title: Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study.

text: RATIONALE Several Surviving Sepsis Campaign Guidelines recommendations are reevaluated. OBJECTIVES To analyze the effectiveness of treatments recommended in the sepsis guidelines. METHODS In a prospective observational study, we studied all adult patients with severe sepsis from 77 intensive care units. We recorded compliance with four therapeutic goals (central venous pressure 8 mm Hg or greater for persistent hypotension despite fluid resuscitation and/or lactate greater than 36 mg/dl, central venous oxygen saturation 70% or greater for persistent hypotension despite fluid resuscitation and/or lactate greater than 36 mg/dl, blood glucose greater than or equal to the lower limit of normal but less than 150 mg/dl, and inspiratory plateau pressure less than 30 cm H(2)O for mechanically ventilated patients) and four treatments (early broad-spectrum antibiotics, fluid challenge in the event of hypotension and/or lactate greater than 36 mg/dl, low-dose steroids for septic shock, drotrecogin alfa [activated] for multiorgan failure). The primary outcome measure was hospital mortality. The effectiveness of each treatment was estimated using propensity scores. MEASUREMENTS AND MAIN RESULTS Of 2,796 patients, 41.6% died before hospital discharge. Treatments associated with lower hospital mortality were early broad-spectrum antibiotic treatment (treatment within 1 hour vs. no treatment within first 6 hours of diagnosis; odds ratio, 0.67; 95% confidence interval, 0.50-0.90; P = 0.008) and drotrecogin alfa (activated) (odds ratio, 0.59; 95% confidence interval, 0.41-0.84; P = 0.004). Fluid challenge and low-dose steroids showed no benefits. CONCLUSIONS In severe sepsis, early administration of broad-spectrum antibiotics in all patients and administration of drotrecogin alfa (activated) in the most severe patients reduce mortality.


title: Percutaneous radiofrequency ablation for patients with malignant lung tumors: a phase II prospective multicenter study (JIVROSG-0702).

text: PURPOSE This prospective multicenter study aimed to evaluate the efficacy and safety of percutaneous radiofrequency (RF) ablation for lung cancer. MATERIALS AND METHODS From May 2008 to April 2012, 33 patients (26 men, 7 women; mean age 70.5 years) were enrolled. RF ablation was performed using an internally cooled or expandable multitined electrode. The primary endpoint was complete response (CR) determined using (18)F fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) performed 6 months after RF ablation. The secondary endpoint was the incidence and grade of adverse events (AEs) evaluated using the Common Toxicity Criteria for Adverse Events, version 3.0. RESULTS All patients underwent RF ablation and had efficacy analyses evaluated; however, FDG-PET/CT images before RF ablation were not available for two patients. The CR rate was 68 % (21 of 31 patients). One patient had a grade 5 AE unrelated to RF ablation. Grade ≥3 AEs occurred in 12 % of patients. During the follow-up period (median 37 months; range 1-55 months), five patients developed local tumor progression and nine (29 %) died. Overall survival at 1, 2, and 3 years was 97, 82, and 74 %, respectively. CONCLUSION Percutaneous RF ablation is a safe, feasible, and effective treatment for small malignant lung tumors.


Biological treatment during COVID-19 outbreak.


title: Extent of collateralization predicting symptomatic cerebral vasospasm among pediatric patients: correlations among angiography, transcranial Doppler ultrasonography, and clinical findings.

text: OBJECT Although the development and prevalence of cerebral vasospasm (CV) has been extensively investigated in adults, little data exist on the development of CV in children. The authors hypothesized that even though children have highly vasoreactive arteries, because of a robust cerebral collateral blood flow, they rarely develop symptomatic CV. METHODS The authors retrospectively reviewed their university hospital's neurointerventional database for children (that is, patients ≤ 18 years) who were examined or treated for aneurysmal or traumatic subarachnoid hemorrhage (SAH) during the period 1990-2013. Images from digital subtraction angiography (DSA) were analyzed for the extent of CV and collateralization of the cerebral circulation. Results from transcranial Doppler (TCD) ultrasonography were correlated with those from DSA. Cerebral vasospasm on TCD ultrasonography was defined according to criteria developed for adults. Clinical outcomes of CV were assessed with the pediatric modified Rankin Scale (mRS). RESULTS Among 37 children (21 boys and 16 girls ranging in age from 8 months to 18 years) showing symptoms of an aneurysmal SAH (comprising 32 aneurysms and 5 traumatic pseudoaneurysms), 17 (46%) had CV confirmed by DSA; CV was mild in 21% of these children, moderate in 50%, and severe in 29%. Only 3 children exhibited symptomatic CV, all of whom had poor collateralization of cerebral vessels. Among the 14 asymptomatic children, 10 (71%) showed some degree of vessel collateralization. Among 16 children for whom TCD data were available that could be correlated with the DSA findings, 13 (81%) had CV according to TCD criteria. The sensitivity and specificity of TCD ultrasonography for diagnosing CV were 95% and 59%, respectively. The time to CV onset detected by TCD ultrasonography was 5 ± 3 days (range 2-10 days). Twenty-five (68%) of the children had good long-term outcomes (that is, had mRS scores of 0-2). CONCLUSIONS Children have a relatively high incidence of angiographically detectable, moderate-to-severe CV. Children rarely develop symptomatic CV and have good long-term outcomes, perhaps due to robust cerebral collateral blood flow. Criteria developed for detecting CV with TCD ultrasonography in adults overestimate the prevalence of CV in children. Larger studies are needed to define TCD ultrasonography-based CV criteria for children.


title: Predictors of portal and splenic vein thrombosis after laparoscopic splenectomy: a retrospective analysis of a single-center experience.

text: PURPOSE Laparoscopic splenectomy (LS) has become the standard operative approach for splenectomy. Portal or splenic vein thrombosis (PSVT) is a serious and common complication after LS, and lethal complications of PSVT can occur when the portal vein is completely occluded by portal vein thrombosis (PVT). We aimed to clarify the predictors of PSVT after LS and to determine which of them were also predictors of PVT. METHODS A total of 56 consecutive patients who underwent elective LS were enrolled in this study. The patients were divided into two groups based on the presence or absence of PSVT after LS. In addition, patients with PSVT were divided into two groups: a PVT group and a non-PVT group. The preoperative and intraoperative clinical data were compared among the groups. RESULTS Thirty (53.6%) patients developed PSVT. The splenic vein diameter was the most useful predictor for the development of PSVT, and 10 mm was an accurate splenic vein diameter cut-off value for use as a predictive factor for PSVT. In addition, the splenic vein diameter was the most useful predictor of the development of PVT from splenic vein thrombosis (SVT), and 14 mm was found to be an accurate cut-off value. CONCLUSION PSVT is a common postoperative complication that is identified on enhanced computed tomography. The splenic vein diameter is not only a predictor of PSVT but also of the development of PVT from SVT.


Covid-19: recording their stories provides emotional benefit to healthcare workers.


title: Patients with 3-vessel coronary artery disease and impaired ventricular function undergoing PCI with Impella 2.5 hemodynamic support have improved 90-day outcomes compared to intra-aortic balloon pump: a sub-study of the PROTECT II trial.

text: OBJECTIVES To evaluate the efficacy of hemodynamic support using Impella 2.5 (IR2.5) vs intra-aortic balloon pump (IABP) in patients with 3-vessel coronary artery disease (3VD). BACKGROUND PROTECT II demonstrated favorable 90-day outcomes in patients with impaired LVEF and left main or 3VD undergoing PCI with hemodynamic support with IR2.5 compared to IABP. It is unclear if this was due to a specific benefit in a patient sub-population and if certain patients may derive particular benefit from PCI with IR2.5 support. METHODS Patients in PROTECT II were stratified upon enrollment into the left main/last patent vessel or 3VD subgroups and randomized to IR2.5 or IABP within those groups. Patients in the 3VD substratum were required to have LVEF ≤30%. RESULTS Among the 3VD subgroup (n = 325 patients; IR2.5 167, IABP 158) patients were well matched, except for prior heart failure or CABG, which were more common in the IR2.5 group (both P ≤ 0.01). Mean number of lesions treated was 3.0 ± 1.5 vs. 2.9 ± 1.4 (P = 0.61). At 30 days after PCI, patients that received IR2.5 compared to IABP support trended toward a reduction in incidence of major adverse events (MAE): 32.9% vs. 42.4% (P = 0.078). At 90 days after PCI, there was a significant difference favoring IR2.5 for incidence of MAE: 39.5% vs. 51.0% (P = 0.039), with this effect being consistent across multiple clinical subgroups. Use of IR2.5 was an independent predictor of improved 90-day outcomes. CONCLUSIONS Patients with 3VD and reduced LVEF show improved outcomes when PCI is performed with IR2.5 hemodynamic support.


title: The biomarker TP53 divides patients with neoadjuvantly treated esophageal cancer into 2 subgroups with markedly different outcomes. A p53 Research Group study.

text: BACKGROUND Fluorouracil and cisplatin have been used most frequently as neoadjuvant therapy for esophageal cancer. Both drugs are believed to act via a p53-dependent apoptosis pathway. The TP53 gene is frequently mutated in esophageal cancer. OBJECTIVE To test the value of TP53 as a biomarker prognosing outcome in patients with neoadjuvantly treated esophageal cancer. PATIENTS AND METHODS The investigation included 36 patients with primary operable esophageal cancer who were treated neoadjuvantly with cisplatin and fluorouracil. The TP53 genotype was assessed from paraffin-embedded diagnostic tumor biopsies using a standardized gene-specific TP53 sequencing protocol (mark53 kit; mark53 Ltd, Vienna, Austria). RESULTS Mutations in the TP53 gene were present in 50% of tumors. Two-year overall survival rates were 55.6% in patients with a normal TP53 marker status, compared with 16.7% in those with a mutant TP53 gene. In patients with normal TP53, neoadjuvant treatment resulted in significant advantages in terms of tumor-associated survival (P=.0049) and overall survival (P=.0304) compared with those with mutant TP53. The median tumor-associated survival was 34.2 months for patients with normal TP53, compared with 8.9 months for those with mutant TP53. The latter had a 3-fold higher risk of dying (hazard ratio, 3.01; 95% confidence interval, 1.359-6.86). CONCLUSIONS The biomarker TP53 divides esophageal cancer patients into 2 categories with markedly different outcomes: patients with a normal TP53 marker status may experience notable benefits from neoadjuvant chemotherapy with cisplatin/fluorouracil, whereas those with a mutant TP53 marker status appear to be at risk for lack of response.


title: A barbed suture repair for flexor tendons: a novel technique with no exposed barbs.

text: BACKGROUND Barbed suture technology has shown promise in flexor tendon repairs, as there is an even distribution of load and the need for a knot is eliminated. We propose that a quick and simple, novel, barbed technique without any exposed barbs on the tendon surface has comparable strength and a smaller cross-sectional area at the repair site than traditional methods of repair. METHODS Forty porcine flexor tendons were randomized to polybutester 4-strand barbed repair or to 4-strand Adelaide monofilament repair. The cross-sectional area was measured before and after repair. Biomechanical testing was carried out and 2-mm gap formation force, ultimate strength of repair, and method of failure were recorded. RESULTS The mean ultimate strength of the barbed repairs was 54.51 ± 17.9 while that of the Adelaide repairs was 53.17 ± 16.35. The mean 2-mm gap formation force for the barbed group was 44.71 ± 17.86 whereas that of the Adelaide group was 20.25 ± 4.99. The postrepair percentage change in cross-sectional area at the repair site for the Adelaide group and barbed group was 12.0 ± 2.3 and 4.6 ± 2.8, respectively. CONCLUSIONS We demonstrated that a 4-strand knotless, barbed method attained comparable strength to that of the traditional Adelaide repair technique. The barbed method had a significantly reduced cross-sectional area at the repair site compared with the Adelaide group. The 2-mm gap formation force was less in the barbed group than the Adelaide group. Barbed repairs show promise for tendon repairs; this simple method warrants further study in an animal model.


How Strong Is the Duty to Treat in a Pandemic? Ethics in Practice: Point-Counterpoint.


title: Hybrid surgery in excision of a Shamblin II glomus tumor.

text: Glomus tumors are rare benign neoplasms originating from paraganglionic cells of the neural crest developing in the adventitious layer of the vessel. They are nonencapsulated and highly vascularized. A 64-year-old female patient was identified with a hypervascularized glomus tumor measuring 5 cm, posterior to the left carotid bifurcation and contralateral carotid occlusion. We performed preoperative embolization via endovascular access followed by direct percutaneous puncture, guided by angiography, to fill the remaining area. After embolization, surgical excision of the tumor was performed with reduced bleeding and it was easier to find the cleavage planes to adjacent structures. At late follow-up, the patient is free from tumor recurrence. The tumor was classified as Shamblin II, measuring 4 to 6 cm with moderate arterial insertion. Through this double approach we observed a relative reduction in intraoperative bleeding and improved identification of the cleavage plane, facilitating excision and avoiding surgical clamping.


title: Opioid therapy for chronic pain in the United States: promises and perils.

text: Opioid therapy offers the promise of reducing the burden of chronic pain in not just individual patients, but among the broad population of patients with chronic pain. Randomized trials have demonstrated that opioid therapy for up to 12-16weeks is superior to placebo, but have not addressed longer-term use. In the United States, opioid sales have quadrupled during 2000-2010, with parallel increases in opioid accidental overdose deaths and substance abuse admissions. Clinical use of long-term opioid therapy is characterized by a pattern of adverse selection, where high-risk patients are prescribed high-risk opioid regimens. This adverse selection may link these trends in use, abuse, and overdose. Long-term opioid therapy appears to be associated with iatrogenic harm to the patients who receive the prescriptions and to the general population. The United States has, in effect, conducted an experiment of population-wide treatment of chronic pain with long-term opioid therapy. The population-wide benefits have been hard to demonstrate, but the harms are now well demonstrated.


title: Ablative therapies for small renal tumours.

text: Improvements in imaging technology have resulted in an increase in detection of small renal masses (SRMs). Minimally invasive ablation modalities, including cryoablation, radiofrequencey ablation, microwave ablation and irreversible electroporation, are currently being used to treat SRMs in select groups of patients. Cryoablation and radiofrequency ablation have been extensively studied. Presently, cryoablation is gaining popularity because the resulting ice ball can be visualized easily using ultrasonography. Tumour size and location are strong predictors of outcome of radiofrequency ablation. One of the main benefits of microwave ablation is that microwaves can propagate through all types of tissue, including desiccated and charred tissue, as well as water vapour, which might be formed during the ablation. Irreversible electroporation has been shown in animal studies to affect only the cell membrane of undesirable target tissues and to spare adjacent structures; however, clinical studies that depict the efficacy and safety of this treatment modality in humans are still sparse. As more experience is gained in the future, ablation modalities might be utilized in all patients with tumours <4 cm in diameter, rather than just as an alternative treatment for high-risk surgical patients.


title: Risk factors for hand, foot, and mouth disease and herpangina and the preventive effect of hand-washing.

text: BACKGROUND Hygiene and social distancing are recommended control measures for hand, foot, and mouth disease (HFMD) and herpangina. However, empirical data to support this recommendation are limited. METHODS During an outbreak of HFMD and herpangina due to infection by the human enterovirus 71, we defined a case as a vesicular papular rash on the hands, feet, buttocks, or oral mucosa and onset from April 30 to June 26, 2008. We selected 176 HFMD and herpangina case-children and a stratified random sample of 201 asymptomatic control-children; frequency matched according to residency status. We administered a questionnaire to the parents about their children's exposures and hygienic behaviors. RESULTS Risk factors for HFMD and herpangina included playing with neighborhood children (odds ratio [OR]: 11 [95% confidence interval (CI): 6.2-17]), visiting an outpatient clinic for another reason ≤ 1 week before onset (OR: 20 [95% CI: 5.0-88]), and community exposures to crowded places (OR: 7.3 [95% CI: 4.1-13]). By using a score summarizing responses to 4 hand-washing questions, we found that 50% of the case-children and 2.5% of control-children had a poor score of 1 to 3, whereas 12% of the case-children and 78% of control-children had a good score of ≥ 7 (OR: 0.00069 [95% CI: 0.0022-0.022]) after we adjusted for residency, age, and community exposures by using logistic regression. CONCLUSIONS Hand-washing by preschool-aged children and their caregivers had a significant protective effect against community-acquired HFMD and herpangina from the human enterovirus 71 infection.


title: Resuscitation of the patient with suspected/confirmed COVID-19 when wearing personal protective equipment: A randomized multicenter crossover simulation trial.

text: BACKGROUND The aim of the study was to evaluate various methods of chest compressions in patients with suspected/confirmed SARS-CoV-2 infection conducted by medical students wearing full personal protective equipment (PPE) for aerosol generating procedures (AGP). METHODS This was prospective, randomized, multicenter, single-blinded, crossover simulation trial. Thirty-five medical students after an advanced cardiovascular life support course, which included performing 2-min continuous chest compression scenarios using 3 methods: (A) manual chest compression (CC), (B) compression with CPRMeter, (C) compression with LifeLine ARM device. During resuscitation they are wearing full personal protective equipment for aerosol generating procedures. RESULTS The median chest compression depth using manual CC, CPRMeter and LifeLine ARM varied and amounted to 40 (38-45) vs. 45 (40-50) vs. 51 (50-52) mm, respectively (p = 0.002). The median chest compression rate was 109 (IQR; 102-131) compressions per minute (CPM) for manual CC, 107 (105-127) CPM for CPRMeter, and 102 (101-102) CPM for LifeLine ARM (p = 0.027). The percentage of correct chest recoil was the highest for LifeLine ARM - 100% (95-100), 80% (60-90) in CPRMeter group, and the lowest for manual CC - 29% (26-48). CONCLUSIONS According to the results of this simulation trial, automated chest compression devices (ACCD) should be used for chest compression of patients with suspected/confirmed COVID-19. In the absence of ACCD, it seems reasonable to change the cardiopulmonary resuscitation algorithm (in the context of patients with suspected/confirmed COVID-19) by reducing the duration of the CPR cycle from the current 2-min to 1-min cycles due to a statistically significant reduction in the quality of chest compressions among rescuers wearing PPE AGP.


title: Dimensions of the posterior cerebral circulation: an analysis based on advanced non-invasive imaging.

text: BACKGROUND Our goal was to provide measurements of the posterior cerebral circulation using non-invasive imaging and advanced software analysis tools. METHODS 100 consecutive patients aged ≥ 40 years (50 men and 50 women) who had undergone CT angiography (CTA) but had no vascular abnormality were analyzed. Specific software was used to make vessel measurements along the center line. The length of the intracranial vertebral artery (VA), the basilar artery (BA) and the distance from the mid-basilar artery to the posterior cerebral artery (mBA-PCA) was recorded. Vessel diameter was measured at the proximal and distal ends of these vessel lengths. Vessel taper was calculated as the change in diameter in millimeters per centimeter of length. RESULTS The mean lengths of the intracranial VA, the BA and the mBA-PCA were 40 ± 10.6 mm, 27.3 ± 5.7 mm and 25.6 ± 4.3 mm, respectively. The proximal and distal diameters were 3.9 ± 0.8 mm and 2.8 ± 0.6 mm for the VA and 3.6 ± 0.6 mm and 3.1 ± 0.5 mm for the BA, respectively. The mean mid-BA diameter and the proximal PCA diameter were 3.2 ± 0.5 mm and 2.2 ± 0.4 mm, respectively. There was a significant increase in arterial caliber in patients aged ≥ 60 years compared with those aged 40-59 years. Men also tended to have longer vessels with a larger diameter than women. CONCLUSIONS Advanced software and non-invasive imaging can be used to perform accurate vessel analysis. The posterior circulation measurements showed an increase in arterial caliber with age. This baseline information may be useful in planning neurovascular procedures and endovascular device development.


title: Angiostrongylosis-related restrictive pneumopathy assessed by arterial blood gas analysis in a dog.

text: Pulmonary angiostrongylosis was diagnosed by the Baermann method and larval identification from faecal and bronchoalveolar lavage samples in a five-month- old male mongrel dog with dyspnoea and cough. Arterial blood gas analysis indicated arterial hypoxaemia and restrictive pneumopathy. In addition to the palliative treatment, fenbendazole was administered (50 mg/kg/24 h per os) for 14 days. The respiratory signs subsided within a short time clinically, but serial arterial blood gas analysis demonstrated an ongoing ventilation disorder. Repeated haematology, thoracic radiography, bronchoscopy and blood gas analysis were performed to follow the course of the disease. The most severe eosinophilia was detected after the beginning of the anthelmintic therapy, and the arterial pO2 level was permanently low. Arterial blood gas analysis provided the most adequate information about the course of the pneumopathy and it greatly facilitated the patient's medical management.


title: Murine Model of Intestinal Ischemia-reperfusion Injury.

text: Intestinal ischemia is a life-threatening condition associated with a broad range of clinical conditions including atherosclerosis, thrombosis, hypotension, necrotizing enterocolitis, bowel transplantation, trauma and chronic inflammation. Intestinal ischemia-reperfusion (IR) injury is a consequence of acute mesenteric ischemia, caused by inadequate blood flow through the mesenteric vessels, resulting in intestinal damage. Reperfusion following ischemia can further exacerbate damage of the intestine. The mechanisms of IR injury are complex and poorly understood. Therefore, experimental small animal models are critical for understanding the pathophysiology of IR injury and the development of novel therapies. Here we describe a mouse model of acute intestinal IR injury that provides reproducible injury of the small intestine without mortality. This is achieved by inducing ischemia in the region of the distal ileum by temporally occluding the peripheral and terminal collateral branches of the superior mesenteric artery for 60 min using microvascular clips. Reperfusion for 1 hr, or 2 hr after injury results in reproducible injury of the intestine examined by histological analysis. Proper position of the microvascular clips is critical for the procedure. Therefore the video clip provides a detailed visual step-by-step description of this technique. This model of intestinal IR injury can be utilized to study the cellular and molecular mechanisms of injury and regeneration.


Heart transplantation management in northern Italy during COVID-19 pandemic: single-centre experience.


title: SEROSURVEY, HEMATOLOGY, AND CAUSES OF MORTALITY OF FREE-RANGING AMERICAN MARTENS ( MARTES AMERICANA) IN MICHIGAN.

text: To better understand the clinical pathology, diseases, and causes of mortality of reintroduced American martens ( Martes americana) in Michigan, a study was conducted from 2011 to 2015 in the Upper and Lower Peninsulas of Michigan. Samples obtained from live trapping ( n = 58) or harvested carcasses ( n = 34) were serologically tested for select pathogens. Antibodies against Toxoplasma gondii and canine distemper virus were detected in 58 and 3.4% of samples, respectively. All samples were seronegative for Leptospira spp. and negative for Dirofilaria immitis antigen. Urine samples tested for Leptospira spp. via immunofluorescent antibody assay ( n = 7), polymerase chain reaction ( n = 6) , or both ( n = 3) were all negative. Parvovirus DNA was detected in 9.1% of small intestine samples ( n = 22) collected from carcasses and in 3.7% of fecal samples ( n = 27) collected during live trapping. Complete blood counts ( n = 64) and serum biochemistries ( n = 63) were obtained from 49 live-trapped martens. Biochemical parameters found to be significantly different ( P < 0.05) between genders were calcium, creatinine, glucose, and phosphorus. There was no significant difference between genders for any hematologic parameter. Significant differences ( P < 0.05) between summer and winter seasons were found in total estimated white blood cell count, neutrophils, lymphocytes, monocytes, alkaline phosphatase, bicarbonate, calcium, creatinine, globulin, glucose, phosphorus, potassium, sodium, and total protein. There was no significant difference in blood cell count or serum biochemistry values between radio-collared ( n = 17) and noncollared ( n = 47) martens. Animals seropositive for T. gondii were found to have significantly higher ( P < 0.05) eosinophil and globulin levels than seronegative animals. The primary natural cause for mortality of radio-collared American martens was predation. Histologic examinations revealed a high percentage (60%) of martens with verminous or granulomatous pneumonia.


Reflections on collective versus individual rights related to communicable diseases.


Rehabilitation of COVID-19 patients.


title: Angiotensin-(1-7)/Mas Signaling Inhibits Lipopolysaccharide-Induced ADAM17 Shedding Activity and Apoptosis in Alveolar Epithelial Cells.

text: A disintegrin and metalloproteinase (ADAM) 17, constitutively expressed in alveolar epithelium, is the pivotal shedding enzyme mediating acute lung inflammation. On the other hand, angiotensin (Ang)-(1-7)/Mas signaling has been shown to improve acute respiratory distress syndrome and protect alveolar epithelial cells from apoptosis. In this study, we explored the effect of Ang-(1-7)/Mas signaling on the expression and activity of ADAM17 and assessed its impact on apoptosis in lipopolysaccharide (LPS)-treated human alveolar epithelial cells. LPS markedly induced the shedding activity of ADAM17 in alveolar epithelial cells, which was blocked by selective c-Jun N-terminal kinase (JNK) inhibitor SP600125. Ang-(1-7) concentration-dependently inhibited LPS-induced ADAM17 shedding activity, which was abolished by selective Mas blocker A779 and Mas shRNA. LPS and Ang-(1-7) showed no significant effect on the expression of ADAM17. Overexpression of ADAM17 synergized with LPS on increasing the shedding activity of ADAM17 and apoptosis in alveolar epithelial cells, counteracting the inhibitory effects of Ang-(1-7). In addition, LPS significantly increased the JNK activity in alveolar epithelial cells; Ang-(1-7) concentration-dependently inhibited LPS-induced JNK activity, which was abolished by A779 and Mas shRNA. In conclusion, this study suggests that Ang-(1-7)/Mas signaling inhibits LPS-induced alveolar epithelial cell apoptosis by inhibiting LPS-induced shedding activity of ADAM17, likely by a JNK-dependent mechanism.


title: Sustained RNA virome diversity in Antarctic penguins and their ticks.

text: Despite its isolation and extreme climate, Antarctica is home to diverse fauna and associated microorganisms. It has been proposed that the most iconic Antarctic animal, the penguin, experiences low pathogen pressure, accounting for their disease susceptibility in foreign environments. There is, however, a limited understanding of virome diversity in Antarctic species, the extent of in situ virus evolution, or how it relates to that in other geographic regions. To assess whether penguins have limited microbial diversity we determined the RNA viromes of three species of penguins and their ticks sampled on the Antarctic peninsula. Using total RNA sequencing we identified 107 viral species, comprising likely penguin associated viruses (n = 13), penguin diet and microbiome associated viruses (n = 82), and tick viruses (n = 8), two of which may have the potential to infect penguins. Notably, the level of virome diversity revealed in penguins is comparable to that seen in Australian waterbirds, including many of the same viral families. These data run counter to the idea that penguins are subject to lower pathogen pressure. The repeated detection of specific viruses in Antarctic penguins also suggests that rather than being simply spill-over hosts, these animals may act as key virus reservoirs.


title: A familial cluster of coronavirus disease 2019 (COVID-19) caused by one family member during his asymptomatic incubation period.

text: An ongoing outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread in the world, whereas asymptomatic carriers may also play a critical role in the pandemic. We report a familial cluster of COVID-19 caused by one family member before his onset of illness, indicating that it seems to be potentially infectious during the incubation period, even earlier than we expected. Close contact, especially in a small enclosed space, might be the cause of familial transmission. The unsynchronized changes in the clinical symptoms and COVID-19 nucleic acid were found in this case, so consecutive nucleic acid detection of pretty suspected cases was recommended. Family members, especially of whom the confirmed cases contacted with since one incubation period before onset rather than 2 days before onset, should be regarded as close contact and centrally isolated in case of asymptomatic infection already existed in the family.


Novel use of a hydrogel spacer permits reirradiation in otherwise incurable recurrent gynecologic cancers.


title: Epidemiology and familial risk of synchronous and metachronous colorectal cancer: a population-based study in Utah.

text: BACKGROUND & AIMS Patients diagnosed with colorectal cancer (CRC) are at risk for synchronous and metachronous lesions at the time of diagnosis or during follow-up evaluation. We performed a population-based study to evaluate the rate, predictors, and familial risk for synchronous and metachronous CRC in Utah. METHODS All newly diagnosed cases of CRC between 1980 and 2010 were obtained from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. RESULTS Of the 18,782 patients diagnosed with CRC, 134 were diagnosed with synchronous CRC (0.71%) and 300 were diagnosed with metachronous CRC (1.60%). The risk for synchronous CRC was significantly higher in men (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.02-2.06) and in patients aged 65 years or older (OR, 1.50; 95% CI, 1.02-2.21). Synchronous CRCs were located more often in the proximal colon (OR, 1.70; 95% CI, 1.20-2.41). First-degree relatives of cases with synchronous (OR, 1.86; 95% CI, 1.37-2.53), metachronous (OR, 2.34; 95% CI, 1.62-3.36), or solitary CRC (OR, 1.75; 95% CI, 1.63-1.88) were at increased risk for developing CRC, compared with relatives of CRC-free individuals. Four percent of first-degree relatives of patients with synchronous or metachronous cancer developed CRC at younger ages than the age recommended for initiating CRC screening (based on familial risk), and therefore would not have been screened. CONCLUSIONS Of patients diagnosed with CRC, 2.3% are found to have synchronous lesions or develop metachronous CRC during follow-up evaluation. Relatives of these patients have a greater risk of CRC than those without a family history of CRC. These results highlight the importance of obtaining a thorough family history and adhering strictly to surveillance guidelines during management of high-risk patients.


title: Planum Sphenoidale and Tuberculum Sellae Meningiomas: Operative Nuances of a Modern Surgical Technique with Outcome and Proposal of a New Classification System.

text: BACKGROUND The resection of planum sphenoidale and tuberculum sellae meningiomas is challenging. A universally accepted classification system predicting surgical risk and outcome is still lacking. OBJECTIVES We report a modern surgical technique specific for planum sphenoidale and tuberculum sellae meningiomas with associated outcome. A new classification system that can guide the surgical approach and may predict surgical risk is proposed. METHODS We conducted a retrospective review of the patients who between 2005 and March 2015 underwent a craniotomy or endoscopic surgery for the resection of meningiomas involving the suprasellar region. Operative nuances of a modified frontotemporal craniotomy and orbital osteotomy technique for meningioma removal and reconstruction are described. RESULTS Twenty-seven patients were found to have tumors arising mainly from the planum sphenoidale or the tuberculum sellae; 25 underwent frontotemporal craniotomy and tumor removal with orbital osteotomy and bilateral optic canal decompression, and 2 patients underwent endonasal transphenoidal resection. The most common presenting symptom was visual disturbance (77%). Vision improved in 90% of those who presented with visual decline, and there was no permanent visual deterioration. Cerebrospinal fluid leak occurred in one of the 25 cranial cases (4%) and in 1 of 2 transphenoidal cases (50%), and in both cases it resolved with treatment. There was no surgical mortality. CONCLUSION An orbitotomy and early decompression of the involved optic canal are important for achieving gross total resection, maximizing visual improvement, and avoiding recurrence. The visual outcomes were excellent. A new classification system that can allow the comparison of different series and approaches and indicate cases that are more suitable for an endoscopic transsphenoidal approach is presented.


title: The Pivotal Roles of US3 Protein in Cell-to-Cell Spread and Virion Nuclear Egress of Duck Plague Virus.

text: The duck plague virus (DPV) US3 protein, a homolog of the herpes simplex virus-1 (HSV-1) US3 protein that is reported to be critical for viral replication, has been minimally studied. Therefore, to investigate the function of the DPV US3 protein, we used scarless Red recombination technology based on an infectious bacterial artificial chromosome (BAC) containing the DPV Chinese virulent strain (CHv) genome and successfully constructed and rescued a US3-deleted mutant and the corresponding revertant virus (BAC-CHv-ΔUS3 and BAC-CHv-ΔUS3R, respectively). For viral growth characteristics, compared to the parental and revertant viruses, the US3-deleted mutant showed an approximately 100-fold reduction in viral titers but no significant reduction in genome copies, indicating that the US3-deleted mutant exhibited decreased viral replication but not decreased viral DNA generation. In addition, the US3-deleted mutant formed viral plaques that were 33% smaller on average than those formed by the parental and revertant viruses, demonstrating that US3 protein affected the viral cell-to-cell spread of DPV. Finally, the results of electron microscopy showed that the deletion of US3 resulted in a large number of virions accumulating in the nucleus and perinuclear space, thus blocking virion nuclear egress. In this study, we found that the DPV US3 protein played pivotal roles in viral replication by promoting viral cell-to-cell spread and virion nuclear egress, which may provide some references for research on the function of the DPV US3 protein.


title: Questionnaire assessment helps the self-management of patients with inflammatory bowel disease during the outbreak of Coronavirus Disease 2019.

text: OBJECTIVE This study aimed to assess the disease conditions of patients with inflammatory bowel disease (IBD) in Hubei Province during the outbreak of Coronavirus Disease 2019 (COVID-19) by questionnaire online and guide their self-management during this epidemic. RESULTS A total of 102 eligible questionnaires were included. No patient we surveyed reported a diagnosis of COVID-19. Our result showed that 67.86% of patients with ulcerative colitis (UC) and 80.43% of patients with Crohn's disease (CD) were in remission, 85.29%of patients had a good quality of life. Part of the patients (21.57%) reported their disease conditions worsening. The reduction in physical exercise was a risk factor for worsening conditions (OR=17.593, p=0.009). Some patients reported an alteration of medication regimens during the epidemic. CONCLUSIONS The epidemic of COVID-19 might have a certain impact on many aspects of Hubei IBD patients within four weeks after the traffic control. Doctors could utilize the results from our questionnaire to guide IBD patients' self-management. METHODS A questionnaire was designed containing the Harvey-Bradshaw Index (HBI), the 6-point Mayo Score, the short inflammatory bowel disease questionnaire (SIBDQ) and distributed to Hubei IBD patients online within four weeks of traffic control after the outbreak, it also included questions about patients' self-reported disease conditions and their epidemiological features of COVID-19.


title: Routine upper gastrointestinal imaging is superior to clinical signs for detecting gastrojejunal leak after laparoscopic Roux-en-Y gastric bypass.

text: BACKGROUND There are myriad symptoms and signs of gastrojejunal leak; prompt recognition is essential. Many surgeons use clinical predictors to guide selective use of upper gastrointestinal imaging (UGI). The appropriate practice remains undefined. STUDY DESIGN A review of patients who underwent primary laparoscopic Roux-en-Y gastric bypass between January 2002 and December 2008 was conducted. All underwent routine UGI studies on postoperative day 1. Actual gastrojejunal leak within 7 days of surgery (actual leak [AL], radiologic leaks), operative reports, patient charts, and postoperative vital signs were retrospectively reviewed. RESULTS There were 2,099 operations. Eight ALs (0.43%) occurred without associated mortality. UGI was positive in 7 AL patients and falsely positive in 6 patients. The AL patients underwent laparoscopy on postoperative days 1 and 3 (n = 5 and n = 1, respectively), laparotomy on postoperative day 3 (n = 1), and peritoneal drainage (n = 1). False-positive UGIs prompted laparoscopy (n = 3) and close observation (n = 3). Pulse was 100 to 120 beats per minute in 2 patients and fever (>38.5°C) was present in 0 AL patients. AL patients had osteogenesis imperfecta (n = 1), macronodular cirrhosis (n = 1), positive bubble test (n = 3), and concomitant splenectomy (n = 1). No jejunojejunostomy leaks were identified. CONCLUSIONS Routine UGI after laparoscopic Roux-en-Y gastric bypass has greater sensitivity than clinical signs for detecting gastrojejunal leak. Delay in the diagnosis of leakage can impact mortality, and this suggests that indications for routine UGI might still exist. Tachycardia is not a reliable early marker of leak. There might be risk factors for leak in addition to vital signs, including patient medical history or intraoperative events, which should prompt routine UGI on postoperative day 1.


title: Transanal rectosigmoidectomy using a single port in a Swine model.

text: BACKGROUND Natural orifice transluminal endoscopic surgery (NOTES) and single access surgery are emerging techniques that reduce surgical invasiveness. This study was performed to evaluate the feasibility of NOTES transanal rectosigmoidectomy using a single port in a swine model. METHODS Ten male pigs were used to conduct 2 studies, 4 for a nonsurvival study and 6 for a survival study. After anesthesia, the rectum was occluded transanally with a purse-string suture, and then a single port was placed. CO(2) gas was insufflated, and full-thickness rectal dissection was extended using laparoscopic instruments as far cephalad as possible. A 5-mm trocar was placed on the abdominal wall for transabdominal laparoscopic view, and then further colonic mobilization was performed using the endoscope through the anus. When the dissection was completed, the specimen was exteriorized and colorectal anastomosis was performed using a circular stapler. In the survival study, necropsies were performed on postoperative day 7. RESULTS Full-thickness circumferential rectosigmoid mobilization was achieved in all cases. The mean length of resected colon was 10 cm (range = 8-15 cm). No anastomotic defects were noted. All resected rectosigmoid specimens were grossly intact. No mortality or significant postoperative complications was observed in the survival group. On necropsy, a small abscess in the pelvic cavity was noted in 1 case and bladder distention was noted in 3 cases. CONCLUSIONS NOTES transanal rectosigmoidectomy using the single port is feasible and safe. Further experimental studies are warranted, especially in human cadaver model.


title: Contribution of Lewis X Carbohydrate Structure to Neuropathogenic Murine Coronaviral Spread.

text: Although Lewis X (Le(x)), a carbohydrate structure, is involved in innate immunity through cell-to-cell and pathogen recognition, its expression has not been observed in mouse monocytes/macrophages (Mo/Mas). The Mo/Mas that infiltrate the meninges after infection with the neuropathogenic murine coronavirus strain srr7 are an initial target of infection. Furthermore, higher inflammatory responses were observed in gene-manipulated mice lacking α1,3-fucosyltransferase 9, which determines the expression of the Le(x) structure, than in wild type mice after infection. We investigated Le(x) expression using CD11b-positive peritoneal exudate cells (PECs) and found that Le(x) is inducible in Mo/Mas after infection with srr7, especially in the syncytial cells during the late phase of infection. The number of syncytial cells was reduced after treatment of the infected PECs with anti-Le(x) antibody, during the late phase of infection. In addition, the antibody treatment induced a marked reduction in the number of the infected cells at 24 hours post inoculation, without changing the infected cell numbers during the initial phase of infection. These data indicate that the Le(x) structure could play a role in syncytial formation and cell-to-cell infection during the late phase of infection.


title: Impact of a selective use of episiotomy combined with Couder's maneuver for the perineal protection.

text: PURPOSE To evaluate the impact of a selective use of episiotomy combined with Couder's maneuver on the incidence of perineal tears in spontaneous term deliveries. METHODS A comparative, retrospective, mono-centric study in a university maternity unit was designed and included all primiparous women who delivered spontaneously after 37 weeks of gestation in cephalic presentation. Two cohorts were studied, before and after the practice of Couder's maneuver. In the first cohort, the ''OSE cohort'' only selective episiotomies were performed from January 2009 to December 2010. In the second cohort, from January 2016 to December 2017, the ''SEC cohort'' selective episiotomies combined with Couder's maneuver were performed by midwives and obstetricians. The primary outcome was the type of perineal tears, according to the Royal College of Obstetricians and Gynaecologists (RCOG) classification. RESULTS A total of 2081 patients were included: 909 patients in the OSE cohort and 1172 patients in the SEC cohort. Couder's maneuver was performed in 59% of the SEC cohort. In the SEC cohort, there were an increase in the number of intact perinea (55% versus 63%, p < 0.001), a decrease in second-degree perineal tears (18% versus 11%, p < 0.001) and a decrease in labia minora tears (48% versus 37%, p < 0.001). The rate of obstetrical anal sphincter injuries was less than 1% in both cohorts (0.3% versus 0.5%, p = 0.7). CONCLUSION A selective use of episiotomy combined with Couder's maneuver could reduce the incidence of perineal tears, particularly second-degree perineal tears, without increasing the rate of obstetrical anal sphincter injuries.


title: Willingness, perceived barriers and motivators in adopting mobile applications for health-related interventions among older adults: a scoping review protocol.

text: INTRODUCTION The world's older population continues to grow at an unprecedented rate. An ageing population poses a great challenge to our healthcare system that requires new tool to tackle the complexity of health services as well as the increasing expenses. Mobile health applications (mHealth app) is seen to have the potential to address these challenges, alleviating burdens on the healthcare system and enhance the quality of life for older adults. Despite the numerous benefits of mHealth apps, relatively little is known about whether older adults perceive that these apps confer such benefits. Their perspectives towards the use of mobile applications for health-related purposes have also been little studied. Therefore, in this paper, we outline our scoping review protocol to systematically review literature specific to older adults' willingness, perceived barriers and motivators towards the use of mobile applications to monitor and manage their health. METHODS AND ANALYSIS Arksey and O'Malley's scoping review methodology framework will guide the conduct of this scoping review. The search strategy will involve electronic databases including PubMed, Excerpta Medica Database, Cumulative Index of Nursing and Allied Health Literature, Cochrane Library, Google Scholar and ScienceDirect, in addition to grey literature sources and hand-searching of reference lists. Two reviewers will independently screen all abstracts and full-text studies for inclusion. Data will be charted and sorted through an iterative process by the research team. The extracted data will undergo a descriptive analysis and simple quantitative analysis will be conducted using descriptive statistics. Engagement with relevant stakeholders will be carried out to gain more insights into our data from different perspectives. ETHICS AND DISSEMINATION Since the data used are from publicly available sources, this study does not require ethical approval. Results will be disseminated through academic journals, conferences and seminars. We anticipate that our findings will aid technology developers and health professionals working in the area of ageing and rehabilitation.


To Face Coronavirus Disease 2019, Surgeons Must Embrace Palliative Care.


title: A case of long-term dasatinib-induced proteinuria and glomerular injury.

text: A 52-year-old woman was diagnosed with chronic myeloid leukemia. Treatment with dasatinib, a second-generation Bcr-Abl tyrosine kinase inhibitor, was initiated, and complete cytogenetic remission was achieved. Two years later, proteinuria occurred, and the urinary protein level increased gradually in the next 3 years. Moreover, the serum creatinine level increased mildly during this period. The urinary protein level reached 2.18 g/gCr; hence, a renal biopsy was conducted. Light microscopy revealed mild proliferation of mesangial cells, and immunofluorescence analysis revealed IgG and C3 depositions in the mesangial area. Electron microscopy revealed electron-dense deposition in the paramesangial area, partial podocyte foot process effacement, and segmental endothelial cell swelling with a slight expansion of the subendothelial space. Dasatinib was discontinued, and within 3 weeks, the proteinuria disappeared, with improvements in her renal function. After switching to bosutinib, a new second-generation of tyrosine kinase inhibitor, the proteinuria remained negative. The rapid cessation of proteinuria following dasatinib discontinuation indicated that proteinuria was induced by the long-term administration of dasatinib. Proteinuria and renal function should be regularly monitored during dasatinib therapy.


title: Aromatic amino acids in the juxtamembrane domain of severe acute respiratory syndrome coronavirus spike glycoprotein are important for receptor-dependent virus entry and cell-cell fusion.

text: The severe acute respiratory syndrome coronavirus (SARS-CoV) spike glycoprotein (S) is a class I viral fusion protein that binds to its receptor glycoprotein, human angiotensin converting enzyme 2 (hACE2), and mediates virus entry and cell-cell fusion. The juxtamembrane domain (JMD) of S is an aromatic amino acid-rich region proximal to the transmembrane domain that is highly conserved in all coronaviruses. Alanine substitutions for one or two of the six aromatic residues in the JMD did not alter the surface expression of the SARS-CoV S proteins with a deletion of the C-terminal 19 amino acids (S Delta19) or reduce binding to soluble human ACE2 (hACE2). However, hACE2-dependent entry of trypsin-treated retrovirus pseudotyped viruses expressing JMD mutant S Delta19 proteins was greatly reduced. Single alanine substitutions for aromatic residues reduced entry to 10 to 60% of the wild-type level. The greatest reduction was caused by residues nearest the transmembrane domain. Four double alanine substitutions reduced entry to 5 to 10% of the wild-type level. Rapid hACE2-dependent S-mediated cell-cell fusion was reduced to 60 to 70% of the wild-type level for all single alanine substitutions and the Y1188A/Y1191A protein. S Delta19 proteins with other double alanine substitutions reduced cell-cell fusion further, from 40% to less than 20% of wild-type levels. The aromatic amino acids in the JMD of the SARS-CoV S glycoprotein play critical roles in receptor-dependent virus-cell and cell-cell fusion. Because the JMD is so highly conserved in all coronavirus S proteins, it is a potential target for development of drugs that may inhibit virus entry and/or cell-cell fusion mediated by S proteins of all coronaviruses.


Covid-19 and ethnic minorities: an urgent agenda for overdue action.


title: Stress urinary incontinence and LUTS in women--effects on sexual function.

text: The sexual impact of urinary incontinence in women depends on a host of parameters, including physical, psychological, social and cultural dimensions. Evaluation of the effects of stress urinary incontinence (SUI) and lower urinary tract symptoms on sexual function is often biased by their common association with other pelvic floor disorders, such as pelvic organ prolapse, which also affect sexual satisfaction. Indeed, these complexities are reflected in the literature, which shows considerable disparity in sexual functional characteristics in women with incontinence both before and after treatment. This discordance is further emphasized by heterogeneity in study design, quality and analysis. Here, we describe the nature of sexual dysfunction in women with incontinence, including coital incontinence. The various treatments for SUI, which include transvaginal tape surgeries, can also affect sexual function, positively or negatively. Coital incontinence seems to be a good predictor of an improvement in postoperative sexual parameters: its cure, achieved by >90% of women, to a large extent explains the sexual benefits reported in several studies. By contrast, deterioration in sexual function is sometimes reported after surgery, with de novo or worsened dyspareunia being the most common cause. The literature does not contain any convincing arguments for one treatment or another on the basis of sexual functional outcome.


title: Role of robotic surgery in urogynecologic surgery and radical hysterectomy: how far can we go?

text: PURPOSE OF REVIEW The purpose is to review the current literature regarding robotic assistance in urogynecologic surgery and radical pelvic surgery and to discuss the future of robotics in these two areas of gynecology. RECENT FINDINGS When the first and only Food and Drug Administration-approved robot-assisted device, the daVinci surgical system, was approved for use in gynecology in April 2005, many procedures were translated to a robotic approach. In the field of urogynecology, much attention was given to the use of robotic assistance for sacrocolpopexy. In oncology, there was an attraction to the use of robotics for radical hysterectomies. There are a number of published observational studies comparing the outcomes of both robot-assisted laparoscopic sacrocolpopexy (RALS) and robot-assisted radical hysterectomy (RRH) to their conventional laparoscopic and open versions. Overall, the literature suggests that the use of robotics for these procedures increases operative time and cost, but decreases estimated blood loss and length of stay. The complication rates appear to be similar. Recurrence of apical prolapse after RALS appears to be similar to that in conventional laparoscopic or open sacrocolpopexy. The number of lymph nodes harvested is the same or increases with RRH, whereas the disease-free progression and overall survival are similar for all the methods of radical hysterectomy. SUMMARY Literature suggests that RALS and RRH have equivalent outcomes when compared to conventional laparoscopic and open techniques. The question is whether the use of robotics that combines the outcomes of an open procedure, the benefits of minimally invasive surgery, and easy adoptability will outweigh the increased cost and time associated with robotic surgery.


title: Gender-related long-term outcome of primary femoropopliteal stent placement for peripheral artery disease.

text: PURPOSE To evaluate gender-related long-term outcomes in patients undergoing stent treatment of femoropopliteal peripheral artery disease. METHODS Between September 2006 and August 2010, all 517 patients (333 men and 184 women; mean age 70.6 years) undergoing primary stent placement in femoropopliteal atherosclerotic lesions at 2 European vascular centers were prospectively enrolled in the study. The main study outcome was primary stent patency. Secondary outcomes included secondary patency, limb salvage, and all-cause mortality. RESULTS Women had a higher incidence of critical limb ischemia (32.1% vs. 16.9%, p<0.001). Lesion characteristics according to the TransAtlantic Inter-Society Consensus (TASC) classification were comparable in both genders (p=0.52), although total occlusions and popliteal involvement were observed more frequently in female patients (p=0.043 and p=0.001, respectively). Both genders showed similar 5-year primary patency rates (64.3% men vs. 58.1% women, p=0.11). A statistically significant difference was observed concerning the secondary patency rates in favor of men (71.9% vs. 66.8% at 5 years, p=0.005). Limb salvage rates did not vary between the groups (p=0.83). Survival rates were comparable at 5 years (83.3% and 82.6% for men and women, respectively; p=0.63), although female patients were older at their presentation (68.5 vs. 74.3 years, p<0.001). Female gender was an independent risk factor for restenosis for TASC C/D lesions (primary patency rate 39.8% in women vs. 62.0% in men; p=0.002). Finally, critical limb ischemia was an independent risk factor for restenosis in women (odds ratio 1.5). CONCLUSION Female gender was associated with a higher prevalence of critical limb ischemia, poorer secondary patency, and more frequent restenosis in TASC C/D lesions. Endovascular treatment of femoropopliteal lesions provides equal results between genders in terms of primary stent patency in the long term.


title: Vertical Midface Lifting with Periorbital Anchoring in the Management of Lower Eyelid Retraction: A 10-Year Clinical Retrospective Study.

text: BACKGROUND Lower eyelid retraction can be the unfortunate result of aesthetic surgery, trauma, disease, or the aging processes. The purpose of this article is to assess whether midface lifting based on purely vertical repositioning constitutes an effective procedure for its correction. METHODS A retrospective study was carried out on 199 patients (311 eyelids) operated on between January of 2004 and January of 2014. The various causes of eyelid retraction in this population included cosmetic blepharoplasty (56.8 percent), involutional ectropion (23.1 percent), tumor resection (9.5 percent), facial nerve paralysis (8.5 percent), and trauma and related surgery (2 percent). The study was restricted exclusively to cases of moderate and severe lower eyelid retraction addressed by means of midface lifting. The mean follow-up time was 16.8 months. All of the patients were subjected to midface lifting with strengthening of the lateral canthus. A spacer graft was also used in 37.7 percent of the cases. RESULTS One hundred ninety-five patients (97.9 percent) displayed objective improvement of the eyelid retraction and a marked degree of improvement both in aesthetic terms and as regards the functional disorders reported. Only four patients (2 percent) presented complications such as needing another operation. CONCLUSION Midface lifting based on purely vertical repositioning makes it possible to recruit a considerable amount of "new" skin at the lower eyelid, thus ensuring a decrease in vertical distraction and correct recovery of the height of the external lamellar plane. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, IV.


title: Acute-phase response following full-mouth versus quadrant non-surgical periodontal treatment: A randomized clinical trial.

text: AIM A moderate acute-phase response occurs 24-h following full-mouth non-surgical treatment (FM-SRP). The aim of this study was to compare acute-phase (24-h) and medium-term (3 months) inflammation after quadrant scaling (Q-SRP) versus FM-SRP. MATERIAL & METHODS Thirty-eight periodontitis-affected subjects were randomly allocated to FM-SRP or Q-SRP after a baseline visit. Periodontal and anthropometric parameters were collected at baseline and 3 months. Serum samples were drawn at baseline, 1, 7, and 90 days after treatment. High-sensitivity assays of inflammation and endothelial assays were performed. RESULTS FM-SRP produced a greater acute-phase response after 24 h [threefold increase in C-reactive protein (CRP), twofold increase in interleukin (IL-6), and a slight increase in tumour necrosis factor]. No differences in systemic biomarkers were noted between groups at any later follow-ups. Both periodontal treatments produced a comparable improvement in clinical periodontal parameters with no between-group differences. Treatment time was positively associated with the relative 24-h increase in CRP (R = 0.5, p < 0.001) and IL-6 (R = 0.5, p = 0.002), while the number of deeper (>6 mm) pockets predicted only the relative increase in IL-6 (R = 0.4, p < 0.05). CONCLUSIONS FM-SRP triggers a moderate acute-phase response of 24 h duration compared to Q-SRP. Further research is needed to assess the eventual impact of such findings on the risk of vascular events is advocated. (ClinicalTrials.gov NCT01857804).


title: Corking the WEB and coiling through a jailed microcatheter: WEB assisted coiling, a useful technique avoiding the use of stents in treating wide-necked large intracranial aneurysms.

text: The WEB is an endovascular flow-disrupting device used in treating wide-necked intracranial aneurysms. Although the device is available in varying sizes, large aneurysms pose a challenge with the need for custom-made devices. We describe the use of coils as an adjunct to the WEB device in successfully treating large aneurysms in two patients, one with an acutely ruptured aneurysm. This novel technique of jailing a microcatheter, deploying the WEB and then coiling the aneurysm saves the need for intracranial stenting, thereby avoiding the need for antiplatelet therapy, which is of benefit in the setting of acute aneurysm rupture.


title: Laparoscopic sleeve gastrectomy using a synthetic bioabsorbable staple line reinforcement material: Post-operative complications and 6 year outcomes.

text: BACKGROUND Gastric leak after laparoscopic sleeve gastrectomy (LSG) is a serious complication. Currently, the literature lacks long-term outcomes in LSG and leak rates after reinforcement of the staple line. The aims are two-fold: to present leak rates from using staple line reinforcement and six year outcomes of LSG in relation to resolution of obesity-related comorbidities and long-term weight loss. MATERIALS AND METHODS This is a single-institution, retrospectively reviewed study of 204 patient case files. Data from all patients undergoing LSG between December 2007 and May 2013 was collected. RESULTS The total complication rate was 6.9% (14/204), with no recorded staple line leaks. The mean postoperative Body Mass Index (BMI) at 1 year, 2 years, 3 years, 4 years, 5 years, and 6 years was 39.3 ± 8, 38.7 ± 8, 40.4 ± 9, 40.5 ± 10, 43.0 ± 10, and 42.4 ± 7, respectively. The mean % excess weight loss at 1 year, 3 years, and 6 years was 48.4 ± 19, 51.7 ± 28, and 41.0 ± 21, respectively. There were no significant differences between follow-ups at year 1 and 3 (p > 0.05), and between year 3 and 6 (p > 0.05) for the mean % excess weight loss. The resolution rates for all patients were 74%, 61%, 79%, and 90% for hypertension, hypercholesterolemia, diabetes mellitus type 2 and obstructive sleep apnea, respectively. CONCLUSION The synthetic bioabsorbable reinforcement material shows no staple line leaks making it safe to use. LSG as a procedure had a high resolution of obesity-related comorbidities as well as sustainable long-term weight loss.


title: Preoperative embolization of intracranial hemangiopericytomas: case series and introduction of the transtumoral embolization technique.

text: BACKGROUND AND PURPOSE Hemangiopericytomas (HPCs) are rare dural-based neoplasms. Preoperative embolization of these notoriously hypervascular tumors can be challenging as they often receive their dominant blood supply from pial feeders arising from the internal carotid artery (ICA) or vertebrobasilar (VB) circulation. This study reviews our historical experience with HPC embolization and introduces the transtumoral technique for backfilling pial tumor vasculature by delivering Onyx-18 through diminutive external carotid artery (ECA) feeders. METHODS A retrospective review of all preoperative HPC embolizations performed at Anonymous University #1 (September 2002-November 2014) and Anonymous University #2 (January 2014-November 2014) is presented. RESULTS Fifteen patients with pathologically confirmed HPC underwent 17 embolizations. More extensive devascularization percentages were achieved for HPCs with primarily ECA blood supply (76.4±10.7%; n=6) than with HPCs supplied via the ICA/VB circulation (57.9±26.9%; n=8; p=0.046). There was a trend towards greater devascularization of ICA/VB-dominant HPCs embolized with Onyx (70.0±34.6%; n=4) versus polyvinyl alcohol particles (33.3±15.3%; n=3). The extent of angiographic devascularization negatively correlated with intraoperative blood loss (rho=-0.71; p=0.005). There were no embolization-related complications. CONCLUSIONS The extent of preoperative embolization of HPCs correlates with decreased intraoperative blood loss. However, HPCs with an ICA/VB-dominant blood supply remain challenging embolization targets, demonstrating reduced devascularization percentages compared with ECA-dominant counterparts. The authors favor the use of Onyx for ICA/VB-dominant HPCs, noting a trend towards an improved devascularization rate.


Covid-19: Questions remain over UK government's PPE guidance.


Increased CSF levels of IL-1β, IL-6, and ACE in SARS-CoV-2-associated encephalitis.


title: Integrating biophysics with HTS-driven drug discovery projects.

text: Over the past decade biophysics has become an established discipline in HTS hit triaging, owing to its high fidelity in detecting protein-ligand interactions. Many pharma companies are using biophysical techniques to filter HTS output for false positives, as will be discussed in this review. Moreover, I will demonstrate how the earlier application of biophysics, already at the HTS assay development stage, is potentially even more impactful. Two key areas here are early mode-of-action studies and ensuring that the HTS assay and subsequent cascade are fit for purpose. Top-level results from 20 in-house projects are shown to underpin the impact of these studies.


title: Humidification performance of heat and moisture exchangers for pediatric use.

text: Background. While heat and moisture exchangers (HMEs) have been increasingly used for humidification during mechanical ventilation, the efficacy of pediatric HMEs has not yet been fully evaluated. Methods. We tested ten pediatric HMEs when mechanically ventilating a model lung at respiratory rates of 20 and 30 breaths/min and pressure control of 10, 15, and 20 cmH(2)O. The expiratory gas passed through a heated humidifier. We created two rates of leakage: 3.2 L/min (small) and 5.1 L/min (large) when pressure was 10 cmH(2)O. We measured absolute humidity (AH) at the Y-piece. Results. Without leakage, eight of ten HMEs maintained AH at more than 30 mg/L. With the small leak, AH decreased below 30 mg/L (26.6 to 29.5 mg/L), decreasing further (19.7 to 27.3 mg/L) with the large leak. Respiratory rate and pressure control level did not affect AH values. Conclusions. Pediatric HMEs provide adequate humidification performance when leakage is absent.


title: Respiratory Outbreak Investigations: How Many Specimens Should Be Tested?

text: To determine the optimal number of specimens for virus detection in a respiratory outbreak, laboratory results from 2 Canadian public health laboratories were reviewed. The evidence suggests that 3 specimens are sufficient for detection of a virus in >95% of outbreaks, thereby reducing laboratory costs.


title: A Virtual Comparison of the eCLIPs Device and Conventional Flow-Diverters as Treatment for Cerebral Bifurcation Aneurysms.

text: PURPOSE Effective, consistent, and complication-free treatment of cerebral bifurcation aneurysms remains elusive despite a pressing need, with the majority of lesions presenting in such locations. Current treatment options focus either on aneurysm coil retention, supported by a stent-like device positioned in the parent vessel lumen, or intrasaccular devices that disrupt flow within the aneurysm dome. A third alternative, i.e., the use of conventional (intraluminal) flow-diverters to treat such bifurcation aneurysms raises the problem that at least one daughter vessel needs to be jailed in such a deployment. The eCLIPs is a stent-like device that offers the possibility of flow-diversion at the aneurysm neck, without the drawbacks of daughter vessel occlusion or those of intrasaccular deployment. METHODS In this study the eCLIPs device was virtually deployed in five cerebral bifurcation aneurysms and compared with a conventional tubular flow-diverter device. Computational fluid dynamics (CFD) simulations of the aneurysm haemodynamic environment pre- and post-implantation were conducted, and focussed on metrics associated with successful aneurysm occlusion. Absolute and relative reductions in aneurysm inflow rate (Q) and time-averaged wall shear stress (TAWSS) were recorded. RESULTS The eCLIPs device was found to perform in a similar qualitative fashion to tubular flow-diverters, with overall reduction of metrics being somewhat more modest however, when compared to such devices. Aneurysm inflow reduction and TAWSS reduction were typically 10-20% lower for the eCLIPs, when compared to a generic flow diverter (FDBRAIDED) similar to devices currently in clinical use. The eCLIPs was less effective at diffusing inflow jets and at reducing the overall velocity of the flow, when compared to these devices. This result is likely due to the larger device pore size in the eCLIPs. Notably, it was found that the eCLIPs provided approximately equal resistance to flow entering and exiting the aneurysm, which was not true for the FDBRAIDED device, where high-speed concentrations of outflow were seen at the aneurysm neck along with local TAWSS elevation. The clinical implications of such behaviour are not examined in detail here but could be significant. CONCLUSIONS Our findings indicate that the eCLIPs device acts as a flow-diverter for bifurcation aneurysms, with somewhat diminished occlusion properties comparing to tubular flow diverters but without the jailing and diminished flow evident in a daughter vessel associated with use of conventional devices.


In considerations of robotic colorectal surgery within a COVID-19 pandemic.


Mission control on Skype: how to fly a spacecraft during a pandemic.


COVID-19 and lockdown: living in 'interesting times'.


title: Genetic progression of Barrett's oesophagus to oesophageal adenocarcinoma.

text: Barrett's oesophagus (BE) is the premalignant condition associated with the development of oesophageal adenocarcinoma (OAC). Diagnostically, p53 immunohistochemistry remains the only biomarker recommended clinically to aid histopathological diagnosis. The emerging mutational profile of BE is one of highly heterogeneous lesions at the genomic level with many mutations already occurring in non-dysplastic tissue. As well as point mutations, larger scale copy-number changes appear to have a key role in the progression to OAC and clinically applicable assays for the reliable detection of aneuploidy will be important to incorporate into future clinical management of patients. For some patients, the transition to malignancy may occur rapidly through a genome-doubling event or chromosomal catastrophe, termed chromothripsis, and detecting these patients may prove especially difficult. Given the heterogeneous nature of this disease, sampling methods to overcome inherent bias from endoscopic biopsies coupled with the development of more objective biomarkers than the current reliance on histopathology will be required for risk stratification. The aim of this approach will be to spare low-risk patients unnecessary procedures, as well as to provide endoscopic therapy to the patients at highest risk, thereby avoiding the burden of incurable metastatic disease.


title: Electronic versus traditional chest tube drainage following lobectomy: a randomized trial.

text: OBJECTIVES Electronic drainage systems have shown superiority compared with traditional (water seal) drainage systems following lung resections, but the number of studies is limited. As part of a medico-technical evaluation, before change of practice to electronic drainage systems for routine thoracic surgery, we conducted a randomized controlled trial (RCT) investigating chest tube duration and length of hospitalization. METHODS Patients undergoing lobectomy were included in a prospective open label RCT. A strict algorithm was designed for early chest tube removal, and this decision was delegated to staff nurses. Data were analysed by Cox proportional hazard regression model adjusting for lung function, gender, age, BMI, video-assisted thoracic surgery (VATS) or open surgery and presence of incomplete fissure or pleural adhesions. Time was distinguished as possible (optimal) and actual time for chest tube removal, as well as length of hospitalization. RESULTS A total of 105 patients were randomized. We found no significant difference between the electronic group and traditional group in optimal chest tube duration (HR = 0.83; 95% CI: 0.55-1.25; P = 0.367), actual chest tube duration (HR = 0.84; 95% CI: 0.55-1.26; P = 0.397) or length of hospital stay (HR = 0.91; 95% CI: 0.59-1.39; P = 0.651). No chest tubes had to be reinserted. Presence of pleural adhesions or an incomplete fissure was a significant predictor of chest tube duration (HR = 1.72; 95% CI: 1.15-2.77; P = 0.014). CONCLUSIONS Electronic drainage systems did not reduce chest tube duration or length of hospitalization significantly compared with traditional water seal drainage when a strict algorithm for chest tube removal was used. This algorithm allowed delegation of chest tube removal to staff nurses, and in some patients chest tubes could be removed safely on the day of surgery.


title: Impact of irbesartan, an angiotensin receptor blocker, on uric acid level and oxidative stress in high-risk hypertension patients.

text: Hyperuricemia is a known cardiovascular risk factor. The angiotensin II receptor blocker (ARB) losartan is known to decrease serum uric acid (UA) level. A recent in vitro study demonstrated a strong interaction between irbesartan and UA transporters that exceeded that of losartan. The purpose of the present study was to evaluate the hypouricemic effect of irbesartan in a clinical setting. A total of 40 high-risk hypertensive outpatients with coronary artery disease, cerebrovascular disease and/or diabetes complications who were taking ARBs other than irbesartan and losartan were enrolled in this study. After a 4-week control period, the patients' prescribed ARBs were exchanged for an equivalent dose of irbesartan. We assessed blood pressure, heart rate, serum UA level, parameters of lipid and glucose metabolism, cardiac and renal function and inflammatory and oxidative stress markers in blood samples taken immediately before the initiation of irbesartan treatment and again after 12 weeks of treatment. All 40 recruited patients were followed (31 men and 9 women, mean age: 68 years) without any dropouts. During the 12 weeks of irbesartan treatment, no significant changes in blood pressure, heart rate, parameters of lipid or glucose metabolism or other biomarkers of cardiac function, renal function, or inflammation were observed. However, UA level (5.9±1.6 to 5.5±1.6 mg ml(-1), P=0.028) and the oxidative stress marker derivative reactive oxygen metabolites (dROMs) (354±83 to 310±65 U.CARR, P<0.001) were significantly lower at 12 weeks of treatment compared with before treatment. These results suggest that irbesartan has beneficial effects on hyperuricemia and oxidative stress.


title: Designing liver resections and pushing the envelope with resections for hepatic colorectal metastases.

text: Current concepts in the management of hepatic metastases have changed dramatically over the past two decades. Multidisciplinary therapies including chemotherapy, surgery, and regional therapy have alone and in combination significantly improved the survival of patients with metastatic colorectal cancer. Conditions that were previously considered hopeless and treated merely for palliation can now be approached with curative intent. In this paper, we review the surgical treatment for colorectal cancer liver metastasis (CRLM) and describe a paradigm-shift in the management of complex heretofore-considered unresectable CRLM. Utilizing advanced multidisciplinary treatment strategies has improved the prognosis of patients with stage IV colorectal cancer to the point where we may question whether CRLM are now a chronic disease.


title: Lumbar spinal epidural arteriovenous fistula with perimedullary venous drainage after endoscopic lumbar surgery.

text: Spinal epidural arteriovenous fistulas (AVFs) with perimedullary venous drainage are rare. This report describes a case of lumbar epidural AVF in a patient with a history of endoscopic lumbar discectomy at the same level 8 years prior to presenting with progressive myelopathy secondary to retrograde venous reflux into the perimedullary vein. A 69-year-old man presented with progressive lower extremity weakness and sensory disturbance and loss of sphincter control 8 years after endoscopic lumbar discectomy for a disc herniation at L4-5 level. Magnetic resonance imaging showed spinal cord edema and dilated intradural perimedullary vessels. Spinal angiography revealed an epidural AVF at the site of the previous endoscopic lumbar surgery with intradural perimedullary venous drainage. The fistula was successfully occluded via endovascular transarterial embolization, and the patient had stabilization of his neurological deficits. Lumbar spinal epidural AVFs, especially those associated with iatrogenic trauma, are rare. Endoscopic surgical procedure can occlude the epidural venous plexus and disturb venous drainage, thereby inducing local venous hypertension and leading to epidural AVF with perimedullary venous drainage. This type of pathology should be considered within the differential diagnosis of delayed neurological deterioration after spinal surgery.


title: Associations of Ischemic Lesion Volume With Functional Outcome in Patients With Acute Ischemic Stroke: 24-Hour Versus 1-Week Imaging.

text: BACKGROUND AND PURPOSE Ischemic lesion volume (ILV) on noncontrast computed tomography at 1 week can be used as a secondary outcome measure in patients with acute ischemic stroke. Twenty-four-hour ILV on noncontrast computed tomography has greater availability and potentially allows earlier estimation of functional outcome. We aimed to assess lesion growth 24 hours after stroke onset and compare the associations of 24-hour and 1-week ILV with functional outcome. METHODS We included 228 patients from MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), who received noncontrast computed tomography at 24-hour and 1-week follow-up on which ILV was measured. Relative and absolute lesion growth was determined. Logistic regression models were constructed either including the 24-hour or including the 1-week ILV. Ordinal and dichotomous (0-2 and 3-6) modified Rankin scale scores were, respectively, used as primary and secondary outcome measures. RESULTS Median ILV was 42 mL (interquartile range, 21-95 mL) and 64 mL (interquartile range: 30-120 mL) at 24 hours and 1 week, respectively. Relative lesion growth exceeding 30% occurred in 121 patients (53%) and absolute lesion growth exceeding 20 mL occurred in 83 patients (36%). Both the 24-hour and 1-week ILVs were similarly significantly associated with functional outcome (both P<0.001). In the logistic analyses, the areas under the curve of the receiver-operator characteristic curves were similar: 0.85 (95% confidence interval, 0.80-0.90) and 0.87 (95% confidence interval, 0.82-0.91) for including the 24-hour and 1-week ILV, respectively. CONCLUSIONS Growth of ILV is common 24-hour poststroke onset. Nevertheless, the 24-hour ILV proved to be a valuable secondary outcome measure as it is equally strongly associated with functional outcome as the 1-week ILV. CLINICAL TRIAL REGISTRATION URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758.


Triage of functional, female and neuro-urology patients during and immediately after the Covid-19 outbreak.


title: Is the Pace of Biomedical Innovation Slowing?

text: The pace of biomedical innovation is important because it determines the rate of progress in medicine and allied disciplines. A review of the history of medical advances reveals that the three decades from 1950 to 1980 were a particularly innovative time. Subsequent decades have seen fewer seminal advances, despite continued improvements in many biomedical technologies. Although the biomedical sciences continue to be innovative, the question posed in this essay is whether the rate of innovation has slowed relative to the available knowledge base. The pace of innovation varies tremendously depending on the specific field considered. Overall, the pace of innovation may be slower than in the past, especially when measured against the biomedical knowledge base available today versus that available then. Ten factors are discussed that could be slowing biomedical innovation. If biomedical innovation is slowing, then restoring a faster pace would require the cooperation of government, industry and academia, for the problems are multifaceted and intertwined.


title: Temperature-sensitive mutants and revertants in the coronavirus nonstructural protein 5 protease (3CLpro) define residues involved in long-distance communication and regulation of protease activity.

text: Positive-strand RNA virus genomes are translated into polyproteins that are processed by viral proteases to yield functional intermediate and mature proteins. Coronaviruses (CoVs) carry genes that encode an nsp5 protease (also known as 3CLpro or Mpro) responsible for 11 maturation cleavages. The nsp5 structure contains two chymotrypsin-like domains (D1 and D2) and a unique domain (D3), and forms functional dimers. However, little is known of interactions or communication across the structure of the protease during nsp5 activity. Using reverse genetic mutagenesis of the CoV murine hepatitis virus (MHV) nsp5, we identified a new temperature-sensitive (ts) mutation in D2 of nsp5 (Ser133Ala) and confirmed a ts residue in D3 (Phe219Leu). Both D2-tsS133A and D3-tsF219L were impaired for viral replication and nsp5-mediated polyprotein processing at the nonpermissive temperature. Passage of tsS133A and tsF219L at the nonpermissive temperature resulted in emergence of multiple second-site suppressor mutations, singly and in combinations. Among the second-site mutations, a D2 His134Tyr change suppressed the ts phenotype of D2-tsS133A and D3-tsF219L, as well as the previously reported D2-tsV148A. Analysis of multiple CoV nsp5 structures, and alignment of nonredundant nsp5 primary sequences, demonstrated that ts and suppressor residues are not conserved across CoVs and are physically distant (>10 Å) from each other, from catalytic and substrate-binding residues, and from the nsp5 dimer interface. These findings demonstrate that long-distance communication pathways between multiple residues and domains of nsp5 play a significant role in nsp5 activity and viral replication, suggesting possible novel targets for non-active site inhibitors of nsp5.


title: The efficacy and safety of preoperative lumbar drain placement in anterior skull base surgery.

text: This study assesses the efficacy of preoperative lumbar drain (LD) placement prior to elective open cranial and endoscopic anterior skull base (ASB) surgery in reducing postoperative cerebrospinal fluid (CSF) leak. A retrospective review of 93 patients who underwent LD placement at our institution between 2006 and 2011 was performed. Of these patients, 43 underwent elective LD placement prior to ASB surgery; 2 patients had evidence of CSF rhinorrhea prior to surgery, and 41 had no evidence of a preoperative CSF leak. Of those 41 patients, 2 developed CSF rhinorrhea (2/41= 4.9%) as a result of surgery-all in our endoscopic patient population (N = 21; 2/21= 9.5%). No postoperative CSF leaks were noted in our open ASB surgery cohort (N = 20). Other complications were rare, but we encountered two instances of delayed malignant cerebral edema in the open ASB cohort that are discussed in detail. Overall, preoperative LD placement was found to be an effective means of preventing postoperative CSF leaks after ASB approaches, but potential and significant intracranial complications may occur in select patients that merit careful consideration prior to LD placement.


title: Respective impact of lowering body temperature and heart rate on mortality in septic shock: mediation analysis of a randomized trial.

text: PURPOSE We previously showed that external cooling decreases day 14 mortality in febrile septic shock. Because cooling may participate in heart rate control, we studied the respective impact of heart rate and temperature lowering on mortality. METHODS Post hoc analysis of the Sepsiscool randomized controlled trial database (NCT00527007). Cooling was applied to maintain normothermia (36.5-37 °C) during 48 h. We assessed the time spent below different thresholds of temperature and heart rate on day 14 mortality. The best threshold was selected by AUC-ROC and tested as a potential mediator of mortality reduction. Mediation analysis was adjusted for severity and treatments influencing temperature and heart rate evolution. Sensitivity analysis was done using only patients with appropriate antimicrobial therapy. RESULTS A total of 197/200 patients with adequate heart rate and temperature monitoring were analyzed. The best threshold differentiating survivors and nonsurvivors was 38.4 °C for temperature and 95 b/min for heart rate. During the 48 h of intervention, cooling significantly increased the time spent with a temperature below 38.4 °C, p = 0.001, and with a heart rate below 95 b/min, p < 0.01. The longer was the time spent with a temperature below 38.4 °C, the lower was the mortality [adjOR 0.17 (0.06-0.49), p = 0.001]. The time spent with a heart rate below 95 b/min was similar in survivors and nonsurvivors [adjOR 0.68 (0.27-1.72), p = 0.42]. Mediation analysis showed that the time spent with a temperature below 38.4 °C was a significant mediator of mortality. CONCLUSION The time spent with a temperature below 38.4 °C was independently associated with patient's outcome and explained 73% of the effect of the randomization on the day 14 mortality. Heart rate lowering was not a mediator of mortality.


title: Local recurrence after microwave thermosphere ablation of malignant liver tumors: results of a surgical series.

text: BACKGROUND Microwave thermosphere ablation is a new treatment modality that creates spherical ablation zones using a single antenna. This study aims to analyze local recurrence associated with this new treatment modality in patients with malignant liver tumors. METHODS This is a prospective clinical study of patients who underwent microwave thermosphere ablation of malignant liver tumors between September 2014 and March 2017. Clinical, operative, and oncologic parameters were analyzed using Kaplan-Meier survival and Cox proportional hazards model. RESULTS One hundred patients underwent 301 ablations. Ablations were performed laparoscopically in 87 and open in 13 patients. Pathology included neuroendocrine liver metastasis (n = 115), colorectal liver metastasis (n = 100), hepatocellular cancer (n = 21), and other tumor types (n = 65). Ninety-day morbidity was 7% with one not procedure-related mortality. Median follow-up was 16 months with 65% of patients completing at least 12 months of follow-up. The rate of local tumor recurrence rate per lesion was 6.6% (20/301). Local tumor, new hepatic, and extrahepatic recurrences were detected in 15%, 40%, and 40% of patients, respectively. Local recurrence rate per pathology was 12% for both colorectal liver metastasis (12/100) and other metastatic tumors (8/65). No local recurrence was observed to date in the neuroendocrine liver metastasis and in the limited number of patients with hepatocellular cancers. Tumor size >3 cm and tumor type were independent predictors of local recurrence. CONCLUSION This is the first study to analyze local recurrence after microwave thermosphere ablation of malignant liver tumors. Short-term local tumor control rate compares favorably with that reported for radiofrequency and other microwave technologies in the literature.


title: Constructing Ebola transmission chains from West Africa and estimating model parameters using internet sources.

text: During the recent Ebola crisis in West Africa, individual person-level details of disease onset, transmissions, and outcomes such as survival or death were reported in online news media. We set out to document disease transmission chains for Ebola, with the goal of generating a timely account that could be used for surveillance, mathematical modeling, and public health decision-making. By accessing public web pages only, such as locally produced newspapers and blogs, we created a transmission chain involving two Ebola clusters in West Africa that compared favorably with other published transmission chains, and derived parameters for a mathematical model of Ebola disease transmission that were not statistically different from those derived from published sources. We present a protocol for responsibly gleaning epidemiological facts, transmission model parameters, and useful details from affected communities using mostly indigenously produced sources. After comparing our transmission parameters to published parameters, we discuss additional benefits of our method, such as gaining practical information about the affected community, its infrastructure, politics, and culture. We also briefly compare our method to similar efforts that used mostly non-indigenous online sources to generate epidemiological information.


title: Communication Between Infectious Disease Physicians and US State and Local Public Health Agencies: Strengths, Challenges, and Opportunities.

text: Strong working relationships between infectious disease (ID) physicians and public health have resulted in the early detection of emerging infectious threats. From May 6 through June 5, 2015, we surveyed ID physicians in the Infectious Diseases Society of America's Emerging Infections Network about communications with public health. A total of 688 of 1491 (46%) members completed the survey, 624 (91%) of whom knew how to reach their health department directly for an urgent issue. Only 38 (6%) described communications with their health department as poor. Interest in newer technologies (eg, mobile smartphone applications) showed mixed results. Interest in a smartphone application differed significantly by years of ID experience, with 81 of 146 (55%) respondents with <5 years of ID experience, 172 of 359 (48%) respondents with 5 to 24 years of ID experience, and 61 of 183 (33%) respondents with ≥25 years of ID experience in favor of a smartphone application (P < .001). As more physicians adopt newer communication technologies, health departments should be prepared to incorporate these tools to communicate with ID physicians.


title: Electrogastrography, Near-infrared Spectroscopy, and Acoustics to Measure Gastrointestinal Development in Preterm Babies.

text: OBJECTIVES The aim of the study was to obtain objective measures indicative of gastrointestinal maturity using 3 noninvasive technologies. METHODS Electrogastrography (EGG), abdominal near-infrared spectroscopy (NIRS), and bowel sound/acoustics (AC) monitoring were used simultaneously to obtain physiologic measures of the gastrointestinal system of 18 preterm and 5 term neonates who were tolerating enteral feedings. Measures of EGG slow wave voltage (EGG dominant power) and AC signal amplitude (AC dominant power) were obtained after spectral density analysis. Mean abdominal regional saturations (A-rSO2) were obtained directly from NIRS. The relationship of these 3 measures with postmenstrual age (PMA) was assessed. RESULTS The results of the 3 methods differed depending on whether the measurements were pre- or postprandial. Postprandial EGG dominant power increases with PMA (r = 0.67, P = 0.003), both pre- and postprandial abdominal NIRS mean regional saturation increase with PMA (r = 0.73, P < 0.001 and r = 0.55, P = 0.009), and postprandial AC dominant power (at 300-500 Hz) increases with PMA (r = -0.48, P = 0.025). CONCLUSIONS EGG, abdominal NIRS, and AC, whenever used simultaneously, can provide objective and synergistic measures that correlate with PMA. These findings may be helpful in the assessment of feeding readiness because they reveal quantitative measures suggestive of the developmental process of the gut.


Corrigendum to Canadian Association of Thoracic Radiology/Canadian Association of Radiologists Consensus Statement Regarding Chest Imaging in Suspected and Confirmed COVID-19.


title: Gastrointestinal Behavior of Weakly Acidic BCS Class II Drugs in Man--Case Study of Diclofenac Potassium.

text: This study aimed to investigate the gastrointestinal supersaturation and precipitation behavior of a weakly acidic Biopharmaceutics Classification System (BCS) Class II drug in healthy volunteers. For this purpose, a tablet containing 50 mg diclofenac potassium (Cataflam(®)) was predissolved in 240 mL of water and this solution was subsequently orally administered to five healthy volunteers under fasted and fed state conditions with or without concomitant use of a proton-pump inhibitor (PPI) (40 mg esomeprazole, Nexiam(®)). Subsequently, total diclofenac content and dissolved intraluminal drug concentrations as well as drug thermodynamic solubility were determined in gastrointestinal aspirates. In all volunteers, gastric supersaturation resulted in precipitation of diclofenac in the stomach. The extent of precipitation correlated well with gastric pH (r = - 0.78). pH dependency of precipitation was corroborated by the absence of precipitate in the stomach after coadministration of a meal and/or a PPI. Diclofenac was found to be fully dissolved in the duodenum in all test conditions. It can be concluded that substantial pH-dependent gastric precipitation of a weakly acidic BCS Class II drug administered as a solution occurs in humans. With regard to its implications for intestinal absorption, results suggest the instantaneous redissolution of gastric drug precipitate upon transfer to the duodenum.


title: Combined Selective Cerebral Hypothermia and Mechanical Artery Recanalization in Acute Ischemic Stroke: In Vitro Study of Cooling Performance.

text: BACKGROUND AND PURPOSE Therapeutic hypothermia represents a promising neuroprotective treatment for patients with ischemic stroke. Selective, intracarotid blood cooling may initiate rapid and early brain hypothermia, reduce systemic effects, and allow combined endovascular mechanical thrombectomy. For this approach, a balloon cooling catheter system was designed and studied in vitro to optimize its cooling performance. MATERIALS AND METHODS Computational fluid dynamics of blood cooling was performed within the common carotid artery lumen by using 3 different catheter designs (1-, 2-, and 4-balloon array). On the basis of these results, a first catheter prototype was manufactured, and its heat-exchange performance was tested in an artificial in vitro circulation simulating the common carotid artery lumen at different flow rates (inflow temperature of 37°C). RESULTS In the computational fluid dynamics model, the catheter with the 4-balloon array achieved the highest cooling rate of -1.6°C, which may be attributed to disruption of the thermal boundary layers. In the in vitro study, cooling of the blood substitute at flow rates of 400 mL/min (normal common carotid artery flow) and 250 mL/min (reduced common carotid artery flow due to distal MCA occlusion) achieved a temperature drop inside the blood substitute along the cooling balloons of -1.6°C and -2.2°C, respectively. CONCLUSIONS The feasibility of intracarotid blood cooling using a new catheter system was demonstrated in vitro. A serial 4-balloon array led to an optimized cooling capacity approaching optimum target temperatures of mild therapeutic hypothermia. To determine the therapeutic efficacy of combined selective therapeutic hypothermia and mechanical thrombectomy, further in vivo studies by using a model of temporary ischemia with large-vessel occlusion and recanalization are required.


Deadly MERS coronavirus not yet a global concern.


title: Shattered social identity and moral injuries: Work-related conditions in health care professionals during the COVID-19 pandemic.

text: The present article assesses the effects of shattered social identity and moral injuries experienced by health care professionals (HCPs) due to the COVID-19 pandemic. Professional expertise and emotional-cognitive demands as key aspects of HCPs' social identity are introduced, and the effects of moral injuries-in terms of violation of medical-ethical and social-ethical norms-on the mental health of HCPs are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: The p48MW Flow Diverter-Initial Human Experience.

text: BACKGROUND AND PURPOSE The use of flow diverters to treat aneurysms arising from small caliber parent vessels has been reported. This article reports the results of the first in experiences with the p48MW (p48 Movable Wire) in humans, a device specifically designed to target vessels 1.75-3 mm in diameter. METHODS This monocentric study retrospectively reviewed the prospectively maintained database to identify all patients treated with the p48MW device between January 2017 and January 2019 at this institution. Patient demographics, aneurysm characteristics, angiographic and clinical follow-up were recorded as well as complications. RESULTS A total of 25 patients (20 female) with an average age of 55 ± 12.9 years (range 34-84) with 25 aneurysms were identified. The majority of the aneurysms was located in the anterior circulation (19/25, 76%). The average aneurysm dome width was 3.98 ± 3.6 mm (range 1.2-13 mm). Complete occlusion was seen in 18/24 (75%) aneurysms with neck remnants in 1/24 (4.2%) and continued aneurysm filling seen in the remaining cases (5/24, 20.8%). Adequate occlusion was seen in 79.2% of aneurysms (Raymond Roy Classification [RRC] grade I or II) during the follow-up period. There was a single technical complication with inappropriate deployment of the first p48MW. There was a single clinical complication (4%); however, the patient made a complete recovery (modified Rankin Scale [mRS] 0) and one patient died secondary to uncontrollable status epilepticus following acute subarachnoid hemorrhage unrelated to the treatment. CONCLUSION The p48MW is safe and effective for the treatment of aneurysms including those arising from distal vessels.