title: Recruitment Maneuvers and Positive End-Expiratory Pressure Titration in Morbidly Obese ICU Patients.

text: OBJECTIVE The approach to applying positive end-expiratory pressure in morbidly obese patients is not well defined. These patients frequently require prolonged mechanical ventilation, increasing the risk for failed liberation from ventilatory support. We hypothesized that lung recruitment maneuvers and titration of positive end-expiratory pressure were both necessary to improve lung volumes and the elastic properties of the lungs, leading to improved gas exchange. DESIGN Prospective, crossover, nonrandomized interventional study. SETTING Medical and surgical ICUs at Massachusetts General Hospital. PATIENTS Critically ill, mechanically ventilated morbidly obese (body mass index > 35 kg/m(2)) patients (n = 14). INTERVENTIONS This study evaluated two methods of titrating positive end-expiratory pressure; both trials were done utilizing positive end-expiratory pressure titration and recruitment maneuvers while measuring hemodynamics and respiratory mechanics. Measurements were obtained at the baseline positive end-expiratory pressure set by the clinicians, at zero positive end-expiratory pressure, at best positive end-expiratory pressure identified through esophageal pressure measurement before and after a recruitment maneuver, and at best positive end-expiratory pressure identified through a best decremental positive end-expiratory pressure trial. MEASUREMENTS AND MAIN RESULTS The average body mass index was 50.7 ± 16.0 kg/m(2). The two methods of evaluating positive end-expiratory pressure identified similar optimal positive end-expiratory pressure levels (20.7 ± 4.0 vs 21.3 ± 3.8 cm H2O; p = 0.40). End-expiratory pressure titration increased end-expiratory lung volumes (Δ11 ± 7 mL/kg; p < 0.01) and oxygenation (Δ86 ± 50 torr; p < 0.01) and decreased lung elastance (Δ5 ± 5 cm H2O/L; p < 0.01). Recruitment maneuvers followed by titrated positive end-expiratory pressure were effective at increasing end-expiratory lung volumes while decreasing end-inspiratory transpulmonary pressure, suggesting an improved distribution of lung aeration and reduction of overdistension. The positive end-expiratory pressure levels set by the clinicians (11.6 ± 2.9 cm H2O) were associated with lower lung volumes, worse elastic properties of the lung, and lower oxygenation. CONCLUSIONS Commonly used positive end-expiratory pressure by clinicians is inadequate for optimal mechanical ventilation of morbidly obese patients. A recruitment maneuver followed by end-expiratory pressure titration was found to significantly improve lung volumes, respiratory system elastance, and oxygenation.


Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China.


title: Inhibitors of the renin-angiotensin system: The potential role in the pathogenesis of COVID-19.

text: Coronavirus disease 2019 (COVID-19), which initially began in China, has spread to other countries of Asia, Europe, America, Africa and Oceania, with the number of confirmed cases and suspected cases increasing each day. According to recently published research, it was found that the majority of the severe cases were elderly, and many of them had at least one chronic disease, especially cardiovascular diseases. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are the most widely used drugs for cardiovascular diseases. The clinical effect of ACEIs/ARBs on patients with COVID-19 is still uncertain. This paper describes their potential role in the pathogenesis of COVID-19, which may provide useful in the advice of cardiologists and physicians.


title: Impact of COVID-19 on Canadian medical oncologists and cancer care: Canadian Association of Medical Oncologists survey report.

text: Background The covid-19 pandemic has presented unprecedented professional and personal challenges for the oncology community. Under the auspices of the Canadian Association of Medical Oncologists, we conducted an online national survey to better understand the impact of the pandemic on the medical oncology community in Canada. Methods An English-language multiple-choice survey, including questions about demographics, covid-19 risk, use of personal protective equipment (ppe), personal challenges, and chemotherapy management was distributed to Canadian medical oncologists. The survey was open from 30 March to 4 April 2020, and attracted 159 responses. Results More than 70% of medical oncologists expressed moderate-to-extreme concern about personally contracting covid-19 and about family members or patients (or both) contracting covid-19 from them. Despite that high level of concern, considerable variability in the use of ppe in direct cancer care was reported at the time of this survey, with 33% of respondents indicating no routine ppe use at their institutions and 69% indicating uncertainty about access to adequate ppe. Of the respondents, 54% were experiencing feelings of nervousness or anxiety on most days, and 52% were having feelings of depression or hopelessness on at least some days. Concern about aging parents or family and individual wellness represented the top personal challenges identified. The management of cancer patients has been affected, with adoption of telemedicine reported by 82% of respondents, and cessation of clinical trial accrual reported by 54%. The 3 factors deemed most important for treatment decision-making were■ cancer prognosis and anticipated benefit from treatment,■ risk of treatment toxicity during scarce health care access, and■ patient risk of contracting covid-19. Conclusions This report describes the results of the first national survey assessing the impact of the covid-19 on Canadian medical oncologists and how they deliver systemic anticancer therapies. We hope that these data will provide a framework to address the challenges identified.


title: Retrospective Analysis of Delayed Intraparenchymal Hemorrhage after Flow-Diverter Treatment: Presentation of a Retrospective Multicenter Trial.

text: BACKGROUND AND PURPOSE Intracranial aneurysm treatment with flow diverters has shown satisfying results in terms of aneurysm occlusion, and while some cases of delayed intraparenchymal hemorrhage have been described, no systematic analysis of the risk factors affecting its occurrence has been conducted in a large series of patients. This retrospective analysis of delayed intraparenchymal hemorrhage after flow-diverter treatment is a multicenter, retrospective study using a large series of treated patients to analyze factors affecting the occurrence of delayed intraparenchymal hemorrhage. MATERIALS AND METHODS Patients treated with flow diverters and presenting with delayed intraparenchymal hemorrhage were included from December 2007 to December 2014 in 7 participating centers in France. Patient and aneurysm characteristics were recorded as were characteristics of bleeding (size, lateralization, and time to bleed), treatment, and clinical outcome after 1, 3, and 6 months. RESULTS Delayed intraparenchymal hemorrhage occurred in 11 patients between 1 and 21 days after the procedure. In 10 of these patients, hemorrhages were ipsilateral to the treated aneurysms. Five of the 11 underwent surgery, and 9 of the 11 had good clinical outcomes at 6 months (mRS ≤2). CONCLUSIONS The pathogenesis of delayed intraparenchymal hemorrhage occurring after flow-diverter treatment remains unclear. The multidisciplinary management of delayed intraparenchymal hemorrhage yields a relatively low morbidity-mortality rate compared with the initial clinical presentation.


title: A high C-reactive protein/procalcitonin ratio predicts Mycoplasma pneumoniae infection.

text: Background Discriminating Mycoplasma pneumoniae (MP) from Streptococcus pneumoniae (SP) and viral etiologies of community-acquired pneumonia (CAP) is challenging but has important implications regarding empiric antibiotic therapy. We investigated patient parameters upon hospital admission to predict MP infection. Methods All patients hospitalized in a tertiary care hospital between 2013 and 2017 for CAP with a confirmed etiology were analyzed using logistic regression analyses and area under the receiver operator characteristics (ROC) curves (AUC) for associations between demographic, clinical and laboratory features and the causative pathogen. Results We analyzed 568 patients with CAP, including 47 (8%) with MP; 152 (27%) with SP and 369 (65%) with influenza or other viruses. Comparing MP and SP by multivariate logistic regression analysis, younger age (odds ration [OR] 0.56 per 10 years, 95% CI 0.42-0.73), a lower neutrophil/lymphocyte ratio (OR 0.9, 0.82-0.99) and an elevated C-reactive protein/procalcitonin (CRP/PCT) ratio (OR 15.04 [5.23-43.26] for a 400 mg/μg cut-off) independently predicted MP. With a ROC curve AUC of 0.91 (0.80 for the >400 mg/μg cutoff), the CRP/PCT ratio was the strongest predictor of MP vs. SP. The discriminatory value resulted from significantly lower PCT values (p < 0.001) for MP, while CRP was high in both groups (p = 0.057). Comparing MP and viral infections showed similar results with again the CRP/PCT ratio providing the best information (AUC 0.83; OR 5.55 for the >400 mg/μg cutoff, 2.26-13.64). Conclusions In patients hospitalized with CAP, a high admission CRP/PCT ratio predicts M. pneumoniae infection and may improve empiric management.


title: Guidelines for Perioperative Care for Liver Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations.

text: BACKGROUND Enhanced Recovery After Surgery (ERAS) is a multimodal pathway developed to overcome the deleterious effect of perioperative stress after major surgery. In colorectal surgery, ERAS pathways reduced perioperative morbidity, hospital stay and costs. Similar concept should be applied for liver surgery. This study presents the specific ERAS Society recommendations for liver surgery based on the best available evidence and on expert consensus. METHODS A systematic review was performed on ERAS for liver surgery by searching EMBASE and Medline. Five independent reviewers selected relevant articles. Quality of randomized trials was assessed according to the Jadad score and CONSORT statement. The level of evidence for each item was determined using the GRADE system. The Delphi method was used to validate the final recommendations. RESULTS A total of 157 full texts were screened. Thirty-seven articles were included in the systematic review, and 16 of the 23 standard ERAS items were studied specifically for liver surgery. Consensus was reached among experts after 3 rounds. Prophylactic nasogastric intubation and prophylactic abdominal drainage should be omitted. The use of postoperative oral laxatives and minimally invasive surgery results in a quicker bowel recovery and shorter hospital stay. Goal-directed fluid therapy with maintenance of a low intraoperative central venous pressure induces faster recovery. Early oral intake and mobilization are recommended. There is no evidence to prefer epidural to other types of analgesia. CONCLUSIONS The current ERAS recommendations were elaborated based on the best available evidence and endorsed by the Delphi method. Nevertheless, prospective studies need to confirm the clinical use of the suggested protocol.


title: Effect of Electroencephalography-Guided Anesthetic Administration on Postoperative Delirium Among Older Adults Undergoing Major Surgery: The ENGAGES Randomized Clinical Trial.

text: Importance Intraoperative electroencephalogram (EEG) waveform suppression, often suggesting excessive general anesthesia, has been associated with postoperative delirium. Objective To assess whether EEG-guided anesthetic administration decreases the incidence of postoperative delirium. Design, Setting, and Participants Randomized clinical trial of 1232 adults aged 60 years and older undergoing major surgery and receiving general anesthesia at Barnes-Jewish Hospital in St Louis. Recruitment was from January 2015 to May 2018, with follow-up until July 2018. Interventions Patients were randomized 1:1 (stratified by cardiac vs noncardiac surgery and positive vs negative recent fall history) to receive EEG-guided anesthetic administration (n = 614) or usual anesthetic care (n = 618). Main Outcomes and Measures The primary outcome was incident delirium during postoperative days 1 through 5. Intraoperative measures included anesthetic concentration, EEG suppression, and hypotension. Adverse events included undesirable intraoperative movement, intraoperative awareness with recall, postoperative nausea and vomiting, medical complications, and death. Results Of the 1232 randomized patients (median age, 69 years [range, 60 to 95]; 563 women [45.7%]), 1213 (98.5%) were assessed for the primary outcome. Delirium during postoperative days 1 to 5 occurred in 157 of 604 patients (26.0%) in the guided group and 140 of 609 patients (23.0%) in the usual care group (difference, 3.0% [95% CI, -2.0% to 8.0%]; P = .22). Median end-tidal volatile anesthetic concentration was significantly lower in the guided group than the usual care group (0.69 vs 0.80 minimum alveolar concentration; difference, -0.11 [95% CI, -0.13 to -0.10), and median cumulative time with EEG suppression was significantly less (7 vs 13 minutes; difference, -6.0 [95% CI, -9.9 to -2.1]). There was no significant difference between groups in the median cumulative time with mean arterial pressure below 60 mm Hg (7 vs 7 minutes; difference, 0.0 [95% CI, -1.7 to 1.7]). Undesirable movement occurred in 137 patients (22.3%) in the guided and 95 (15.4%) in the usual care group. No patients reported intraoperative awareness. Postoperative nausea and vomiting was reported in 48 patients (7.8%) in the guided and 55 patients (8.9%) in the usual care group. Serious adverse events were reported in 124 patients (20.2%) in the guided and 130 (21.0%) in the usual care group. Within 30 days of surgery, 4 patients (0.65%) in the guided group and 19 (3.07%) in the usual care group died. Conclusions and Relevance Among older adults undergoing major surgery, EEG-guided anesthetic administration, compared with usual care, did not decrease the incidence of postoperative delirium. This finding does not support the use of EEG-guided anesthetic administration for this indication. Trial Registration ClinicalTrials.gov Identifier: NCT02241655.


title: Xpert MTB/RIF and Xpert MTB/RIF Ultra for pulmonary tuberculosis and rifampicin resistance in adults.

text: BACKGROUND Xpert MTB/RIF (Xpert MTB/RIF) and Xpert MTB/RIF Ultra (Xpert Ultra), the newest version, are the only World Health Organization (WHO)-recommended rapid tests that simultaneously detect tuberculosis and rifampicin resistance in persons with signs and symptoms of tuberculosis, at lower health system levels. A previous Cochrane Review found Xpert MTB/RIF sensitive and specific for tuberculosis (Steingart 2014). Since the previous review, new studies have been published. We performed a review update for an upcoming WHO policy review. OBJECTIVES To determine diagnostic accuracy of Xpert MTB/RIF and Xpert Ultra for tuberculosis in adults with presumptive pulmonary tuberculosis (PTB) and for rifampicin resistance in adults with presumptive rifampicin-resistant tuberculosis. SEARCH METHODS We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature, Scopus, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number Registry, and ProQuest, to 11 October 2018, without language restriction. SELECTION CRITERIA Randomized trials, cross-sectional, and cohort studies using respiratory specimens that evaluated Xpert MTB/RIF, Xpert Ultra, or both against the reference standard, culture for tuberculosis and culture-based drug susceptibility testing or MTBDRplus for rifampicin resistance. DATA COLLECTION AND ANALYSIS Four review authors independently extracted data using a standardized form. When possible, we also extracted data by smear and HIV status. We assessed study quality using QUADAS-2 and performed meta-analyses to estimate pooled sensitivity and specificity separately for tuberculosis and rifampicin resistance. We investigated potential sources of heterogeneity. Most analyses used a bivariate random-effects model. For tuberculosis detection, we first estimated accuracy using all included studies and then only the subset of studies where participants were unselected, i.e. not selected based on prior microscopy testing. MAIN RESULTS We identified in total 95 studies (77 new studies since the previous review): 86 studies (42,091 participants) evaluated Xpert MTB/RIF for tuberculosis and 57 studies (8287 participants) for rifampicin resistance. One study compared Xpert MTB/RIF and Xpert Ultra on the same participant specimen.Tuberculosis detectionOf the total 86 studies, 45 took place in high tuberculosis burden and 50 in high TB/HIV burden countries. Most studies had low risk of bias.Xpert MTB/RIF pooled sensitivity and specificity (95% credible Interval (CrI)) were 85% (82% to 88%) and 98% (97% to 98%), (70 studies, 37,237 unselected participants; high-certainty evidence). We found similar accuracy when we included all studies.For a population of 1000 people where 100 have tuberculosis on culture, 103 would be Xpert MTB/RIF-positive and 18 (17%) would not have tuberculosis (false-positives); 897 would be Xpert MTB/RIF-negative and 15 (2%) would have tuberculosis (false-negatives).Xpert Ultra sensitivity (95% confidence interval (CI)) was 88% (85% to 91%) versus Xpert MTB/RIF 83% (79% to 86%); Xpert Ultra specificity was 96% (94% to 97%) versus Xpert MTB/RIF 98% (97% to 99%), (1 study, 1439 participants; moderate-certainty evidence).Xpert MTB/RIF pooled sensitivity was 98% (97% to 98%) in smear-positive and 67% (62% to 72%) in smear-negative, culture-positive participants, (45 studies). Xpert MTB/RIF pooled sensitivity was 88% (83% to 92%) in HIV-negative and 81% (75% to 86%) in HIV-positive participants; specificities were similar 98% (97% to 99%), (14 studies).Rifampicin resistance detectionXpert MTB/RIF pooled sensitivity and specificity (95% Crl) were 96% (94% to 97%) and 98% (98% to 99%), (48 studies, 8020 participants; high-certainty evidence).For a population of 1000 people where 100 have rifampicin-resistant tuberculosis, 114 would be positive for rifampicin-resistant tuberculosis and 18 (16%) would not have rifampicin resistance (false-positives); 886 would be would be negative for rifampicin-resistant tuberculosis and four (0.4%) would have rifampicin resistance (false-negatives).Xpert Ultra sensitivity (95% CI) was 95% (90% to 98%) versus Xpert MTB/RIF 95% (91% to 98%); Xpert Ultra specificity was 98% (97% to 99%) versus Xpert MTB/RIF 98% (96% to 99%), (1 study, 551 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS We found Xpert MTB/RIF to be sensitive and specific for diagnosing PTB and rifampicin resistance, consistent with findings reported previously. Xpert MTB/RIF was more sensitive for tuberculosis in smear-positive than smear-negative participants and HIV-negative than HIV-positive participants. Compared with Xpert MTB/RIF, Xpert Ultra had higher sensitivity and lower specificity for tuberculosis and similar sensitivity and specificity for rifampicin resistance (1 study). Xpert MTB/RIF and Xpert Ultra provide accurate results and can allow rapid initiation of treatment for multidrug-resistant tuberculosis.


title: Pure Laparoscopic Versus Open Right Hepatectomy for Hepatocellular Carcinoma in Patients With Cirrhosis: A Propensity Score Matched Analysis.

text: OBJECTIVE We aimed to describe our experience with pure laparoscopic right hepatectomy (LRH) and to compare its outcomes with those of open right hepatectomy (ORH) in hepatocellular carcinoma (HCC) patients with liver cirrhosis. BACKGROUND Laparoscopic liver resection has been reported as a safe and effective approach for the management of liver cancer; however, its outcomes have not been evaluated in a large cohort of HCC patients with liver cirrhosis. METHODS We retrospectively reviewed the medical records of 152 patients who underwent pure LRH (n = 37) or ORH (n = 115) between June 2008 and July 2015 at the Asan Medical Center in Seoul, Korea. We performed 1:1 propensity score matching between the LRH and ORH groups. Subsequently, 33 patients were included in each group. RESULTS There was no statistically significant difference between the LRH and ORH groups regarding the rate of complications (P = 0.053). However, the mean comprehensive complication index, which accounts for the severity of complications, was significantly lower in the LRH group (0.63 vs 4.42; P = 0.025). There were no significant differences between the LRH and ORH groups regarding 2-year disease-free survival rate or 2-year overall survival rate (P = 0.645 and P = 0.090, respectively). CONCLUSIONS Even in patients with cirrhosis, pure LRH is not less safe than the traditional open approach. The oncological outcomes of HCC were also comparable between the two groups. In selected patients, pure LRH for HCC appears to represent a viable alternative to ORH.


title: Early Outcomes with Single-antenna High-powered Percutaneous Microwave Ablation for Primary and Secondary Hepatic Malignancies: Safety, Effectiveness, and Predictors of Ablative Failure.

text: Objective Microwave ablation (MWA) of liver malignancies has gained much traction over the past 5 years. However, MWA carries relatively higher rates of residual disease compared to resection. Likelihood of MWA success is multifactorial and newer devices with more reliable ablation zones are being developed to overcome these drawbacks. This manuscript is a review of our first 100 liver ablations with the newer single antenna high powered MWA system. Materials and Methods Retrospective chart review of patients that underwent MWA for either primary or secondary hepatic malignancies between March 2015 and July 2016 was conducted. The complete ablation rates, rate of new lesions, complications, and short-term survival were analyzed. Multiple statistical tests, including multivariate regression, were used to assess risk factors for local residual and recurrent disease. Results Fifty-three patients (median age 61 ± 9 years, 39 males) underwent 100 MWAs. Of the 100 lesions ablated, 76 were hepatocellular cancers (HCCs) and 24 were metastases. Median lesion size was 16 ± 9 mm. Seventy- five of these patients had multifocal disease targeted in the same session. Seventy patients had cirrhosis (median model for end-stage liver disease score 9 ± 3; Child-Pugh B and C in 42%). An 83% complete lesion ablation rate was seen on follow-up imaging with liver protocol magnetic resonance imaging/computed tomography (median follow-up of 1 year). The minor complication rate was 9.4% with no major complications or 30-day mortality. Despite this, evidence of new foci of hepatic disease was found in 47% of patients, the majority (80%) of which were in HCC patients (P < 0.01) and most of these new lesions were in a different hepatic segment (64%). Degree of cirrhosis (P < 0.01), presence of non-alcoholic steatohepatitis (NASH) (P = 0.01) and lesion's subcapsular location (P = 0.03) was significant predictors of residual disease. With the subset analysis of only HCC lesions larger than 1 cm, only the presence of NASH remained significant. Conclusion The single probe high power MWA of malignant hepatic lesions is safe and effective with minimal morbidity. Degree of cirrhosis, NASH, and subcapsular location was associated with an increased rate of residual disease on short-term follow-up.


title: Ablation of skeletal metastases: current status.

text: Image-guided percutaneous ablation of bone metastases is an effective, minimally invasive alternative to conventional therapies in the palliation of pain from metastatic disease. Ablative technologies applied in the treatment of skeletal metastases include radiofrequency ablation, cryoablation, microwave ablation, laser ablation, ethanol ablation, and, most recently, focused ultrasound. These ablative methods may be performed in combination with percutaneous cementoplasty to provide support and stabilization for metastases in weight-bearing bones at risk for pathologic fracture.


title: The cutting edge: membrane-anchored serine protease activities in the pericellular microenvironment.

text: The serine proteases of the trypsin-like (S1) family play critical roles in many key biological processes including digestion, blood coagulation, and immunity. Members of this family contain N- or C-terminal domains that serve to tether the serine protease catalytic domain directly to the plasma membrane. These membrane-anchored serine proteases are proving to be key components of the cell machinery for activation of precursor molecules in the pericellular microenvironment, playing vital functions in the maintenance of homoeostasis. Substrates activated by membrane-anchored serine proteases include peptide hormones, growth and differentiation factors, receptors, enzymes, adhesion molecules and viral coat proteins. In addition, new insights into our understanding of the physiological functions of these proteases and their involvement in human pathology have come from animal models and patient studies. The present review discusses emerging evidence for the diversity of this fascinating group of membrane serine proteases as potent modifiers of the pericellular microenvironment through proteolytic processing of diverse substrates. We also discuss the functional consequences of the activities of these proteases on mammalian physiology and disease.


title: Pharmacological and pharmacokinetic profile of the novel ocular hypotensive prodrug CKLP1 in Dutch-belted pigmented rabbits.

text: Elevated intraocular pressure is the only treatable risk factor for glaucoma, an eye disease that is the leading cause of irreversible blindness worldwide. We have identified cromakalim prodrug 1 (CKLP1), a novel water-soluble ATP-sensitive potassium channel opener, as a new ocular hypotensive agent. To evaluate the pharmacokinetic and safety profile of CKLP1 and its parent compound levcromakalim, Dutch-belted pigmented rabbits were treated intravenously (0.25 mg/kg) or topically (10 mM; 4.1 mg/ml) with CKLP1. Body fluids (blood, aqueous and vitreous humor) were collected at multiple time points and evaluated for the presence of CKLP1 and levcromakalim using a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) based assay. Histology of tissues isolated from Dutch-belted pigmented rabbits treated once daily for 90 days was evaluated in a masked manner by a certified veterinary pathologist. The estimated plasma parameters following intravenous administration of 0.25 mg/kg of CKLP1 showed CKLP1 had a terminal half-life of 61.8 ± 55.2 min, Tmax of 19.8 ± 23.0 min and Cmax of 1968.5 ± 831.0 ng/ml. Levcromakalim had a plasma terminal half-life of 85.0 ± 37.0 min, Tmax of 61.0 ± 32.0 min and Cmax of 10.6 ± 1.2 ng/ml. Topical CKLP1 treatment in the eye showed low levels (<0.3 ng/mL) of levcromakalim in aqueous and vitreous humor, and trace amounts of CKLP1 and levcromakalim in the plasma. No observable histological changes were noted in selected tissues that were examined following topical application of CKLP1 for 90 consecutive days. These results suggest that CKPL1 is converted to levcromakalim in the eye and likely to some extent in the systemic circulation.


title: Preliminary experience with the percutaneous embolization of juvenile angiofibromas using only ethylene-vinyl alcohol copolymer (Onyx) for preoperative devascularization prior to surgical resection.

text: BACKGROUND AND PURPOSE Juvenile angiofibromas are hypervascular tumors that may benefit from preoperative devascularization to reduce intraoperative blood loss. Our purpose was to evaluate the extent of angiographic devascularization and intraoperative blood loss by using only Onyx for percutaneous juvenile angiofibroma tumor embolization. MATERIALS AND METHODS We reviewed the clinical records and preoperative and postoperative imaging studies of a consecutive series of 9 patients with juvenile angiofibromas who were treated with preoperative embolization with direct percutaneous injection of Onyx followed by resection from a standard open surgical or endoscopic approach. RESULTS Two Fisch type I, 1 Fisch type II, 5 Fisch type IIIa, and 1 Fisch type IVa tumor were treated. Complete devascularization was achieved in all cases percutaneously with only Onyx. There were no complications. The average intraoperative blood loss was 567.7 mL (range, 10-1700 mL). An average of 2.2 needles (range, 1-5 needles) was placed into the tumor. An average of 14.6 mL of Onyx (range, 2-25 mL) was injected into each tumor. Four Fisch type IIIa tumors were removed completely from only an ENE approach. CONCLUSIONS Presurgical direct percutaneous embolization of a juvenile angiofibroma with only EVOH before surgical resection is safe and feasible. Our preliminary experience suggests that Onyx may offer a higher degree of devascularization compared with other embolic agents. This may facilitate an easier surgical resection with lower blood loss.


title: Validation of a radioimmunoassay of serum trypsin-like immunoreactivity in ferrets.

text: Measurement of serum trypsin-like immunoreactivity (TLI) is used to assess exocrine pancreatic function in dogs and cats. Ferrets ( Mustela putorius furo) serve as valuable animal models for human diseases such as cystic fibrosis and other pulmonary diseases, and may be a useful model of other diseases including pancreatitis. We developed and analytically validated a competitive radioimmunoassay (RIA) for measurement of TLI in ferret serum by determination of analytical sensitivity, assay linearity, accuracy of spiking recovery, precision, and reproducibility. Analytical sensitivity of the assay was 0.55 μg/L. Observed-to-expected (O/E) ratio for dilutional parallelism was 90.2-127.9% (mean: 108.1 ± 11.9%). The O/E ratio for spiking recovery was 94.5-113.0% (mean: 103.9 ± 7.2%). The intra- and inter-assay coefficients of variation (CVs) were 2.7-5.7% and 3.5-8.2%, respectively. The reference interval (RI) for serum TLI derived from 31 healthy ferrets was 28-115 μg/L; the 90% confidence interval for the lower and upper limits of the RI were 10.0-32.1 μg/L and 103-126 μg/L, respectively. This TLI RIA is analytically sensitive, sufficiently linear, accurate, precise, and reproducible for the measurement of TLI in ferret serum samples.


This scientist hopes to test coronavirus drugs on animals in locked-down Wuhan.


title: Performance of blow-by methods in delivering oxygen to pediatric patients during transport: A laboratory study.

text: BACKGROUND Providing supplemental oxygen with a blow-by method is used to provide additional oxygen to patients who will not tolerate an oxygen delivery device in direct contact with their face. Blow-by methods are often improvised from parts of standard equipment. The performance is very dependent on the distance to the face and the direction of the gas flow. Blow-by methods are used by anesthetists during transport but their performance in delivering supplemental oxygen has only been tested in static situations. The aim of this nonclinical study was to determine the performance of different blow-by methods in the delivery of additional oxygen to pediatric patients during transport. METHODS A manikin of a child with a facemask of appropriate size was transported along a 60 m corridor from the operating theater to the PACU. Oxygen delivery to the face of the manikin was measured during transport. Six blow-by methods were tested with oxygen flows of 3, 6, and 10 L/min and with the facemask at 0 cm from the face and at 5 cm from the face. The outcome parameter was: blow-by method reaching and maintaining an FiO2 >50% during transport from the pediatric operating theater to the PACU. RESULTS At 0 cm from the face, five out of six blow-by methods maintained a FiO2 >50% with all three flow rates. At 5 cm only two of the blow-by methods were able to maintain an FiO2 >50% and this only at flow rates of 10 L/min. All other blow-by methods provided lower FiO2 s; in three, the FiO2 decreased to values only marginally above 21%. The decrease in FiO2 typically started within 6-12 m from the start of the transport. CONCLUSION It is concluded that the ability of blow-by methods to deliver a FiO2 >50% depends on the method used and distance from the face.


title: Predictors of malignant brain edema after mechanical thrombectomy for acute ischemic stroke.

text: BACKGROUND Malignant brain edema (MBE) is a devastating complication in ischemic stroke. Data on MBE in patients who have had mechanical thrombectomy (MT) are relatively scarce. OBJECTIVE To investigate the incidence, predictors, and clinical outcomes of MBE in patients after MT. METHODS We included 130 consecutive patients after MT caused by anterior circulation large vessel occlusion stroke, treated with MT. MBE was defined as a midline shift of ≥5 mm on the follow-up imaging within 72 hours after MT. Characteristics of patients at admission and details of treatment were collected. The 90-day modified Rankin scale score was used as a measure of functional outcomes. RESULTS Of the 130 patients (age, 68.6±10.9 years; male, 50%), 35 (26.9%) patients developed MBE. The patients with MBE had a lower rate of functional independence (OR=7.831; 95% CI 1.731 to 35.427; p=0.008) and significantly higher mortality at 90 days (OR=7.958; 95% CI 2.274 to 27.848; p=0.001) than patients without MBE. In 104 (80%) patients with successful recanalization (modified Thrombolysis in Cerebral Infarction score of 2b-3), 24 (23.1%) patients exhibited MBE. After adjustment for confounding, ICA occlusion (OR=3.746; 95% CI 1.169 to 12.006; p=0.026) and worse collateral score (grade 1 vs grade 0: OR=0.727; 95% CI 0.192 to 2.753; p=0.638; grade 2 vs grade 0: OR=0.130; 95% CI 0.021 to 0.819; p=0.030) were significantly associated with the development of MBE, despite successful recanalization. CONCLUSIONS MBE after MT is not uncommon and was related to poor functional outcomes. Localization of a vessel occlusion and collateral status may play a role in the development of MBE.


title: Pure transanal total mesorectal excision for rectal cancer: experience with 55 cases.

text: Background Although the anatomic difficulties of laparoscopic surgery for rectal cancer have been resolved by hybrid transanal total mesorectal excision (h-taTME), a completely incisionless surgical procedure has not yet been developed. This study was performed to explore the efficacy of pure taTME (p-taTME) without laparoscopic assistance as a completely non-invasive surgical procedure for rectal cancer. Methods We retrospectively evaluated all patients with rectal cancer who underwent p-taTME between December 2015 and April 2018. Relevant patient characteristics and clinical information including the surgical procedure, specimens, pathological characteristics, and patients' post-operative state were analysed and the feasibility of p-taTME in patients with rectal cancer was assessed. Results Fifty-five patients who had undergone p-taTME were included in this study. They comprised 32 (58.2%) men and 23 (41.8%) women with a mean age of 65.6 ± 10.6 years and mean body mass index of 23.4 ± 3.3 kg/m2. The median surgical time was 180.0 (range, 130-360) min and estimated blood loss was 25.0 (range, 15-80) mL. The commonest post-operative complication was varying degrees of faecal incontinence (56.4%). However, such incontinence greatly improved after pelvic-floor-function-rehabilitation exercises and did not seriously affect the patients' quality of life. Conclusions p-taTME is a relatively safe and incisionless procedure for patients with middle and low rectal cancer, especially in those with obesity or a narrow pelvis. However, further studies of the indications and long-term efficacy are needed to verify the suitability of this procedure.


title: Exercise for reducing falls in people living with and beyond cancer.

text: BACKGROUND Current treatment modalities for cancer have been successful in achieving improved survivorship; however, they come with a number of long-term adverse effects. Accidental falls are a common and clinically significant adverse event in people living with and beyond cancer and rates are higher than in the rest of the population. OBJECTIVES To assess the effects of prescribed or provided exercise for reducing accidental falls, and falls risk factors of strength, flexibility and balance, in people living with and beyond cancer. SEARCH METHODS We searched the following electronic databases from inception to 10 July 2018, with no restrictions: CENTRAL, MEDLINE, Embase, and seven other databases. We searched clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) for ongoing trials, and reference lists of reviews and retrieved articles for additional studies. SELECTION CRITERIA We included all randomised controlled trials investigating exercise interventions versus no treatment, usual care or non-exercise interventions on falls incidence or falls risk factors in adults living with and beyond cancer (18 years of age or older at diagnosis). We excluded cross-over studies and studies in acute or inpatient hospice care. DATA COLLECTION AND ANALYSIS At least two review authors independently completed data extraction for included papers. We used Covidence software to manage screening, data collection and extraction. We assessed evidence using GRADE and presented results in a 'Summary of findings' table. MAIN RESULTS Eleven studies (835 participants) compared exercise to usual care. No studies compared exercise with no treatment or non-exercise interventions. The quality of the evidence was very low for the primary outcome rates of falls, and very low to low for the secondary outcomes. We downgraded the evidence due to study limitations (risk of bias), and issues of imprecision due to small sample sizes, inconsistency and indirectness. All studies were at high risk of bias for blinding of participants and personnel due to inability to blind participants to an exercise intervention. Risk of bias was generally low or unclear for other categories.There was generally little information on the important outcomes comparing exercise to usual care.Rates of falls and number of fallers: one study (223 participants) measured accidental falls, but reported neither the rate of falls or the number of fallers; there was no difference in the number of falls between exercise and usual care (very low-quality evidence).Strength: 10 studies (813 participants) reported on strength outcomes. Two analyses favoured exercise over usual care: quadriceps strength (2 studies, 72 participants; mean difference (MD) 8.99 kg, 95% confidence interval (CI) 1.29 to 16.70; low-quality evidence), and leg press (4 studies, 388 participants; MD 21.1 kg, 95% CI 8.47 to 33.74; low-quality evidence). In one analysis of the Sit-to-Stand Test, there was no difference between exercise and usual care (4 studies, 214 participants; standardised mean difference (SMD) -0.45, 95% CI -1.05 to 0.14; very low-quality evidence).Flexibility: one study (21 participants) reported on flexibility for Sit-and-Reach Distance (MD 2.05 cm, 95% CI 0.59 to 3.51; very low-quality evidence).Balance: five studies (350 participants) measured three different balance outcomes. Two analyses favoured exercise over usual care: postural balance (4 studies, 127 participants; standardised mean difference (SMD) 0.44, 95% CI 0.08 to 0.79; very low-quality evidence), and Backward Walk Test (2 studies, 280 participants; SMD -0.24, 95% CI -0.48 to -0.01; low-quality evidence). There was no difference between exercise and usual care for the Timed Up-and-Go Test (1 study, 15 participants; MD -0.35 seconds, 95% CI -1.47 to 0.77; low-quality evidence).Number of people sustaining a fall-related fracture: the quality of the evidence for exercise reducing fall-related fractures was very low.Adverse events: a single study (223 participants) noted some temporary muscle soreness on initiation of exercise or when there was an increase in the weight lifted. As no occurrence data were reported, we could not assess this variable further. No studies reported musculoskeletal injury. Analysis indicated that there was very low-quality evidence that exercise did not increase fatigue. AUTHORS' CONCLUSIONS There is a paucity of evidence for exercise training to reduce fall rates in people living with and beyond cancer. Exercise training may improve strength, flexibility and balance for people in this population, but the evidence is very low quality.


[Management of Patients with COVID-19 - Recommendations from a Palliative Care Perspective].


title: Management of gynecomastia-changes in psychological aspects after surgery-a systematic review.

text: Gynecomastia affects up to two-thirds of the male population. For many patients the psychological impact of the disease is substantial. Surgical treatment is indicated when medical treatments fail. Until now, most published research on the subject has focused on how effective surgical treatment is on correcting the cosmetic appearance of the breast. Little is known about the effect of surgical treatment on the psychological aspects of the disease. The aim of this review was to identify the psychological domains affected by the disease and the effect of surgical treatment on these. A systematic search of the published literature was performed. All studies on the subject were evaluated for inclusion and six studies were included in the review. Several of the included studies reported improvement in quality of life and several psychological domains after surgical treatment for gynecomastia. Among these domains, are; vitality, emotional discomfort, limitations due to physical aspects and limitations due to pain. Impact of surgical treatment for gynecomastia seems to be beneficial for several psychological domains. The current level of evidence on this subject is very low and future studies, examining the impact of the surgical intervention for gynecomastia on psychological domains, are greatly needed. More data on this subject could improve the pre-operative evaluation of these patients and help identify the patients that will benefit from treatment.


Viewpoint: The COVID-19 and climate crises.


title: The covariation of acoustic features of infant cries and autonomic state.

text: The evolution of the autonomic nervous system provides an organizing principle to interpret the adaptive significance of physiological systems in promoting social behavior and responding to social challenges. This phylogenetic shift in neural regulation of the autonomic nervous system in mammals has produced a neuroanatomically integrated social engagement system, including neural mechanisms that regulate both cardiac vagal tone and muscles involved in vocalization. Mammalian vocalizations are part of a conspecific social communication system, with several mammalian species modulating acoustic features of vocalizations to signal affective state. Prosody, defined by variations in rhythm and pitch, is a feature of mammalian vocalizations that communicate emotion and affective state. While the covariation between physiological state and the acoustic frequencies of vocalizations is neurophysiologically based, few studies have investigated the covariation between vocal prosody and autonomic state. In response to this paucity of scientific evidence, the current study explored the utility of vocal prosody as a sensitive index of autonomic activity in human infants during the Still Face challenge. Overall, significant correlations were observed between several acoustic features of the infant vocalizations and autonomic state, demonstrating an association between shorter heart period and reductions in heart period and respiratory sinus arrhythmia following the challenge with the dampening of the modulation of acoustic features (fundamental frequency, variance, 50% bandwidth, and duration) that are perceived as prosody.


title: A novel approach in retrieving retained pulmonary bullet injury.

text: Video-assisted thoracoscopic surgery can be a useful tool in selected penetrating chest trauma patients for diagnostic and therapeutic purposes. It is currently a safe and feasible alternative to thoracotomy in the management of chest trauma especially for hemodynamically stable patients. Penetrating chest trauma with retained bullet was removed successfully in a 25 years old patient using double-port VATS technique in combination with fluoroscopy, he made full recovery, hospital stay was very short.


The many uncertainties of COVID-19.


title: Impact of System-Wide King LT Airway Implementation on Orotracheal Intubation.

text: OBJECTIVES Orotracheal intubation is a key component of prehospital airway management and success rates are dependent on procedural experience. Supraglottic airway devices are increasingly being used in the prehospital setting. As a result, paramedics may have fewer opportunities for performing intubation, limiting their proficiency in the procedure. We aimed to determine the trends in intubation versus supraglottic airway use over an 8 year period. We also aimed to determine the association between system-wide introduction of King LT guidelines and ETI success rates. METHODS We performed a retrospective observational study of 37 Emergency Medical Services (EMS) agencies in a 10 county region of Southwestern Pennsylvania. Cases between January 1, 2005 and December 31, 2012 were included if an advanced airway procedure was performed. We determined trends in advanced airway placement and compared the proportion of cases with first pass intubation success before and after the King LT was introduced and promoted by statewide protocol starting in 2007. Use of airway devices before and after King LT implementation were presented using descriptive statistics and compared using Pearson's Chi-square or Fishers Exact test as appropriate. We compared first pass success rate of orotracheal intubation between study periods using multivariable logistic regression, controlling for other factors that may impact success of orotracheal intubation (year, EMS agency, age category, traumatic injury, and cardiac arrest). RESULTS There were 712 cases of orotracheal intubation before and 2,835 cases after introduction of the King LT. The proportion of cases ultimately managed with orotracheal intubation before and after 2007 decreased from 72.3% (95% CI 68.9-75.6%) to 67.1% (95% CI 65.3-68.8%) (p = 0.007). In the multivariable analysis, success of orotracheal intubation was not associated with implementation of the King LT airway (OR 1.02, 95% CI 0.74-1.41). CONCLUSION Fewer patients with advanced airway management received orotracheal intubation since introduction of the King LT. In spite of this modest change in airway management, there has not been a change in orotracheal intubation success rate since introduction of this supraglottic device as a primary or rescue airway in this regional EMS setting.


title: Glucose and Insulin Response of Horses Grazing Alfalfa, Perennial Cool-Season Grass, and Teff Across Seasons.

text: Elevated nonstructural carbohydrate (NSC) values in pasture forages can cause adverse health effects in some horses (Equus caballus L.). The objectives of this study were to determine the impact of different forage species on blood glucose and insulin concentrations of horses throughout the grazing season. Research was conducted in July (summer) and September (fall) in St. Paul, MN. Alfalfa (Medicago sativa L.), mixed perennial cool-season grasses (CSG), and teff (Eragrostis tef [Zucc.] Trotter) pastures were grazed by six horses (24 ± 2 years) that were randomly assigned to one of three forage types in a replicated Latin-square design. Jugular catheters were inserted 1 hour before the start of grazing and horses had access to pasture each day from 08:00 to 16:00 hours. Jugular venous blood samples were collected from each horse before being turned out (0 hours) and then at 2-hour intervals following turnout. Plasma and serum samples were collected and analyzed for glucose and insulin, respectively. Corresponding forage samples were taken by hand harvest. Seasons were analyzed separately and data were analyzed using the MIXED procedure in SAS with P ≤ .05. Teff generally had lower (P ≤ .05) equine digestible energy, crude protein, and NSC compared to the other forages. Differences in peak insulin were observed between horses grazing CSG and teff during the fall grazing (P ≤ .05). These results suggest grazing teff could lower the glucose and insulin response of some horses.


title: Preparing emergency personnel in dialysis: a just-in-time training program for additional staffing during disasters.

text: BACKGROUND There are 341 000 patients in the United States who are dependent on routine dialysis for survival. Recent large-scale disasters have emphasized the importance of disaster preparedness, including supporting dialysis units, for people with chronic disease. Contingency plans for staffing are important for providing continuity of care for a technically challenging procedure such as dialysis. PReparing Emergency Personnel in Dialysis (PREP-D) is a just-in-time training program designed to train individuals having minimum familiarity with the basic steps of dialysis to support routine dialysis staff during a disaster. METHODS A 5-module educational program was developed through a collaborative, multidisciplinary effort. A pilot study testing the program was performed using 20 nontechnician dialysis facility employees and 20 clinical-year medical students as subjects. RESULTS When comparing pretest and posttest scores, the entire study population showed a mean improvement of 28.9%, with dialysis facility employees and medical students showing improvements of 21.8% and 36.4%, respectively (P < .05 for all comparisons). CONCLUSIONS PREP-D participants were able to demonstrate improved tests scores when taught in a just-in-time training format. The knowledge gained by using the PREP-D program during a staffing shortage may allow for continuity of care for critical services such as dialysis during a disaster.


title: The establishment of a bank of stored clinical bone marrow stromal cell products.

text: BACKGROUND Bone marrow stromal cells (BMSCs) are being used to treat a variety of conditions. For many applications a supply of cryopreserved products that can be used for acute therapy is needed. The establishment of a bank of BMSC products from healthy third party donors is described. METHODS The recruitment of healthy subjects willing to donate marrow for BMSC production and the Good Manufacturing Practices (GMP) used for assessing potential donors, collecting marrow, culturing BMSCs and BMSC cryopreservation are described. RESULTS Seventeen subjects were enrolled in our marrow collection protocol for BMSC production. Six of the 17 subjects were found to be ineligible during the donor screening process and one became ill and their donation was cancelled. Approximately 12 ml of marrow was aspirated from one posterior iliac crest of 10 donors; one donor donated twice. The BMSCs were initially cultured in T-75 flasks and then expanded for three passages in multilayer cell factories. The final BMSC product was packaged into units of 100 × 106 viable cells, cryopreserved and stored in a vapor phase liquid nitrogen tank under continuous monitoring. BMSC products meeting all lot release criteria were obtained from 8 of the 11 marrow collections. The rate of growth of the primary cultures was similar for all products except those generated from the two oldest donors. One lot did not meet the criteria for final release; its CD34 antigen expression was greater than the cut off set at 5%. The mean number of BMSC units obtained from each donor was 17 and ranged from 3 to 40. CONCLUSIONS The production of large numbers of BMSCs from bone marrow aspirates of healthy donors is feasible, but is limited by the high number of donors that did not meet eligibility criteria and products that did not meet lot release criteria.


title: Peptides as protein binding site mimetics.

text: The rational/structure-based design and/or combinatorial development of molecules capable of structurally and functionally mimicking the binding sites of proteins represents a promising strategy for the exploration and understanding of protein structure and function. The ultimate goal of using such molecules is the modulation of protein function through controlled interference with the underlying binding events. In addition to their basic significance, such proteinmimetics are also useful tools for a range of biomedical applications, in particular the inhibition of disease-associated protein-ligand interactions. Owing to their chemical and structural relation to proteins, as well as the relative simplicity of their chemical or recombinant synthesis, peptides have emerged as adequate molecules for the mimicry of protein binding sites, as well as the inhibition of protein-protein interactions.


title: Completely intracorporeal robotic-assisted laparoscopic ileovesicostomy.

text: We present a report of a completely intracorporeal robotic-assisted laparoscopic ileovesicostomy with long term follow-up. The patient was a 55-year-old man with paraplegia secondary to tropical spastic paresis resulting neurogenic bladder dysfunction. The procedure was performed using a da Vinci Surgical system (Intuitive Surgical, Sunnyvale, CA) and took 330 minutes with an estimated blood loss of 100 mL. The patient recovered without perioperative complications. He continues to have low pressure drainage without urethral incontinence over two years postoperatively.


title: A monoclonal antibody against transmissible gastroenteritis virus generated via immunization of a DNA plasmid bearing TGEV S1 gene.

text: Transmissible gastroenteritis virus (TGEV) is a member of the coronaviruses. The viral spike (S) protein of TGEV mediates interaction between TGEV and its susceptible cells. Herein, DNA plasmid bearing TGEV S1 gene (the N terminal half of TGEV S gene) was used to immunize BALB/c mice followed by generation of a monoclonal antibody (MAb) using the hybridoma technique. The generated MAb (1H4) was identified by ELISA. Immunofluorescence assays showed that MAb 1H4 was able to detect infection of cells with TGEV. The MAb 1H4 distinguished TGEV from other control viruses. Additionally, although the type of MAb 1H4 was IgM, it could reduce cell infection by TGEV in a dose-dependent manner.


title: Tensile strength and adhesion formation of mesh fixation systems used in laparoscopic incisional hernia repair.

text: BACKGROUND Mesh tearoff from the tissue is the most common reason for hernia recurrence after hernia surgery involving the use of a synthetic mesh. Various fixation systems were critically compared in terms of their retention strength and the formation of adhesions. METHODS In a prospective study with 25 Sprague-Dawley rats, two pieces of Parietex composite meshes measuring 2 x 3 cm were fixed intraperitoneally in a paramedian location. The randomized mesh fixation groups included transfascial fixed suture, ProTack, AbsorbaTack, and I-Clip. Of the 25 rats, 12 were killed and analyzed 1 week after implantation, with the remaining 13 rats killed and analyzed after 2 months. Adhesions observed at the time of mesh removal were measured according to an adhesion scoring system, and the fixation strengths of the individual fixation systems were tested. Additionally, the foreign body reaction to the mesh and fixation systems was measured as well as their potential degradation. RESULTS After 1 week, the retention strength of transfascial fixed suture was significantly higher (8.7 N/cm(2)) than that of ProTack (5.6 N/cm(2)) or AbsorbaTack (5.7 N/cm(2)). After 2 months, the retention strength had increased to 13.2 N/cm(2) in the transfascial fixed suture group, which was significantly higher than in the ProTack (9.7 N/cm(2)) or AbsorbaTack (8.7 N/cm(2)) groups. In contrast, the mesh could be fixed with the I-Clip only in 56% of the cases, and then achieved rather poor retention strength. Adhesion was significantly greater in the ProTack group than in any of the other groups (p < 0.001). At 2 months, scanning electron microscopy showed only marginal degradation of the absorbable elements. CONCLUSIONS Suture fixation led to satisfactory attachment of the prosthesis. Additional widespread anchorage of the mesh was achieved with ProTack or AbsorbaTack. The feasibility and retention strength of the I-Clip were poor.


title: Modern technical approaches in resectional hepatic surgery.

text: Techniques in liver surgery have improved considerably during the last decades, allowing for liver resections with low morbidity and mortality. Preoperative patient selection, perioperative management, and intraoperative blood-sparing techniques are the cornerstones of modern liver surgery. Multimodal treatment of colorectal liver metastases has expanded the group of patients who are potential candidates for liver resection. Adjunctive techniques, including preoperative portal vein embolization and staged hepatectomy, have facilitated the safe performance of extensive liver resection. This article provides an overview of indications for liver resection and a systematic description of the technical approach to the most commonly performed resections.


title: Adjudin protects against cerebral ischemia reperfusion injury by inhibition of neuroinflammation and blood-brain barrier disruption.

text: Neuroinflammation mediated by activation of microglia and interruption of the blood-brain barrier (BBB) is an important factor that contributes to neuron death and infarct area diffusion in ischemia reperfusion injury. Finding novel molecules to regulate neuroinflammation is of significant clinical value. We have previously shown that adjudin, a small molecule compound known to possess antispermatogenic function, attenuates microglia activation by suppression of the NF-κB pathway. In this study we continued to explore whether adjudin could be neuroprotective by using the transient middle cerebral artery occlusion (tMCAO) model. Adjudin treatment after reperfusion significantly decreased the infarction volume and neuroscore compared to the vehicle group. Staining of CD11b showed that adjudin markedly inhibited microglial activation in both the cortex and the striatum, accompanied by a reduction in the expression and release of cytokines TNF-α, IL-1β and IL-6. Concomitantly, adjudin noticeably prevented BBB disruption after ischemia and reperfusion, as indicated by the reduction of IgG detection in the brain cortex and striatum versus the vehicle group. This finding was also corroborated by immunofluorescence staining and immunoblotting of tight junction-related proteins ZO-1, JAM-A and Occludin, where the reduction of these proteins could be attenuated by adjudin treatment. Moreover, adjudin obviously inhibited the elevated MMP-9 activity after stroke. Together these data demonstrate that adjudin protects against cerebral ischemia reperfusion injury, and we present an effective neuroinflammation modulator with clinical potential.


title: Impact of General Anesthesia on Safety and Outcomes in the Endovascular Arm of Interventional Management of Stroke (IMS) III Trial.

text: BACKGROUND AND PURPOSE General anesthesia (GA) for endovascular therapy (EVT) of acute ischemic stroke may be associated with worse outcomes. METHODS The Interventional Management of Stroke III trial randomized patients within 3 hours of acute ischemic stroke onset to intravenous tissue-type plasminogen activator±EVT. GA use within 7 hours of stroke onset was recorded per protocol. Good outcome was defined as 90-day modified Rankin Scale ≤2. A multivariable analysis adjusting for dichotomized National Institutes of Health Stroke Scale (NIHSS; 8-19 versus ≥20), age, and time from onset to groin puncture was performed. RESULTS Four hundred thirty-four patients were randomized to EVT, 269 (62%) were treated under local anesthesia and 147 (33.9%) under GA; 18 (4%) were undetermined. The 2 groups were comparable except for median baseline NIHSS (16 local anesthesia versus 18 GA; P<0.0001). The GA group was less likely to achieve a good outcome (adjusted relative risk, 0.68; confidence interval, 0.52-0.90; P=0.0056) and had increased in-hospital mortality (adjusted relative risk, 2.84; confidence interval, 1.65-4.91; P=0.0002). Those with medically indicated GA had worse outcomes (adjusted relative risk, 0.49; confidence interval, 0.30-0.81; P=0.005) and increased mortality (relative risk, 3.93; confidence interval, 2.18-7.10; P<0.0001) with a trend for higher mortality with routine GA. There was no significant difference in the adjusted risks of subarachnoid hemorrhage (P=0.32) or symptomatic intracerebral hemorrhage (P=0.37). CONCLUSIONS GA was associated with worse neurological outcomes and increased mortality in the EVT arm; this was primarily true among patients with medical indications for GA. Relative risk estimates, though not statistically significant, suggest reduced risk for subarachnoid hemorrhage and symptomatic intracerebral hemorrhage under local anesthesia. Although the reasons for these associations are not clear, these data support the use of local anesthesia when possible during EVT. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424.


title: Endoscopic suturing for transoral outlet reduction increases weight loss after Roux-en-Y gastric bypass surgery.

text: BACKGROUND & AIMS Weight regain or insufficient loss after Roux-en-Y gastric bypass (RYGB) is common. This is partially attributable to dilatation of the gastrojejunostomy (GJ), which diminishes the restrictive capacity of RYGB. Endoluminal interventions for GJ reduction are being explored as alternatives to revision surgery. We performed a randomized, blinded, sham-controlled trial to evaluate weight loss after sutured transoral outlet reduction (TORe). METHODS Patients with weight regain or inadequate loss after RYGB and GJ diameter greater than 2 cm were assigned randomly to groups that underwent TORe (n = 50) or a sham procedure (controls, n = 27). Intraoperative performance, safety, weight loss, and clinical outcomes were assessed. RESULTS Subjects who received TORe had a significantly greater mean percentage weight loss from baseline (3.5%; 95% confidence interval, 1.8%-5.3%) than controls (0.4%; 95% confidence interval, 2.3% weight gain to 3.0% weight loss) (P = .021), using a last observation carried forward intent-to-treat analysis. As-treated analysis also showed greater mean percentage weight loss in the TORe group than controls (3.9% and 0.2%, respectively; P = .014). Weight loss or stabilization was achieved in 96% subjects receiving TORe and 78% of controls (P = .019). The TORe group had reduced systolic and diastolic blood pressure (P < .001) and a trend toward improved metabolic indices. In addition, 85% of the TORe group reported compliance with the healthy lifestyle eating program, compared with 53.8% of controls; 83% of TORe subjects said they would undergo the procedure again, and 78% said they would recommend the procedure to a friend. The groups had similar frequencies of adverse events. CONCLUSIONS A multicenter randomized trial provides Level I evidence that TORe reduces weight regain after RYGB. These results were achieved using a superficial suction-based device; greater levels of weight loss could be achieved with newer, full-thickness suturing devices. TORe is one approach to avoid weight regain; a longitudinal multidisciplinary approach with dietary counseling and behavioral changes are required for long-term results. ClinicalTrials.gov identifier: NCT00394212.


title: Patency of the vein of Labbé after venous stenting of the transverse and sigmoid sinuses.

text: BACKGROUND Venous sinus stenting is an emerging treatment for patients with idiopathic intracranial hypertension and evidence of venous stenosis. Stents placed across the transverse and sigmoid sinuses often cover the vein of Labbé (VOL), a major anastomotic vein draining the cerebral hemisphere. The patency of the VOL after stenting and its clinical implications are poorly understood. METHODS A retrospective analysis was performed of a prospectively collected database of patients undergoing venous sinus stenting. Pre- and post-stent angiography were compared to assess changes in VOL patency, clinical and radiographic outcomes. RESULTS The study cohort comprised 56 patients. The stent covered the VOL in 92.9% of cases. Thirty-two cases with VOL coverage had evaluable angiograms immediately after stent placement. Among these, VOL filled normally in 75.0%, exhibited diminished caliber with normal transit time in 3.1%, filled sluggishly in 18.8%, and was occluded in 3.1%. Follow-up was assessed in patients with at least 3 months' angiographic follow-up (46 patients, mean 7.2 months). Of these, normal filling was seen in 71.7%, diminished caliber in 26.1%, and sluggish filling in 2.2% of cases. Neither stent coverage of the VOL nor its patency immediately after stenting or at follow-up correlated with stent-adjacent stenosis. There were no neurological sequelae from coverage of the VOL or alteration of its drainage pattern. CONCLUSIONS In the majority of venous stenting cases involving the transverse and sigmoid sinuses, the VOL remains widely patent. Complete VOL occlusion rarely occurs after stenting and may not result in clinical sequelae. Stent coverage of the VOL should not deter the therapeutic use of venous sinus stenting.


Follow the data: bivalirudin (and not heparin alone) during percutaneous coronary intervention provides the best clinical outcomes.


title: The hospitalist perspective on treatment of community-acquired bacterial pneumonia.

text: Community-acquired bacterial pneumonia (CABP) is an important health care concern in the United States and worldwide, and is associated with significant morbidity, mortality, and health care expenditure. Streptococcus pneumoniae is the most frequent causative pathogen of CABP. Other common pathogens include Staphylococcus aureus, Haemophilus influenzae, Enterobacteriaceae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae. However, in clinical practice, the causative pathogen of CABP is most often not identified. Therefore, a common treatment approach for patients hospitalized with CABP is empiric antibiotic therapy with a β-lactam in combination with a macrolide, respiratory fluoroquinolones, or tetracyclines. An increase in the incidence of S. pneumoniae that is resistant to frequently used antibiotics, including β-lactams, macrolides, and tetracyclines, provides a challenge for the physician when selecting empiric antimicrobial therapy. When patients with CABP do not respond to initial therapy, they must be adequately reevaluated with further diagnostic testing, change in antimicrobial regimen, and/or transfer of the patient to a higher level of care. The role of hospital medicine physicians is crucial in treating patients who are hospitalized with CABP. An important focus of hospitalists is to provide care improvement in a way that addresses both patient and hospital needs. It is essential that the hospitalist provides best possible patient care, including adherence to quality measures, optimizing the patient's hospital length of stay, and arranging adequate post-discharge care in an effort to prevent readmission and provide appropriate ongoing outpatient care.


title: Comparison of Postoperative Pain Following Laparoscopic Versus Open Gastrostomy/Jejunostomy in Patients with Complete Obstruction Caused by Advanced Esophageal Cancer.

text: BACKGROUND When percutaneous endoscopic gastrostomy is not feasible, a gastrostomy tube may be inserted for enteral access by a laparoscopic or open technique. The aim of this study was to compare the postoperative pain of laparoscopic versus open gastrostomy in patients with complete obstruction caused by advanced esophageal cancer. METHODS Fifteen patients who had undergone either a reduced port access laparoscopic gastrostomy/jejunostomy (LGJ, n=7) or open gastrostomy/jejunostomy (OGJ, n=8) between July 2011 and December 2015 were retrospectively studied. Variables examined comprised age, sex, body mass index (BMI), operative time, blood loss volume, and American Society of Anesthesiologist physical status (ASA-PS) scores. The degree of postoperative pain was also assessed in both groups during the first seven postoperative days. RESULTS The patients in the two groups were comparable in age, sex, BMI, ASA-PS scores, intraoperative blood loss or postoperative complication rates. Operative time was shorter in the LGJ group than the OGJ group. No patients in the LGJ group required conversion to open laparotomy. Tube feedings were started on postoperative Day 1 in both groups; there were no postoperative complications. The duration of rescue nonopioid analgesic use was significantly shorter in the LGJ than the OGJ group (1.3 versus 3.5 days; P=0.0005). There was a significant difference in frequency of postoperative nonopioid analgesic use: 7.9 times in the LGJ group versus 17.9 times in the OGJ group (P=0.0219). CONCLUSIONS LGJ is associated with less postoperative pain than OGJ in patients with complete obstruction caused by advanced esophageal cancer.


title: Effect of VEGFC on lymph flow and inflammation-induced alveolar bone loss.

text: The lymphatic system plays a crucial role in the maintenance of tissue fluid homeostasis and the immunological response to inflammation. The effects of lymphatic drainage dysfunction on periodontitis have not been well-studied. Here we show that lymphatic vessel endothelial receptor 1 (LYVE1)+ /podoplanin (PDPN)+ lymphatic vessels (LVs) are increased in the periodontal tissues, with accumulation close to the alveolar bone surface, in two murine periodontitis models: rheumatoid arthritis (RA)-associated periodontitis and ligature-induced periodontitis. Further, PDPN+ / alpha-smooth muscle actin (αSMA)- lymphatic capillaries are increased, whereas PDPN+ / αSMA+ collecting LVs are decreased significantly in the inflamed periodontal tissues. Both mouse models of periodontitis have delayed lymph flow in periodontal tissues, increased TRAP-positive osteoclasts, and significant alveolar bone loss. Importantly, the local administration of adeno-associated virus for vascular endothelial growth factor C, the major growth factor that promotes lymphangiogenesis, increases the area and number of PDPN+ / αSMA+ collecting LVs, promotes local lymphatic drainage, and reduces alveolar bone loss in both models of periodontitis. Lastly, LYVE1+ / αSMA- lymphatic capillaries are increased, whereas LYVE1+ / αSMA+ collecting LVs are decreased significantly in gingival tissues of patients with chronic periodontitis compared with those of clinically healthy controls. Thus, our findings reveal an important role of local lymphatic drainage in periodontal inflammation-mediated alveolar bone loss. This article is protected by copyright. All rights reserved.


title: Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

text: Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules.


title: Exercise-based rehabilitation programmes for pulmonary hypertension.

text: BACKGROUND Individuals with pulmonary hypertension (PH) have reduced exercise capacity and quality of life. Despite initial concerns that exercise training may worsen symptoms in this group, several studies have reported improvements in functional capacity and well-being following exercise-based rehabilitation in PH. OBJECTIVES To assess the efficacy and safety of exercise-based rehabilitation for people with PH. Primary outcomes were exercise capacity, adverse events during the intervention period and health-related quality of life (HRQoL). Secondary outcomes included cardiopulmonary haemodynamics, functional class, clinical worsening during follow-up, mortality and changes in B-type natriuretic peptide. SEARCH METHODS We searched the Cochrane Airways Specialised Register of Trials up to August 2016, which is based on regular searches of CINAHL, AMED, Embase, PubMed, MEDLINE, PsycINFO and registries of clinical trials. In addition we searched CENTRAL and the PEDro database up to August 2016 and handsearched relevant journals. SELECTION CRITERIA All randomised controlled trials (RCTs) focusing on exercise-based rehabilitation programmes for PH. DATA COLLECTION AND ANALYSIS Two reviewers extracted data independently. For binary outcomes, we calculated odds ratios and their 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. MAIN RESULTS We included six RCTs and were able to extract data from five studies. The majority of participants were Group I pulmonary artery hypertension (PAH). Study duration ranged from three to 15 weeks. Exercise programmes included both inpatient- and outpatient-based rehabilitation that incorporated both upper and lower limb exercise. The mean six-minute walk distance following exercise training was 60.12 metres higher than control (30.17 to 90.07 metres, n = 165, 5 RCTs, low-quality evidence; minimal important difference was 30 metres), the mean peak oxygen uptake was 2.4 ml/kg/minute higher (1.4 to 3.4 ml/kg/min, n = 145, 4 RCTs, low-quality evidence) and the mean peak power in the intervention groups was 16.4 W higher (10.9 to 22.0 higher, n = 145, 4 RCTs, low-quality evidence). The mean change in HRQoL for the SF-36 physical component score was 4.63 points higher (0.80 to 8.47 points, n = 33, 2 RCTs, low-quality evidence) and for the SF-36 mental component score was 4.17 points higher (0.01 to 8.34 points; n = 33; 2 RCTs, low-quality evidence). One study reported a single adverse event, where a participant stopped exercise training due to lightheadedness. AUTHORS' CONCLUSIONS In people with PH, exercise-based rehabilitation results in clinically relevant improvements in exercise capacity. Exercise training was not associated with any serious adverse events. Whilst most studies reported improvements in HRQoL, these may not be clinically important. Overall, we assessed the quality of the evidence to be low. The small number of studies and lack of information on participant selection makes it difficult to generalise these results across the spectrum of people with PH.


title: Choledochotomy for Obstructive Choledocholithiasis in Two Dogs.

text: Two geriatric (> 9 years old) dogs presented for vomiting, lethargy, and anorexia. Obstructive choledocholithiasis was diagnosed based on analysis of a serum biochemical analysis and abdominal radiographs and ultrasonography. In both dogs, choledocholiths were removed from the common bile duct via a choledochotomy without a cholecystectomy, and survival without recurrence occurred in both dogs for more than 1 year.


title: Evaluation of two methods for topical application of contrast medium to the pharyngeal and laryngeal region of horses.

text: OBJECTIVE To determine the pharyngeal and laryngeal distribution of radiopaque contrast medium administered orally or via nasopharyngeal catheter to standing horses. ANIMALS 5 healthy adult horses. PROCEDURES A crossover study was conducted. Radiopaque contrast medium (12 mL) was administered orally and via nasopharyngeal catheter to each horse. Pharyngeal and laryngeal distribution of contrast medium was determined by examination of radiographs obtained immediately after administration of contrast medium, compared with those obtained before administration. Regional distribution of contrast medium was graded. Endoscopic examination of the nasopharynx, laryngopharynx, and larynx was performed to confirm radiographic results. RESULTS Examination of radiographs obtained after nasopharyngeal administration revealed contrast medium in the nasopharynx (n = 5), oropharynx (2), laryngopharynx (3), and larynx (5) of the 5 horses. Examination of radiographs obtained after oral administration revealed contrast medium in the oropharynx (n = 4) and larynx (1) of the 5 horses. Endoscopic examination confirmed radiographic findings and was found to be sensitive for detection of contrast medium in the laryngopharynx, whereby detection rates were higher for both administration methods. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that medication administered by use of a nasopharyngeal catheter will result in topical distribution within the nasopharynx, including the dorsal surface of the soft palate, and larynx, although distribution should be evaluated in horses with clinical airway disease to confirm these findings. Oral administration did not result in consistently detectable topical laryngeal distribution but could be used for selected conditions (eg, palatitis).


title: Quest for the optimal technique of laparoscopic splenectomy - vessels first or hilar transection?

text: Introduction Throughout our 20 years of experience, we have used several different techniques for laparoscopic splenectomy (LS). However, two methods have been used most frequently: "vessels first" and "hilar transection". Aim To evaluate the outcomes of LS performed with these two different approaches. Material and methods It was an observational study based on retrospective analysis of consecutive patients undergoing LS in a tertiary referral surgical center in the period 1998-2017. We excluded patients with splenic trauma, initially submitted to open surgery, stapled transection of splenic hilum, partial resections of the spleen and other spleen-preserving procedures. Patients were divided into two groups: group 1 ("vessels first") with 188 patients, and group 2 ("hilar transection") with 287 patients. Results Mean operative time was shorter (p < 0.001) and blood loss was lower (p < 0.001) in group 2. The need for blood transfusions and the conversion rate were higher in group 1 (p = 0.044 and p = 0.003 respectively). There was no difference in intraoperative adverse events (p = 0.179). Overall postoperative morbidity did not differ between groups (p = 0.081) and we noted mortality of 0.21% (1 patient of group 2). The morbidity rate associated with accidental injury of the pancreatic parenchyma was significantly higher in group 1 (p = 0.028). Median length of hospital stay was 4 days (range: 1-99) and did not differ between groups (p = 0.175). Conclusions The "vessels first" technique is associated with longer operative time, higher blood loss and increased risk of conversion. "Hilar transection" is associated with lower incidence of local complications related most likely to accidental injury of the pancreatic tail. In the case of a large caliber of splenic vessels the "vessels first" approach remains the technique of choice.


title: Assessment of cisplatin concentration and depth of penetration in human lung tissue after hyperthermic exposure.

text: OBJECTIVES The effects of cisplatin on the lung parenchyma during hyperthermic intrathoracic chemotherapy perfusion have not been analysed in detail. The objective of this study was to evaluate both the concentration and depth of the penetration of cisplatin in human lung tissue after hyperthermic exposure under ex vivo conditions. METHODS This experimental study was approved by the local ethics committee. Twelve patients underwent pulmonary wedge resections after elective thoracic lobectomies were performed (resected lobe), and the lung tissue (approximately 1-2 cm(3)) was incubated (in vitro) with cisplatin (0.05 mg/ml; 60 min, 42°C). Subsequent tissue beds (depth, 0.5 mm; median weight, 70-92 mg) were prepared from the outside to the middle, and the amount of cisplatin per tissue weight was analysed using atomic absorption spectrometry. Afterwards, the penetration of cisplatin depth was calculated and related to the different concentrations per tissue. RESULTS Cisplatin penetrated into the human lung tissue after ex vivo hyperthermic exposure. The median amount of platinum [nmol cisplatin/g lung tissue] decreased significantly (P ≤ 0.05) depending on the penetration depth: 32 nmol/g (1 mm), 20 nmol/g (2 mm) and 6.8 nmol/g (4 mm). The calculated median concentrations of cisplatin (µg/ml) were 2.4 µg/ml (1 mm), 1.4 µg/ml (2 mm) and 0.5 µg/ml (4 mm), respectively. CONCLUSIONS Under ex vivo hyperthermic conditions, cisplatin diffused into human lung tissue. The median penetration depth of the cisplatin was approximately 3-4 mm. The penetration of cisplatin into lung tissue may affect the local therapy of residual tumour cells on the lung surface using hyperthermic intrathoracic chemotherapy perfusion in patients with malignant pleural tumours.


title: Laparoscopic liver resection-understanding its role in current practice: the Henri Mondor Hospital experience.

text: OBJECTIVE To report our complete experience with laparoscopic liver resection (LLR) to understand what role it may play in the broader context of liver surgery. BACKGROUND The goal of LLR is to extend the benefits of the laparoscopic approach without compromising the fundamental principles of open liver surgery. LLR, however, presents unique technical challenges and its evaluation is made difficult by the restricted indications for this approach, the few centers world-wide experienced in the technique, and the heterogeneity of procedures and pathologies involved. METHODS Retrospective analysis of a prospectively maintained database of liver resections from a unit with a comprehensive liver program, including resection and transplantation. RESULTS There were 166 laparoscopic liver resections between May 23, 1996 and December 31, 2007, including 100 (60%) for malignant pathology (64 HCC, 3 cholangiocarcinoma, 33 hepatic metastases) and 66 for benign pathology (adenoma, 23; FNH, 19; cystic, 17; other, 7). Numbers of resections for benign indications remained stable over time whereas those for malignant indications increased. There were 31 major resections, 56 left lateral sectionectomies, 28 segmentectomies, and 51 tumorectomies. There was 0% mortality and 15.1% morbidity. Median blood loss was 200 mL, 9 patients (5.4%) required transfusion, and median operating time was 180 minutes. Left lateral sectionectomies demonstrated reduced bleeding (median, 175 vs. 300 mL, P = 0.0015) and faster operating time (median, 170 vs. 180 minutes, P = 0.0265). In the second half of the experience, there was reduced bleeding (median, 200 vs. 300 mL, P = 0.0022) and a lower conversion rate (2.4% vs. 16.9%, P = 0.0015). CONCLUSIONS Good patient selection and refined surgical technique are the keys to successful LLR. The indications for resection of asymptomatic benign lesions should not be increased because the laparoscopic approach is available. Hepatocellular carcinomas (HCCs) are more likely to be suitable to a laparoscopic approach than colorectal liver metastases. Left lateral sectionectomy and limited resection of solitary peripheral lesions are particularly suitable while hemihepatectomies remain challenging procedures. LLR requires an ongoing robust audit to identify any emerging problems.


title: The case for a milestone-based simulation curriculum in modern neuroendovascular training.

text: The role of simulation in formal neuroendovascular training has not been defined. This report details the general principles underlying the use of simulation in training, the critical aspects of the simulation environment which would aid it as a teaching tool specific to the field of neuroendovascular care, summarizes the available evidence to support a milestone-based curriculum, and outlines an example of what such a curriculum would entail. Building on these foundations, we articulate the rationale for the development and widespread adoption of a simulation curriculum for formal neuroendovascular training.


title: Xanthomonas diversity, virulence and plant-pathogen interactions.

text: Xanthomonas spp. encompass a wide range of plant pathogens that use numerous virulence factors for pathogenicity and fitness in plant hosts. In this Review, we examine recent insights into host-pathogen co-evolution, diversity in Xanthomonas populations and host specificity of Xanthomonas spp. that have substantially improved our fundamental understanding of pathogen biology. We emphasize the virulence factors in xanthomonads, such as type III secreted effectors including transcription activator-like effectors, type II secretion systems, diversity resulting in host specificity, evolution of emerging strains, activation of susceptibility genes and strategies of host evasion. We summarize the genomic diversity in several Xanthomonas spp. and implications for disease outbreaks, management strategies and breeding for disease resistance.


title: Perspectives of physicians in general and ophthalmologists in particular about restarting services post-COVID-19 lockdown.

text: Purpose To assess the perspectives of physicians in general and ophthalmologists in particular about restarting elective out-patient (OP) and operating (OT) services after relaxation of lockdown for COVID-19. Methods An online survey, containing 31 questions, was conducted among medical doctors using a secure Google forms link. The survey was open for 48 hours from 16th-18th April 2020. Results Responses were received from 556 physicians (including 266 ophthalmologists). About a third (n = 205) wanted to start OP immediately after lockdown. In OP, mask of any kind for patient (60.8%), 3-ply for assistants (52.7%) and N95 for doctors (72.7%) were most common preferences. In OP, 31.5% and 46.6% felt full PPE and gloves alone were sufficient respectively. Ophthalmologists were more likely to start immediately after lockdown compared to other specialists (P = 0.004). Among 299 surgeons, an almost equal number (27%) wanted to start routine OT services immediately and 2 weeks post lockdown. A large majority (76.9%) would mandate COVID-19 tests before elective surgeries. In OT, 34.1% wanted N95 for surgical team and 3-ply for patient, 23.4% wanted 3-ply masks for everyone. 40.5% felt additional personal protective equipment (PPE) is not required and 33.1% felt that full PPE is required for everyone in OT. Ophthalmic surgeons preferred 3-ply masks and were less inclined to use full PPE (P < 0.001). Conclusion Perspectives of doctors vary, especially with regarding to timing of restarting services and precautions to be taken in the OT. Ophthalmologists may tend to err on the side of taking lesser stringent precautions when restarting services post lockdown.


title: Influence of additional resection of the gastric fundus on excessive weight loss in laparoscopic very very long limb Roux-en-Y gastric bypass.

text: Roux-en-Y gastric bypass (RYGB) is the gold standard in bariatric surgery. The effect of the procedure is based on restriction, malabsorption and changes in hormonal axis. Ghrelin is an important appetite hormone which is produced mainly in the gastric fundus. By adding a resection of the gastric fundus, we hypothesized that excessive weight loss will be more prominent and the satiety feelings less pronounced compared to standard RYGB. A total of 73 patients with standard very very long limb (VVLL) RYGB (group A) were compared with 44 patients with VVLL RYGB with resection of the fundus (group B). Outcome measures were excessive weight loss (EWL), body mass index (BMI), early postoperative morbidity, change of co-morbidities, and appetite reduction as assessed by an appetite questionnaire over a postoperative period of 24 months. Groups were comparable in basic preoperative descriptions. Additional fundus resection did not influence EWL (group A 66.1 % vs. group B 70.6 %, p = 0.383) or BMI (group A 29 kg/m(2) vs. group B 27 kg/m(2), p = 0.199). No significant difference in morbidity or change of co-morbidities occurred. The appetite and satiety questionnaire showed no difference between group A and group B, respectively. Adding a resection of the gastric fundus in RYGB did not alter the clinical results, i.e., increased excessive weight loss, decrease of appetite, or increase of satiety. The value of removing a part of the ghrelin-producing cells might be overestimated.


title: Staple-line recurrence arising 10 years after functional end-to-end anastomosis for colon cancer: a case report.

text: We report a rare case of late staple-line recurrence arising 10 years after functional end-to-end anastomosis for splenic flexure colon cancer. An 80-year-old man, who underwent partial colectomy with functional end-to-end anastomosis for splenic flexure colon cancer 10 years earlier, presented with a chief complaint of anorexia. Complete blood count showed anemia, and the fecal occult blood test was positive. Lower gastrointestinal series showed an irregular defect of the splenic flexure, and colonoscopy showed an ulcerated tumor on the staple line of the primary surgery. Partial colectomy was performed, and the tumor was pathologically diagnosed as moderately differentiated tubular adenocarcinoma, resembling the pathology of primary colon cancer. This case suggests the importance of considering staple-line recurrence after functional end-to-end anastomosis for colon cancer even more than 5 years after primary surgery.


title: Disaster Preparedness and Social Justice in a Public Health Emergency.

text: The United States is now experiencing public health catastrophe on a scale we have not seen for more than a century. COVID-19 puts into stark relief our mutual obligations that reflect our interdependence as participants in a common society. Drawing on the work of Amartya Sen concerning famine and related challenges, I discuss the accompanying implications for social justice. Social justice in catastrophe requires strong social insurance structures and legal protections for the most vulnerable people, who would otherwise lack economic resources and political influence to protect their essential interests. Social justice also requires greater and more-sustained attention to disaster preparedness and public health infrastructure-both of which are characteristically neglected, in part because the public health enterprise is identified with politically weak and often stigmatized populations.


title: Pharmacokinetics and Pharmacodynamics of an Oral Formulation of Apixaban in Horses After Oral and Intravenous Administration.

text: Horses with inflammatory and infectious disorders are often treated with injectable heparin anticoagulants to prevent thrombotic complications. In humans, a new class of direct oral acting anticoagulants (DOAC) appear as effective as heparin, while eliminating the need for daily injections. Our study in horses evaluated apixaban, a newly approved DOAC for human thromboprophylaxis targeting activated factor X (Xa). Our goals were to: (1) Determine pharmacokinetics and pharmacodynamics of apixaban after oral (PO) and intravenous (IV) administration in horses; (2) Detect any inhibitory effects of apixaban on ex vivo Equid herpesvirus type 1 (EHV-1)-induced platelet activation, and (3) Compare an anti-Xa bioactivity assay with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) for measuring apixaban concentrations. In a blinded placebo-controlled cross-over study, five horses received a single dose (0.2 mg/kg) of apixaban or placebo PO or IV. Blood was collected before and at 3 (IV) or 15 (PO) min, 30 and 45 min, and 1, 2, 3, 4, 6, 8, and 24 h after dosing for measuring apixaban UPLC-MS concentrations and anti-Xa activity. Pharmacodynamic response was measured in a dilute prothrombin time (dPT) assay. Flow cytometric EHV-1-induced platelet P-selectin expression and clinical pathologic safety testing were performed at baseline, 2 and 24 h and baseline and 24 h, respectively. We found no detectable apixaban in plasma PO administration. After IV administration, plasma apixaban levels followed a two-compartment model, with concentrations peaking at 3 min and decreasing to undetectable levels by 8 h. The elimination half-life was 1.3 ± 0.2 h, with high protein binding (92-99%). The dPT showed no relationship to apixaban UPLC-MS concentration and apixaban did not inhibit EHV-1-induced platelet activation after IV dosing. Apixaban anti-Xa activity showed excellent correlation to UPLC-MS (r 2 = 0.9997). Our results demonstrate that apixaban has no apparent clinical utility as an anticoagulant for horses due to poor oral availability.


title: Radiofrequency energy antenna coupling to common laparoscopic instruments: practical implications.

text: BACKGROUND Electromagnetic coupling can occur between the monopolar "Bovie" instrument and other laparoscopic instruments without direct contact by a phenomenon termed antenna coupling. The purpose of this study was to determine if, and to what extent, radiofrequency energy couples to other common laparoscopic instruments and to describe practical steps that can minimize the magnitude of antenna coupling. METHODS In a laparoscopic simulator, monopolar radiofrequency energy was delivered to an L-hook. The tips of standard, nonelectrical laparoscopic instruments (either an unlit 10 mm telescope or a 5 mm grasper) were placed adjacent to bovine liver tissue and were never in contact with the active electrode. Thermal imaging quantified the change in tissue temperature nearest the tip of the telescope or grasper at the end of a 5 s activation of the active electrode. RESULTS A 5 s activation (30 watts, coagulation mode, 4 cm separation between instruments) increased tissue temperature compared with baseline adjacent to the grasper tip (2.2 ± 2.2 °C; p = 0.013) and telescope tip (38.2 ± 8.0 °C; p < 0.001). The laparoscopic telescope tip increased tissue temperature more than the laparoscopic grasper tip (p < 0.001). Lowering the generator power from 30 to 15 Watts decreased the heat generated at the telescope tip (38.2 ± 8.0 vs. 13.5 ± 7.5 °C; p < 0.001). Complete separation of the camera/light cords and the active electrode cord decreased the heat generated near the telescope tip compared with parallel bundling of the cords (38.2 ± 8.0 vs. 15.7 ± 11.6 °C; p < 0.001). CONCLUSIONS Commonly used laparoscopic instruments couple monopolar radiofrequency energy without direct contact with the active electrode, a phenomenon that results in heat transfer from a nonelectrically active instrument tip to adjacent tissue. Practical steps to minimize heat transfer resulting from antenna coupling include reducing the monopolar generator power setting and avoiding of parallel bundling of the telescope and active electrode cords.


title: Health economics in the field of osteoarthritis: an expert's consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).

text: OBJECTIVES There is an important need to evaluate therapeutic approaches for osteoarthritis (OA) in terms of cost-effectiveness as well as efficacy. METHODS The ESCEO expert working group met to discuss the epidemiological and economic evidence that justifies the increasing concern of the impact of this disease and reviewed the current state-of-the-art in health economic studies in this field. RESULTS OA is a debilitating disease; it is increasing in frequency and is associated with a substantial and growing burden on society, in terms of both burden of illness and cost of illness. Economic evaluations in this field are relatively rare, and those that do exist, show considerable heterogeneity of methodological approach (such as indicated population, comparator, decision context and perspective, time horizon, modeling and outcome measures used). This heterogeneity makes comparisons between studies problematic. CONCLUSIONS Better adherence to guidelines for economic evaluations is needed. There was strong support for the definition of a reference case and for what might constitute "standard optimal care" in terms of best clinical practice, for the control arms of interventional studies.