing attention. Here, we present a large animal model of hemorrhagic shock to investigate the effects of a novel partial aortic balloon occlusion catheter and compare it with a catheter that works on the principles of complete aortic occlusion. Swine are anesthetized and instrumented in order to conduct controlled fixed-volume hemorrhage, and hemodynamic and physiological parameters are monitored. Following hemorrhage, aortic balloon occlusion catheters are inserted and inflated in the supraceliac aorta for 60 min, during which the animals receive whole-blood resuscitation as 20% of the total blood volume (TBV). Following balloon deflation, the animals are monitored in a critical care setting for 4 h, during which they receive fluid resuscitation and vasopressors as needed. The partial aortic balloon occlusion demonstrated improved distal mean arterial pressures (MAPs) during the balloon inflation, decreased markers of ischemia, and decreased fluid resuscitation and vasopressor use. As swine physiology and homeostatic responses following hemorrhage have been well-documented and are like those in humans, a swine hemorrhagic shock model can be used to test various treatment strategies. In addition to treating hemorrhage, aortic balloon occlusion catheters have become popular for their role in cardiac arrest, cardiac and vascular surgery, and other high-risk elective surgical procedures.


Uncertainty and COVID-19: how are we to respond?


title: Value of the Glasgow Prognostic Score as a Prognostic Factor in Resectable Non-Small Cell Lung Cancer.

text: BACKGROUND Over the past decade, the Glasgow prognostic score (GPS), which is based on serum C-reactive protein and albumin levels, has been reported to be associated with the prognosis of patients with several types of inoperable and operable cancers. However, its applicability to operable non-small cell lung cancer (NSCLC) has not yet been established. METHODS We retrospectively collected data from patients with pathological stage I or II NSCLC who underwent complete resection. A total of 1048 patients were categorized as either GPS-0 (n = 817 [78.0%]), GPS-1 (184 [17.6%]), or GPS-2 (47 [4.5%]). Survival curves were estimated using the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the relationship between prognosis and GPS status. RESULTS The 5-year overall survival (OS) rates were 91.2%, 78.3%, and 75.8% for GPS-0, GPS-1, and GPS-2, respectively. There were significant differences in OS between GPS-0 and GPS-1 (p < 0.001) and between GPS-0 and GPS-2 (p < 0.001). Ten variables demonstrated to be associated with OS in a univariate analysis were subjected to a multivariate analysis. The results showed that male sex (p = 0.031), vascular invasion (p < 0.001), lymph node metastasis (p < 0.001), and GPS (p = 0.025) were significantly associated with OS. CONCLUSIONS A high GPS is significantly associated with poor OS. Although the biological mechanism that underlies this association is not clear, this inflammation-based score may be a useful indicator of the prognosis in patients with resectable NSCLC.


title: Ultrasonographic findings and outcomes of dogs with suspected migrating intrathoracic grass awns: 43 cases (2010-2013).

text: OBJECTIVE To describe ultrasonographic findings and outcomes for dogs with suspected migrating intrathoracic grass awns. DESIGN Retrospective case series. ANIMALS 43 client-owned dogs. PROCEDURES Records for dogs with suspected migrating intrathoracic grass awns examined between 2010 and 2013 were reviewed. Ultrasonographic images and additional information such as signalment and pleural fluid analysis, radiographic, bronchoscopic, and CT findings were collected. Surgical treatments and outcomes were also reviewed. RESULTS Transthoracic or transesophageal ultrasonography revealed grass awns in the pleural space (n = 13) or pulmonary parenchyma (10) of 23 dogs. Surgical removal of grass awns was successful on the first attempt in 21 of these 23 dogs (including 11/23 that had intraoperative ultrasonography performed to aid localization and removal of the awn). In the remaining 2 dogs, a second surgery was required. Twenty dogs with evidence of migrating intrathoracic grass awns had no foreign body identified on initial ultrasonographic evaluation and were treated medically; 16 developed draining fistulas, and awns identified ultrasonographically at follow-up visits were subsequently removed from the sublumbar region (n = 10) or thoracic wall (6). The remaining 4 dogs had no grass awn visualized. Clinical signs resolved in all dogs. CONCLUSIONS AND CLINICAL RELEVANCE Transthoracic, transesophageal, and intraoperative ultrasonography were useful for localization and removal of migrating intrathoracic grass awns. Ultrasonography may be considered a valuable and readily available diagnostic tool for monitoring dogs with suspected migrating intrathoracic grass awns.


Family Engagement in the Cardiovascular Intensive Care Unit in the COVID Era.


title: The Italian COVID-19 outbreak: experiences and recommendations from clinical practice.

text: Novel coronavirus 2019 is a single-stranded, ribonucleic acid virus that has led to an international pandemic of coronavirus disease 2019 (COVID-19). Clinical data from the Chinese outbreak have been reported, but experiences and recommendations from clinical practice during the Italian outbreak have not. We report the impact of the COVID-19 outbreak on regional and national healthcare infrastructure. We also report on recommendations based on clinical experiences of managing patients throughout Italy. In particular, we describe key elements of clinical management, including safe oxygen therapy, airway management, personal protective equipment and non-technical aspects of caring for patients diagnosed with COVID-19. Only through planning, training and team working will clinicians and healthcare systems be best placed to deal with the many complex implications of this new pandemic.


title: The 5C Concept and 5S Principles in Inflammatory Bowel Disease Management.

text: Background and Aims The international Inflammatory Bowel Disease [IBD] Expert Alliance initiative [2012-2015] served as a platform to define and support areas of best practice in IBD management to help improve outcomes for all patients with IBD. Methods During the programme, IBD specialists from around the world established by consensus two best practice charters: the 5S Principles and the 5C Concept. Results The 5S Principles were conceived to provide health care providers with key guidance for improving clinical practice based on best management approaches. They comprise the following categories: Stage the disease; Stratify patients; Set treatment goals; Select appropriate treatment; and Supervise therapy. Optimised management of patients with IBD based on the 5S Principles can be achieved most effectively within an optimised clinical care environment. Guidance on optimising the clinical care setting in IBD management is provided through the 5C Concept, which encompasses: Comprehensive IBD care; Collaboration; Communication; Clinical nurse specialists; and Care pathways. Together, the 5C Concept and 5S Principles provide structured recommendations on organising the clinical care setting and developing best-practice approaches in IBD management. Conclusions Consideration and application of these two dimensions could help health care providers optimise their IBD centres and collaborate more effectively with their multidisciplinary team colleagues and patients, to provide improved IBD care in daily clinical practice. Ultimately, this could lead to improved outcomes for patients with IBD.


title: Is reaction time altered by mental or physical exertion?

text: PURPOSE Reaction time, classically divided into premotor time and electromechanical delay (EMD), can be determinant in daily life or sport situations. While some previous studies reported a negative impact of both muscle and mental fatigue on reaction time, the respective contributions of premotor time and EMD to the changes of reaction time remains unclear. The aim of the study was, therefore, to assess the effects of both muscle and mental effort on reaction time and its components. METHODS Thirteen subjects performed three conditions (mental effort condition, i.e., 14 min of a mathematical cognitive task; muscle effort condition, i.e., intermittent contractions of the biceps brachii; control condition, i.e., watching a documentary). Before and after each condition, reaction time, premotor time and EMD were measured during voluntary contractions of the biceps brachii. EMD was also measured during evoked contractions of the biceps brachii to separate the parts due to the onset of muscle fascicle motion and the onset of force production. RESULTS Reaction time and premotor time remained stable regardless of the condition considered (all P values > 0.05). EMD increased only after the muscle effort condition (+ 25% during voluntary contractions, no significant; + 17% during evoked contractions, P = 0.001), mainly due to an increase in the passive part of the series elastic component. CONCLUSION Our study showed that neither mental nor muscle effort has a negative effect on simple reaction time during voluntary contractions.


title: The COVID-19 pandemic: is our medicine still evidence-based?

text: There is no randomized controlled trial that demonstrated the efficacy of antiviral therapy against COVID-19 yet. However, physicians are prescribing different drugs to a large part of COVID-19 population in the hope they will cure them. This does not reflect the evidence-based medicine approach. What we need is more evidence-based knowledge about what routine care practices we should to apply to ameliorate symptoms of patients and fight COVID-19 pathology.


title: History, Evolution, and Importance of Emergency Endovascular Treatment of Acute Ischemic Stroke.

text: More than 800,000 people in North America suffer a stroke each year, with ischemic stroke making up the majority of these cases. The outcomes of ischemic stroke range from complete functional and cognitive recovery to severe disability and death; outcome is strongly associated with timely reperfusion treatment. Historically, ischemic stroke has been treated with intravenous thrombolytic agents with moderate success. However, five recently published positive trials have established the efficacy of endovascular treatment in acute ischemic stroke. In this review, we will discuss the history of stroke treatments moving from various intravenous thrombolytic drugs to intra-arterial thrombolysis, early mechanical thrombectomy devices, and finally modern endovascular devices. Early endovascular therapy failures, recent successes, and implications for current ischemic stroke management and future research directions are discussed.


title: Comparison of Anyplex II RV16 with the xTAG respiratory viral panel and Seeplex RV15 for detection of respiratory viruses.

text: A novel multiplex real-time PCR approach (Anyplex II RV16 [RV16]; Seegene, South Korea) was compared with a multiplex endpoint PCR kit (Seeplex RV15 ACE detection kit [RV15]; Seegene) and a liquid bead-based assay (xTAG respiratory viral panel [xTAG]; Abbott, United States). Of nasopharyngeal swabs or aspirates and bronchoalveolar lavage fluid samples submitted for RV15 testing, 199 retrospectively collected positive specimens and 283 prospectively collected specimens were further tested with RV16 and xTAG. A true-positive result was defined as a positive result from all three methods or RV16 and xTAG or RV15 and xTAG. For specimens with discrepant results, monoplex PCR and sequencing of the target viruses were performed. In total, 300 virus-positive specimens yielded 386 viruses. When the bocavirus results were excluded, the overall sensitivities of RV16, RV15, and xTAG were 95.2%, 93.3%, and 87.2%, respectively (95% confidence intervals, 93.0 to 97.4%, 90.8 to 95.8%, and 83.8 to 90.6%, respectively). RV16 was more sensitive than xTAG for coronavirus OC43/HKU1 (100% versus 26.1%; P < 0.0001) and adenovirus (100% versus 79.5%; P < 0.01) but was less sensitive than xTAG for rhinovirus/enterovirus (89.4% versus 97.9%; P < 0.05). RV16 demonstrated higher sensitivity than RV15 for the detection of adenovirus (100% versus 82.1%; P < 0.05). The specificities of all three methods ranged from 98.6% to 100%. Sequencing analysis of 64 rhinovirus-positive samples revealed that RV16 accurately differentiated between rhinovirus and enterovirus. RV16 most frequently missed rhinovirus C. In conclusion, the overall sensitivity of RV16 was better than that of xTAG. However, improvement of the sensitivity for rhinovirus is required.


title: Survival After In-Hospital Cardiac Arrest In Critically Ill Patients: Implications For Covid-19 Outbreak?

text: The coronavirus disease 2019 (COVID-19) outbreak is placing a considerable strain on U.S. healthcare systems by requiring both significant acute resources and endangering healthcare team members through airborne infection. Many U.S. healthcare systems are now considering how to treat COVID-19 patients who suffer cardiac arrest based on a presumption of poor survival after resuscitation in COVID-19 patients. However, empiric data on cardiac arrest survival in COVID-19 from the United States are not available at the moment. To inform this debate, we report survival data following cardiopulmonary resuscitation in a cohort of critically ill patients with pneumonia or sepsis who were receiving mechanical ventilation in an intensive care unit (ICU) at the time of arrest.


title: ISG15 Is Upregulated in Respiratory Syncytial Virus Infection and Reduces Virus Growth through Protein ISGylation.

text: UNLABELLED Human respiratory syncytial virus (RSV), for which neither a vaccine nor an effective therapeutic treatment is currently available, is the leading cause of severe lower respiratory tract infections in children. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that is highly increased during viral infections and has been reported to have an antiviral or a proviral activity, depending on the virus. Previous studies from our laboratory demonstrated strong ISG15 upregulation during RSV infection in vitro. In this study, an in-depth analysis of the role of ISG15 in RSV infection is presented. ISG15 overexpression and small interfering RNA (siRNA)-silencing experiments, along with ISG15 knockout (ISG15(-/-)) cells, revealed an anti-RSV effect of the molecule. Conjugation inhibition assays demonstrated that ISG15 exerts its antiviral activity via protein ISGylation. This antiviral activity requires high levels of ISG15 to be present in the cells before RSV infection. Finally, ISG15 is also upregulated in human respiratory pseudostratified epithelia and in nasopharyngeal washes from infants infected with RSV, pointing to a possible antiviral role of the molecule in vivo. These results advance our understanding of the innate immune response elicited by RSV and open new possibilities to control infections by the virus. IMPORTANCE At present, no vaccine or effective treatment for human respiratory syncytial virus (RSV) is available. This study shows that interferon-stimulated gene 15 (ISG15) lowers RSV growth through protein ISGylation. In addition, ISG15 accumulation highly correlates with the RSV load in nasopharyngeal washes from children, indicating that ISG15 may also have an antiviral role in vivo. These results improve our understanding of the innate immune response to RSV and identify ISG15 as a potential target for virus control.


title: Six years after: complications and long-term results after stapled hemorrhoidopexy with different devices.

text: PURPOSE Stapled hemorrhoidopexy (SH) was introduced in 1998. Early in the experience, a standard circular stapler was often used, while later specifically designed staplers for SH were developed. Although the diameter of the circular cutting knife differ significantly, it remains unclear, if the volume of the excised tissue differs and if this has an influence on the long-term results and complications. METHODS We evaluated in a prospective consecutive database that underwent SH from January 2003 through April 2004. There were three devices used during the study period: end-to-end-anastomosis (EEA) 31, stapler device for haemorrhoids (SDH) and procedure for prolapse and haemorrhoids (PPH). Procedure selection was at the discretion of the surgeon; however, the indications for surgery were similar for all involved surgeons. Demographic and operative characteristics were analysed. Follow-up data were collected continuously over the time, and in May 2010, these patients received a questionnaire. Data were compared by t test and chi-square test, respectively. RESULTS There were 214 (97 females) evaluable patients. Seventy-three patients were operated with EEA-31, 52 with SDH- and 89 with PPH. The median follow-up was 6.8 years and complete data were available for 131 (61.2%) patients. Demographic characteristics were comparable within the three groups. SDH (6 ml) and PPH (6.5 ml) resected significantly (p < 0.05) more tissue than EEA (5 ml). Early postoperative incontinence rate was significantly higher in the PPH group (6%) as compared to EEA (1%) and SDH (0%). The incidence of other early complications was similar across techniques. The overall complication rates and reoperation rates were similar. Although 41% of the patients had minor anorectal complaints (itching and soiling), incontinence rates were low (2-3%) without any significant differences between the devices. CONCLUSIONS The results of cohort of SH patients support the conclusion that short- and long-term outcomes are device independent, although each approach is associated with a modest degree of ongoing anorectal symptoms.


title: Life-threatening hemorrhage from a congenital hemangioma caused by birth trauma.

text: Pediatric surgeons frequently diagnose and treat vascular malformations. We present the case of a boy born with a large congenital hemangioma of the flank that ruptured during birth, resulting in life-threatening hemorrhage, requiring emergent excision. Prenatal diagnosis may help to identify such lesions, and pediatric surgeons must be ready to treat emergent complications of vascular malformations.


Renal artery denervation for the treatment of resistant hypertension. Update after Medtronic announcement that its Symplicity HTN3 study failed to meet its primary efficacy end point.