title: COVID-19 and U.S.-based refugee populations: Commentary.

text: The arrival of the pandemic known as COVID-19 has resulted in an emergency appraisal of the way mental health services are delivered to refugee and asylum-seeker populations at the Boston Medical Center in Massachusetts. The following commentary summarizes some of the main approaches used to address the unique needs of this vulnerable population under lockdown. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Effects of laparoscopic surgery on survival, quality of care and utilization in patients with colon cancer: a population-based study.

text: OBJECTIVE Laparoscopy is a safe and effective treatment for colon cancer. However, its effects on short- and long-term health outcomes and medical utilization are not fully elucidated. This study aimed to compare short- and long-term utilization and health outcomes of colon cancer patients who underwent either laparoscopic or open surgery in a population-based cohort. METHODS This study was conducted by linking data from Taiwan Cancer Registry, National Health Insurance claims and Death Registry. Patients aged 18 and older with colon cancer between 2009 and 2012 were included in the study. Propensity score matching was used to minimize selection bias between laparoscopic and open surgery groups. Cox proportional hazard regression and generalized linear mixed logistic regression were used to test hypotheses. RESULTS Among the 11,269 colon cancer patients who underwent colectomy, 3236 (28.72%) received laparoscopy and 8033 (71.28%) underwent open surgery. Patients who received laparoscopic surgery had better overall survival (HR = 0.82; 95% CI: 0.70-0.97). These patients also had lower 30 day mortality (0.44% vs. 0.91%), lower 1 year mortality (2.83% vs. 4.68%), lower overall occurrence of complications (6.16% vs. 8.77%), shorter mean length of stay (12.53 vs. 14.93 days) and lower cost for index hospitalization (US$4325.34 vs. US$4453.90). No significant differences were observed in medical utilization over a period of 365 days after the surgery. CONCLUSIONS Our results demonstrate that, in both the short- and long-term post-operation periods, laparoscopic surgery reduced the likelihood of postoperative complications, 30 day, and 1 year mortality while being no more expensive than open surgery for colon cancer.


title: Emergency Flexibility for States to Increase and Maintain Medicaid Eligibility for LTSS under COVID-19.

text: Medicaid provides essential coverage for health care and long-term services and supports (LTSS) to low-income older adults and disabled individuals but eligibility is complicated and restrictive. In light of the current public health emergency, states have been given new authority to streamline and increase the flexibility of Medicaid LTSS eligibility, helping them enroll eligible individuals and ensure that current beneficiaries are not inadvertently disenrolled. Though state budgets are under increased pressure during the economic crisis created by the coronavirus, we caution states against cutting Medicaid LTSS eligibility or services to balance their budgets. These services are critical to an especially vulnerable population during a global pandemic.


Palliative Care, Spiritual Care, and Clinical Ethics: Widely Available, but Underused.


title: Lessons from Ebola: Improving infectious disease surveillance to inform outbreak management.

text: The current Ebola virus disease outbreak in West Africa has revealed serious shortcomings in national and international capacity to detect, monitor, and respond to infectious disease outbreaks as they occur. Recent advances in diagnostics, risk mapping, mathematical modeling, pathogen genome sequencing, phylogenetics, and phylogeography have the potential to improve substantially the quantity and quality of information available to guide the public health response to outbreaks of all kinds.


title: Oncologists' perceived barriers to an expanded role for primary care in breast cancer survivorship care.

text: Concern exists about the sustainability of traditional, oncologist-led models of breast cancer survivorship care. However, many oncologists are hesitant about deferring survivorship care to primary care providers (PCPs). Our objective was to examine oncologists' perceptions of the role PCPs play in breast cancer survivorship and the rationale underlying these perceptions. One-on-one interviews with medical, radiation, and surgical oncologists in Wisconsin were conducted (n = 35) and transcribed. Data analysis was performed using an inductive approach to content analysis. Oncologist-perceived barriers included: PCP's level of experience with cancer care; Lack of PCP comfort in providing survivorship care; Existing demands on PCPs' time; Patient preference for oncology-led survivorship care. Oncologists described familiarity and trust in individual PCPs as factors that could mitigate barriers and lead to increased PCP involvement in survivorship care. Although a number of perceived barriers to PCP participation in survivorship were identified by Wisconsin oncologists, our findings support the direction of ongoing initiatives to facilitate PCP involvement. Our findings also suggest that early PCP involvement in survivorship may increase PCP comfort and patients' trust in PCPs in this role. The identified barrier most challenging to address may be the limited capacity of the current primary care system to manage follow-up for breast cancer survivors.


title: Symptoms-Based Phenotypes Among Women With Dysmenorrhea: A Latent Class Analysis.

text: Dysmenorrhea is highly prevalent and may increase women's risk for developing other chronic pain conditions. Although it is highly variable, symptom-based dysmenorrhea phenotypes have not been identified. The aims of the study were to identify symptom-based dysmenorrhea phenotypes and examine their relationships with demographic and clinical characteristics. In a cross-sectional study, 762 women with dysmenorrhea rated severity of 14 dysmenorrhea-related symptoms. Using latent class analysis, we identified three distinctive phenotypes. Women in the "mild localized pain" phenotype ( n = 202, 26.51%) had mild abdominal cramps and dull abdominal pain/discomfort. Women in the "severe localized pain" phenotype ( n = 412, 54.07%) had severe abdominal cramps. Women in the "multiple severe symptoms" phenotype ( n = 148, 19.42%) had severe pain at multiple locations and multiple gastrointestinal symptoms. Race, ethnicity, age, and comorbid chronic pain conditions were significantly associated with phenotypes. Identification of these symptom-based phenotypes provides a foundation for research examining genotype-phenotype associations, etiologic mechanisms, and/or variability in treatment responses.


Massive Hemothorax Due to Intrathoracic Herniation of the Gastric Remnant After Roux-en-Y Gastric Bypass with Concurrent Hiatal Hernia Repair.


title: Management of Acute Lower Gastrointestinal Bleeding.

text: Acute lower gastrointestinal bleeding (LGIB), defined as hemorrhage into the gastrointestinal tract distal to the ligament of Treitz, is a major cause of morbidity and mortality among adults. Overall, mortality rates are estimated between 2.4% and 3.9%. The most common etiology for LGIB is diverticulosis, implicated in approximately 30% of cases, with other causes including hemorrhoids, ischemic colitis, and postpolypectomy bleeding. Transcatheter visceral angiography has begun to play an increasingly important role in both the diagnosis and treatment of LGIB. Historically, transcatheter visceral angiography has been used to direct vasopressin infusion with embolization reserved for treatment of upper gastrointestinal bleeding. However, advances in microcatheter technology and embolotherapy have enabled super-selective embolization to emerge as the treatment of choice for many cases of LGIB.


title: Impact of incision length on the short-term outcomes of laparoscopic colorectal surgery.

text: BACKGROUND The recent introduction of hand-assist devices in laparoscopic colorectal surgery has renewed interest in the influence of incision length. This study aimed to define the impact of extraction incision length on the postoperative outcomes of laparoscopic left-sided colon and rectal resections. METHODS Consecutive patients undergoing laparoscopic left-sided colorectal resection from 1991 to 2007 were retrieved from a prospectively collected database. The association between incision length and patient characteristics, diagnosis, and perioperative outcomes were analyzed using logistic regression, Spearman correlation, Wilcoxon test, and chi-square test. RESULTS A total of 494 laparoscopic colorectal resections (left, sigmoid, anterior, and low anterior resections) were retrieved. Patients with conversions to open surgery (n = 59) and missing data (n = 53) were excluded. As a result, 382 cases were included in the study. A slight majority of the patients had malignant disease (n = 202, 53%). The median incision length was 5 cm (interquartile range, 4-6 cm). Increasing weight was positively correlated with incision length (p = 0.0001). Male patients had modestly larger mean incisions than female patients (5.5 vs. 5.0 cm; p = 0.0075). Age, previous surgery, diagnosis, days to resumption of normal diet, and days to discharge from hospital showed no significant relationship with incision length. No association was observed between the incision length and intraoperative or postoperative complications. CONCLUSIONS Patients undergoing laparoscopic colorectal surgery appear to achieve the same perioperative outcomes irrespective of their extraction incision lengths. To maintain the short-term benefits of laparoscopy, surgeons should consider pursuing a minimally invasive technique, even when a larger extraction incision will ultimately be required.


title: Double Cycling During Mechanical Ventilation: Frequency, Mechanisms, and Physiologic Implications.

text: OBJECTIVES Double cycling generates larger than expected tidal volumes that contribute to lung injury. We analyzed the incidence, mechanisms, and physiologic implications of double cycling during volume- and pressure-targeted mechanical ventilation in critically ill patients. DESIGN Prospective, observational study. SETTING Three general ICUs in Spain. PATIENTS Sixty-seven continuously monitored adult patients undergoing volume control-continuous mandatory ventilation with constant flow, volume control-continuous mandatory ventilation with decelerated flow, or pressure control-continuous mandatory mechanical ventilation for longer than 24 hours. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We analyzed 9,251 hours of mechanical ventilation corresponding to 9,694,573 breaths. Double cycling occurred in 0.6%. All patients had double cycling; however, the distribution of double cycling varied over time. The mean percentage (95% CI) of double cycling was higher in pressure control-continuous mandatory ventilation 0.54 (0.34-0.87) than in volume control-continuous mandatory ventilation with constant flow 0.27 (0.19-0.38) or volume control-continuous mandatory ventilation with decelerated flow 0.11 (0.06-0.20). Tidal volume in double-cycled breaths was higher in volume control-continuous mandatory ventilation with constant flow and volume control-continuous mandatory ventilation with decelerated flow than in pressure control-continuous mandatory ventilation. Double-cycled breaths were patient triggered in 65.4% and reverse triggered (diaphragmatic contraction stimulated by a previous passive ventilator breath) in 34.6% of cases; the difference was largest in volume control-continuous mandatory ventilation with decelerated flow (80.7% patient triggered and 19.3% reverse triggered). Peak pressure of the second stacked breath was highest in volume control-continuous mandatory ventilation with constant flow regardless of trigger type. Various physiologic factors, none mutually exclusive, were associated with double cycling. CONCLUSIONS Double cycling is uncommon but occurs in all patients. Periods without double cycling alternate with periods with clusters of double cycling. The volume of the stacked breaths can double the set tidal volume in volume control-continuous mandatory ventilation with constant flow. Gas delivery must be tailored to neuroventilatory demand because interdependent ventilator setting-related physiologic factors can contribute to double cycling. One third of double-cycled breaths were reverse triggered, suggesting that repeated respiratory muscle activation after time-initiated ventilator breaths occurs more often than expected.


title: Efficacy and Cost-Effectiveness of Portable Small-Bore Chest Tube (Thoracic Egg Catheter) in Spontaneous Pneumothorax.

text: Background Primary spontaneous pneumothorax is commonly treated with chest tube insertion, which requires hospitalization. In this study, we evaluated the efficacy, costs, and benefits of a portable small-bore chest tube (Thoracic Egg; Sumitomo Bakelite Co. Ltd., Tokyo, Japan) compared with a conventional chest tube. Methods We retrospectively analyzed all primary spontaneous pneumothorax patients who underwent treatment at Gangnam Severance Hospital between August 2014 and May 2018. Results A total of 279 patients were divided into 2 groups: the conventional group (n=236) and the Thoracic Egg group (n=43). Of the 236 patients in the conventional group, 100 were excluded because they underwent surgery during the study period. The efficacy and cost were compared between the 2 groups. There was no statistically significant difference between the groups regarding recurrence (conventional group, 36 patients [26.5%]; Thoracic Egg group, 15 patients [29.4%]; p=0.287). However, the Egg group had statistically significantly lower mean medical expenses than the conventional group (433,413 Korean won and 522,146 Korean won, respectively; p<0.001). Conclusion Although portable small-bore chest tubes may not be significantly more efficacious than conventional chest tubes, their use is significantly less expensive. We believe that the Thoracic Egg catheter could be a less costly alternative to conventional chest tube insertion.


COVID 19 uncertainty.


title: Evaluation of the willingness for cadaveric donation in Greece: a population-based study.

text: Despite the importance of body donation for medical education and the advancement of medical science, cadaveric donation remains suboptimal worldwide. The purpose of this study was to evaluate the willingness of body donation in Greece and determine the characteristics of donors. This cross-sectional questionnaire survey was conducted from January to June 2011. A specially designed questionnaire was distributed to 1,700 individuals who were randomly selected from five major Greek cities. It was found that higher educational levels (P = 0.002), annual family income below 30,000 Euros (P = 0.001), guaranteed employment status (P = 0.02), and the presence of comorbid conditions (P = 0.004) seemed to affect potential donors' willingness for cadaveric donation. Those with strong religious beliefs were found to be unwilling to donate their bodies to medical science. Interestingly, the majority of participants who believed that hospitalized patients are deceived or are used for harmful experiments were willing to become whole body donors (P = 0.043). In Greece, the rate of body donation to medical science remains low, and most Greek citizens are not willing to become body donors. Efforts to encourage discussions about whole body donation should be implemented in order to improve current low levels of donation.


title: A "Train-Track" Technique in Anatomic Reconstruction of SVC Bifurcation Complicated by Cardiac Tamponade: An Introspection.

text: This report describes a stenting technique used to anatomically reconstruct superior vena cava (SVC) bifurcation in a patient with benign SVC syndrome. After recanalizing the SVC bifurcation, we exchanged two 0.035-in. wires for two 0.018-in. wires, deployed the SVC stent over these two wires ("train-track" technique), and stented each innominate vein over one wire. However, our decisions to recanalize both innominate veins, use the "buddy-wire" technique for SVC dilation, and dilate the SVC to 16 mm before stent deployment likely contributed to SVC tear, which was managed by resuscitation, SVC stent placement, and pericardial drainage. Here, we describe the steps of the train-track technique, which can be adopted to reconstruct other bifurcations; we also discuss the controversial aspects of this case.


Restarting Essential Surgery in the Era of COVID-19: A Cautious Data Driven Approach Based on the Literature and Local Data.


title: Use of Pipeline Embolization Devices for treatment of a direct carotid-cavernous fistula.

text: BACKGROUND The use of minimally porous endoluminal devices (MPEDs) such as the Pipeline Embolization Device (PED) has been described for the treatment of brain aneurysms. The benefit of using MPEDs to assist embolization of a direct high-flow carotid cavernous fistula resulting from a ruptured cavernous carotid artery aneurysm is not well documented. METHODS We describe our experience with deploying a tailored multidevice PED construct across the cavernous internal carotid artery (ICA) wall defect in combination with transarterial coil embolization using the "jailed microcatheter" technique. RESULTS A 59-year-old woman presented with acute left-sided ophthalmoplegia. Diagnostic cerebral angiography demonstrated a ruptured giant cavernous carotid aneurysm with fistulous outflow via the ipsilateral left superior ophthalmic vein and into the pterygoid venous plexi bilaterally. Via the Marksman microcatheter, a total of three PEDs measuring 4.5 mm × 18 mm, 4.5 mm × 20 mm, and 4.75 mm × 16 mm were telescoped within the ICA across the aneurysm neck. Coiling of the aneurysm fundus and cavernous sinus via the "jailed" Rapidtransit microcatheter was subsequently achieved. A 2-year follow-up digital subtraction angiography (DSA) demonstrated stable obliteration of the aneurysm and the fistula, coincident with complete resolution of the patient's symptoms. CONCLUSIONS Based on our long-term clinical and angiographic results, we advocate that the presented method be a valid treatment option for selected cases.


title: Effect of implementation interventions on nurses' behaviour in clinical practice: a systematic review, meta-analysis and meta-regression protocol.

text: BACKGROUND Practitioner-level implementation interventions such as audit and feedback, communities of practice, and local opinion leaders have shown potential to change nurses' behaviour in clinical practice and improve patients' health. However, their effectiveness remains unclear. Moreover, we have a paucity of data regarding the use of theory in implementation studies with nurses, the causal processes-i.e. mechanisms of action-targeted by interventions to change nurses' behaviour in clinical practice, and the constituent components-i.e. behaviour change techniques-included in interventions. Thus, our objectives are threefold: (1) to examine the effectiveness of practitioner-level implementation interventions in changing nurses' behaviour in clinical practice; (2) to identify, in included studies, the type and degree of theory use, the mechanisms of action targeted by interventions and the behaviour change techniques constituting interventions and (3) to examine whether intervention effectiveness is associated with the use of theory or with specific mechanisms of action and behaviour change techniques. METHODS We will conduct a systematic review based on the Cochrane Effective Practice and Organization of Care (EPOC) Group guidelines. We will search six databases (CINAHL, EMBASE, ERIC, PsycINFO, PubMed and Web of Science) with no time limitation for experimental and quasi-experimental studies that evaluated practitioner-level implementation interventions aiming to change nurses' behaviour in clinical practice. We will also hand-search reference lists of included studies. We will perform screening, full-text review, risk of bias assessment, and data extraction independently with the Covidence systematic review software. We will assess the quality of evidence using the GRADEpro software. We will code included studies independently for theory use (Theory Coding Scheme), mechanisms of action (coding guidelines from Michie) and behaviour change techniques (Behaviour Change Technique Taxonomy v1) with QSR International's NVivo qualitative data analysis software. Meta-analyses will be performed using the Review Manager (RevMan) software. Meta-regression analyses will be performed with IBM SPSS Statistics software. DISCUSSION This review will inform knowledge users and researchers interested in designing, developing and evaluating implementation interventions to support nurses' behaviour change in clinical practice. Results will provide key insights regarding which causal processes-i.e. mechanisms of action-should be targeted by these interventions, and which constituent components-i.e. behaviour change techniques-should be included in these interventions to increase their effectiveness. SYSTEMATIC REVIEW REGISTRATION The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42019130446).


title: Proteolytic processing, deubiquitinase and interferon antagonist activities of Middle East respiratory syndrome coronavirus papain-like protease.

text: The emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe pulmonary disease in humans and represents the second example of a highly pathogenic coronavirus (CoV) following severe acute respiratory syndrome coronavirus (SARS-CoV). Genomic studies revealed that two viral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro), process the polyproteins encoded by the MERS-CoV genomic RNA. We previously reported that SARS-CoV PLpro acts as both deubiquitinase (DUB) and IFN antagonist, but the function of the MERS-CoV PLpro was poorly understood. In this study, we characterized MERS-CoV PLpro, which is a protease and can recognize and process the cleavage sites (CS) of nsp1-2, nsp2-3 and nsp3-4. The LXGG consensus cleavage sites in the N terminus of pp1a/1ab, which is generally essential for CoV PLpro-mediated processing, were also characterized in MERS-CoV. MERS-CoV PLpro, like human SARS-CoV PLpro and NL63-CoV PLP2, is a viral deubiquitinating enzyme. It acts on both K48- and K63-linked ubiquitination and ISG15-linked ISGylation. We confirmed that MERS-CoV PLpro acts as an IFN antagonist through blocking the phosphorylation and nuclear translocation of IFN regulatory factor 3 (IRF3). These findings indicate that MERS-CoV PLpro acts as a viral DUB and suppresses production of IFN-β by an interfering IRF3-mediated signalling pathway, in addition to recognizing and processing the CS at the N terminus of replicase polyprotein to release the non-structural proteins. The characterization of proteolytic processing, DUB and IFN antagonist activities of MERS-CoV PLpro would reveal the interactions between MERS-CoV and its host, and be applicable to develop strategies targeting PLpro for the effective control of MERS-CoV infection.


title: The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks.

text: Coronavirus disease 2019, abbreviated to COVID-19 and sustained by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the latest biological hazard to assume the relevance of insidious worldwide threat. One obvious question that is now engaging the minds of many scientists and healthcare professionals is whether and eventually how laboratory medicine could efficiently contribute to counteract this and other (future) viral outbreaks. Despite there being evidence that laboratory tests are vital throughout many clinical pathways, there are at least three major areas where in vitro diagnostics can also provide essential contributions to diagnostic reasoning and managed care of patients with suspected or confirmed SARS-CoV-2 infection. These include etiological diagnosis, patient monitoring, as well as epidemiologic surveillance. Nonetheless, some structural and practical aspects may generate substantial hurdles in providing timely and efficient response to this infectious emergency, which basically include inadequate (insufficient) environment and shortage of technical and human resources for facing enhanced volume of tests on many infected patients, some of whom are with severe disease. Some proactive and reactive strategies may hence be identified to confront this serious healthcare challenge, which entail major investments on conventional laboratory resources, reinforcement of regional networks of clinical laboratories, installation of mobile laboratories, as well as being proactive in establishing laboratory emergency plans.


title: Triiodothyronine is an indicator of nutritional status in adolescent girls with eating disorders.

text: AIM Circulating thyroid hormone concentrations are influenced by nonthyroidal disease and changes in nutritional status. We studied thyroid hormones as possible indicators of nutrition in adolescent girls with eating disorders. METHOD Blood samples for analyses of thyroid hormones were obtained at 360 assessments of 298 patients and biweekly during 42 treatment periods in 36 patients. RESULTS At assessment, when most of the girls were on a weight losing course, serum triiodothyronine (T3) concentrations were low. Great weight loss and rapid rate of weight loss were the most important predictors of low T3 concentrations. Serum free thyroxine concentrations were in the lower normal range. In premenarcheal girls, weight loss was the most important predictor of free thyroxine but this relationship was weaker in postmenarcheal girls. Serum TSH concentrations were within the normal range and only weakly related to weight changes. During treatment, T3 increased in parallel with weight but was also influenced by the short-term weight trend. CONCLUSION Serum T3 concentration is an indicator of nutritional status in adolescent girls with eating disorders. It is sensitive to short-term weight changes and could be used to monitor progress throughout nutritional rehabilitation.


title: When Going Digital Becomes a Necessity: Ensuring Older Adults' Needs for Information, Services, and Social Inclusion During COVID-19.

text: Older adults are in triple jeopardy during COVID-19: compared with younger people, older adults are (1) more likely to develop serious conditions and experience higher mortality; (2) less likely to obtain high quality information or services online; and (3) more likely to experience social isolation and loneliness. Hybrid solutions, coupling online and offline strategies, are invaluable in ensuring the inclusion of vulnerable populations. Most of these solutions require no new inventions. Finding the financial resources for a rapid, well-coordinated implementation is the biggest challenge. Setting up the requisite support systems and digital infrastructure is important for the present and future pandemics.


Children are being sidelined by covid-19.


title: Hypoxemia adds to the CURB-65 pneumonia severity score in hospitalized patients with mild pneumonia.

text: BACKGROUND Hypoxemia may influence the prognosis of patients with mild pneumonia, regardless of the initial CURB-65 score (confusion, blood urea nitrogen > 20 mg/dL, respiratory rate > 30 breaths/min, blood pressure < 90/60 mm Hg, and age ≥ 65 y). OBJECTIVE To determine the risk factors associated with hypoxemia and the influence of hypoxemia on clinical outcomes in hospitalized patients with mild pneumonia. METHODS We performed a multicenter prospective cohort study of 585 consecutive hospitalized patients with mild pneumonia (CURB-65 groups 0 and 1). We stratified the patients according to the presence of hypoxemia, defined as a P(aO(2))/F(IO(2)) < 300 mm Hg on admission. We assessed the risk factors associated with hypoxemia, hypoxemia's influence on the course of pneumonia, and clinical outcomes (mortality, hospital stay, and need for intensive care unit admission), with multivariable regression. RESULTS Fifty percent of the patients (294 cases) had hypoxemia on admission. The risk factors independently associated with hypoxemia were: bilateral radiological involvement (odds ratio 2.8, 95% CI 1.1-7.5), history of COPD (odds ratio 2.5, 95% CI 1.4-4.3), and hypoalbuminemia (odds ratio 2.0, 95% CI 1.1-3.5). The hypoxemic patients had longer hospital stay, higher intensive care unit admission rate, higher rate of severe sepsis, and higher mortality than the non-hypoxemic patients. CONCLUSIONS Hypoxemia in patients with mild pneumonia is independently associated with several adverse clinical and radiological variables, and the hypoxemic patients had worse clinical outcomes than the non-hypoxemic patients. Therefore, additional attention should be paid to the presence of hypoxemia, regardless of a low CURB-65 score.


title: Role of lipids in virus replication.

text: Viruses intricately interact with and modulate cellular membranes at several stages of their replication, but much less is known about the role of viral lipids compared to proteins and nucleic acids. All animal viruses have to cross membranes for cell entry and exit, which occurs by membrane fusion (in enveloped viruses), by transient local disruption of membrane integrity, or by cell lysis. Furthermore, many viruses interact with cellular membrane compartments during their replication and often induce cytoplasmic membrane structures, in which genome replication and assembly occurs. Recent studies revealed details of membrane interaction, membrane bending, fission, and fusion for a number of viruses and unraveled the lipid composition of raft-dependent and -independent viruses. Alterations of membrane lipid composition can block viral release and entry, and certain lipids act as fusion inhibitors, suggesting a potential as antiviral drugs. Here, we review viral interactions with cellular membranes important for virus entry, cytoplasmic genome replication, and virus egress.


Non-office-hours admission affects intravenous thrombolysis treatment times and clinical outcome.


title: Percutaneous laparoscopic assisted gastrostomy (PLAG)--a new technique for cases of pharyngoesophageal obstruction.

text: PURPOSE Percutaneous endoscopic gastrostomy (PEG) is the preferable method to provide enteral nutrition for a longer time period. Safe placement of a PEG tube requires passage of the esophagus and transillumination of the stomach through the abdominal wall. Surgical placement of a PEG tube has been shown to be feasible although the local complication rate ranges above the endoscopic procedure. We are presenting a new technique (percutaneous laparoscopically assisted gastrostomy, PLAG) to provide enteral access for patients with pharyngoesophageal obstruction not suitable for PEG placement. METHODS We have developed a laparoscopic method that allows full control of the stoma location at the anterior gastric wall. The tube has a deployable bumper mechanism, which can be inserted through a minimal gastric incision. Combined with the fixation by transcutaneous sutures, the risk for leakage or dislodgement is low. RESULTS Fifty-one PLAGs were inserted in 45 male and six female patients suffering from pharyngoesophageal obstruction due to malignancy. Patients were referred after unsuccessful endoscopic PEG placement (n = 39) or received their PLAG when they underwent staging laparoscopy (n = 12). Success rate was 96.2%. No procedure-related mortality was observed. Infectious complications occurred in three (5.9%) cases. In five patients, minor leaks were managed conservatively (n = 4) or required relaparoscopy (n = 1) and placement of an additional suture (overall complication rate of 15.8%, n = 8). Nutritional goals were reached after 7.8 ± 2.3 days. CONCLUSION PLAG is a safe and easy procedure. It can well be used to provide enteral access for patients with pharyngoesophageal obstruction not suitable for endoscopic PEG placement.


title: Self-gripping mesh versus staple fixation in laparoscopic inguinal hernia repair: a prospective comparison.

text: BACKGROUND Transabdominal preperitoneal (TAPP) repair is widely used to treat bilateral or recurrent inguinal hernias. Recently a self-gripping mesh has been introduced into clinical practice. This mesh does not need staple fixation and thus might reduce the incidence of chronic pain. This prospective study aimed to compare two groups of patients with bilateral (BIH) or monolateral (MIH) primary or recurrent inguinal hernia treated with TAPP using either a self-gripping polyester and polylactic acid mesh (SGM) or a polypropylene and poliglecaprone mesh fixed with four titanium staples [standard technique (ST)]. METHODS In this study, 96 patients (mean age, 58 years) with BIH (73 patients with primary and recurrent hernia) or MIH (22 patients with recurrent hernia) underwent a TAPP repair. For 49 patients, the repairs used SGM, and for 46 patients, ST was used. The patients were clinically evaluated 1 week and then 30 days postoperatively. After at least 6 months, a phone interview was conducted. The short-form McGill Pain Questionnaire was administered to all the patients at the 6-month follow-up visit. RESULTS The mean length of the procedure was 83 min in the SGM group and 77.5 min in the ST group. The mean follow-up period was 13.8 months (range 1.3-42.0 months) for the SGM group and 18.2 months (range 1.9-27.1 months) for the ST group. The recurrence rate at the last follow-up visit was 0 % in the SGM group and 2.2 % (1 patient) in the ST group. The incidence of mild chronic pain at the 6-month follow-up visit was 4.1 % in the SGM group and 9.1 % in the ST group, and the incidence of moderate or severe pain was respectively 2.1 and 6.8 %. CONCLUSIONS The study population was not large enough to obtain statistically significant results. However, the use of SGM for TAPP repairs appeared to give good results in terms of chronic pain, and the incidence of recurrences was not higher than with ST. In our unit, SGM during TAPP repair of inguinal hernias has become the standard.


title: Alnuheptanoid A: a new diarylheptanoid derivative from Alnus japonica.

text: Extensive chromatographic investigation of the ethanolic extract of Alnus japonica Steud stem bark led to the isolation of a new diarylheptanoid named alnuheptanoid A [(5S)-7-(3,4-dihydroxyphenyl)-1-(4-hydroxyphenyl)-5-methoxyheptan-3-one] (8), together with seven known diarylheptanoid derivatives: platyphyllenone (5), (5S)-1,7-bis(4-hydroxyphenyl)-5-methoxyheptan-3-one (6), 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-4-hepten-3-one (7), hirsutenone (9), (5R)-O-methylhirsutanonol (10), hirsutanonol (11) and oregonin (13), three triterpenes: α-amyrin (1), betulinaldehyde (3) and betulinic acid (4), and two sterols: β-sitosterol (2) and daucosterol (12). Compound 6 was isolated for the first time from natural source. The structures of the isolated compounds were determined on the basis of spectroscopic measurements (UV, IR, HR-ESI-MS, 1D and 2D NMR).


title: Direct Versus Indirect Bypass for Moyamoya Disease.

text: Moyamoya disease is a progressive occlusive vasculopathy that involves the supraclinoid internal carotid arteries and Circle of Willis, and results in the formation of collateral vessels at the skull base. The progressive nature of this disease leads to cerebral ischemia and sometimes intracerebral hemorrhage. The treatment of moyamoya disease is mainly surgical revascularization, using revascularization techniques that include direct, indirect, and combined strategies. Here we discuss the available options for revascularization as well as our opinions regarding the surgical management of patients with moyamoya disease.


title: A comparative-descriptive analysis of clinical characteristics in 2019-Coronavirus-infected children and adults.

text: Acute respiratory disease (ARD) caused by 2019 novel coronavirus (2019-nCoV) has rapidly spread throughout China. Children and adults show a different clinical course. The purpose of the current study is to comparatively analyze the clinical characteristics of 2019-nCoV infection in children and adults and to explore the possible causes for the discrepancies present. The medical records of 25 adults and 7 children confirmed cases of 2019-nCoV ARD were reviewed retrospectively. All children were family clusters. The total adult patients were differentiated into: the local residents of Wuhan, a history of travel to Wuhan and direct contact with people from Wuhan. The numbers were 14 (56%), 10 (40%) & 1 (4%), respectively. The median incubation period of children and adults was 5 days (range 3-12 days) and 4 days (range 2-12 days), respectively. Diarrhoea and/or vomiting (57.1%) were more common in children, whereas for adults it was myalgia or fatigue (52%). On admission, the percentage of children having pneumonia (5, 71.4%) was roughly the same as adults (20, 80%). 20% of adults had leucopoenia, but leukocytosis was more frequently in children (28.6%, P=0.014). A higher number of children had elevated creatine kinase isoenzyme (57.1% vs. 4%, P=0.004). Antiviral therapy was given to all adult patients but to none of the children. In summary, knowledge of these differences between children and adults will not only be helpful for the clinical diagnosis of 2019 novel coronavirus disease (COVID-19), but also for a future discussion on age-specific coronavirus infection. This article is protected by copyright. All rights reserved.


Aykaç K, Karadağ-Öncel E, Bayhan C, Tanır-Başaranoğlu S, Akın MŞ, Özsürekci Y, Alp A, Cengiz AB, Kara A, Ceyhan M. Prevalence and seasonal distribution of viral etiology of respiratory tract infections in inpatients and outpatients of the pediatric population: 10 year follow-up. Turk J Pediatr 2018; 60: 642-652. The aim of this study was to investigate the prevalence and seasonal distribution of respiratory viruses in pediatric patients. Nasopharyngeal swab specimens, demographic and clinical information were collected from 1240 pediatric patients aged < 18 years between 2006 and 2015 in Hacettepe University Children`s Hospital. Multiplex RT-PCR (multiplex reverse transcriptase polymerase chain reaction) was performed to detect viral pathogens. A total of 1240 pediatric outpatients and inpatients who had been admitted to the hospital with symptoms of upper and lower respiratory tract infections (RTIs) were enrolled. Viruses were identified in 339 (27.3%) of cases, with the leading three viruses being respiratory syncytial virus (RSV, 74/339; 21.8%), human rhinovirus (62/339; 18.3%), and multiple viruses (56/339; 16.5%). Most of the patients were diagnosed with lower RTI (264/339; 77.8%) and antibiotics were administered to three quarters of positive patients (254/339; 74.9%). With an overall viral agent detection rate of 27.3%, the findings of the present study suggest that other respiratory pathogens, whether viral or bacterial, may also lead to hospital visits due to respiratory tract symptoms in children.


title: Urologic surgery and invasive procedures during coronavirus pandemic: Retrospective comparison of risk infection in a referral Covid hospital and in a free-Covid hospital.

text: INTRODUCTION On 21 February 2020, 'Luigi Sacco' Hospital was identified as a Covid-19 referral Hospital in Lombardy. The Department of Urology of our Healthcare Institution consists of two Urology Units, one at 'L.Sacco' Hospital (hereinafter referred to as Covid-19 hospital) and one at 'Fatebenefratelli' Hospital (hereinafter referred to as Covid-19-free hospital). The Healthcare System's Administration communicated to all personnel the implementation of a planned 'biological risk protocol' at the Covid-19 hospital, while the Covid-19-free hospital followed regular government recommendations. We evaluated the risk of Sars-Cov-2 infection in the patients treated for surgical or invasive urologic procedures during the epidemic in the two different hospitals. MATERIALS AND METHODS At the Covid-19 hospital, 12 patients underwent surgery and 51 patients invasive diagnostic procedures between 22 February and 8 March 2020; in the same period, at the Covid-19-free hospital, 21 patients underwent surgery and 56 patients invasive diagnostic procedures. We compared the incidence of Sars-Cov-2 infection among the patients who were accessed in the two Urology Units in the period of different restrictive measures after the outbreak of the epidemic. RESULTS We registered no cases of Sars-Cov-2 infection in the patients hospitalized in that period in Covid-19 hospital, despite three cases of swab positivity in the Covid-19-free hospital. CONCLUSION The early implementation of extraordinary measures to restrict the spread of the virus offers a good protection also in a Covid-19 referral Hospital. The adoption of safety measures may be considered even after the end of the pandemic in all the health systems.


Transoral endoscopic surgical resection of a giant pedunculated polyp.


Interventional endovascular management of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a position statement by the Society of Interventional Radiology, endorsed by the Canadian Interventional Radiology Association.


Lung Mechanics in COVID-19 Resemble RDS not ARDS: Could Surfactant be a Treatment?


title: 'Calibrating to scale: a framework for humanitarian health organizations to anticipate, prevent, prepare for and manage climate-related health risks'.

text: Climate Change is adversely affecting health by increasing human vulnerability and exposure to climate-related stresses. Climate change impacts human health both directly and indirectly, through extreme weather events, changing distribution of health risks, increased risks of undernutrition, population displacement, and greater risks of injuries, disease, and death (Ebi, K., Campbell-Lendrum, D., & Wyns, A. The 1. 5 health report. WHO. 2018). This risk amplification is likely to increase the need for humanitarian support. Recent projections indicate that under a business as usual scenario of sustained greenhouse gas emissions, climate change could double the demand for humanitarian assistance by 2050 (World Health Organization. Operational Framework for building climateresilient health systems. WHO. 2015). Humanitarian assistance is currently not meeting the existing needs, therefore, any additional burden is likely to be highly challenging.Global health advocates, researchers, and policymakers are calling for urgent action on climate change, yet there is little clarity on what that action practically entails for humanitarian organizations. While some humanitarian organizations may consider themselves well designed to respond, climate change as a transversal threat requires the incorporation of a resilience approach to humanitarian action and policy responses.By bringing together authors from two historically disparate fields - climate change and health, and humanitarian assistance - this paper aims to increase the capacity of humanitarian organizations to protect health in an unstable climate by presenting an adapted framework. We adapted the WHO operational framework for climate-resilient health systems for humanitarian organizations and present concrete case studies to demonstrate how the framework can be implemented. Rather than suggest a re-design of humanitarian operations we recommend the application of a climate-lens to humanitarian activities, or what is also referred to as mainstreaming climate and health concerns into policies and programs. The framework serves as a starting point to encourage further dialogue, and to strengthen collaboration within, between, and beyond humanitarian organizations.


The status surrounding chloroquine and other drugs as potential anti-infective agents for COVID-19.


title: Residual mesorectum on postoperative magnetic resonance imaging following transanal total mesorectal excision (TaTME) and laparoscopic total mesorectal excision (LapTME) in rectal cancer.

text: BACKGROUND The standard treatment for mid- and low-rectal cancer is total mesorectal excision. Incomplete excision is an important predictor of local recurrence after rectal cancer surgery. Transanal TME (TaTME) is a new treatment option in which the rectum is approached with both laparoscopic and transanal endoscopic techniques. The aim of the present study was to determine the prevalence and localisation of residual mesorectal tissue by postoperative magnetic resonance imaging (MRI) of the pelvis and compare this between TaTME and laparoscopic TME (LapTME) patients. In addition, we assessed correspondence with histopathological quality. METHODS Two groups of patients with cT1-T3 rectal cancer who underwent TME surgery with primary anastomosis were included, each group consisting of 32 patients. Postoperative T2-weighted MRI of the pelvis was performed at least 6 months after TME surgery and evaluated by two radiologists independently. Residual mesorectum was defined as any residual mesorectal tissue detectable after TME. Localisation of the tissue was categorised in relation to height in the pelvis and position of the level of anastomosis. RESULTS Residual mesorectal tissue was detected in 3.1% of TaTME patients and of 46.9% in LapTME patients (p < 0.001). Multivariate analysis identified only type of surgery as a significant risk factor for leaving residual mesorectum. Other known risk factors for incomplete TME, such as body mass index (BMI) and male gender, were not significant. No relation was seen between specimen quality and prevalence of residual mesorectum. CONCLUSIONS The completeness of mesorectal excision was significantly better with TaTME than with standard laparoscopic technique.


title: In Vitro and Ex Vivo Evaluations of Lipid Anti-Cancer Nanoformulations: Insights and Assessment of Bioavailability Enhancement.

text: Lipid-based nanoformulations have been extensively investigated for improving oral efficacy of plethora of drugs. Chemotherapeutic agents remain a preferred option for effective management of cancer; however, most chemotherapeutic agents suffer from limitation of poor oral bioavailability that is associated with their physicochemical properties. Drug delivery via lipid-based nanosystems possesses strong rational and potential for improving oral bioavailability of such anti-cancer molecules through various mechanisms, viz. improving their gut solubilisation owing to micellization, improving mucosal permeation, improving lymphatic uptake, inhibiting intestinal metabolism and/or inhibiting P-glycoprotein efflux of molecules in the gastrointestinal tract. Various in vitro characterization techniques have been reported in literature that aid in getting insights into mechanisms of lipid-based nanodevices in improving oral efficacy of anti-cancer drugs. The review focuses on different characterization techniques that can be employed for evaluation of lipid-based nanosystems and their role in effective anti-cancer drug delivery.


title: Activated HIF1α of tumor cells promotes chemoresistance development via recruiting GDF15-producing tumor-associated macrophages in gastric cancer.

text: Chemotherapy is the preferred treatment for advanced stage gastric cancer (GC) patients, and developing chemoresistance is a tremendous challenge to efficacy of GC treatment. The treatments of anti-tumor chemo-agents recruit more tumor-associated macrophages (TAMs) which are highly implicated in the chemoresistance development, but the underlying molecular mechanism is unclear. Here, we demonstrate that hypoxia-inducible factor 1α (HIF1α) in GC cells is activated upon 5-fluorouracil (5-FU) treatment and results in much more accumulation of M2-type TAMs which protect tumor cells from chemo-agents. Mechanistically, in the GC cells under the 5-FU treatment, reactive oxygen species is accumulated and then induces the activation of HIF1α signaling to drive the expression of high-mobility group box 1, which leads to more macrophage's infiltration into GC tumor. In turn, the recruited TAMs exhibit tumor-protected M2-type phenotype and promote the chemoresistance of GC cells via producing growth differentiation factor 15 (GDF15) to exacerbate the fatty acid β-oxidation in tumor cells. Blocking GDF15 using antibody or inhibiting FAO of tumor cells by etomoxir efficiently gave rise to the tumor cell sensitivity to 5-FU. Therefore, our study demonstrates a novel insight in understanding the cross talking between tumor cells and immune microenvironment and provides new therapeutic targets for clinic treatments of gastric cancer.


title: Performance of a rapid molecular multiplex assay for the detection of influenza and picornaviruses.

text: BACKGROUND Multiplex assays are a new strategy for diagnosing respiratory infections. These assays are better than those based on cultures or antigen detection, but few data are available for comparing them to monoplex polymerase chain reactions (PCRs). This study evaluated the performance of the Luminex xTAG Respiratory Viral Panel (RVP) Fast assay with reference to 2 real-time PCR assays for detecting type A influenza H1 viruses and human enteroviruses and rhinoviruses. METHODS This was an analysis of nasal swab specimens obtained from 590 outpatients suffering from acute respiratory tract disease between September 2009 and February 2010. RESULTS The RVP Fast assay performed well in less than 4 h for detecting type A influenza H1 viruses, particularly (H1N1)pdm09, and human entero/rhinoviruses, with 95.2% and 90.05% agreement, respectively, when compared to monoplex real-time PCR assays. This multiplex assay also detected at least 1 virus in 69.3% of the specimens and detected multiple infections in 40 samples. CONCLUSIONS The multiplex assay detected clinically important viruses in a single genomic test. It will thus be useful for detecting several viruses causing respiratory tract disorders.


title: Progesterone and its metabolite allopregnanolone differentially regulate hemostatic proteins after traumatic brain injury.

text: Our laboratory has shown in numerous experiments that the neurosteroids progesterone (PROG) and allopregnanolone (ALLO) improve molecular and functional outcomes after traumatic brain injury (TBI). As coagulopathy is an important contributor to the secondary destruction of nervous tissue, we hypothesized that PROG and ALLO administration may also have a beneficial effect on coagulation protein expression after TBI. Adult male Sprague-Dawley rats were given bilateral contusions of the medial frontal cortex followed by treatments with PROG (16 mg/kg), ALLO (8 mg/kg), or vehicle (22.5% hydroxypropyl-beta-cyclodextrin). Controls received no injury or injections. Progesterone generally maintained procoagulant (thrombin, fibrinogen, and coagulation factor XIII), whereas ALLO increased anticoagulant protein expression (tissue-type plasminogen activator, tPA). In addition, PROG significantly increased the ratio of tPA bound to neuroserpin, a serine protease inhibitor that can reduce the activity of tPA. Our findings suggest that in a model of TBI, where blood loss may exacerbate injury, it may be preferable to treat patients with PROG, whereas it might be more appropriate to use ALLO as a treatment for thrombotic stroke, where a reduction in coagulation would be more beneficial.


title: Management of COVID-19 Virus Infection by Convalescent Plasma.

text: No Abstract.


COVID-19 and Calcineurin Inhibitors: Should They Get Left Out in the Storm?


title: Locoregional therapy for hepatocellular carcinoma.

text: Locoregional therapies for hepatocellular carcinoma have progressed greatly in the last 30 years, beginning with the introduction of chemoembolization. Embolization techniques have evolved with the use of drug-eluting beads and radioembolization with yttrium-90. In the last 10 years, several new ablation techniques were developed including radiofrequency ablation, microwave ablation, cryoablation, laser ablation, and irreversible electroporation. Isolated or in combination, these techniques have already shown that they can improve patient survival and/or provide acceptable palliation.


title: Culture-based virus isolation to evaluate potential infectivity of clinical specimens tested for COVID-19.

text: Real-time reverse transcription (RT)-PCR is currently the most sensitive method to detect severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, the correlation between detectable viral RNA and culturable virus in clinical specimens remains unclear. Here, we performed virus culture for 60 specimens that were confirmed to be positive for SARS-CoV-2 RNA by real-time RT-PCR. The virus could be successfully isolated from 12 throat and nine nasopharyngeal swabs, and two from sputum specimens. The lowest copy number required for virus isolation was determined to be 5.4, 6.0, and 5.7 log10 genome copies/mL sample for detecting the nsp12, E, and N gene, respectively. We further examined the correlation of genome copy number and virus isolation in different regions of the viral genome, demonstrating that culturable specimens are characterized by high copy numbers with a linear correlation observed between copy numbers of amplicons targeting structural and non-structural regions. Overall, these results indicate that in addition to the copy number, the integrity of the viral genome should be considered when evaluating the infectivity of clinical SARS-CoV-2 specimens.


title: Urinary angiotensin converting enzyme 2 increases in patients with type 2 diabetic mellitus.

text: BACKGROUND/AIMS Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and recognized to be renoprotective by degrading Angiotensin II to Angiotensin (1-7) in diabetic nephropathy. However, little is known about the role of urinary ACE2 (UACE2) in diabetes. The present study was performed to evaluate UACE2 levels in type 2 diabetic patients with various degrees of albuminuria and its associations with metabolic parameters. The effect of RAS inhibitors on UACE2 excretion was also assessed. METHODS A total of 132 type 2 diabetic patients with different degrees of albuminuria and 34 healthy volunteers were studied. UACE2 levels and activity were measured. RESULTS Compared to healthy controls, UACE2 to creatinine (UACE2/Cr) levels were significantly increased in both albuminuric and non-albuminuric diabetic patients. UACE2/Cr levels were much higher in hypertensive diabetic patients compared with their normotensive counterparts and treatment with RAS inhibitors markedly attenuated the augmentation. Furthermore, UACE2/Cr was positively correlated with fasting blood glucose, hemoglobin A1C (HbA1C), triglyceride, and total cholesterol. In multiple regression analysis, UACE2/Cr was independently predicted by HbA1C and RAS inhibitors treatment. CONCLUSIONS UACE2 increased in type 2 diabetic patients with various degrees of albuminuria and RAS inhibitors suppresses UACE2 excretion. UACE2 might potentially function as a marker for monitoring the metabolic status and therapeutic response of RAS inhibitors in diabetes.


title: Exploring Diseases/Traits and Blood Proteins Causally Related to Expression of ACE2, the Putative Receptor of SARS-CoV-2: A Mendelian Randomization Analysis Highlights Tentative Relevance of Diabetes-Related Traits.

text: OBJECTIVE COVID-19 has become a major public health problem. There is good evidence that ACE2 is a receptor for SARS-CoV-2, and high expression of ACE2 may increase susceptibility to infection. We aimed to explore risk factors affecting susceptibility to infection and prioritize drug repositioning candidates, based on Mendelian randomization (MR) studies on ACE2 lung expression. RESEARCH DESIGN AND METHODS We conducted a phenome-wide MR study to prioritize diseases/traits and blood proteins causally linked to ACE2 lung expression in GTEx. We also explored drug candidates whose targets overlapped with the top-ranked proteins in MR, as these drugs may alter ACE2 expression and may be clinically relevant. RESULTS The most consistent finding was tentative evidence of an association between diabetes-related traits and increased ACE2 expression. Based on one of the largest genome-wide association studies on type 2 diabetes mellitus (T2DM) to date (N = 898,130), T2DM was causally linked to raised ACE2 expression (P = 2.91E-03; MR-IVW). Significant associations (at nominal level; P < 0.05) with ACE2 expression were observed across multiple diabetes data sets and analytic methods for T1DM, T2DM, and related traits including early start of insulin. Other diseases/traits having nominal significant associations with increased expression included inflammatory bowel disease, (estrogen receptor-positive) breast cancer, lung cancer, asthma, smoking, and elevated alanine aminotransferase. We also identified drugs that may target the top-ranked proteins in MR, such as fostamatinib and zinc. CONCLUSIONS Our analysis suggested that diabetes and related traits may increase ACE2 expression, which may influence susceptibility to infection (or more severe infection). However, none of these findings withstood rigorous multiple testing corrections (at false discovery rate <0.05). Proteome-wide MR analyses might help uncover mechanisms underlying ACE2 expression and guide drug repositioning. Further studies are required to verify our findings.


title: Radiation Exposure of Interventional Radiologists During Computed Tomography Fluoroscopy-Guided Renal Cryoablation and Lung Radiofrequency Ablation: Direct Measurement in a Clinical Setting.

text: INTRODUCTION Computed tomography (CT) fluoroscopy-guided renal cryoablation and lung radiofrequency ablation (RFA) have received increasing attention as promising cancer therapies. Although radiation exposure of interventional radiologists during these procedures is an important concern, data on operator exposure are lacking. MATERIALS AND METHODS Radiation dose to interventional radiologists during CT fluoroscopy-guided renal cryoablation (n = 20) and lung RFA (n = 20) was measured prospectively in a clinical setting. Effective dose to the operator was calculated from the 1-cm dose equivalent measured on the neck outside the lead apron, and on the left chest inside the lead apron, using electronic dosimeters. Equivalent dose to the operator's finger skin was measured using thermoluminescent dosimeter rings. RESULTS The mean (median) effective dose to the operator per procedure was 6.05 (4.52) μSv during renal cryoablation and 0.74 (0.55) μSv during lung RFA. The mean (median) equivalent dose to the operator's finger skin per procedure was 2.1 (2.1) mSv during renal cryoablation, and 0.3 (0.3) mSv during lung RFA. CONCLUSION Radiation dose to interventional radiologists during renal cryoablation and lung RFA were at an acceptable level, and in line with recommended dose limits for occupational radiation exposure.


title: Recurrence of an internal carotid artery aneurysm after complete exclusion by a Willis covered stent.

text: Treatment of selective intracranial aneurysms treated with a Willis covered stent is safe and effective. We describe a previously unreported case of a large, irregular, carotid-ophthalmic aneurysm that was treated with a Willis covered stent. An immediate angiogram after the procedure showed complete occlusion of the aneurysm. However, a six-month follow-up angiogram demonstrated contrast media filling of the aneurysm neck. To the best of our knowledge, this is the first report of a recurrent aneurysm treated with a Willis covered stent because of a membrane partially isolated with the stent. This case suggests that an aneurysm that is treated with a Willis covered stent might recanalise, and the risk of aneurysm rupture persists when the membrane of the stent is isolated with the stent. Therefore, follow-up angiography is necessary, even if an immediate angiogram shows complete aneurysm occlusion. Long-term follow-up is required, and the final outcome of such a case is still unknown.


title: Monitoring wound healing in minor burns-A novel approach.

text: Assessment of minor burn wound closure is predominately determined by visual inspection and clinical specialist assessment, which remains largely a subjective analysis and results may vary depending on the clinician's experience. Bioimpedance spectroscopy (BIS) is an instrument that has a demonstrated ability to objectively monitor the wound healing process in various patient populations but has not yet been used in acute burn wounds. The aim of the pilot study was to examine whether the BIS technique is a valid measure of wound healing. Localised BIS resistance and phase angle triplicate measures, of minor limb burns, were collected on two serial occasions. Circumference limb measures were taken at the localised burn site to determine a truncated limb volume. Proportional-odds ordered logistic regression analyses determined resistance at zero frequency (R0, indicative of edema) and resistance of total body fluid (Rinf) were significantly associated with healing after adjustment for the influence of surgery. A one unit increase in R0 and Rinf increased the odds of wound healing by 6% and 5% respectively (p<0.01). Phase angle at 50kHz and Ri were not significantly associated with the markers of the wound healing process. Spearman's correlation determined there was a significant association between a healing wound and limb segment volume (ml) (rho -0.30, p<0.01). BIS is a technique, which has the potential to monitor the progress of wound healing.


title: Intracisternal cyclodextrin prevents cerebellar dysfunction and Purkinje cell death in feline Niemann-Pick type C1 disease.

text: Niemann-Pick type C1 (NPC) disease is a lysosomal storage disease caused by mutations in the NPC1 gene, leading to an increase in unesterified cholesterol and several sphingolipids, and resulting in hepatic disease and progressive neurological disease. We show that subcutaneous administration of the pharmaceutical excipient 2-hydroxypropyl-β-cyclodextrin (HPβCD) to cats with NPC disease ameliorated hepatic disease, but doses sufficient to reduce neurological disease resulted in pulmonary toxicity. However, direct administration of HPβCD into the cisterna magna of presymptomatic cats with NPC disease prevented the onset of cerebellar dysfunction for greater than a year and resulted in a reduction in Purkinje cell loss and near-normal concentrations of cholesterol and sphingolipids. Moreover, administration of intracisternal HPβCD to NPC cats with ongoing cerebellar dysfunction slowed disease progression, increased survival time, and decreased the accumulation of brain gangliosides. An increase in hearing threshold was identified as a potential adverse effect. These studies in a feline animal model have provided critical data on efficacy and safety of drug administration directly into the central nervous system that will be important for advancing HPβCD into clinical trials.


title: Evaluation of rotation and visual outcomes after implantation of monofocal and multifocal toric intraocular lenses.

text: PURPOSE To evaluate rotational stability and its influence on postoperative visual acuity of different monofocal and multifocal toric intraocular lenses (IOLs). METHODS A prospective interventional study was designed. Ninety-one patients with a mean age of 71.65 ± 11.82 years were implanted with toric IOLs after phacoemulsification. Three monofocal toric IOLs (the Lentis LT [Oculentis, Berlin, Germany], enVista [Bausch & Lomb, Rochester, NY], and AcrySof IQ [Alcon Laboratories, Inc., Fort Worth, TX]) and one multifocal toric IOL (AcrySof IQ ReSTOR; Alcon Laboratories, Inc.) were implanted. Preoperative and postoperative images were taken to calculate the misalignment due to the marking method. To evaluate rotation in the different follow-up visits, another photograph was taken 1 hour and 1, 7 and 30 days postoperatively. Refraction, uncorrected distance visual acuity (UDVA), and corrected distance visual acuity were measured 30 days postoperatively. RESULTS Postoperative UDVA was 0.1 logMAR or better in 64.6% of eyes implanted with monofocal IOLs and 46.4% of eyes implanted with multifocal IOLs. The enVista toric IOL showed the best UDVA compared to the other monofocal IOLs, with 81% of eyes with 0.1 logMAR or better. The mean misalignment in the total group studied was 0.07° ± 0.60°; 69.6% of monofocal IOLs and 67.9% of multifocal IOLs showed less than 5° of rotation. A correlation was found between postoperative UDVA and rotation in the monofocal and multifocal IOLs implanted (r = 0.439 [P < .011] and = 0.787 [P = .001], respectively). CONCLUSIONS At 1 month postoperatively, UDVA was slightly more affected by IOL rotation in multifocal than monofocal toric IOLs. The marking method was also effective.


title: Intraoperative ultrasound and tissue elastography measurements do not predict the size of hepatic microwave ablations.

text: RATIONALE AND OBJECTIVES Image-guided thermal ablation is used to treat primary and secondary liver cancers. Evaluating completeness of ablation is difficult with standard intraoperative B-mode ultrasound. This study evaluates the ability of B-mode ultrasound (US) and tissue elastography to adequately measure the extent of ablation compared to pathologic assessment. MATERIALS AND METHODS An in vivo porcine model was used to compare B-mode ultrasonography and elastography to pathologic assessment of the microwave ablation zone area. In parallel, intraoperative ablations in patients were used to assess the ability of B-mode US and elastographic measures of tissue strain immediately after ablation to predict ablation size, compared to postprocedural computed tomography (CT). RESULTS In the animal model, ablation zones appeared to decrease in size when monitored with ultrasound over a 10-minute span with both B-mode US and elastography. Both techniques estimated smaller zones than gross pathology, however, the differences did not reach statistical significance. Biopsies from the edges of the ablation zone, as assessed by US, contained viable tissue in 75% of the cases. In the human model, B-mode US and elastography estimated similar ablation sizes; however, they underestimate the final size of the ablation defect as measured on postprocedure CT scan (median area [interquartile range]: CT, 7.3 cm(2) [5.2-9.5] vs. US 3.6 cm(2) [1.7-6.3] and elastography 4.1 cm(2) [1.4-5.1]; P = .005). CONCLUSIONS Ultrasound and elastography provide an accurate gross estimation of ablation zone size but are unable to predict the degree of cellular injury and significantly underestimate the ultimate size of the ablation.


title: Quick Evaluation of Cerebral Autoregulation Limits with Near Infrared Spectroscopic Techniques in the Intraoperative Period.

text: In this manuscript, we describe a significant advantage of the intraoperative near infrared spectroscopic techniques (NIRS) using in a malignant hypertensive patient during kidney transplantation. This patient underwent operation becasue of the presence of a suitable cadaveric kidney. Moreover, although the patient's hypertension was intensively treated by cardiology for a long time, it could not be controlled. Thus, despite severe hypertension, the patient was anaesthetized. Mean arterial pressures of about 70-90 mmHg, which are considered to be normal for most people, could cause cerebral hypoperfusion in such a patient. It is a significant advantage that the lower limit of cerebral autoregulation is quickly assessed by NIRS in the case of a kidney transplant performed under general anaesthesia.


A COVID-19 recovery for climate.


title: Surgical nuances for removal of tuberculum sellae meningiomas with optic canal involvement using the endoscopic endonasal extended transsphenoidal transplanum transtuberculum approach.

text: Tuberculum sellae meningiomas frequently extend into the optic canals. Radical tumor resection including the involved dural attachment, underlying hyperostotic bone, and intracanalicular tumor in the optic canal offers the best chance of a Simpson Grade I resection to minimize recurrence. Decompression of the optic canal with removal of the intracanalicular tumor also improves visual outcome since this portion of the tumor is usually the cause of asymmetrical visual loss. The purely endoscopic endonasal extended transsphenoidal approach offers a direct midline trajectory and immediate access to tuberculum sellae meningiomas without brain retraction and manipulation of neurovascular structures. Although the endoscopic approach has been previously criticized for its inability to remove tumor within the optic canals, complete Simpson Grade I tumor removal including intracanalicular tumor, dural attachment, and involved hyperostotic bone can be achieved in properly selected patients. Excellent visualization of the suprasellar region and the inferomedial aspects of both optic canals allows for extracapsular, extraarachnoid dissection of the tumor from the critical structures using bimanual microsurgical dissection. In this report, the authors describe the operative nuances for removal of tuberculum sellae meningiomas with optic canal involvement using a purely endoscopic endonasal extended transsphenoidal (transplanum transtuberculum) approach. They specifically highlight the technique for endonasal bilateral optic nerve decompression and removal of intracanalicular tumor to improve postoperative visual function, as demonstrated in 2 illustrative cases. Special attention is also given to cranial base reconstruction to prevent CSF leakage using the vascularized pedicled nasoseptal flap.


title: SURVEILLANCE FOR VIRAL AND PARASITIC PATHOGENS IN A VULNERABLE AFRICAN LION (PANTHERA LEO) POPULATION IN THE NORTHERN TULI GAME RESERVE, BOTSWANA.

text: African lion ( Panthera leo ) numbers are decreasing rapidly and populations are becoming smaller and more fragmented. Infectious diseases are one of numerous issues threatening free-ranging lion populations, and low-density populations are particularly at risk. We collected data on the prevalence and diversity of viral and parasitic pathogens in a small lion population in eastern Botswana. During 2012 and 2014, blood samples were collected from 59% (n=13) of the adult-subadult lions in the Northern Tuli Game Reserve in eastern Botswana. One lion had antibodies to feline panleukopenia virus, two had antibodies to canine distemper virus, and two had feline calicivirus antibodies. Ten of the 13 had antibodies to feline immunodeficiency virus and 11 had feline herpesvirus antibodies. All lions were negative for antibodies to feline coronavirus. Blood samples from all lions were negative for Trypanosoma, Anaplasma, Theileria, and Ehrlichia spp. by molecular testing; however, all lions were positive for Babesia spp. by reverse line blot hybridization assay. Sequencing of amplicons from four lions revealed four groups of Babesia spp. including several genetic variants of Babesia felis , Babesia lengau, and Babesia canis and a group of novel Babesia sequences which were only 96% similar to other Babesia spp. Six lions were infested with four species of ticks (Rhipicentor nuttalli, Rhipicephalus simus, Rhipicephalus sulcatus, and Rhipicephalus appendiculatus). These data provide the first health assessment of this population and can be used to identify management and conservation strategies to decrease the impact of pathogens on this population. This is particularly important as there is an initiative to incorporate this population into a larger metapopulation of lions from adjacent South Africa and Zimbabwe.


title: LocaPep: localization of epitopes on protein surfaces using peptides from phage display libraries.

text: The use of peptides from a phage display library selected by binding to a given antibody is a widespread technique to probe epitopes of antigenic proteins. However, the identification of interaction sites mimicked by these peptides on the antigen surface is a difficult task. LocaPep is a computer program developed to localize epitopes using a new clusters algorithm that focuses on protein surface properties. The program is constructed with the aim of providing a flexible computational tool for predicting the location of epitopes on protein structures. As a first set of testing results, the localization of epitope regions in eight different antigenic proteins for which experimental data on their antibody interactions exist is correctly identified by LocaPep. These results represent a disparate sample of biologically different systems. The program is freely available at http://atenea.montes.upm.es.


Swine flu.


title: [Chinese experts' consensus on diagnosis and treatment of severe and critical coronavirus disease 2019 (revised edition)].

text: The outbreak of coronavirus disease 2019 (COVID-19) is serious and there is no effective treatment to date. In order to reduce the mortality of severe and critical COVID-19, experts from the first-line in related fields in China were organized to analyze, discuss and summarize the diagnosis and treatment of severe and critical COVID-19 patients in Wuhan and other severe epidemic areas, and formulate the expert consensus. The first edition was released on February 22, 2020, and the revised one on March 4, 2020.


title: New York City COVID-19 resident physician exposure during exponential phase of pandemic.

text: BackgroundFrom March 2-April 12, 2020, New York City (NYC) experienced exponential growth of the COVID-19 pandemic due to novel coronavirus (SARS-CoV-2). Little is known regarding how physicians have been affected. We aimed to characterize COVID-19 impact on NYC resident physicians.MethodsIRB-exempt and expedited cross-sectional analysis through survey to NYC residency program directors (PDs) April 3-12, 2020, encompassing events from March 2-April 12, 2020.ResultsFrom an estimated 340 residency programs around NYC, recruitment yielded 91 responses, representing 24 specialties and 2,306 residents. 45.1% of programs reported at least one resident with confirmed COVID-19: 101 resident physicians were confirmed COVID-19-positive, with an additional 163 residents presumed positive for COVID-19 based on symptoms but awaiting or unable to obtain testing. Two COVID-19-positive residents were hospitalized, with one in intensive care. Among specialties with >100 residents represented, negative binomial regression indicated that infection risk differed by specialty (p=0.039). 80% of programs reported quarantining a resident. 90/91 programs reported reuse or extended mask use, and 43 programs reported that personal protective equipment (PPE) was suboptimal. 65 programs (74.7%) have redeployed residents elsewhere to support COVID-19 efforts.ConclusionMany resident physicians around NYC have been affected by COVID-19 through direct infection, quarantine, or redeployment. Lack of access to testing and concern regarding suboptimal PPE are common among residency programs. Infection risk may differ by specialty.FundingAHA, MPB, RWSC, CGM, LRDG, JDH: NEI Core Grant P30EY019007, RPB Unrestricted Grant. ACP and JS: Parker Family Chair. SXX: University of Pennsylvania.


title: Gastrostomy tube placement via a laparotomic procedure in growing conventional piglets to perform multi-dose preclinical paediatric drug studies.

text: The use of juvenile conventional pigs as a preclinical animal model to perform pharmacokinetic (PK), pharmacodynamic (PD) and safety studies for the paediatric population is increasing. Repetitive oral administration of drugs to juvenile pigs is however challenging. A representative method which can be used from birth till adulthood is necessary. The current study presents the placement and use of a gastrostomy button in pigs with a weight ranging from 2.4 to 161 kg. The surgical placement was performed via a laparotomic procedure on, each time, 12 pigs (six male, six female) of 1 week, 4 weeks, 8 weeks and 6-7 months old. For every age category, eight pigs were part of a PK study with a non-steroidal anti-inflammatory drug (NSAID) and four pigs served as a control group. No severe complications were observed during surgery. The button remained functional for 10 days in 40 out of 48 pigs. No significant differences in body temperature or white blood cell count were observed during the trial. Three control pigs showed signs of inflammation indicating a NSAID might be warranted. Autopsy revealed minimal signs of major inflammation in the abdominal cavity or the stomach. A limited number of pigs showed mucosal inflammation, ulcers or abscesses in the stomach or around the fistula. These results indicate that the laparotomic placement of a gastrostomy button might be considered safe and easy in growing pigs to perform repetitive oral dosing preclinical studies. However, the method is not advised in pigs weighing more than 100 kg.


Impact of COVID-19 and Future Emerging Viruses on Hematopoietic Cell Transplantation and Other Cellular Therapies.


title: Facile continuous production of soy peptide nanogels via nanoscale flash desolvation for drug entrapment.

text: A facile continuous production of soy peptide nanogels was demonstrated using a multi-inlet vortex micromixer for the entrapment of active ingredients. The full flow regime in the micromixer was systematically studied to understand the flow impact on nanogel size, drug encapsulation efficiency and drug loading efficiency. Ibuprofen was chosen as a model drug to demonstrate encapsulation capability. The study showed that the nanogel size, drug encapsulation efficiency and drug loading efficiency did not alter significantly as long as the flow rates were in transition and turbulent regimes. The driving force behind the folding of peptides within the microenvironment is kinetic mixing with high flow rates, which dominates in comparison to molecular diffusion, nucleation, and growth. Moreover, the hydrophilic-lipophilic balance of the soy peptides determined the drug encapsulation efficiency and the drug loading efficiency, which did not vary much under different manufacturing parameters. Both characteristics are beneficial to mass production of drug-entrapped peptide. In a 50% water-ethanol mixture, the encapsulation efficiency achieved 70% and the drug loading efficiency was up to 25% in transition and turbulent flow regimes. This work opens the avenues to continuous production of drug-entrapped soy peptide nanogels using a multi-inlet vortex micromixer.


title: HINCUTs in cancer: hypoxia-induced noncoding ultraconserved transcripts.

text: Recent data have linked hypoxia, a classic feature of the tumor microenvironment, to the function of specific microRNAs (miRNAs); however, whether hypoxia affects other types of noncoding transcripts is currently unknown. Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs). Interestingly, several hypoxia-upregulated T-UCRs, henceforth named 'hypoxia-induced noncoding ultraconserved transcripts' (HINCUTs), are also overexpressed in clinical samples from colon cancer patients. We show that these T-UCRs are predominantly nuclear and that the hypoxia-inducible factor (HIF) is at least partly responsible for the induction of several members of this group. One specific HINCUT, uc.475 (or HINCUT-1) is part of a retained intron of the host protein-coding gene, O-linked N-acetylglucosamine transferase, which is overexpressed in epithelial cancer types. Consistent with the hypothesis that T-UCRs have important function in tumor formation, HINCUT-1 supports cell proliferation specifically under hypoxic conditions and may be critical for optimal O-GlcNAcylation of proteins when oxygen tension is limiting. Our data gives a first glimpse of a novel functional hypoxic network comprising protein-coding transcripts and noncoding RNAs (ncRNAs) from the T-UCRs category.


title: Near-infrared Spectroscopy Monitoring During Cardiac Arrest: A Systematic Review and Meta-analysis.

text: BACKGROUND Tissue oximetry using near-infrared spectroscopy (NIRS) is a noninvasive monitor of cerebral oxygenation. This new technology has been used during cardiac arrest (CA) because of its ability to give measures in low-blood-flow situations. The aim of this study was to assess the evidence regarding the association between the types of NIRS measurements (mean, initial, and highest values) and resuscitation outcomes (return of spontaneous circulation [ROSC], survival to discharge, and good neurologic outcome) in patients undergoing cardiopulmonary resuscitation. METHODS This review was registered (Prospero CRD42015017380) and is reported as per the PRISMA guidelines. Medline, Embase, and CENTRAL were searched. All studies, except case reports and case series of fewer than five patients, reporting on adults that had NIRS monitoring during CA were eligible for inclusion. Two reviewers assessed the quality of the included articles and extracted the data. The outcome effect was standardized using standardized mean difference (SMD). RESULTS Twenty nonrandomized observational studies (15 articles and five conference abstracts) were included in this review, for a total of 2,436 patients. We found a stronger association between ROSC and mean NIRS values (SMD = 1.33; 95% confidence interval [CI] = 0.92 to 1.74) than between ROSC and initial NIRS measurements (SMD = 0.51; 95% CI = 0.23 to 0.78). There was too much heterogeneity among the highest NIRS measurements group to perform meta-analysis. Only two of the 75 patients who experienced ROSC had a mean NIRS saturation under 30%. Patients who survived to discharge and who had good neurologic outcome displayed superior combined initial and mean NIRS values than their counterparts (SMD = 1.63; 95% CI = 1.34 to 1.92; and SMD = 2.12; 95% CI = 1.14 to 3.10). CONCLUSIONS Patients with good resuscitation outcomes have significantly higher NIRS saturations during resuscitation than their counterparts. The types of NIRS measurements during resuscitation influenced the association between ROSC and NIRS saturation. Prolonged failure to obtain a NIRS saturation higher than 30% may be included in a multimodal approach to the decision of terminating resuscitation efforts (Class IIb, Level of Evidence C-Limited Data).


title: Towards effective emerging infectious disease surveillance.

text: In this plenary talk given at the annual meeting of the Association for Politics and the Life Sciences at Texas Tech University last October, Professor Sophal Ear, then of the U.S. Naval Postgraduate School in Monterey, discussed his research on the political economy of emerging infectious disease (EID) surveillance programs. His talk reviews lessons learned for U.S. military medical research laboratories collaborating with developing countries and is comprised of three case studies: Cambodia (U.S. Naval Area Medical Research Unit 2 or NAMRU-2), Indonesia (also NAMRU-2 in the context of H5N1 or Highly Pathogenic Avian Influenza), (1) and Mexico (that country's handling of A/H1N1 or Swine Flu in 2009). (2) Professor Ear's research provides policymakers with tools for improving the effectiveness of new or existing EID surveillance programs. His work also offers host countries the opportunity to incorporate ideas, provide opinions, and debate the management of political and economic constraints facing their programs. In this analysis, constraints are found for each case study and general recommendations are given for improving global emerging infectious disease surveillance across political, economic, and cultural dimensions.


Cobalt and chromium measurement in patients with metal hip prostheses.


title: Association of gynecological endoscopy surgeons of Nigeria (AGES) advisory on laparoscopic and hysteroscopic procedures during the COVID-19 Pandemic.

text: Coronavirus 2, or SARS-CoV-2 disease (COVID-19) is a global public health concern. Although there is a paucity of evidence to advise on the best practice, we recommend postponement of elective gynecological endoscopic surgeries until the pandemic is contained. Emergency surgeries should preferably be done through open surgeries than laparoscopy or hysteroscopy approach. However, if or when laparoscopy or hysteroscopy is considered, health personnel in theatre must wear appropriate personal protective equipment (PPE) and all standard precautions should be observed to prevent COVID-19 infection. When COVID-19 is highly suspected or confirmed, the patient should be referred to centers equipped in taking care of such cases.


Response to Elmaraghi et al. re: "A Guide to Facial Trauma Triage and Precautions in the COVID-19 Pandemic".


title: Isolation and Molecular Characterization of Novel Infectious Bronchitis Virus Variants from Vaccinated Broiler Flocks in Egypt.

text: The present study aimed to determine the molecular characteristics of circulating infectious bronchitis virus (IBV) strains in vaccinated broiler flocks in the Giza and Fayoum governorates. Thirty-four isolates were collected, and egg propagation revealed their ability to induce typical IBV lesions after three to five successive passages. Three selected isolates were identified as IBV using a real-time reverse transcriptase-PCR assay targeted the nucleocapsid (N) gene and further characterized by partial spike (S) gene sequence analysis. Phylogenetic analysis revealed their clustering into two variant groups. Group I consisted of one variant (VSVRI_F3), which had 99.1% nucleotide sequence identity to the Q1 reference strain. Group II consisted of variants VSVRI_G4 and VSVRI_G9, which showed 92.8%-94.3% nucleotide identity with the Egyptian variants Eg/12120S/2012, Eg/12197B/2012, and Eg/1265B/2012. Regarding the deduced amino acid sequence, the three variants had 77.1%-85.2% similarity with the vaccine strains currently used in Egypt. These findings highlight the importance of monitoring the prevalence of IBV variants in vaccinated broiler flocks as well as adopting an appropriate vaccination strategy.


24th Collegium Ramazzini statement. Prevention of work-related infection in the COVID-19 pandemic.


COVID-19 Lung Injury Is Different From High Altitude Pulmonary Edema (Re: High Alt Med Biol [Epub ahead of print]; DOI: 10.1089/ham.2020.0055).


title: Response and long-term control of bone metastases after peptide receptor radionuclide therapy with (177)Lu-octreotate.

text: UNLABELLED Peptide receptor radionuclide therapy (PRRT) is an efficient treatment for gastroenteropancreatic neuroendocrine tumors (GEP NETs), with outstanding overall response rates and survival. However, little is known about the particular efficacy regarding bone metastasis (BM). METHODS We retrospectively analyzed a consecutive subgroup of 42 patients with BM of GEP NETs treated with PRRT ((177)Lu-octreotate, 4 intended cycles at 3 monthly intervals [10-14 wk]; mean activity per cycle, 8.1 GBq). Availability of restaging and outcome data was required for patient inclusion. Baseline characteristics, including age, tumor origin, performance score, Ki-67 index, tumor load, tumor uptake, plasma chromogranin A, and neuron-specific enolase, were analyzed regarding impact on tumor regression (modified M.D. Anderson criteria) and time to progression. Survival analyses were performed using Kaplan-Meier curves, log-rank test at a significance level of P less than 0.05, and Cox proportional hazards model for uni- and multivariate analyses. RESULTS Median follow-up was 32 mo. The observed response of BMs consisted of complete remission in 2 (4.8%), partial remission in 14 (33.3%), minor response in 5 (11.9%), stable disease in 16 (38.1%), and progressive disease in 5 (11.9%) patients. Median progression-free survival and overall survival (OS) were 35 mo (26-44, 95% confidence interval) and 51 mo (37-65, 95% confidence interval), respectively. Patients with responding BMs (complete remission, partial remission, or minor response) exhibited a trend toward better OS (median OS not reached after 53 mo) when compared to nonresponding patients (39 mo, P = 0.076). Only Ki-67 index (>10%) and chromogranin A level (>600 ng/mL) contributed to regression analysis. CONCLUSION BM of GEP NETs is effectively controlled by PRRT, with long progression-free survival and OS. Poor patient condition and multifocality of BMs do not clearly affect treatment efficacy, possibly encouraging the use of PRRT in advanced bone metastatic disease. Larger studies are needed to assess predictors of treatment outcome in these patients.


Virus-driven conditional expression of an interferon antagonist as a tool to circumvent host restriction.


title: Commercial SARS-CoV-2 Molecular Assays: Superior Analytical Sensitivity of cobas SARS-CoV-2 Relative to NxTAG Cov Extended Panel and ID NOW COVID-19 Test.

text: Context - We implemented multiple nucleic acid amplification test platforms because of the limited availability of test kits for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the early stages of the pandemic. Interpretation of results generated by different platforms and prioritization for testing algorithms required cross-comparison. Objective - To compare the analytical sensitivity of three commercial SARS-CoV-2 molecular assays, selected samples were studied in parallel with Cobas SARS-CoV-2 test, NxTAG CoV Extended Panel, and ID NOW COVID-19 assays. Design - A total of 8043 SARS-CoV-2 tests performed from March 22 to April 19, 2020, were included in this study. For all 1794 positive specimens detected by the cobas SARS-CoV-2 assay, the cycle threshold (Ct) values were manually tracked and plotted, to demonstrate the distribution of sample viral levels. Additionally, 50 and 63 low positive specimens (Ct values >32) as well as 50 and 61 consecutive positive specimens by the cobas assay were tested with NxTAG and ID NOW, respectively, to estimate their relative sensitivities. Results - Ct values of cobas SARS-CoV-2 positive samples were evenly distributed over ranges of 13.32-39.50 (mean: 25.06) and 13.60-42.49 (mean: 26.45) for ORF1 and E gene targets, respectively. NxTAG only reliably detected specimens with E gene Ct values lower than 33, and is estimated to detect 89.4% of positive specimens detected by cobas assay. ID NOW had performance variation independent of Ct value and is estimated to detect 83.5% of cobas positives. Conclusions - Clinical specimens exhibit a wide range of viral burden, with a significant portion at low levels. Analytical sensitivity of testing platforms is critical for reliable detection of SARS-CoV-2 and uniform care to patients.


title: Revisional Gastric Bypass After Failed Adjustable Gastric Banding-One-Stage or Two-Stage Procedure?

text: BACKGROUND Revisional laparoscopic Roux-en-Y gastric bypass (R-LRYGB) is the preferred procedure after failed adjustable gastric banding. Little is known about whether a one-stage procedure (one surgery for band removal and R-LRYGB) or a two-stage procedure (first band removal and later R-LRYGB) is superior. Aim of this study is to compare early- and long-term results of both methods at our institution. METHODS Retrospective analysis of 165 (m 26/f 139) consecutive patients (98 one-stage, 67 two-stage) with R-LRYGB. Mean follow-up time was 50.1 ± 38.8 months. Indications for one-stage vs. two-stage procedures, operating time, peri- and postoperative complications, morbidity, mortality, and length of stay (LOS) were analyzed. Data are reported as total numbers (%) and mean ± standard deviation. RESULTS Mean age at R-LRYGB was 43.9 ± 10.7 vs. 44.3 ± 10.7 years with a BMI of 37.1 ± 6.8 vs. 39.8 ± 7.1 (one-stage vs. two-stage). In the one-stage group, the main indication for revisional surgery was weight regain (57.1%), followed by dilatation of the esophagus or pouch (37.7%) and gastroesophageal reflux disease (GERD) (36.7%), whereas in the two-stage group, it was band erosion (52.2%) and dilatation of the esophagus or pouch (17.9%) and GERD (11.9%). There was no significant difference in operative time (208.5 ± 61.2 vs. 206.3 ± 73.5 min), LOS (8.6 ± 3.4 vs. 9.3 ± 5.7 days) or mortality (0% overall). Major complications (Clavien-Dindo ≥ IIIa) occurred similarly often in both groups: 15.3% vs. 16.9% (one-stage vs. two-stage). CONCLUSION Both approaches achieve good results. However, the one-stage R-LRYGB is the preferable procedure because it reduces costs and LOS by doing without an additional surgical procedure.


title: Branched-Chain Amino Acids and Seizures: A Systematic Review of the Literature.

text: BACKGROUND Up to 40% of patients with epilepsy experience seizures despite treatment with antiepileptic drugs; however, branched-chain amino acid (BCAA) supplementation has shown promise in treating refractory epilepsy. OBJECTIVES The purpose of this systematic review was to evaluate all published studies that investigated the effects of BCAAs on seizures, emphasizing therapeutic efficacy and possible underlying mechanisms. METHODS On 31 January, 2017, the following databases were searched for relevant studies: MEDLINE (OvidSP), EMBASE (OvidSP), Scopus (Elsevier), the Cochrane Library, and the unindexed material in PubMed (National Library of Medicine/National Institutes of Health). The searches were repeated in all databases on 18 February, 2019. We only included full-length preclinical and clinical studies that were published in the English language that examined the effects of BCAA administration on seizures. RESULTS Eleven of 2045 studies met our inclusion criteria: ten studies were conducted in animal models and one study in human subjects. Seven seizure models were investigated: the strychnine (one study), pentylenetetrazole (two studies), flurothyl (one study), picrotoxin (two studies), genetic absence epilepsy in rats (one study), kainic acid (two studies), and methionine sulfoximine (one study) paradigms. Three studies investigated the effect of a BCAA mixture whereas the other studies explored the effects of individual BCAAs on seizures. In most animal models and in humans, BCAAs had potent anti-seizure effects. However, in the methionine sulfoximine model, long-term BCAA supplementation worsened seizure propagation and caused neuron loss, and in the genetic absence epilepsy in rats model, BCAAs exhibited pro-seizure effects. CONCLUSIONS The contradictory effects of BCAAs on seizure activity likely reflect differences in the complex mechanisms that underlie seizure disorders. Some of these mechanisms are likely mediated by BCAA's effects on glucose, glutamate, glutamine, and ammonia metabolism, activation of the mechanistic target of rapamycin signaling pathway, and their effects on aromatic amino acid transport and neurotransmitter synthesis. We propose that a better understanding of mechanisms by which BCAAs affect seizures and neuronal viability is needed to advance the field of BCAA supplementation in epilepsy.


title: Endovascular Treatment of Acute Ischemic Stroke Due to Tandem Occlusions: Large Multicenter Series and Systematic Review.

text: BACKGROUND Ischemic strokes due to tandem occlusions (TOs) have poor outcomes if they have been treated with only medical interventions. Recent trials demonstrated the effectiveness of endovascular treatment of acute ischemic stroke due to intracranial occlusions; however, most studies excluded patients with TOs. METHODS Retrospective review of prospectively collected thrombectomy databases from 3 stroke centers between 2011 and 2015. Consecutive patients with tandem extracranial steno-occlusive carotid disease and intracranial occlusions who underwent emergent thrombectomy were selected. Angiographic and clinical outcomes were analyzed; baseline and procedural variables were included in univariate and multivariate analyses to define the independent predictors of good outcomes (90-day modified Rankin Scale ≤2). RESULTS A total of 100 patients met the study inclusion criteria. The mean age was 64.4 ± 12.5, baseline National Institutes of Health Stroke Scale (NIHSS) 17.6 ± 5.0, time from last known well to puncture 7.3 ± 5.8 h, and Alberta Stroke Program Early CT Score (ASPECTS) 7.5 ± 1.6. Forty percent received intravenous tissue plasminogen activator. Intracranial occlusion sites included: internal carotid artery thrombus, 31%; middle cerebral artery (MCA)-M1, 53%; MCA-M2, 10%; and anterior cerebral artery, 6%. Good outcome was achieved in 42% and successful reperfusion modified thrombolysis in cerebral infarction (mTICI ≥2B) in 88% of the cases, including complete (mTICI 3) reperfusion in 40%. Severe parenchymal hematoma (PH)-2 occurred in 6% of the patients and 90-day mortality was 20%. In the multivariate analysis, younger age (OR 0.93; 95% CI 0.88-0.98; p = 0.004), lower baseline NIHSS (OR 0.84; 95% CI 0.74-0.94; p = 0.003), higher ASPECTS (OR 1.50; 95% CI 1.02-2.19; p = 0.038), and mTICI 3 reperfusion (OR 3.56; 95% CI 1.18-10.76; p = 0.024) were independent predictors of good outcome at 90 days. CONCLUSIONS Acute endovascular treatment of tandem anterior circulation occlusions yields good outcomes and has similar outcome predictors to isolated intracranial occlusions. Given their comparable clinical behavior, these patients should be included in future trials.


title: Pig empire under infectious threat: risk of African swine fever introduction into the People's Republic of China.

text: Pig production and pork consumption are very important to the People's Republic of China for both economic and cultural reasons. The incursion and spread of a disease such as African swine fever (ASF), which emerged in Eastern Europe in 2007, could have devastating socioeconomic consequences for both the Chinese and the global pig industry. The Chinese government consequently attributes a very high priority to ASF and is actively seeking to improve its preparedness. This paper discusses different drivers and pathways of potential emergence of ASF in China in light of the country's specificities, including international movements of people, pigs and pig products, swill feeding practices and wild boar populations. It suggests that effective ASF risk management in China will require a comprehensive and integrated approach linking science and policy and will need to involve all relevant stakeholders to develop realistic policies.


Decreased in-hospital mortality in patients with COVID-19 pneumonia.