title: Parameters Influencing Brain Oxygen Measurement by Regional Oxygen Saturation in Postcardiac Arrest Patients with Targeted Temperature Management.

text: In several studies, regional cerebral oxygen saturation (rSO2) has been measured in patients with postcardiac arrest syndrome (PCAS) to analyze the brain's metabolic status. However, the significance of rSO2 in PCAS patients remains unclear. In the present study, we investigated the relationship between rSO2 and physiological parameters. Comatose survivors of out-of-hospital PCAS with targeted temperature management (TTM) at 34°C for 24 hours were included. All patients were monitored for their rSO2 and additional parameters (arterial oxygen saturation [SaO2], hemoglobin [Hb], mean arterial pressure [MAP], arterial carbon dioxide pressure [PaCO2], and body temperature]) measured at the start of monitoring and 24 and 48 hours after return of spontaneous circulation (ROSC). Patients were divided into favorable and unfavorable groups, and the correlation between rSO2 and these physiological parameters was evaluated by multiple regression analysis. Forty-nine patients were included in the study, with 15 in the favorable group and 34 in the unfavorable group. There was no significant difference in the rSO2 value between the two groups at any time point. The multiple regression analysis of the favorable group revealed a moderate correlation between rSO2 and SaO2, Hb, and PaCO2 only at 24 hours (coefficients: 0.482, 0.422, and 0.531, respectively), whereas that of the unfavorable group revealed moderate correlations between rSO2 and Hb values at all time points, PaCO2 at 24 hours and MAP at 24 and 48 hours. rSO2 was moderately correlated to MAP in unfavorable patients. To optimize brain oxygen metabolic balance for PCAS patients with TTM measuring rSO2, we suggest total evaluation of each parameters of SaO2, Hb, MAP, and PaCO2.


title: Intrapapillary capillary loop classification in magnification endoscopy: open dataset and baseline methodology.

text: PURPOSE Early squamous cell neoplasia (ESCN) in the oesophagus is a highly treatable condition. Lesions confined to the mucosal layer can be curatively treated endoscopically. We build a computer-assisted detection system that can classify still images or video frames as normal or abnormal with high diagnostic accuracy. METHODS We present a new benchmark dataset containing 68K binary labelled frames extracted from 114 patient videos whose imaged areas have been resected and correlated to histopathology. Our novel convolutional network architecture solves the binary classification task and explains what features of the input domain drive the decision-making process of the network. RESULTS The proposed method achieved an average accuracy of 91.7% compared to the 94.7% achieved by a group of 12 senior clinicians. Our novel network architecture produces deeply supervised activation heatmaps that suggest the network is looking at intrapapillary capillary loop patterns when predicting abnormality. CONCLUSION We believe that this dataset and baseline method may serve as a reference for future benchmarks on both video frame classification and explainability in the context of ESCN detection. A future work path of high clinical relevance is the extension of the classification to ESCN types.


title: Is there any supportive evidence for low dose radiotherapy for COVID-19 pneumonia?

text: Since early April 2020, there has been intense debate over proposed clinical use of ionizing radiation to treat life-threatening pneumonia in Coronavirus Disease 2019 (COVID-19) patients. At least twelve relevant papers appeared by 20 May 2020. The radiation dose proposed for clinical trials are a single dose (0.1-1 Gy) or two doses (a few mGy followed by 0.1-0.25 Gy involving a putative adaptive response, or 1-1.5 Gy in two fractions 2-3 days apart). The scientific rationale for such proposed so-called low dose radiotherapy (LDRT) is twofold (note that only doses below 0.1 Gy are considered as low doses in the field of radiation protection, but here we follow the term as conventionally used in the field of radiation oncology). Firstly, the potentially positive observations in human case series and biological studies in rodent models on viral or bacterial pneumonia that were conducted in the pre-antibiotic era. Secondly, the potential anti-inflammatory properties of LDRT, which have been seen when LDRT is applied locally to subacute degenerative joint diseases, mainly in Germany. However, the human and animal studies cited as supportive evidence have significant limitations, and whether LDRT produces anti-inflammatory effects in the inflamed lung or exacerbates ongoing COVID-19 damage remains unclear. Therefore, we conclude that the available scientific evidence does not justify clinical trials of LDRT for COVID-19 pneumonia, with unknown benefit and known mortality risks from radiogenic cancer and circulatory disease. Despite the significant uncertainties in these proposals, some clinical trials are ongoing and planned. This paper gives an overview of current situations surrounding LDRT for COVID-19 pneumonia.


title: Influence of different menstrual phases on the Bispectral Index during dexmedetomidine sedation.

text: To investigate the influence of different menstrual phases on the Bispectral Index (BIS) during dexmedetomidine (Dex) sedation, 40 patients with regular menstrual cycle, American Society of Anesthesiologists I-II, aged 18-40 years, undergoing selective gynecologic laparoscopic surgery, were enrolled. According to different menstrual phases and the serum progesterone concentration, they were divided into two groups: the follicular phase group (Group F) and the luteal phase group (Group L), and each group had 20 patients. Before anesthesia induction, patients were infused with an initial loading dose of Dex (1 μg/kg) for 10 minutes and then 0.5 μg/kg/h for 20 minutes. BIS and the changes in hemodynamic and respiratory parameters were recorded within those 30 minutes. Time to lower BIS to 70 and 60 in Group L was shorter than that in Group F (9.4 ± 1.3 minutes vs. 11.3 ± 2.1 minutes, p = 0.005; 11.3 ± 2.4 minutes vs. 14.0 ± 3.6 minutes, p = 0.021). The number of patients whose BIS reached 50 in Group L was greater than that in Group F (15 vs. 8, p < 0.05). The lowest BIS value in the Group L was lower than that in Group F (46.8 ± 6.3 vs. 55.3 ± 5.5, p = 0.006), and the heart rate of patients in both groups showed a decrease (p < 0.05). The sedative effect of Dex was more significant in patients during the luteal phase than during the follicular phase.


title: Complaints of olfactory disorders: epidemiology, assessment and clinical implications.

text: PURPOSE OF REVIEW Recent studies illuminate the difficulties that patients with olfactory disorder face in daily life, which underlines the need to understand its prevalence, and to diagnose and treat these patients. The purpose of the present review is to characterize olfactory disorders and describe associated complaints, present recent insights into epidemiology, suggest procedures to assess these disorders, and discuss clinical implications. RECENT FINDINGS A compilation of previous and new studies of olfactory disorders suggests associated complaints of poor quality of life, depression, and various specific consequences. Epidemiological studies show that loss in odor sensitivity is common in both general and clinical populations, whereas dysosmia is less common in general populations but frequent in clinical populations. The most common etiologies are post-upper respiratory infection, nasal/sinus disease and head trauma. SUMMARY Procedures to diagnose olfactory disorders and to identify etiologies are available. Depending on etiology, certain types of treatment are often successful, such as endoscopic sinus surgery and corticosteroid administration in nasal/sinus disease. In post-upper respiratory infection and head trauma, spontaneous recovery is fairly high. In any case, it is advisable to counsel the patient with regards to strategies to cope with olfactory disorders.


title: Age and Multimorbidity Predict Death Among COVID-19 Patients: Results of the SARS-RAS Study of the Italian Society of Hypertension.

text: Several factors have been proposed to explain the high death rate of the coronavirus disease 2019 (COVID-19) outbreak, including hypertension and hypertension-related treatment with Renin Angiotensin System inhibitors. Also, age and multimorbidity might be confounders. No sufficient data are available to demonstrate their independent role. We designed a cross-sectional, observational, multicenter, nationwide survey in Italy to verify whether renin-angiotensin system inhibitors are related to COVID-19 severe outcomes. We analyzed information from Italian patients diagnosed with COVID-19, admitted in 26 hospitals. One thousand five hundred ninety-one charts (male, 64.1%; 66±0.4 years) were recorded. At least 1 preexisting condition was observed in 73.4% of patients, with hypertension being the most represented (54.9%). One hundred eighty-eight deaths were recorded (11.8%; mean age, 79.6±0.9 years). In nonsurvivors, older age, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease, coronary artery diseases, and heart failure were more represented than in survivors. The Charlson Comorbidity Index was significantly higher in nonsurvivors compared with survivors (4.3±0.15 versus 2.6±0.05; P<0.001). ACE (angiotensin-converting enzyme) inhibitors, diuretics, and β-blockers were more frequently used in nonsurvivors than in survivors. After correction by multivariate analysis, only age (P=0.0001), diabetes mellitus (P=0.004), chronic obstructive pulmonary disease (P=0.011), and chronic kidney disease (P=0.004) but not hypertension predicted mortality. Charlson Comorbidity Index, which cumulates age and comorbidities, predicts mortality with an exponential increase in the odds ratio by each point of score. In the COVID-19 outbreak, mortality is predicted by age and the presence of comorbidities. Our data do not support a significant interference of hypertension and antihypertensive therapy on COVID-19 lethality. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT04331574.


title: Barbed sutures in breast reconstruction.

text: Postoperative closure techniques in breast reconstruction have remained largely unchanged over the past 75 years, despite recent use of adhesives and subcuticular staples and the advent of self-anchoring barbed sutures. In this article, the author discusses the applications for barbed sutures in breast reconstruction and describes specific techniques. Innovations in barbed suture material are also described, and the author's personal experiences are presented in comparison with traditional suturing techniques.


title: Stroke prevention following modified endoscopic ablation and appendectomy for atrial fibrillation.

text: We reported the results of stroke prevention following modified endoscopic procedure for atrial fibrillation. 82 patients underwent modified endoscopic procedure for atrial fibrillation (AF), in whom 47 had paroxysmal, 28 had persistent, and 7 had long-standing atrial fibrillation. CHA2DS2VASC median score was 3 (range from 0 to 8). The procedure was performed on the beating heart, through 3 ports on the left chest wall. Pulmonary vein isolation and ablation of the left atrium were achieved by bipolar radiofrequency ablation. Left atrial appendage (LAA) was excluded by stapler. Brain CT, cardiac CT and 24-h Holter monitoring were performed following the procedure. The procedure was successfully completed for all patients. The mean duration was 122 ± 40.1 min. LAA was excluded after appendectomy and checked by intraoperative transesophageal echocardiography. The mean follow-up duration was 24.3 ± 3.5 months. No patients showed signs and symptoms of transient ischemic attack or stroke. No new positive findings were demonstrated by recurring brain CT scan performed after the procedure. Cardiac CT confirmed the absence of LAA and thrombosis in the left atrium. 87.8 % (72/82) of all patients were in sinus rhythm. Our results demonstrate that the modified endoscopic procedure is a safe, effective, and appropriate treatment for AF, which restores sinus rhythm and may be associated with the prevention of AF-related stroke.


title: Laparoscopic and natural orifice transluminal restorative proctocolectomy: no abdominal incision for specimen extraction or ileostomy.

text: The aim of this study was to demonstrate the feasibility of laparoscopic restorative proctocolectomy (LRPC) without additional abdominal incisions. Two sisters with familial adenomatous polyposis were enrolled. The colon and rectum were mobilized entirely through the five abdominal trocars. The terminal ileum and distal rectum were transected with endoscopic staplers. The entire colorectal specimen was extracted transanally. A circular stapler anvil was introduced transanally. The J-pouch was created intracorporeally. The rectal stump was re-closed and a pouch-anal anastomosis was created using a circular stapler. We used a transanal tube for decompression of the pouch instead of a diverting ileostomy. The patients were discharged on the 10(th) and 12(th) days uneventfully. Both were doing well with their pouches after 18.5 and 12.1 months of follow-up. With the help of transanal specimen extraction and transanal tube decompression, additional abdominal incisions can be avoided following LRPC.


title: Preparation of a polylactic acid knitting mesh for pelvic floor repair and in vivo evaluation.

text: The health warning report by the Food and Drug Administration (FDA) in 2011 has drawn attention to the need for developing a suitable bio-scaffold for repairing female pelvic from disease. This work prepared a pure polylactic acid knitting mesh (PPA) and compared its structure and properties with a commercial mesh - Surgimesh® Prolapse (SP; Aspide Medical, France). Mechanical tests showed that the PPA mesh was stronger than SP with higher breaking strength and bursting strength. The in vivo property of PPA was evaluated with an animal model. Both PPA-tissue and SP-tissue were tested to have lower strength and initial elastic modulus; tissue layer played a vital role in the bio-mechanics, especially after 3 months of implantation. New tissues on the surface of PPA grew faster and thicker than that on SP at each observation period. The final shrinkage rate of PPA (2.13 ± 0.41%) was much lower than that of SP (30.35 ± 1.7%). Obvious adhesion phenomenon was observed on both PPA and SP meshes at each test point. Two meshes showed different adhesion level, that PPA was assessed of severe adhesion, even causing host tissue rupture. By histological evaluation, both PPA and SP groups showed obvious tissue inflammation reaction evidenced by rich lymphocytes. However the surrounding tissues on the PPA recovered better, with higher inflammation response scores and presence of significant vascularization and adipogenesis after six months of implantation.


title: Operative techniques in robotic thoracic surgery for inferior or posterior mediastinal pathology.

text: OBJECTIVE Thoracic surgeons are performing robotic resections for anterior mediastinal tumors; however, tumors located in the posterior and especially the inferior chest can be difficult to approach robotically. The objective of this study was to evaluate the efficacy of the robot for resection of these tumors. METHODS We performed a retrospective review of the evolution and outcomes of our surgical technique for inferior or posterior mediastinal pathology. RESULTS During a 30-month period, 153 patients underwent robotic surgery for pathology in the mediastinum, located in the inferior or posterior mediastinum in 75 of these patients. The most common indications for surgery were posterior mediastinal mass or lymph node in 41 patients, esophageal or bronchogenic cysts in 11 patients, esophageal leiomyoma in 7 patients, and diaphragmatic elevation in 7 patients. The median tumor size was 4.4 cm, and the median length of stay was 1 day. One patient was converted to thoracotomy, but no patients were converted for bleeding. Morbidity occurred in 9 patients (12%), major in 1 patient (a delayed esophageal leak after epiphrenic diverticulectomy). There was no mortality. Technical improvements included using robotic arm 3 posteriorly for retraction, side-docking, or coming over the back of the patient for tumors inferior to the inferior pulmonary vein and for diaphragmatic plication and using the lateral decubitus position for extraction of tumors larger than 3 cm via an access port over the tenth rib above the diaphragmatic fibers. CONCLUSIONS The robot affords safe access using a completely portal approach for resection of and surgical intervention for inferior and posterior chest pathology and for anterior tumors. Specific techniques can be used to improve the operation.


title: Activation of RNase L by Murine Coronavirus in Myeloid Cells Is Dependent on Basal Oas Gene Expression and Independent of Virus-Induced Interferon.

text: UNLABELLED The oligoadenylate synthetase (OAS)-RNase L pathway is a potent interferon (IFN)-induced antiviral activity. Upon sensing double-stranded RNA, OAS produces 2',5'-oligoadenylates (2-5A), which activate RNase L. Murine coronavirus (mouse hepatitis virus [MHV]) nonstructural protein 2 (ns2) is a 2',5'-phosphodiesterase (PDE) that cleaves 2-5A, thereby antagonizing RNase L activation. PDE activity is required for robust replication in myeloid cells, as a mutant of MHV (ns2(H126R)) encoding an inactive PDE fails to antagonize RNase L activation and replicates poorly in bone marrow-derived macrophages (BMM), while ns2(H126R) replicates to high titer in several types of nonmyeloid cells, as well as in IFN receptor-deficient (Ifnar1(-/-)) BMM. We reported previously that myeloid cells express significantly higher basal levels of OAS transcripts than nonmyeloid cells. Here, we investigated the contributions of Oas gene expression, basal IFN signaling, and virus-induced IFN to RNase L activation. Infection with ns2(H126R) activated RNase L in Ifih1(-/-) BMM to a similar extent as in wild-type (WT) BMM, despite the lack of IFN induction in the absence of MDA5 expression. However, ns2(H126R) failed to induce RNase L activation in BMM treated with IFNAR1-blocking antibody, as well as in Ifnar1(-/-) BMM, both expressing low basal levels of Oas genes. Thus, activation of RNase L does not require virus-induced IFN but rather correlates with adequate levels of basal Oas gene expression, maintained by basal IFN signaling. Finally, overexpression of RNase L is not sufficient to compensate for inadequate basal OAS levels. IMPORTANCE The oligoadenylate synthetase (OAS)-RNase L pathway is a potent antiviral activity. Activation of RNase L during murine coronavirus (mouse hepatitis virus [MHV]) infection of myeloid cells correlates with high basal Oas gene expression and is independent of virus-induced interferon secretion. Thus, our data suggest that cells with high basal Oas gene expression levels can activate RNase L and thereby inhibit virus replication early in infection upon exposure to viral double-stranded RNA (dsRNA) before the induction of interferon and prior to transcription of interferon-stimulated antiviral genes. These findings challenge the notion that activation of the OAS-RNase L pathway requires virus to induce type I IFN, which in turn upregulates OAS gene expression, as well as to provide dsRNA to activate OAS. Our data further suggest that myeloid cells may serve as sentinels to restrict viral replication, thus protecting other cell types from infection.


title: Abdominal and pelvic aneurysms and pseudoaneurysms: imaging review with clinical, radiologic, and treatment correlation.

text: Abnormally enlarged visceral arteries in the abdomen and pelvis must be recognized radiologically because early treatment can improve the quality of life and prevent life-threatening complications. These lesions, typically classified as aneurysms and pseudoaneurysms, are being detected more frequently with increased utilization of imaging and have various causes (eg, atherosclerosis, trauma, infection) and complications that may be identified radiologically. Ultrasonography, computed tomography, and magnetic resonance imaging often enable detection of visceral vascular lesions, but angiography is important for further diagnosis and treatment. Endovascular treatment is often the first-line therapy. Endovascular intervention or open surgical repair is necessary for all visceral pseudoaneurysms and is likely indicated for visceral aneurysms 2 cm or more in diameter. Endovascular exclusion of flow can be achieved with coils, stents, and injectable liquids. Techniques include embolization ("sandwich" or "sac-packing" technique), exclusion of flow with luminal stents, and stent-assisted coil embolization. Management often depends on the location and technical feasibility of endovascular repair. Embolization is usually preferred for aneurysms or pseudoaneurysms within solid organs, and the sandwich technique is often used when collateral flow is present. Covered stent placement may be preferred to preserve the parent artery when main visceral vessels are being treated. It is usually tailored to lesion location, and a cure can often be effected while preserving end-organ arterial flow. Posttreatment follow-up is usually based on treatment location, modality accuracy, and potential consequences of treatment failure. Follow-up imaging may help identify vessel recanalization, unintended thrombosis of an artery or end organ, or sequelae of nontarget embolization. Retreatment is usually warranted if the clinical risks for which embolization was performed are still present.


Interview with Thomas G. Ksiazek, D.V.M., PH.D. [interview by Vicki Glaser].


title: Intracranial Carotid Artery Calcification and Effect of Endovascular Stroke Treatment.

text: Background and Purpose- Previous studies suggest that intracranial carotid artery calcification (ICAC) volume might influence the clinical outcome of patients after endovascular treatment (EVT) for acute ischemic stroke. Importantly, ICAC can be subtyped into a medial or intimal pattern that may differentially influence the effect of EVT in patients with acute ischemic stroke. Methods- All 500 patients included in the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular treatment for acute ischemic stroke in the Netherlands) were evaluated. Volume (mm3) and location pattern (tunica intima or tunica media) of ICAC could be determined on baseline noncontrast computed tomography in 344 patients. Functional outcome at 90 days was assessed with the modified Rankin Scale. Next, we investigated the association of ICAC volume and pattern with functional outcome using adjusted ordinal logistic regression models. Effect modification by EVT was assessed with an interaction term between treatment allocation and ICAC aspect. Results- We found evidence for treatment effect modification by ICAC pattern ( P interaction=0.04). Patients with predominantly medial calcification had better functional outcome with EVT than without this treatment (adjusted common odds ratio, 2.32; 95% CI, 1.23-4.39), but we observed no effect of EVT in patients with predominantly intimal calcifications (adjusted common odds ratio, 0.82; 95% CI, 0.40-1.68). We did not find an association of ICAC volume with functional outcome (adjusted common odds ratio per unit increase ICAC volume 1.01 (95% CI, 0.89-1.13). Moreover, we found no evidence for effect modification by ICAC volume ( P interaction=0.61). Conclusions- The benefit of EVT in acute ischemic stroke patients with a medial calcification pattern is larger than the benefit in patients with an intimal calcification pattern. Clinical Trial Registration- URL: http://www.trialregister.nl . Unique identifier: NTR1804. URL: http://www.isrctn.com . Unique identifier: ISRCTN10888758.


title: Novel technique for parietal pleural dissection using a laparoscopic hernia balloon.

text: We describe a novel technique for the creation of a pleural tent and pleurectomy via the use of a laparoscopic hernia balloon. In this method a Spacemaker™ Structural Balloon Trocar (Covidien, USA) is tunnelled under the pleura at the site of thoracotomy or video assisted thoracoscopic surgery port and incrementally inflated under vision. This method is less traumatic than traditional methods, is more likely to provide an intact pleural tent, and allows the surgeon to operate in a near bloodless operative field.


title: Rice dwarf virus is engulfed into and released via vesicular compartments in cultured insect vector cells.

text: Vector insect cells infected with Rice dwarf virus had vesicular compartments containing viral particles located adjacent to the viroplasm when examined by transmission electron and confocal microscopy. Such compartments were often at the periphery of infected cells. Inhibitors of vesicular transport, brefeldin A and monensin, and an inhibitor of myosin motor activity, butanedione monoxime, abolished the formation of such vesicles and prevented the release of viral particles from infected cells without significant effects on virus multiplication. Furthermore, the actin-depolymerizing drug, cytochalasin D, inhibited the formation of actin filaments without significantly interfering with formation of vesicular compartments and the release of viruses from treated cells. These results together revealed intracellular vesicular compartments as a mode for viral transport in and release from insect vector cells infected with a plant-infecting reovirus.


title: Integrated flat detector CT and live fluoroscopic-guided external ventricular drain placement within the neuroangiography suite.

text: PURPOSE To demonstrate the feasibility of the application of integrated flat detector (FD) CT and fluoroscopic guidance (iGuide) for the placement of external ventricular drains (EVD) within the neuroangiography suite. METHODS A retrospective review of a prospectively maintained endovascular database identified six patients who underwent EVD placement using iGuide. Patient characteristics, operator, number of passes, accuracy of placement, immediate and delayed periprocedural complications and radiation exposure were assessed. RESULTS Five patients with subarachnoid hemorrhage and one patient with a large cerebellar infarct (average age 45.5 years (range 39-53), four women) underwent EVD placement within the angiography suite using iGuide. Four procedures were performed by a neuroradiologist and two by a neurosurgeon. All catheters were placed with a single pass and all terminated within the frontal horn of the ipsilateral lateral ventricle. No parenchymal or intraventricular hemorrhages were encountered after catheter placement. No patients experienced any immediate or delayed periprocedural complications. Radiation exposure related to the FD CTs required for placement was 593.7 mGy (range 539-673). CONCLUSIONS EVD placement under combined CT and fluoroscopic control within the neuroangiography suite is feasible. The technique predictably allows optimized EVD catheter placement with a single pass. We propose that this technique could improve the accuracy, and potentially reduce the complications, of EVD insertion in cerebrovascular patients.


title: Does advancement in stapling technology with triple-row and enhanced staple configurations confer additional safety? A matched comparison of 340 stapled ileocolic anastomoses.

text: BACKGROUND Over the past few decades, studies have focused on the safety of stapled anastomosis, especially when compared to that of the handsewn technique. However, studies on the improvement of stapling technology are limited. This study aimed to investigate whether linear triple-row staples (tri-staples) had any advantage over double-row staples. METHODS This is a retrospective review of all cases of functional end-to-end anastomoses with linear staplers performed at two centers between 2005 and 2015. Data were retrieved from a prospectively maintained database. Cases of anastomoses performed with double-row (DS) and triple-row (TS) staples were matched according to propensity scores. The rates of anastomotic leakage, bleeding, reoperation, and 30-day mortality were compared. RESULTS Functional end-to-end ileocolic anastomoses were performed in 563 consecutive patients during the study period. Double- and triple-row stapling devices were used in 389 and 174 anastomoses, respectively. With propensity score matching, 170 cases were chosen from each group. Both groups showed comparable baseline characteristics. The anastomotic leakage, anastomotic bleeding, and intra-abdominal collection rates were 2.4 and 0% (p = 0.123), 1.2 and 0% (p = 0.499), and 3.5 and 1.2% (p = 0.283) for DS and TS, respectively. The reoperation and 30-day mortality rates were 5.9 and 1.8% (p = 0.048) and 0.6 and 1.2% (p = 1.000) for DS and TS, respectively. The median lengths of stay were 5 and 6 days (p = 0.072) for DS and TS, respectively. CONCLUSION Anastomoses with triple-row staples tended to have a lower morbidity rate, but a significant advantage over double-row staples was not demonstrated in this study.


title: Working together on developing veterinary vaccines.

text: Suzanne Jarvis reports from the recent conference of the Veterinary Vaccinology Network, which brought together more than 100 delegates to consider some of the successes in vaccine development, as well as the challenges ahead.


title: Beneficial role of vitamin D3 in the prevention of certain respiratory diseases.

text: There is evidence of aberrations in the vitamin D-endocrine system in subjects with respiratory diseases. Vitamin D deficiency is highly prevalent in patients with respiratory diseases, and patients who receive vitamin D have significantly larger improvements in inspiratory muscle strength and maximal oxygen uptake. Studies have provided an opportunity to determine which proteins link vitamin D to respiratory pathology, including the major histocompatibility complex class II molecules, vitamin D receptor, vitamin D-binding protein, chromosome P450, Toll-like receptors, poly(ADP-ribose) polymerase-1, and the reduced form of nicotinamide adenine dinucleotide phosphate. Vitamin D also exerts its effect on respiratory diseases through cell signaling mechanisms, including matrix metalloproteinases, mitogen-activated protein kinase pathways, the Wnt/β-catenin signaling pathway, prostaglandins, reactive oxygen species, and nitric oxide synthase. In conclusion, vitamin D plays a significant role in respiratory diseases. The best form of vitamin D for use in the treatment of respiratory diseases is calcitriol because it is the active metabolite of vitamin D3 and modulates inflammatory cytokine expression. Further investigation of calcitriol in respiratory diseases is needed.


title: FD-OCT and IVUS intravascular imaging modalities in peripheral vasculature.

text: INTRODUCTION Intra-Vascular Ultra-Sound (IVUS) and Frequency Domain-Optical Coherence Tomography (FD-OCT), in vivo, intra-vascular, imaging modalities, widely used in the field of coronary disease, have been recently implemented in peripheral endovascular procedures, for procedural assessment, plaque characterization and determination of predictors of treatment outcomes. Their unique characteristics have also been used in order to provide additional features and improve the performance of re-entry devices and atherotomes. Areas covered: Present review focuses on available literature regarding these two promising imaging technologies in the peripheral vasculature, highlighting the added value produced by their use in endovascular therapy, their limitations and their utilization in new endovascular devices. Authors also provide their future perspective and the possible benefits in understanding vascular behavior and lesion characterization in peripheral endovascular interventions. Expert commentary: By providing both quantitative but also qualitative data on vessel and lesion morphology, intravascular imaging modalities offer a valid solution for endovascular treatment evaluation and outcome presentation homogeneity.


title: Mining the human autoantibody repertoire: isolation of potent IL17A-neutralizing monoclonal antibodies from a patient with thymoma.

text: Anti-cytokine autoantibodies have been widely reported to be present in human plasma, both in healthy subjects and in patients with underlying autoimmune conditions, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) or thymic epithelial neoplasms. While often asymptomatic, they can cause or facilitate a wide range of diseases including opportunistic infections. The potential therapeutic value of specific neutralizing anti-cytokine autoantibodies has not been thoroughly investigated. Here we used mammalian cell display to isolate IL17A-specific antibodies from a thymoma patient with proven high-titer autoantibodies against the same. We identified 3 distinct clonotypes that efficiently neutralized IL17A in a cell-based in vitro assay. Their potencies were comparable to those of known neutralizing antibodies, including 2, AIN457 (secukinumab) and ixekizumab that are currently in clinical development for the treatment of various inflammatory disorders. These data clearly demonstrate that the human autoantibody repertoire can be mined for antibodies with high therapeutic potential for clinical development.


title: The burden, admission, and outcome of COVID-19 in Africa: protocol for a systematic review and meta-analysis.

text: Background: According to the World Health Organization (WHO), the outbreak of coronavirus disease in 2019 (COVID-19) has been declared as pandemic and public health emergency that infected more than 5 million people worldwide at the time of writing this protocol. Strong evidence for the burden, admission, and outcome of COVID-19 has not been published in Africa. Therefore, this protocol will be served as a guideline to conduct a systematic review and meta-analysis of the burden, admission, and outcome of COVID-19 in Africa. Methods: Published and unpublished studies on the burden, admission, and outcome of COVID-19 in Africa and written in any language will be included. Databases (PubMed / MEDLINE, Google Scholar, Google, EMBASE, Web of Science, Microsoft Academic, WHO COVID-19 database, Cochran Library, Africa Wide Knowledge, and Africa Index Medicus) from December 2019 to May 2020 will be searched. Two independent reviewers will select, screen, extract data, and assess the risk of bias. The proportion will be measured using a random-effects model. Subgroup analysis will be conducted to manage hetrogeinity. The presence of publication bias will be assessed using Egger's test and visual inspection of the funnel plots. This systematic and meta-analysis review protocol will be reported per the PRISMA-P guidelines. Conclusion: This systematic review and meta-analysis protocol will be expected to quantify the burden, admission, and outcome of COVID-19 in Africa. Systematic review registration: This protocol was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) in March 2020 and accepted with the registration number: CRD42020179321(https://www.crd.york.ac.uk/PROSPERO).


title: Use of a Supplemental Oxygen Protocol to Suppress Progression of Retinopathy of Prematurity.

text: Purpose To compare progression of retinopathy of prematurity (ROP) before and after institution of an oxygen therapy protocol to inhibit active proliferation and progression of ROP in premature infants. Methods A retrospective cohort study was performed of premature infants undergoing ROP screening before (cohort A) and after (cohort B) implementation of an oxygen therapy protocol to inhibit further progression for those with stage 2 ROP or worse. Statistical analysis with χ2, Fisher's exact test, or Wilcoxon rank sum test was performed; and logistic regression models were created to determine the odds ratio of cohort B developing ROP progression beyond stage 2, compared to cohort A, adjusting for other risk factors for ROP. Results In cohort A, without oxygen therapy protocol (2002-2007), 44% (54/122) of infants progressed beyond stage 2, compared to 23% (24/103) of infants after protocol implementation (cohort B, 2008-2012) (P = 0.001). No significant differences between cohort A and B were found for gestational age, birth weight, survival, sepsis, bronchopulmonary dysplasia, oxygen at discharge, or need for diuretics. Infants with stage 2 ROP in cohort B, with oxygen therapy protocol, had significantly decreased risk of ROP beyond stage 2 (odds ratio 0.37, 95% confidence interval 0.20-0.67; P = 0.0013), compared to cohort A, correcting for differences in birth weight and necrotizing enterocolitis. Conclusions Progression from stage 2 to stage 3 ROP in premature infants was significantly decreased after implementation of an oxygen therapy protocol, without a corresponding increase in pulmonary morbidity. This study suggests that appropriate oxygen therapy may play a role in inhibiting progression of stage 2 ROP, potentially decreasing the risk of lifelong visual loss in this vulnerable population.


title: Coil therapy for patients with severe emphysema and bilateral incomplete fissures - effectiveness and complications after 1-year follow-up: a single-center experience.

text: BACKGROUND Lung volume reduction coil (LVRC) treatment is established in daily endoscopic lung volume reduction routine. The aim of this study was to evaluate the safety and efficacy of LVRC treatment. PATIENTS AND METHODS This was a retrospective analysis of 86 patients (male/female: 40/46, mean age: 64±7 years) with severe COPD and bilateral incomplete fissures. A total of 10 coils were unilaterally implanted in a single lobe, and 28 out of 86 patients were treated bilaterally. At 90-, 180-, and 365-day follow-up, changes in pulmonary function test (PFT), 6-minute walk test (6MWT) and modified Medical Research Council (mMRC) dyspnea scale, as well as possible complications, were recorded. RESULTS At 90 days, the forced expiratory volume in 1 second did improve (P<0.001), but the improvement was not sustained at the 180- and 365-day follow-up (baseline: 0.71±0.21 vs 0.77±0.23 vs 0.73±0.22 vs 0.70±0.18 L). Both vital capacity and residual volume improved significantly (P<0.001) at the 90- and 180-day follow-up, but the improvement was lost after 365 days. Total lung capacity decreased at the 90-day follow-up but returned to baseline values at the 180- and 365-day follow-up. 6MWT (P=0.01) and mMRC (P=0.007) also improved at 90 and 180 days (Δ6MWT of 31±54 and 20±60 m, respectively), but the improvement was also lost at the 365-day follow-up. No significant further improvement was evident at any point in the follow-up after the second procedure. A total of 4 out of 86 patients passed away due to complications. Significant complications in the first 3 months and then at 12 months included the following: severe hemoptysis in 4 (3.5%) and 4 (3.5%) patients, pneumonia requiring hospitalization in 32 (28.1%) and 9 (7.9%) patients and pneumothorax in 7 (6.1%) and 2 (1.7%) patients, respectively. Milder adverse events included self-limited hemoptysis, pneumonias, or COPD exacerbations treated orally. CONCLUSION LVRC improved PFT, 6MWT and mMRC initially, but the improvement was lost after 365 days. Furthermore, we observed 4 deaths and significant severe complications, which need to be further elucidated.


Diagnostic imaging of COVID-19 patients.


title: Transcarotid transcatheter aortic valve implantation: multicentre experience in France.

text: OBJECTIVES Transcatheter aortic valve implantation is a well-recognized treatment option for high-risk patients with aortic stenosis. The femoral approach is possible in 80% of cases and remains the access of choice. When this approach is not feasible, other alternative routes have been proposed such as transapical, transaortic and subclavian. Transcarotid aortic valve implantation has been proposed as another direct vascular access. Its use is relatively new and still under evaluation. METHODS We successfully performed transcarotid aortic valve implantation in 145 consecutive patients through the left or right carotid artery in 3 different French sites over a 2-year period. Data were prospectively entered in the French transcatheter aortic valve implantation database. RESULTS The mean age was 79.8 ± 8.7 years, with a mean logistic EuroSCORE of 20.7 ± 12.6%. The procedure was successful in all patients, and no conversion was necessary. Thirty-day survival was 93.7%, 8 (5.5%) patients presented either minor or major strokes and 1 patient had a localized asymptomatic carotid dissection. All patients were immediately extubated, and none presented respiratory complications. CONCLUSIONS Transcarotid aortic valve implantation is a safe alternative to transfemoral transcatheter aortic valve implantation, with direct access to the aortic valve, which can be performed with limited incision.


Hydroxyethyl starches: what do we still know?


title: The Power of 'Pause'-A Time for Medical Students to Reflect and Mobilize.

text: The COVID-19 pandemic has forced the entire world to stop. Silence occupies side streets while emptiness cleanses our oceans and skies. For those who have the privilege of staying home, the world feels frozen. Everything and everyone are paused, with the exception of healthcare and other essential workers. On the front lines, physicians, nurses, respiratory therapists and other healthcare workers are overwhelmed. Emergency rooms are inundated, and intensive care units are besieged with COVID-19 patients.


title: The exacerbation component of impairment and risk in pediatric asthma.

text: PURPOSE OF REVIEW The new guidelines for assessment of asthma control emphasize two domains: impairment and risk. Exacerbations of asthma are an important component of risk but have not received as much attention as the day-to-day symptoms that make up impairment. The purpose of this review is to report what has recently been learned about exacerbations. RECENT FINDINGS Exacerbations occur in the context of both controlled and uncontrolled asthma. Exacerbations are a strong independent risk factor of further exacerbations. This suggests that unrecognized factors may be involved in susceptibility to exacerbations in addition to more commonly recognized triggers such as viruses, allergens, and poorly controlled asthma. Such factors may be the result of genetic variation. Recent evidence now shows a residual effect on lung function from an exacerbation event. There are no current specific intervention measures to prevent exacerbations but attention to management practices continues to look at the role of the emergency department in improving care. SUMMARY The presence of exacerbations is considered a risk factor of the likelihood of further exacerbations and requires assessment of the triggers identified with history of exacerbations, host factors, atopic disposition, exposure to allergens, adherence to prescribed medications, and preventive measures to reduce future risk of such an event.


Managing heart failure related peripheral oedema in primary care.


title: Family cluster of Middle East respiratory syndrome coronavirus infections.

text: A human coronavirus, called the Middle East respiratory syndrome coronavirus (MERS-CoV), was first identified in September 2012 in samples obtained from a Saudi Arabian businessman who died from acute respiratory failure. Since then, 49 cases of infections caused by MERS-CoV (previously called a novel coronavirus) with 26 deaths have been reported to date. In this report, we describe a family case cluster of MERS-CoV infection, including the clinical presentation, treatment outcomes, and household relationships of three young men who became ill with MERS-CoV infection after the hospitalization of an elderly male relative, who died of the disease. Twenty-four other family members living in the same household and 124 attending staff members at the hospitals did not become ill. MERS-CoV infection may cause a spectrum of clinical illness. Although an animal reservoir is suspected, none has been discovered. Meanwhile, global concern rests on the ability of MERS-CoV to cause major illness in close contacts of patients.


title: Pediatric laparo-endoscopic single site partial nephrectomy: feasibility in infants and small children for upper urinary tract duplication anomalies.

text: OBJECTIVE To assess the feasibility and outcomes of laparo-endoscopic single site (LESS) partial nephrectomy (PN) in infants and small children for upper urinary tract duplication anomalies. MATERIALS AND METHODS The medical records of all patients undergoing LESS PN at a single pediatric institution were retrospectively reviewed for patient demographics, perioperative details, and outcomes. A cystoscopy was initially performed to place an externalized catheter into the ureter of the ipsilateral normal renal moiety. An Olympus TriPort, an Olympus Endoeye flexible tip laparoscope, standard 3- or 5-mm instrumentation, and a LigaSure Blunt were utilized. RESULTS Four children (two boys, two girls) underwent LESS PN. Three patients underwent upper pole PN and one underwent lower pole PN. All procedures were performed for poorly functioning obstructed renal moieties (one ureterocele, one ureteropelvic junction obstruction and vesicoureteral reflux, and two ectopic ureters). Median age was 6.2 months (range 2.5-16.4 months). Median weight was 7.7 kg (range 6.1-12.6 kg). Median operative time was 126 min (range 97-180 min). No patient received inpatient postoperative narcotics. Median follow-up was 9.9 months (range 6.2-19.1 months). No postoperative complications were noted. Postoperative renal ultrasound demonstrated successful resection in all patients. CONCLUSIONS LESS PN is technically feasible, safe, and effective for upper urinary tract duplication anomalies in infants and small children.


title: Techniques of hepatic resection.

text: Liver resections are high risk procedures performed by experienced surgeons. The role of liver resection in malignant disease has changed over the last 100 years with great improvement in morbidity, mortality and long term survival. New understanding in liver anatomy, improved perioperative care, anesthesia techniques, and technological advances has improved this aspect of patient care. With improved techniques, patients previously considered unresectable have an opportunity to undergo curative surgery. This review article describes the various approaches and techniques for liver resection. The relevant anatomy and terminology of hepatic resections is discussed, as well as the role of anatomic vs. nonanatomic resection. Methods of vascular control are examined and the multiple strategies of parenchymal transection are compared, as well as minimally-invasive techniques. Finally, a brief review of the authors' practice in terms of surgical technique is offered.


title: In the shadow of HIV & TB: A commentary on the COVID epidemic in South Africa.

text: While COVID-19 has become a global pandemic that has spread to all regions of the globe, local historic, health, and socio-environmental factors shape the epidemiological contours, response, and social challenges present within each affected nation. Thus, while countries like China, Italy, Iran, Brazil, and the United States have all been hard hit by the pandemic, there are critical differences across these nations in a number of variables (e.g. demographic features, health histories, healthcare systems, infection case rates, case fatality rates, national responses). In other words, within the global pandemic there are multiple importantly distinct national epidemics. Overcoming the grave threats to public health presented by COVID-19 requires both international cooperation and country-specific efforts that reflect local histories, needs, and resources. Already concerns are being expressed among health officials about how COVID-19 might be devastating in Africa. Currently, South Africa has the highest number of diagnosed COVID-19 cases on the continent and has been identified as being at high risk in the pandemic. This paper examines the public health response to the COVID-19 threat, how the prior and ongoing HIV and TB epidemics shape the COVID-19 epidemic and influence the response, and the potential ramifications of the response.


title: The determinants of Chinese provincial government health expenditures: evidence from 2002-2006 data.

text: There is great divergence in provincial government health expenditures in China. Real per capita provincial government health expenditures (GHE) over the period 2002-2006 are examined using panel regression analysis. Key determinants of real per capita provincial GHE are real provincial per capita general budget revenue, real provincial per capita transfers from the central government, the proportion of provincial population under age 15, urban employee basic health insurance coverage, and proportion of urban population. Roughly equal and relatively low elasticities of budget revenue and transfers imply that the GHE is a necessity rather than a luxury good, and transfers have yet to become efficient instruments for the fair allocation of health resources by policy makers. Moreover, severe acute respiratory syndrome outbreak has increased the GHE, but we find no statistical evidence that provincial GHE have fluctuated according to the public health status.


title: Added Value of Breast MRI for Preoperative Diagnosis of Ductal Carcinoma In Situ: Diagnostic Performance on 362 Patients.

text: INTRODUCTION The purpose of this study was to evaluate the added value of breast magnetic resonance imaging (MRI) in preoperative diagnosis of ductal carcinoma in situ (DCIS). We reviewed our institution database of 3499 consecutive patients treated for breast cancer. PATIENTS AND METHODS A total of 362 patients with histologically proven DCIS were selected from the institutional database. Of these, 245 (67.7%) preoperatively underwent conventional imaging (CI) (mammography/ultrasonography) (CI group), and 117 (32.3%) underwent CI and dynamic MRI (CI + MRI group). The pathology of surgical specimens served as a reference standard. The Mann-Whitney U, χ2 test, and Spearman correlation coefficient were performed. RESULTS The CI + MRI group showed a sensitivity of 98.5% with an increase of 10.1% compared with the CI group to detect pure DCIS. Dynamic MRI identified 19.7% (n = 13) additional pure DCIS compared with CI. In the CI + MRI group, a single (1.5%) false negative was reported, whereas in the CI group, 11 (11.6%) false negatives were reported. Moreover, the CI + MRI group showed a sensitivity of 98.0% to detect DCIS + small invasive component. In this group, dynamic MRI identified 21.6% (n = 11) additional DCIS and a single (2.0%) false negative compared with the CI group, whereas in the CI group, 7 (4.7%) false negatives were reported. MRI and histopathologically measured lesion sizes, Breast Imaging Reporting and Data System MRI assessment categories, and enhancement signal intensity curve types showed a significant correlation. The MRI detection rate of DCIS increased significantly with increasing nuclear grade. CONCLUSIONS Preoperative breast MRI showed a better accuracy then CI in preoperative diagnosis for both pure DCIS and DCIS + small invasive component with a precise assessment of lesion size. This can provide a more appropriate management of DCIS patients.


Use of porcine small intestine submucosa as a prosthetic material for laparoscopic hernia repair in infected and potentially contaminated fields: long-term follow-up assessment.


title: Orientation and density control of proteins on solid matters by outer membrane coating: Analytical and diagnostic applications.

text: Autodisplay is an expression system for the display of recombinant proteins on the outer membrane (OM) of gram negative bacteria and has been developed for translocation studies, whole cell biocatalysis, bioremediation, inhibitor screening, and enzyme refolding. Recently, affinity proteins such as IgG-binding Z-domains and biotin-binding streptavidin have been autodisplayed on the OM of Escherichia coli for analytical and biomedical applications. The secretion mechanism of the autodisplay system was used and orientation and density control of these affinity proteins were determined. Affinity protein-autodisplaying E. coli cells have been used to coat solid supports in immunoassays. For this purpose, the OM of autodisplayed E. coli cells was separated and isolated by the aid of detergents. The structure of the resulting OM liposomes as well as their physico-chemical parameters, were analyzed. OM liposomes were used subsequently for coating various solid matters including microplates and biosensor transducer surfaces and the formation of OM layers were monitored. OM layer formation on solid matters was shown to increase the sensitivity of immunoassays and biosensors. In this review, analytical and diagnostic applications are described in particular concerning orientation and density control of autodisplayed affinity proteins.


title: Long-term conditions and severe acute respiratory syndrome SARS-CoV-2 (COVID-19).

text: Observation of infection trends through the course of the ongoing COVID-19 pandemic has indicated that those with certain pre-existing chronic conditions, such as hypertension, chronic obstructive pulmonary disease and obesity, are particularly likely to develop severe infection and experience disastrous sequelae, including near-fatal pneumonia. This article aims to outline how SARS-CoV-2 affects people and to consider why individuals living with long-term conditions are at increased risk from infection caused by this virus. A summary of available clinical guidelines with recommendations is presented, to provide community nurses with the up-to-date information required for protecting individuals living with a number of long-term conditions. Additionally, special measures required are outlined, so that community nurses may reflect on how to best provide nursing care for individuals living with long-term conditions and understand protection measures for individuals at increased risk from severe COVID-19.


title: Hand-Hygiene Mitigation Strategies Against Global Disease Spreading through the Air Transportation Network.

text: The risk for a global transmission of flu-type viruses is strengthened by the physical contact between humans and accelerated through individual mobility patterns. The Air Transportation System plays a critical role in such transmissions because it is responsible for fast and long-range human travel, while its building components-the airports-are crowded, confined areas with usually poor hygiene. Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) consider hand hygiene as the most efficient and cost-effective way to limit disease propagation. Results from clinical studies reveal the effect of hand washing on individual transmissibility of infectious diseases. However, its potential as a mitigation strategy against the global risk for a pandemic has not been fully explored. Here, we use epidemiological modeling and data-driven simulations to elucidate the role of individual engagement with hand hygiene inside airports in conjunction with human travel on the global spread of epidemics. We find that, by increasing travelers engagement with hand hygiene at all airports, a potential pandemic can be inhibited by 24% to 69%. In addition, we identify 10 airports at the core of a cost-optimal deployment of the hand-washing mitigation strategy. Increasing hand-washing rate at only those 10 influential locations, the risk of a pandemic could potentially drop by up to 37%. Our results provide evidence for the effectiveness of hand hygiene in airports on the global spread of infections that could shape the way public-health policy is implemented with respect to the overall objective of mitigating potential population health crises.


title: Who should undergo a comprehensive cognitive assessment after a stroke? A cognitive risk score.

text: OBJECTIVE To validate the ability of a specifically developed cognitive risk score to identify patients at risk of poststroke neurocognitive disorders (NCDs) who are eligible for a comprehensive cognitive assessment. METHODS After assessing 404 patients (infarct 91.3%) in the Groupe de Réflexion pour l'Evaluation Cognitive VASCulaire (GRECogVASC) cross-sectional study with the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network battery 6 months after stroke, we used multivariable logistic regression and bootstrap analyses to determine factors associated with NCDs. Independent, internally validated factors were included in a cognitive risk score. RESULTS Cognitive impairment was present in 170 of the 320 patients with a Rankin Scale score ≥1. The backward logistic regression selected 4 factors (≥73% of the permutations): NIH Stroke Scale score on admission ≥7 (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.29-4.3, p = 0.005), multiple strokes (OR 3.78, 95% CI 1.6-8, p = 0.002), adjusted Mini-Mental State Examination (MMSEadj) score ≤27 (OR 6.69, 95% CI 3.9-11.6, p = 0.0001), and Fazekas score ≥2 (OR 2.34, 95% CI 1.3-4.2, p = 0.004). The cognitive risk score computed with these 4 factors provided good calibration, discrimination (overoptimism-corrected C = 0.793), and goodness of fit (Hosmer-Lemeshow test p = 0.99). A combination of Rankin Scale score ≥1, cognitive risk score ≥1, and MMSEadj score ≥21 selected 230 (56.9%) of the 404 patients for a comprehensive assessment. This procedure yielded good sensitivity (96.5%) and moderate specificity (43%; positive predictive value 0.66, negative predictive value 0.91) and was more accurate (p ≤ 0.03 for all) than the sole use of screening tests (MMSE or Montréal Cognitive Assessment). CONCLUSION The GRECogVASC cognitive risk score comprises 4 easily documented factors; this procedure helps to identify patients at risk of poststroke NCDs who must therefore undergo a comprehensive assessment. CLINICALTRIALSGOV IDENTIFIER NCT01339195.


title: Laparoscopic sacrohysteropexy versus vaginal hysterectomy for uterovaginal prolapse using validated questionnaires: 2-year prospective study.

text: INTRODUCTION Surgical options for uterovaginal prolapse can be categorized into uterus conservation-e.g., laparoscopic sacrohysteropexy (LSHP) or vaginal hysterectomy (VH). There is insufficient reliable information on long-term comparative outcomes of these procedures. The primary aim of this study was to compare subjective and objective outcomes of LSHP and VH. The secondary aim was to record adverse events, recurrent prolapse, and new-onset stress urinary incontinence (SUI) up to 2 years. METHODS Women with symptomatic uterovaginal prolapse who opted for either LSHP or VH were included. Subjective outcomes were compared at 1 and 2 years from baseline using the validated questionnaires. Objective/anatomical outcomes using the Pelvic Organ Prolapse Quantification (POP-Q) system were assessed before and at 3 months after surgery. Adverse events, recurrent prolapse, and new-onset SUI was recorded up to 2 years. RESULTS The study assessed 226 women with uterovaginal prolapse; 125 opted for surgery (44 LSHP, 81 VH). There was no statistically significant difference in symptom domains between groups at baseline and 1 and 2 years. At 3 months POP-Q, greater improvement was seen in points Ba and Ap in the LSHP group compared to VH group and smaller genital hiatus was seen in the VH group. Adverse events, recurrent prolapse, or new-onset SUI were not significantly different in the two groups. CONCLUSIONS Both LSHP and VH are effective surgical options for uterovaginal prolapse. At 2 years, both procedures had similar improvement in symptom domains, overall scores, adverse events, recurrent prolapse, and new-onset SUI. Long-term randomized studies are needed.


title: Effect of gastric bypass surgery on the absorption and bioavailability of metformin.

text: OBJECTIVE Use of gastric bypass surgery is common and increasing. Over 40% of patients in diabetes remission after gastric bypass surgery may redevelop diabetes within 5 years. Metformin, the first-line drug for diabetes, has low bioavailability and slow, incomplete gastrointestinal absorption. We hypothesized that gastric bypass would further reduce the absorption and bioavailability of metformin. RESEARCH DESIGN AND METHODS In a nonblinded, single-dose pharmacokinetic study, 16 nondiabetic post-gastric bypass patients and 16 sex- and BMI-matched control subjects (mean age 40 years and BMI 39.2 kg/m(2)) were administered two 500-mg metformin tablets. Plasma metformin levels were sampled at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 h. Metformin absorption, estimated by the area under the curve (AUC) of the plasma drug concentrations from time 0 to infinity (AUC(0-∞)), was the primary outcome, and metformin bioavailability, assessed by measuring 24-h urine metformin levels, was a secondary outcome. RESULTS Compared with control subjects, metformin AUC(0-∞) was increased in gastric bypass subjects by 21% (13.7 vs. 11.4 μg/mL/h; mean difference 2.3 [95% CI -1.3 to 5.9]) and bioavailability was increased by 50% (41.8 vs. 27.8%; 14.0 [4.1-23.9]). Gastric bypass patients had significantly lower AUC glucose levels over 8 h compared with control subjects (35.8 vs. 41.7 μg/mL/h; 5.9 [3.1-8.8]), but this was likely a result of differences in baseline fasting glucose and not metformin absorption. CONCLUSIONS Metformin absorption and bioavailability seem to be higher after gastric bypass, and this may have implications on dosing and toxicity risk. Studies are needed to confirm these findings and delineate potential mechanisms.


Strategies to support health care providers during the COVID-19 pandemic.


Digestive endoscopy during Covid-19 outbreak in Italy: a tertiary referral center experience.


title: Tuberculosis in public ground transport - is there enough evidence to justify contact tracing?

text: Travel in public transport, especially in confined spaces, provides an opportunity for the transmission of tuberculosis (TB). In air travel, tracing of passengers to control the further spread of a pathogen is a more or less established approach in infectious disease control in many industrialized countries; however, literature reviews on the risk of TB transmission during public ground travel do not show robust evidence. On short trips, contact tracing (CT) of passengers may be unfeasible since passenger data are generally not collected. In long-distance ground travel, passenger data may not be collected routinely; incomplete data and limited or delayed access to passenger details may be further obstacles. The logistic hurdles and limited evidence suggest that CT in public ground transportation should not be a priority of TB control. However, under specific circumstances, CT in public ground transport might be considered on a case-by-case basis after an evidence-based risk assessment.


title: Characteristics of the initial patients hospitalized for COVID-19: a single-center report.

text: BACKGROUND Novel coronavirus 19 infection (COVID-19) has become a global pandemic and Turkey had the first coronavirus patient tested positive in 10 March 2020. AIMS In this analysis we have discussed the characteristics of Turkish patients who have been hospitalized for COVID-19 infection. STUDY DESIGN Cross sectional study Methods: This retrospective study included all the patients who have been hospitalized for novel coronavirus at blinded for peer review -Department of Internal Medicine between 15th March 2020 and 28th March 2020. Patients were screened with real time PCR (2019nCoV), chest X-ray and computer tomography. Also, their demographic characteristics including sex, age, occupation, comorbid disease etc. were recorded. RESULTS There were 70 patients for analysis. Thirty-seven patients (52.9 %) tested positive for coronavirus infection with PCR. Mean age was 55.8 (min 24- max 87). There were 49 men (70.0%). Two patients (2%) were sent home and eleven patients (15.7%) were transferred to intensive care unit (ICU). Patients in ICU had statistically higher, pulse rate, respiratory rate, aspartate aminotransferase, lactate dehydrogenase, c-reactive protein, d-dimer, fibrinogen, activated partial thromboplastin time, troponin and procalcitonin compared to patients followed in clinics. CONCLUSION Turkey has avoided the disease for some time but as inevitable as it is, our country has been added to the countries which are infected.


title: Quantum dot nanometal surface energy transfer based biosensing of sialic acid compositions and linkages in biological samples.

text: Current methods for analyzing sialic acid diversity in modifications and linkages require multistep processing, derivatization, and chromatographic analyses. We here report a single-step optical method for identification and quantification of different compositions of sialoglycans on glycoproteins and in serum. This was achieved by measuring and quantifying nanometal surface energy transfer (NSET) signals between quantum dots and gold nanoparticles bound to specific sialic acid binding proteins (SBPs) and sialic acid moieties, respectively. The biosensing process is based on the NSET turn-on by external sialic acid species that compete for binding to the SBPs. Selectivity of the biosensor toward sialoglycans can be designed to detect the total amount, glycosylation linkages (α2-6 vs α2-3), and modifications (9-O-acetyl and N-glycolyl groups) in the samples. This nanobiosensor is a prototype expected to achieve limits of the detection down to the micromolar range for high-throughput quantification and analysis of different compositions of sialoglycans present in biological or biomedical samples.


title: Comparison of TIVA and Desflurane Added to a Subanaesthetic Dose of Propofol in Patients Undergoing Coronary Artery Bypass Surgery: Evaluation of Haemodynamic and Stress Hormone Changes.

text: Introduction. Increased levels of stress hormones are associated with mortality in patients undergoing coronary artery bypass grafting (CABG). Aim. To compare total intravenous anaesthesia (TIVA) and desflurane added to a subanaesthetic dose of propofol. Material and Methods. Fifty patients were enrolled in this study. Fentanyl (3-5 mcg/kg/h) was started in both groups. Patients were divided into two groups. The PD group (n = 25) received 1 minimum alveolar concentration (MAC) desflurane anaesthesia in addition to propofol infusion (2-3 mg/kg/h), while P group (n = 25) received propofol infusion (5-6 mg/kg/h) only. Biochemical data, cortisol, and insulin levels were measured preoperatively (T0), after initiation of CPB but before cross-clamping the aorta (T1), after removal of the cross-clamp (T2), and at the 24th postoperative hour (T3). Results. Systolic, diastolic, and mean arterial pressure levels were significantly higher in PD group than those in P group in T1 and T2 measurements (p ≤ 0.05). CK-MB showed a significant decrease in group P (p ≤ 0.05). When we compared both groups, cortisol levels were significantly higher in PD group than P group (p ≤ 0.05). Conclusion. Stress and haemodynamic responses were better controlled using TIVA than desflurane inhalation added to a subanaesthetic dose of propofol in patients undergoing CABG.


title: Pretreatment and early-treatment cortical thickness is associated with SSRI treatment response in major depressive disorder.

text: To date, there are no biomarkers for major depressive disorder (MDD) treatment response in clinical use. Such biomarkers could allow for individualized treatment selection, reducing time spent on ineffective treatments and the burden of MDD. In search of such a biomarker, multisite pretreatment and early-treatment (1 week into treatment) structural magnetic resonance (MR) images were acquired from 184 patients with MDD randomized to an 8-week trial of the selective serotonin reuptake inhibitor (SSRI) sertraline or placebo. This study represents a large, multisite, placebo-controlled effort to examine the association between pretreatment differences or early-treatment changes in cortical thickness and treatment-specific outcomes. For standardization, a novel, robust site harmonization procedure was applied to structural measures in a priori regions (rostral and caudal anterior cingulate, lateral orbitofrontal, rostral middle frontal, and hippocampus), chosen based on previously published reports. Pretreatment cortical thickness or volume did not significantly associate with SSRI response. Thickening of the rostral anterior cingulate cortex in the first week of treatment was associated with better 8-week responses to SSRI (p = 0.010). These findings indicate that frontal lobe structural alterations in the first week of treatment may be associated with long-term treatment efficacy. While these associational findings may help to elucidate the specific neural targets of SSRIs, the predictive accuracy of pretreatment or early-treatment structural alterations in classifying treatment remitters from nonremitters was limited to 63.9%. Therefore, in this large sample of adults with MDD, structural MR imaging measures were not found to be clinically translatable biomarkers of treatment response to SSRI or placebo.


title: Cost-effectiveness of an insertable cardiac monitor to detect atrial fibrillation in patients with cryptogenic stroke.

text: BACKGROUND AND AIMS Documentation of atrial fibrillation is required to initiate oral anticoagulation therapy for recurrent stroke prevention. Atrial fibrillation often goes undetected with traditional electrocardiogram monitoring techniques. We evaluated whether atrial fibrillation detection using continuous long-term monitoring with an insertable cardiac monitor is cost-effective for preventing recurrent stroke in patients with cryptogenic stroke, in comparison to the standard of care. METHODS A lifetime Markov model was developed to estimate the cost-effectiveness of insertable cardiac monitors from a UK National Health Service perspective using data from the randomized CRYSTAL-AF trial and other published literature. We also conducted scenario analyses (CHADS2 score) and probabilistic sensitivity analyses. All costs and benefits were discounted at 3.5%. RESULTS Monitoring cryptogenic stroke patients with an insertable cardiac monitor was associated with fewer recurrent strokes and increased quality-adjusted life years compared to the standard of care (7.37 vs 7.22). Stroke-related costs were reduced in insertable cardiac monitor patients, but overall costs remained higher than the standard of care (£19,631 vs £17,045). The incremental cost-effectiveness ratio was £17,175 per quality-adjusted life years gained, compared to standard of care in the base-case scenario, which is below established quality-adjusted life years willingness-to-pay thresholds. When warfarin replaced non-vitamin-K oral anticoagulants as the main anticoagulation therapy, the incremental cost-effectiveness ratio was £13,296 per quality-adjusted life years gained. CONCLUSION Insertable cardiac monitors are a cost-effective diagnostic tool for the prevention of recurrent stroke in patients with cryptogenic stroke. The cost-effectiveness results have relevance for the UK and across value-based healthcare systems that assess costs relative to outcomes.


title: Spontaneous Breathing and Imposed Work During Pediatric Mechanical Ventilation: A Bench Study.

text: OBJECTIVES To calculate imposed work of breathing during simulated spontaneous breathing at a given tidal volume across the range of normal length or shortened pediatric endotracheal tube sizes and endotracheal tubes with an intraluminal catheter in situ. DESIGN In vitro study. SETTING Research laboratory. INTERVENTIONS A bench model (normal compliance, no airway resistance) simulating sinusoid flow spontaneous breathing used to calculate imposed work of breathing for various endotracheal tube sizes (3.0-7.5 mm). Imposed work of breathing was calculated by integrating inspiratory tidal volume over the end-expiratory difference between the positive end-expiratory pressure and the tracheal pressure. Measurements were taken at different combinations of set spontaneous tidal volume (2.5, 5.0, 7.5, and 10 mL/kg), age-appropriate inspiratory times, length of endotracheal tube, and presence of intraluminal catheter. MEASUREMENTS AND MAIN RESULTS Overall median imposed work of breathing (Joules/L) was not significantly different between the four age groups: 0.047 Joules/L (interquartile range, 0.020-0.074 Joules/L) for newborns, 0.077 Joules/L (interquartile range, 0.032-0.127 Joules/L) for infants, 0.109 Joules/L (interquartile range, 0.0399-0.193 Joules/L) for small children, and 0.077 Joules/L (interquartile range, 0.032-0.132 Joules/L) for adolescents. Shortening the endotracheal tubes resulted in a significant difference in reduction in overall imposed work of breathing, but the absolute reduction was most notable in small children (0.030 Joules/L) and the least effect in neonates (0.016 Joules/L). Overall imposed work of breathing increased in each age group when an intraluminal catheter was in situ: 91.09% increase in imposed work of breathing in neonates to 0.168 Joules/L, 84.98% in infants to 0.142 Joules/L, 81.98% in small children to 0.219 Joules/L, and 55.45% in adolescents to 0.140 Joules/L. CONCLUSIONS Calculated imposed work of breathing were not different across the range of endotracheal tube sizes. The low imposed work of breathing values found in this study might be appreciated as clinically irrelevant. Our findings add to the change in reasoning that it is appropriate to perform spontaneous breathing trials without pressure support. Nonetheless, our findings on the measured imposed work of breathing values need to be confirmed in a clinical study.


COVID-19 and Risks Posed to Personnel During Endotracheal Intubation.


title: Interventions to improve emergency department use for mental health reasons: protocol for a mixed-methods systematic review.

text: BACKGROUND Healthcare resources are limited and unnecessary, and inappropriate emergency department use is now a highly visible healthcare priority. Individuals visiting the emergency department for mental health-related reasons are often amongst the most frequent presenters. In response, researchers and clinicians have created interventions to streamline emergency department use and several primary studies describe the effects of these interventions. Yet, no consensus exists on the optimal approach, and information on the quality of development, effectiveness, acceptability, and economic considerations is hard to find. The purpose of this study is to systematically review interventions designed to improve appropriate use of the emergency department for mental health reasons. METHOD A mixed-method systematic review using Joanna Briggs Methodology. Search combining electronic databases (EMBASE, MEDLINE, PsycINFO, CINAHL, HealthSTAR, PROQUEST, Cumulative Index to Nursing and Allied Health) and secondary searches (grey literature and hand search with consultation). Two independent reviewers will screen titles and abstracts using predetermined eligibility criteria and a third reviewer will resolve conflicts. Full texts will also be screened by two independent reviews and conflicts resolved in a consensus meeting with a third reviewer. A pilot-tested data extraction form will be used to retrieve data relevant to the study objectives. We will assess the quality and of all included studies. Data describing interventions will be summarized using logic models and reported narratively. Quality of development will be assessed using the Oxford Implementation Index. For data on intervention effectiveness, we will assess statistical heterogeneity and conduct a meta-analysis using a random effects method, if appropriate. For interventions that cannot be pooled, we will report outcomes narratively and descriptively. Qualitative data on acceptability will be synthesized using meta-aggregation and an economic evaluation of interventions will be done. The reporting of this protocol follows the PRISMA-P statement. DISCUSSION Using a combined systematic review methodology and integrated knowledge translation plan, the project will provide decision makers with concrete evidence to support the implementation and evaluation of interventions to improve emergency department use for mental health reasons. These interventions reflect widespread priorities in the area of mental health care. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42018087430.


Severe acute respiratory syndrome coronavirus (SARS-CoV) is capable of inducing a storm of proinflammatory cytokines. In this study, we show that the SARS-CoV open reading frame 3a (ORF3a) accessory protein activates the NLRP3 inflammasome by promoting TNF receptor-associated factor 3 (TRAF3)-mediated ubiquitination of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). SARS-CoV and its ORF3a protein were found to be potent activators of pro-IL-1β gene transcription and protein maturation, the 2 signals required for activation of the NLRP3 inflammasome. ORF3a induced pro-IL-1β transcription through activation of NF-κB, which was mediated by TRAF3-dependent ubiquitination and processing of p105. ORF3a-induced elevation of IL-1β secretion was independent of its ion channel activity or absent in melanoma 2 but required NLRP3, ASC, and TRAF3. ORF3a interacted with TRAF3 and ASC, colocalized with them in discrete punctate structures in the cytoplasm, and facilitated ASC speck formation. TRAF3-dependent K63-linked ubiquitination of ASC was more pronounced in SARS-CoV-infected cells or when ORF3a was expressed. Taken together, our findings reveal a new mechanism by which SARS-CoV ORF3a protein activates NF-κB and the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of p105 and ASC.-Siu, K.-L., Yuen, K.-S., Castaño-Rodriguez, C., Ye, Z.-W., Yeung, M.-L., Fung, S.-Y., Yuan, S., Chan, C.-P., Yuen, K.-Y., Enjuanes, L., Jin, D.-Y. Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC.


title: Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection.

text: BACKGROUND Experience from treating patients with Spanish influenza and influenza A(H5N1) suggested that convalescent plasma therapy might be beneficial. However, its efficacy in patients with severe pandemic influenza A(H1N1) 2009 virus (H1N1 2009) infection remained unknown. METHODS During the period from 1 September 2009 through 30 June 2010, we conducted a prospective cohort study by recruiting patients aged ≥ 18 years with severe H1N1 2009 infection requiring intensive care. Patients were offered treatment with convalescent plasma with a neutralizing antibody titer of ≥ 1:160, harvested by apheresis from patients recovering from H1N1 2009 infection. Clinical outcome was compared with that of patients who declined plasma treatment as the untreated controls. RESULTS Ninety-three patients with severe H1N1 2009 infection requiring intensive care were recruited. Twenty patients (21.5%) received plasma treatment. The treatment and control groups were matched by age, sex, and disease severity scores. Mortality in the treatment group was significantly lower than in the nontreatment group (20.0% vs 54.8%; P = .01). Multivariate analysis showed that plasma treatment reduced mortality (odds ratio [OR], .20; 95% confidence interval [CI], .06-.69; P = .011), whereas complication of acute renal failure was independently associated with death (OR, 3.79; 95% CI, 1.15-12.4; P = .028). Subgroup analysis of 44 patients with serial respiratory tract viral load and cytokine level demonstrated that plasma treatment was associated with significantly lower day 3, 5, and 7 viral load, compared with the control group (P < .05). The corresponding temporal levels of interleukin 6, interleukin 10, and tumor necrosis factor α (P < .05) were also lower in the treatment group. CONCLUSIONS Treatment of severe H1N1 2009 infection with convalescent plasma reduced respiratory tract viral load, serum cytokine response, and mortality.


title: Comparison of flow diversion with clipping and coiling for the treatment of paraclinoid aneurysms in 115 patients.

text: OBJECTIVEParaclinoid aneurysms represent approximately 5% of intracranial aneurysms (Drake et al. [1968]). Visual impairment, which occurs in 16%-40% of patients, is among the most common presentations of these aneurysms (Day [1990], Lai and Morgan [2013], Sahlein et al. [2015], and Silva et al. [2017]). Flow-diverting stents, such as the Pipeline Embolization Device (PED), are increasingly used to treat these aneurysms, in part because of their theoretical reduction of mass effect (Fiorella et al. [2009]). Limited data on paraclinoid aneurysms treated with a PED exist, and few studies have compared outcomes of patients after PED placement with those of patients after clipping or coiling.METHODSThe authors performed a retrospective analysis of 115 patients with an aneurysm of the cavernous to ophthalmic segments of the internal carotid artery treated with clipping, coiling, or PED deployment between January 2011 and March 2017. Postoperative complications were defined as new neurological deficit, aneurysm rupture, recanalization, or other any operative complication that required reintervention.RESULTSA total of 125 paraclinoid aneurysms in 115 patients were treated, including 70 with PED placement, 23 with coiling, and 32 with clipping. Eighteen (14%) aneurysms were ruptured. The mean aneurysm size was 8.2 mm, and the mean follow-up duration was 18.4 months. Most aneurysms were discovered incidentally, but visual impairment, which occurred in 21 (18%) patients, was the most common presenting symptom. Among these patients, 15 (71%) experienced improvement in their visual symptoms after treatment, including 14 (93%) of these 15 patients who were treated with PED deployment. Complete angiographic occlusion was achieved in 89% of the patients. Complications were seen in 17 (15%) patients, including 10 (16%) after PED placement, 2 (9%) after coiling, and 5 (17%) after clipping. Patients with incomplete aneurysm occlusion had a higher rate of procedural complications than those with complete occlusion (p = 0.02). The rate of postoperative visual improvement was significantly higher among patients treated with PED deployment than in those treated with coiling (p = 0.01). The significant predictors of procedural complications were incomplete occlusion (p = 0.03), hypertension, (p = 0.04), and diabetes (p = 0.03).CONCLUSIONSIn a large series in which patient outcomes after treatment of paraclinoid aneurysms were compared, the authors found a high rate of aneurysm occlusion and a comparable rate of procedural complications among patients treated with PED placement compared with the rates among those who underwent clipping or coiling. For patients who presented with visual symptoms, those treated with PED placement had the highest rate of visual improvement. The results of this study suggest that the PED is an effective and safe modality for treating paraclinoid aneurysms, especially for patients who present with visual symptoms.


title: Antiviral effect of epigallocatechin gallate on enterovirus 71.

text: Oxidative stress is known to be a determinant of a host's susceptibility to pathogens. Natural compounds with antioxidant activity may provide a preventive measure against infection. Tea polyphenols were evaluated for their ability to inhibit enterovirus 71 (EV71) replication in Vero cell culture. Among the polyphenolic compounds tested, epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG) potently inhibited replication of EV71. EGCG and GCG reduced the titer of infectious progeny virus by 95%. Quantitative RT-PCR analysis also revealed that EGCG suppressed replication of genomic RNA. It was accompanied by an increased cytoprotective effect. EGCG and GCG caused 5-fold increase in the viability of EV71-infected cells. The viral inhibitory effect correlated well with the antioxidant capacity of polyphenol. Mechanistically, EV71 infection led to increased oxidative stress, as shown by increased dichlorofluorescein and MitoSOX Red fluorescence. Upon EGCG treatment, reactive oxygen species (ROS) generation was significantly reduced. Consistent with this, EV71 replication was enhanced in glucose-6-phosphate dehydrogenase deficient cells, and such enhancement was largely reversed by EGCG. These findings suggest that EGCG may suppress viral replication via modulation of cellular redox milieu.


title: Correction: Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm.

text: [This corrects the article DOI: 10.1371/journal.ppat.1003971.].


Novel use of LigaSure Impact™ electrosurgical bipolar vessel sealing system in skin-sparing mastectomy.


title: Necrotizing enterocolitis: etiology, presentation, management, and outcomes.

text: Necrotizing enterocolitis is one of the most common gastrointestinal disease processes affecting infants in the neonatal intensive care unit. Its morbidity and mortality are substantial. This devastating and challenging process results in immediate and long-term morbidities for the affected infant and frustrates the clinician who struggles to prevent the process, recognize it when it does develop, and provide management techniques to enhance the outcome.


title: Use of human fibrin glue (Tisseel) versus staples for mesh fixation in laparoscopic transabdominal preperitoneal hernioplasty (TISTA): a randomized controlled trial (NCT01641718).

text: BACKGROUND Inguinal hernia repair is one of the most common surgical procedures worldwide. This procedure is increasingly performed with endoscopic techniques (laparoscopy). Many surgeons prefer to cover the hernia gap with a mesh to prevent recurrence. The mesh must be fixed tightly, but without tension. During laparoscopic surgery, the mesh is generally fixed with staples or tissue glue. However, staples often cause pain at the staple sites, and they can cause scarring of the abdominal wall, which can lead to chronic pain. We designed a trial that aims to determine whether mesh fixation with glue might cause less postoperative pain than fixation with staples during a transabdominal preperitoneal patch plastic repair. METHODS/DESIGN The TISTA trial is a prospective, randomized, controlled, single-center trial with a two-by-two parallel design. All patients and outcome-assessors will be blinded to treatment allocations. For eligibility, patients must be male, ≥18 years old, and scheduled for laparoscopic repair of a primary inguinal hernia. One group comprises patients with a unilateral inguinal hernia that will be randomized to receive mesh fixation with either tissue glue or staples. The second group comprises patients with bilateral inguinal hernias. They will be randomized to receive mesh fixation with tissue glue either on the right or the left side and with staples on the other side. The primary endpoint will be pain under physical stress, measured at 24 h after surgery. Pain will be rated by the patient based on a numeric rating scale from 0 to 10, where 10 equals the worst pain imaginable. A total of 82 patients will be recruited (58 patients with unilateral inguinal hernias and 24 patients with bilateral hernias). This number is estimated to provide 90% power for detecting a pain reduction of one point on a numeric rating scale, with a standard deviation of one. DISCUSSION Patients with bilateral hernias will receive two meshes, one fixed with glue, and the other fixed with staples. This design will eliminate the inter-individual bias inherent in comparing pain measurements between two groups of patients. TRIAL REGISTRATION ClinicalTrials.gov: NCT01641718.


title: On-Demand Formation of Supported Lipid Membrane Arrays by Trehalose-Assisted Vesicle Delivery for SPR Imaging.

text: The fabrication of large-scale, solid-supported lipid bilayer (SLB) arrays has traditionally been an arduous and complex task, primarily due to the need to maintain SLBs within an aqueous environment. In this work, we demonstrate the use of trehalose vitrified phospholipid vesicles that facilitate on-demand generation of microarrays, allowing each element a unique composition, for the label-free and high-throughput analysis of biomolecular interactions by SPR imaging (SPRi). Small, unilamellar vesicles (SUVs) are suspended in trehalose, deposited in a spatially defined manner, with the trehalose vitrifying on either hydrophilic or hydrophobic SPR substrates. SLBs are subsequently spontaneously formed on-demand simply by in situ hydration of the array in the SPR instrument flow cell. The resulting SLBs exhibit high lateral mobility, characteristic of fluidic cellular lipid membranes, and preserve the biological function of embedded cell membrane receptors, as indicated by SPR affinity measurements. Independent fluorescence and SPR imaging studies show that the individual SLBs stay localized at the area of deposition, without any encapsulating matrix, confining coral, or boundaries. The introduced methodology allows individually addressable SLB arrays to be analyzed with excellent label-free sensitivity in a real-time, high-throughput manner. Various protein-ganglioside interactions have been selected as a model system to illustrate discrimination of strong and weak binding responses in SPRi sensorgrams. This methodology has been applied toward generating hybrid bilayer membranes on hydrophobic SPR substrates, demonstrating its versatility toward a range of surfaces and membrane geometries. The stability of the fabricated arrays, over medium to long storage periods, was evaluated and found to be good. The highly efficient and easily scalable nature of the method has the potential to be applied to a variety of label-free sensing platforms requiring lipid membranes for high-throughput analysis of their properties and constituents.


Managing individual and population risk from covid-19.


title: Severe acute respiratory syndrome coronavirus replication is severely impaired by MG132 due to proteasome-independent inhibition of M-calpain.

text: The ubiquitin-proteasome system (UPS) is involved in the replication of a broad range of viruses. Since replication of the murine hepatitis virus (MHV) is impaired upon proteasomal inhibition, the relevance of the UPS for the replication of the severe acute respiratory syndrome coronavirus (SARS-CoV) was investigated in this study. We demonstrate that the proteasomal inhibitor MG132 strongly inhibits SARS-CoV replication by interfering with early steps of the viral life cycle. Surprisingly, other proteasomal inhibitors (e.g., lactacystin and bortezomib) only marginally affected viral replication, indicating that the effect of MG132 is independent of proteasomal impairment. Induction of autophagy by MG132 treatment was excluded from playing a role, and no changes in SARS-CoV titers were observed during infection of wild-type or autophagy-deficient ATG5(-/-) mouse embryonic fibroblasts overexpressing the human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2). Since MG132 also inhibits the cysteine protease m-calpain, we addressed the role of calpains in the early SARS-CoV life cycle using calpain inhibitors III (MDL28170) and VI (SJA6017). In fact, m-calpain inhibition with MDL28170 resulted in an even more pronounced inhibition of SARS-CoV replication (>7 orders of magnitude) than did MG132. Additional m-calpain knockdown experiments confirmed the dependence of SARS-CoV replication on the activity of the cysteine protease m-calpain. Taken together, we provide strong experimental evidence that SARS-CoV has unique replication requirements which are independent of functional UPS or autophagy pathways compared to other coronaviruses. Additionally, this work highlights an important role for m-calpain during early steps of the SARS-CoV life cycle.


title: Frequency and relevance of anterior cerebral artery embolism caused by mechanical thrombectomy of middle cerebral artery occlusion.

text: BACKGROUND AND PURPOSE Spread of thrombus material in previously unaffected vessels is a potential hazard of mechanical thrombectomy, but it has not yet been investigated in detail, to our knowledge. Our purpose was to evaluate the frequency and relevance of these events in mTE of M1 occlusions. MATERIALS AND METHODS We retrospectively reviewed all patients treated for isolated M1 occlusion between January 2008 and July 2012. Angiographic images were analyzed to assess emboli in anterior cerebral artery branches induced by mTE and associated devices. Recanalization attempts in the ACA were reported as well as technical success and adverse events of rescue therapies. ACA infarcts on follow-up imaging served as a surrogate for clinical relevance. ACA infarcts were quantified volumetrically and assessed visually for involvement of motor or supplementary motor areas. RESULTS New ACA emboli occurred in 12 of 105 (11.4%) M1 recanalization procedures and were caused by a stent-retriever in 11 intances. Attempts to recanalize the ACA were made in 6 patients and were deemed technically successful in 5 with no adverse events. We detected 6 (5.7%) new infarcts on follow-up imaging with an average volume of 26.9 cm(3). Involvement of motor or supplementary motor areas was seen in 4 (3.8%) cases. Three patients developed ACA infarcts despite successful endovascular ACA recanalization. CONCLUSIONS The frequency of ACA emboli in mTE of M1 occlusions is relevant, causing ACA infarcts in 5.7% of patients; 3.8% of emboli were likely to hamper motor-function recovery. Endovascular recanalization of major ACA branches reduced the incidence of infarcts with no adverse events.


title: Reducing the risk of contrast-induced nephropathy: a perspective on the controversies.

text: OBJECTIVE Contrast-induced nephropathy (CIN) remains poorly understood despite decades of investigation, and the criteria for diagnosis are variable. The purpose of this article is to discuss current controversies in contrast-induced nephropathy including its prevention. CONCLUSION Patients with normal renal function are at exceptionally low risk for CIN. Patients with preexisting renal insufficiency appear to be at higher risk and precautionary maneuvers may be warranted in some of these patients; however, iodinated contrast material should not be withheld if a contrast-enhanced study is necessary and there is no alternative.


title: [Pharmacotherapeutics for the new coronavirus pneumonia].

text: The new coronavirus pneumonia (NCP), also named as COVID-19 by WHO on Feb 11 2020, is now causing a severe public health emergency in China since. The number of diagnosed cases is more than 40,000 until the submission of this manuscript. Coronavirus has caused several epidemic situations world widely, but the present contagious disease caused by 2019 new coronavirus is unprecedentedly fulminating. The published cohorts of 2019 new coronavirus (n-Cov) are single-center studies, or retrospective studies. We here share the therapeutic experiences of NCP treatment with literature review. Combination of Ribavirin and interferon-α is recommended by the 5(th) edition National Health Commission's Regimen (Revised Edition) because of the effect on Middle East respiratory syndrome (MERS), and the effectiveness of Lopinavir/Ritonavir and Remdisivir needs to be confirmed by randomized controlled trial (RCT), given the situation of no specific antivirus drug on NCP is unavailable. Systemic glucocorticosteroid is recommended as a short term use (1~2 mg·kg(-1)·d(-1), 3~5 d) by the 5(th) edition National Health Commission's Regimen (Revised Edition) yet RCTs are expected to confirm the effectiveness. Inappropriate application of antibiotics should be avoided, especially the combination of broad-spectrum antibiotics, for the NCP is not often complicated with bacterial infection.


title: Extracorporeal Life Support Increases Survival After Prolonged Ventricular Fibrillation Cardiac Arrest in the Rat.

text: BACKGROUND Extracorporeal life support (ECLS) for cardiopulmonary resuscitation (CPR) may increase end organ perfusion and thus survival when conventional CPR fails. The aim was to investigate, if after ventricular fibrillation cardiac arrest in rodents ECLS improves outcome compared with conventional CPR. METHODS In 24 adult male Sprague-Dawley rats (460-510 g) resuscitation was started after 10 min of no-flow with ECLS (consisting of an open reservoir, roller pump, and membrane oxygenator, connected to cannulas in the jugular vein and femoral artery, n = 8) or CPR (mechanical chest compressions plus ventilations, n = 8) and compared with a sham group (n = 8). After return of spontaneous circulation (ROSC), all rats were maintained at 33°C for 12 h. Survival to 14 days, neurologic deficit scores and overall performance categories were assessed. RESULTS ECLS leads to sustained ROSC in 8 of 8 (100%) and neurological intact survival to 14 days in 7 of 8 rats (88%), compared with 5 of 8 (63%) and 1 of 8 CPR rats. The median survival time was 14 days (IQR: 14-14) in the ECLS and 1 day (IQR: 0 to 5) for the CPR group (P = 0.004). CONCLUSION In a rat model of prolonged ventricular fibrillation cardiac arrest, ECLS with mild hypothermia produces 100% resuscitability and 88% long-term survival, significantly better than conventional CPR.