title: The influence of bariatric surgery on oral drug bioavailability in patients with obesity: A systematic review.

text: Anatomical changes in the gastrointestinal tract and subsequent weight loss may influence drug disposition and thus drug dosing following bariatric surgery. This review systematically examines the effects of bariatric surgery on drug pharmacokinetics, focusing especially on the mechanisms involved in restricting oral bioavailability. Studies with a longitudinal before-after design investigating the pharmacokinetics of at least one drug were reviewed. The need for dose adjustment following bariatric surgery was examined, as well as the potential for extrapolation to other drugs subjected to coinciding pharmacokinetic mechanisms. A total of 22 original articles and 32 different drugs were assessed. The majority of available data is based on Roux-en-Y gastric bypass (RYGBP) (18 of 22 studies), and hence, the overall interpretation is more or less limited to RYGBP. In the case of the majority of studied drugs, an increased absorption rate was observed early after RYGBP. The effect on systemic exposure allows for a low degree of extrapolation, including between drugs subjected to the same major metabolic and transporter pathways. On the basis of current understanding, predicting the pharmacokinetic change for a specific drug following RYGBP is challenging. Close monitoring of each individual drug is therefore recommended in the early postsurgical phase. Future studies should focus on the long-term effects of bariatric surgery on drug disposition, and they should also aim to disentangle the effects of the surgery itself and the subsequent weight loss.


title: Transcatheter arterial embolization in normal canine liver.

text: OBJECTIVE To determine the effects of selective transcatheter arterial embolization (TAE) in the normal canine liver. STUDY DESIGN Experimental study. ANIMALS Adult Beagle dogs (n = 5). METHODS Gelatin sponge particles (GSPs) were injected through a microcatheter for selective embolization of the left hepatic artery in normal dogs. Computed tomography (CT) and histology were performed during an 8-week observation period; biochemical analysis data were obtained during a 12-week observation period after TAE. RESULTS Embolization was successful in all dogs and did not induce any change in the clinical appearance of dogs. Postoperative CT was consistent with recanalization of the artery within 2 weeks of embolization in all dogs. Hepatic enzyme levels increased temporarily after embolization but gradually returned to normal ranges. Histological examinations did not differ between treated and untreated liver tissues. CONCLUSION TAE appears safe in normal dogs observed for 12 weeks. Arterial recanalization seems to occur within 2 weeks after injection of GSPs in the left hepatic artery. IMPACT/CLINICAL RELEVANCE Selective TAE of the hepatic artery was well tolerated in normal dogs. Selective TAE may be applicable to canine hepatocellular carcinoma.


title: Effects of the COVID-19 pandemic on anxiety and depressive symptoms in pregnant women: a preliminary study.

text: Objective: The 2019 coronavirus disease (COVID-19) outbreak that began in China has turned into a pandemic that threatens global health, thereby prompting the concentration of studies and clinical routines on treating and preventing the disease. However, research on the psychological effects of the pandemic on the general population, particularly pregnant women, is lacking. Accordingly, the present study investigated the effects of the COVID-19 pandemic on depression and anxiety in pregnant women.Study design: An anonymous survey for assessing depression and anxiety in pregnant women was designed, after which a link to the online questionnaire was sent to the participants, who were being treated in a private medical center. One of the researchers followed up with the respondents, among whom 260 returned their questionnaires.Results: Among the respondents, 35.4% (n = 92, case group) obtained scores higher than 13 on the Edinburgh Postpartum Depression Scale (EPDS). The comparison of the groups by years of education indicated statistically significant effects of COVID-19 on psychology, social isolation, and mean scores in the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). These effects were more severe in the case group than in the control group (psychology: 8.369 ± 2.003, social isolation: 8.000 ± 2.507, mean BDI and BAI scores: 20.565 ± 6.605 and 22.087 ± 8.689, respectively). A regression analysis revealed that the BDI scores and the disease's psychological effects, as well as the BAI scores and the illness's social isolation effects, exerted a statistically significant influence on the EPDS scores of the participants.Conclusion: This study illustrated the effects of the COVID-19 pandemic on the depression and anxiety levels of pregnant women. Our results point to an urgent need to provide psychosocial support to this population during the crisis. Otherwise, adverse events may occur during pregnancy and thus affect both mother and fetus.


Covid-19: Breaking bad news with social distancing in pediatric oncology.


title: Notes from the Field: Nosocomial Outbreak of Middle East Respiratory Syndrome in a Large Tertiary Care Hospital--Riyadh, Saudi Arabia, 2015.

text: Since the first diagnosis of Middle East respiratory syndrome (MERS) caused by the MERS coronavirus (MERS-CoV) in the Kingdom of Saudi Arabia in 2012, sporadic cases and clusters have occurred throughout the country (1). During June-August, 2015, a large MERS outbreak occurred at King Abulaziz Medical City, a 1,200-bed tertiary-care hospital that includes a 150-bed emergency department that registers 250,000 visits per year.


title: Laparoscopic Versus Open Gastrectomy for Gastric Adenocarcinoma in the West: A Case-Control Study.

text: INTRODUCTION Data on laparoscopic gastrectomy in patients with gastric cancer in the Western hemisphere are lacking. This study aimed to compare outcomes following laparoscopic versus open gastrectomy for gastric adenocarcinoma at a Western center. METHODS Eighty-seven consecutive patients who underwent laparoscopic gastrectomy from November 2005 to April 2013 were compared with 87 patients undergoing open resection during the same time period. Patients were matched for age, stage, body mass index, and procedure (distal subtotal vs. total gastrectomy). Endpoints were short- and long-term perioperative outcomes. RESULTS Overall, 65 patients (37 %) had locally advanced disease, and 40 (23 %) had proximal tumors. The laparoscopic approach was associated with longer operative time (median 240 vs.165 min; p < 0.01), less blood loss (100 vs.150 mL; p < 0.01), higher rate of microscopic margin positivity (9 vs.1 %; p = 0.04), decreased duration of narcotic and epidural use (2 vs. 4 days, p = 0.04, and 3 vs. 4 days, p = 0.02, respectively), decreased minor complications in the early (27 vs. 16 %) and late (17 vs. 7 %) postoperative periods (p < 0.01), decreased length of stay (5 vs. 7 days; p = 0.01), and increased likelihood of receiving adjuvant therapy (82 vs. 51 %; p < 0.01). There was no difference in the number of lymph nodes retrieved (median 20 in both groups), major morbidity, or 30-day mortality. CONCLUSIONS Laparoscopic gastrectomy for gastric adenocarcinoma is safe and effective for select patients in the West.


title: Autologous keratinocyte suspension in platelet concentrate accelerates and enhances wound healing - a prospective randomized clinical trial on skin graft donor sites: platelet concentrate and keratinocytes on donor sites.

text: BACKGROUND Wound healing involves complex mechanisms, which, if properly chaperoned, can enhance patient recovery. The abilities of platelets and keratinocytes may be harnessed in order to stimulate wound healing through the formation of platelet clots, the release of several growth factors and cytokines, and cell proliferation. The aim of the study was to test whether autologous keratinocyte suspensions in platelet concentrate would improve wound healing. The study was conducted at the Lausanne University Hospital, Switzerland in 45 patients, randomized to three different topical treatment groups: standard treatment serving as control, autologous platelet concentrate (PC) and keratinocytes suspended in autologous platelet concentrate (PC + K). Split thickness skin graft donor sites were chosen on the anterolateral thighs of patients undergoing plastic surgery for a variety of defects. Wound healing was assessed by the duration and quality of the healing process. Pain intensity was evaluated at day five. RESULTS Healing time was reduced from 13.9 ± 0.5 days (mean ± SEM) in the control group to 7.2 ± 0.2 days in the PC group (P < 0.01). An addition of keratinocytes in suspension further reduced the healing time to 5.7 ± 0.2 days. Pain was reduced in both the PC and PC + K groups. Data showed a statistically detectable advantage of using PC + K over PC alone (P < 0.01). CONCLUSION The results demonstrate the positive contribution of autologous platelets combined with keratinocytes in stimulating wound healing and reducing pain. This strikingly simple approach could have a significant impact on patient care, especially critically burned victims for whom time is of the essence. CLINICAL TRIAL REGISTRY INFORMATION: Protocol Record Identification Number: 132/03Registry URL: http://www.clinicaltrials.gov.


title: Cerebral Oxygenation, Superior Vena Cava Flow, Severe Intraventricular Hemorrhage and Mortality in 60 Very Low Birth Weight Infants.

text: BACKGROUND Brain vulnerability in the critically ill preterm newborn may be related to the burden of cerebral hypoxygenation and hypoperfusion during the immediate postnatal period. OBJECTIVE We determined the association between adverse outcomes [death or high grade intraventricular hemorrhage (IVH)] and continuous cerebral tissue oxygen saturation (rSO2), superior vena cava flow (SVCf) and cerebral fractional oxygen extraction (CFOE) in very low birth weight (VLBW) infants during the first 48 h of life. METHODS We studied a prospective cohort of 60 VLBW infants admitted to our neonatal intensive care unit within the first 6 h of life between March 2010 and June 2012. rSO2 (expressed as a number of summary measures) was continuously monitored with near-infrared spectroscopy (INVOS 5100 Somanetic) during the first 48 h of life, SCVf was measured at 4-6, 12, 24 and 48 h after birth, and CFOE was calculated. RESULTS The mean gestational age was 27.9 (SD 2.39); 8 infants died (13.3%) and 7 developed IVH grade III-IV: 1 in the alive group and 6 in the deceased group (p < 0.001). The odds ratio for death was 1.08 (95% CI: 1.015-1.15, p = 0.016) for each 10 periods of rSO2 values <40% in the first 48 h, and 4.2 (95% CI: 1.27-14.05, p = 0.019) for SVCf values <40 ml/kg/min. Among alive babies, mean CFOE decreased at 24, 36 and 48 h; among deceased babies it did not (p < 0.001). In the multivariate analyses, these results retained significance. CONCLUSIONS Both rSO2 ≤40% and SVCf <40 ml/kg/min independently increase the risk of death. The trend in CFOE supports the ischemic-hypoperfusion hypothesis as a mechanism for cerebral damage.


title: Radiation dosimetry of intraoperative cone-beam compared with conventional CT for radiofrequency ablation of osteoid osteoma.

text: BACKGROUND Radiofrequency (RF) ablation is the standard of care for the surgical treatment of non-spinal osteoid osteoma and has greatly reduced morbidity associated with surgical excision. Precise placement of the RF ablation probe is necessary to avoid incomplete ablation. Limiting radiation exposure is especially advantageous in the pediatric population in whom osteoid osteoma frequently occurs. The aim of this study was to compare the radiation dosimetry and clinical outcomes among patients treated with RF ablation using three different localization techniques. METHODS Case-control methods were used to analyze sixty-six cases. Patients were categorized into three treatment groups: (1) intraoperative three-dimensional cone-beam CT (computed tomography) imaging (O-Arm) with surgical navigation (StealthStation S7), (2) intraoperative three-dimensional imaging (O-Arm) only, and (3) radiology suite-based diagnostic CT imaging. Radiation dosimetry and clinical outcome were analyzed with use of the dose-length product and local-relapse-free survival, respectively. RESULTS Mean age was nineteen years for the twenty-three patients in group 1, twenty years for the seven patients in group 2, and nineteen years for the thirty-six patients in group 3. Mean follow-up was fifty-three months. The mean radiation dose for groups 1, 2, and 3 was 446.62, 379.78, and 1058.83 mGy-cm, respectively. Significant (p < 0.05) differences in the radiation dose existed between groups 1 and 3 and between groups 2 and 3, whereas no difference was found between groups 1 and 2. Local-remission-free survival at three years for groups 1, 2, and 3 was 84.7% (95% confidence interval [CI], 64.5% to 100%), 100% (95% CI, 100% to 100%), and 90.7% (95% CI, 80.7% to 100%), respectively. Fifty-eight (92%) of the sixty-three followed patients were asymptomatic at the latest follow-up visit. CONCLUSIONS RF ablation using intraoperative cone-beam CT imaging, with or without surgical navigation, was associated with a significantly lower radiation dose compared with ablation using a radiology suite-based CT technique. Ablation using each of the three imaging techniques was equally effective in treating osteoid osteomas with a similar risk of relapse.


title: Purification of Highly Active Alphavirus Replication Complexes Demonstrates Altered Fractionation of Multiple Cellular Membranes.

text: Positive-strand RNA viruses replicate their genomes in membrane-associated structures; alphaviruses and many other groups induce membrane invaginations called spherules. Here, we established a protocol to purify these membranous replication complexes (RCs) from cells infected with Semliki Forest virus (SFV). We isolated SFV spherules located on the plasma membrane and further purified them using two consecutive density gradients. This revealed that SFV infection strongly modifies cellular membranes. We removed soluble proteins, the Golgi membranes, and most of the mitochondria, but plasma membrane, endoplasmic reticulum (ER), and late endosome markers were retained in the membrane fraction that contained viral RNA synthesizing activity, replicase proteins, and minus- and plus-strand RNA. Electron microscopy revealed that the purified membranes displayed spherule-like structures with a narrow neck. This membrane enrichment was specific to viral replication, as such a distribution of membrane markers was only observed after infection. Besides the plasma membrane, SFV infection remodeled the ER, and the cofractionation of the RC-carrying plasma membrane and ER suggests that SFV recruits ER proteins or membrane to the site of replication. The purified RCs were highly active in synthesizing both genomic and subgenomic RNA. Detergent solubilization destroyed the replication activity, demonstrating that the membrane association of the complex is essential. Most of the newly made RNA was in double-stranded replicative molecules, but the purified complexes also produced single-stranded RNA as well as released newly made RNA. This indicates that the purification established here maintained the functionality of RCs and thus enables further structural and functional studies of active RCs.IMPORTANCE Similar to all positive-strand RNA viruses, the arthropod-borne alphaviruses induce membranous genome factories, but little is known about the arrangement of viral replicase proteins and the presence of host proteins in these replication complexes. To improve our knowledge of alphavirus RNA-synthesizing complexes, we isolated and purified them from infected mammalian cells. Detection of viral RNA and in vitro replication assays revealed that these complexes are abundant and highly active when located on the plasma membrane. After multiple purification steps, they remain functional in synthesizing and releasing viral RNA. Besides the plasma membrane, markers for the endoplasmic reticulum and late endosomes were enriched with the replication complexes, demonstrating that alphavirus infection modified cellular membranes beyond inducing replication spherules on the plasma membrane. We have developed here a gentle purification method to obtain large quantities of highly active replication complexes, and similar methods can be applied to other positive-strand RNA viruses.


The COVID-19 pandemic prevents patients with pulmonary hypertension from seeking medical help.


title: Novel polyomaviruses in shrews (Soricidae) with close similarity to human polyomavirus 12.

text: Shrews (family Soricidae) have already been reported to host microorganisms pathogenic for humans. In an effort to search for additional infectious agents with zoonotic potential, we detected polyomaviruses (PyVs) in common shrew, crowned shrew, and pygmy shrew (Sorex araneus, S. coronatus and S. minutus). From these, 11 full circular genomes were determined. Phylogenetic analysis based on large T protein sequences showed that these novel PyVs form a separate clade within the genus Alphapolyomavirus. Within this clade, the phylogenetic relationships suggest host-virus co-divergence. Surprisingly, one PyV from common shrew showed a genomic sequence nearly identical to that of the human polyomavirus 12 (HPyV12). This indicated that HPyV12 is a variant of a non-human PyV that naturally infects shrews. Whether HPyV12 is a bona fide human-tropic polyomavirus arising from a recent shrew-to-human transmission event or instead reflects a technical artefact, such as consumable contamination with shrew material, needs further investigation.


title: St John's wort (Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT.

text: Hypericum perforatum (St John's wort: SJW) has been extensively studied as an antidepressant in short-term trials, however little research has been conducted on longer-term efficacy.Our objective was to analyze the continuation data from a 26-week randomized, double-blind, controlled study of SJW (LI-160) vs. sertraline and placebo in major depressive disorder. 124 participant "responders" continued treatment after week 8, until week 26. They continued randomly assigned SJW (900-1 500 mg), sertraline (50-100 mg) or matching placebo.At week 26, on the primary outcome, Hamilton depression rating scale (HAM-D) completer scores were: SJW (6.6±4.5), sertraline (7.1±5.4) and placebo (5.7±5.4) with a significant effect for time (p=0.036). Comparisons between all treatments were however non-significant (p=0.61). This effect was mirrored on the other outcomes: the BDI, CGI-severity, CGI-improvement, and on intention-to-treat analyses.While the continuation data revealed an equivocal outcome between treatments at week 26, both SJW and sertraline were still therapeutically effective, with a pronounced "placebo-effect" impeding a significant result at week 26.


title: Relationship between personality traits and perceived internalized stigma in bipolar patients and their treatment partners.

text: Internalized stigma of mental disorders has significant negative outcomes for patients with bipolar disorder and their families. The aim of this study is to evaluate the association between personality traits and internalized stigma of mental disorders in bipolar patients and their treatment partners. Five different questionnaires were utilized in this study: (1) Demographic data questionnaire, (2) Millon Clinical Multiaxial Inventory-III (MCMI-III) for personality traits, (3) Internalized Stigma of Mental Illness (ISMI) for stigma, (4) Self Report Manic Inventory (SRMI) for mania and (5) Center for Epidemiological Studies-Depression Scale (CES-D) for depression. The scores of personality traits were combined to create externalizing and internalizing personality trait scores. Results showed that patients with bipolar disorder and their treatment partners both experienced internalized stigma of mental health disorders. There was a significant positive correlation between internalized stigma and internalizing personality traits, but not externalizing traits. In a multi-variate regression analysis, internalizing personality trait score was found to be a significant predictor of internalized stigma. In conclusion, patients with bipolar disorder and their treatment partners perceive higher level of internalized stigma of mental disorders if they have internalizing personality traits.


Insights from COVID-Related Accommodation Requests (Alternate Work Assignments) by Clinical Staff at an Academic Medical Center.


title: Triple-stapled quadrilateral anastomosis: a new technique for creation of an esophagogastric anastomosis.

text: BACKGROUND Esophagogastric anastomosis performed after esophagectomy is technically complex and often the source of postoperative complications. The best technique for this anastomosis remains a matter of debate. We describe a new all-stapled side-to-side anastomosis, which we refer to as triple-stapled quadrilateral anastomosis (TRIQ), that can be performed after minimally invasive surgery, and we report results of a retrospective evaluation of postoperative outcomes among the 60 patients in whom this anastomosis has been performed thus far. METHODS The anastomosis is created by apposition of the posterior walls of the esophagus and stomach. A linear stapler is applied to create a V-shaped posterior anastomotic wall. The anterior wall is closed in a gentle chevron-like shape with the use of 2 separate linear staplers, resulting in a wide quadrilateral anastomosis. The anastomosis is then wrapped with a greater omentum flap. RESULTS The patient group comprised 48 men and 12 women with a mean age of 67.8 years. Neoadjuvant chemotherapy was performed in 43 of these patients. Neither the thoracoscopic or laparoscopic procedure was converted to open surgery in any patient. The median operation time was 474 min (range 680-320 min). The intraoperative blood loss volume was 104.4 mL (range 240-30 mL). There were no anastomosis-related complications above Clavien-Dindo grade II. CONCLUSIONS TRIQ can be performed easily and safely, and good short-term outcome can be expected.


COVID-19 Q&A: A fish facility down to its core.


title: Real-time depth of anaesthesia assessment using strong analytical signal transform technique.

text: This paper introduces a new method addressing depth of anaesthesia (DoA) assessment for real-time monitoring. The new method uses a combination of phase and amplitude of electroencephalogram (EEG) signals to assess the DoA level. A strong analytical signal transform is applied to extract the phase and amplitude information of the recorded EEG signals. Based on the extracted features from the EEG signal in each different frequency band, a new DoA index is developed. The proposed new DoA index is evaluated using data from adult patients in an age range from 22 to 75 years. The results show that the new DoA index is able to detect the changing pattern of EEG signals early and agree with the clinical notes of an attending anaesthetist. The results are also closely correlated with the popular BIS index. Furthermore, the proposed new DoA index is able to detect the state changes earlier than the BIS index.


title: Lessons Learned: Gastric Motility Assessment During Driving Simulation.

text: In the era of technological advances and innovations in transportation technologies, application of driving simulators for the investigation and assessment of the driving process provides a safe and suitable testing environment. Although driving simulators are crucial for further improvements in transportation, it is important to resolve one of their main disadvantages-simulator sickness. Therefore, suitable methods for the assessment of simulator sickness are required. The main aim of this paper was to present a non-invasive method for assessing simulator sickness by recording gastric myoelectrical activity-electrogastrography. Open-source hardware for electrogastrography together with recordings obtained in 13 healthy volunteers is presented, and the main aspects of signal processing for artifact cancellation and feature extraction were discussed. Based on the obtained results, it was concluded that slow-wave electrical gastric activity can be recorded during driving simulation by following adequate recommendations and that proposed features could be beneficial in describing non-ordinary electrogastrography signals.


Response to "Does amantadine have a protective effect against COVID-19?"


title: Neuromuscular fatigability during repeated-sprint exercise in male athletes.

text: PURPOSE This study aimed to determine the pattern of neuromuscular fatigability that manifests during repeated-sprint running exercise. METHODS Twelve male participants (mean ± SD: age, 25 ± 6 yr; stature, 180 ± 7 cm; body mass, 77 ± 7 kg), currently training and competing in intermittent sprint sports, performed a repeated maximal sprint running protocol (12 × 30 m, 30-s rest periods). Pre- and postexercise twitch responses to transcutaneous motor point stimulation and transcranial magnetic stimulation were obtained to assess knee extensor neuromuscular and corticospinal function, respectively. Throughout the protocol, during alternate rest periods, blood lactate samples were taken and a single knee extensor maximal voluntary contraction (MVC) of the knee extensors was performed, with motor point stimulation delivered during and 2 s after, to determine voluntary activation (VA) and peripheral fatigue. RESULTS The repeated-sprint protocol induced significant increases in sprint time and blood [lactate] from the third sprint onwards (P < 0.001). Furthermore, knee extensor MVC, resting twitch amplitude, and VA were all significantly reduced after two sprints and reached their nadir after sprint 10 (Δ12%, Δ24%, Δ8%, P < 0.01, respectively). In line with a reduction in motor point-derived VA, there was also a reduction in VA measured with transcranial magnetic stimulation (Δ9%, P < 0.05) immediately after exercise. CONCLUSIONS These data are the first to demonstrate the development of neuromuscular fatigability of the knee extensors during and immediately after repeated-sprint exercise. Peripheral and central factors contributing to muscle fatigability were evident after two maximal sprints, and over half of the drop in postexercise MVC was due to supraspinal fatigue. Thus, peripheral, central, and supraspinal factors all contribute to the performance decrement and fatigability of the knee extensors after maximal repeated-sprint activity.


title: Combined effects of temperature and macronutrient balance on life-history traits in Drosophila melanogaster: implications for life-history trade-offs and fundamental niche.

text: Temperature and nutrition are amongst the most influential environmental determinants of Darwinian fitness in ectotherms. Since the ongoing climate warming is known to alter nutritional environments encountered by ectotherms, a precise understanding of the integrated effects of these two factors on ectotherm performance is essential for improving the accuracy of predictions regarding how ectotherms will respond to climate warming. Here we employed response surface methodology to examine how multiple life-history traits were expressed across a grid of environmental conditions representing full combinations of six ambient temperatures (13, 18, 23, 28, 31, 33 °C) and eight dietary protein:carbohydrate ratios (P:C = 1:16, 1:8, 1:4, 1:2, 1:1, 2:1, 4:1, 8:1) in Drosophila melanogaster. Different life-history traits were maximized in different regions in the two-dimensional temperature-nutrient space. The optimal temperature and P:C ratio identified for adult lifespan (13 °C and 1:16) were lower than those for early-life female fecundity (28 °C and 4:1). Similar divergence in thermal and nutritional optima was found between body mass at adult emergence (18 °C and P:C 1:1) and the rate of pre-adult development (28 °C and P:C 4:1). Pre-adult survival was maximized over a broad range of temperature (18-28 °C) and P:C ratio (1:8-8:1). These results indicate that the occurrence of life-history trade-offs is regulated by both temperature and dietary P:C ratio. The estimated measure of fitness was maximized at 23 °C and P:C 2:1. Based on the shape of the response surface constructed for this estimated fitness, we characterized the fundamental thermal and nutritional niche for D. melanogaster with unprecedented detail.


Stop routine work now, says BVA president.


title: A survey of the year 2007 literature on applications of isothermal titration calorimetry.

text: Elucidation of the energetic principles of binding affinity and specificity is a central task in many branches of current sciences: biology, medicine, pharmacology, chemistry, material sciences, etc. In biomedical research, integral approaches combining structural information with in-solution biophysical data have proved to be a powerful way toward understanding the physical basis of vital cellular phenomena. Isothermal titration calorimetry (ITC) is a valuable experimental tool facilitating quantification of the thermodynamic parameters that characterize recognition processes involving biomacromolecules. The method provides access to all relevant thermodynamic information by performing a few experiments. In particular, ITC experiments allow to by-pass tedious and (rarely precise) procedures aimed at determining the changes in enthalpy and entropy upon binding by van't Hoff analysis. Notwithstanding limitations, ITC has now the reputation of being the "gold standard" and ITC data are widely used to validate theoretical predictions of thermodynamic parameters, as well as to benchmark the results of novel binding assays. In this paper, we discuss several publications from 2007 reporting ITC results. The focus is on applications in biologically oriented fields. We do not intend a comprehensive coverage of all newly accumulated information. Rather, we emphasize work which has captured our attention with originality and far-reaching analysis, or else has provided ideas for expanding the potential of the method.


title: Identification of a novel transcriptional repressor (HEPIS) that interacts with nsp-10 of SARS coronavirus.

text: A novel gene was previously isolated from a cDNA library of human embryo lung tissue by its encoded protein, which interacts with non-structural protein 10 (nsp-10) of the severe acute respiratory syndrome coronavirus (SARS-CoV). The protein was named human embryo lung cellular protein interacting with SARS-CoV nsp-10 (HEPIS), and it is composed of 147 amino acids with several CK II phosphorylation sites. In the present study, we demonstrated that HEPIS was capable of suppressing chloramphenicol acetyltransferase (CAT) gene expression controlled by different enhancerelements in a transcription assay. HEPIS interacted specifically with the HSP70 TATA sequence, and not with various other enhancer elements in a binding test. Furthermore, we co-immunoprecipitated HEPIS with BTF3, a component of the RNA pol II initiation complex, and observed reduced proliferation of HeLa cells transfected with the HEPIS gene. Taken together, our results suggest that HEPIS may function as a potential transcriptional repressor.


Global public health. What's next for disease eradication?


title: Ghost ileostomy in anterior resection for bowel endometriosis: technical description.

text: OBJECTIVE To demonstrate our application of the "ghost ileostomy" in the setting of laparoscopic segmental bowel resection of a symptomatic bowel endometriosis nodule. DESIGN Technical "step-by-step" surgical video description (educative video) SETTING: University Tertiary Hospital. Institutional Review Board ruled that approval was not required for this study. Endometriosis affects the bowel in 3%-37% of all cases, and in 90% of these cases the rectum or sigmoid colon are also involved. Infiltration up to the rectal mucosa and invasion of >50% of the circumference have been suggested as an indication for bowel resection [1]. Apart from general risks (bleeding, infection, direct organ injuries) and bowel/bladder dysfunctions, anastomotic leakage is one of the most serious complications. In women with bowel and vaginal mucosa endometriosis involvement, there is a risk of rectovaginal fistula after concomitant rectum and vagina resections. Hence, for lower colorectal anastomosis, the use of temporal protective ileostomy is usually recommended in order to prevent these complications, but carries on stoma- related risks as hernia, retraction, dehydration, prolapse and necrosis. Ghost ileostomy is a specific technique firstly described in 2010, who gives an ease and safe option to prevent anastomotic leakage with maximum preservation of patient quality of life [2]. In case of anastomotic leakage, the ghost (or virtual) ileostomy is simply converted, under local anesthesia, into a loop (real) ileostomy by extracting the isolated loop through an adequate abdominal wall opening. In principle, avoiding a readmission for performing the closure of the ileostomy, with all the costs related, mean an important saving for the hospital management. Also, applying protective rectal tube in intestinal anastomosis may have a beneficial effect [3]. These options are performed by general surgeons in oncological scenarios, but their use in endometriosis has never been described. INTERVENTIONS In a 32-year-old woman with intense dysmenorrhea, deep dyspareunia, dyschesia, and cyclic rectal bleeding, a complete laparoscopic approach was performed using blunt and sharp dissection with cold scissors, bipolar dissector and a 5mm LigaSure Advance (Covidien, Valleylab, Norwalk, Connecticut). An extensive adhesiolysis restoring the pelvic anatomy and endometriosis excision were done. Afterwards, the segmental bowel resection was performed using linear and circular endo-anal stapler technique with immediate end-to-end bowel anastomosis and transit reconstitution. Once anastomosis was done, the terminal ileal loop was identified, and a window was made in the adjacent mesentery. Then, an elastic tape (vessel loop) was passed around the ileal loop, brought out of the abdomen through the right iliac fossa 5 mm port site incision and, fixed to the abdominal wall using non- absorbable stitches. Finally, a trans-anal tube was placed for five days. Patient was discharged in the 5th day postoperatively without any complications. The tape was removed 10 days after surgery and the loop dropped back. Two months after the intervention, the patient remains asymptomatic. CONCLUSION Ghost ileostomy is a simple, safe and feasible technique available in the setting of lower colorectal anastomosis following bowel endometriosis resection.


title: Obtaining adequate data to determine causes of opioid-related overdose deaths.

text: Current data collected by medical examiners and coroners are incomplete and inadequate to evaluate the factors that lead to fatalities involving prescription opioids. Determining cause of death is critically important. Two methods are proposed to improve consistency and accuracy in the collection and analysis of decedent data in opioid-related poisoning deaths. First, an improved death certificate is needed to collect evaluative data, including: extent to which opioids were judged to 1) cause, 2) contribute to, or 3) be present in investigated deaths; extent to which opioids as a cause of death were found 1) alone, 2) combined with other prescription drugs, 3) combined with alcohol, or 4) combined with illicit drugs; the time of death; the presence or absence of a valid prescription; and the estimated quantity of opioids taken proximal to death. Patient characteristics for analysis include age, gender, race/ethnicity, geographic area (particularly whether urban or rural), body mass index, duration of opioid usage and daily average dose during the last 2 weeks of life, and histories of chronic pain/medical conditions, substance abuse, and mental illness/psychiatric diagnoses. Second, expanding the scope of opioid toxicology categories used to classify and code cause-of-death data reported by death investigators would improve identification of individual drugs and classes most often associated with overdose deaths. Formulation-specific codes should be added to facilitate consistent recording of findings by death investigators and entry into national vital statistics databases.


title: Diagnosis of immediate hypersensitivity reactions to radiocontrast media.

text: BACKGROUND No consensus exists on the diagnostic approach for immediate hypersensitivity reactions (IHR) to radiocontrast media (RCM). We analyzed the diagnostic value of a skin test (ST), drug provocation test (DPT) and basophil activation test (BAT) in patients with symptoms compatible with IHR to RCM. METHODS Ninety patients with symptoms suggestive of IHR to RCM were evaluated. ST with a panel of RCM was performed, and if negative, DPT was carried out with the culprit RCM. If ST or DPT were positive, tolerance was assessed with an alternative RCM and BAT was carried out with the same panel used for ST. RESULTS Eight (8.9%) cases were confirmed as having IHR, 5 (62.5%) by ST and 3 (37.5%) by DPT. Five from those confirmed as IHR (62.5%) had a positive BAT. CONCLUSIONS Hypersensitivity to RCM was confirmed in 9%, by ST or DPT. BAT proved a valuable method for diagnosis.


title: Cost of Alteplase Has More Than Doubled Over the Past Decade.

text: BACKGROUND AND PURPOSE Intravenous alteplase (tissue-type plasminogen activator) has been shown to be cost-effective because of savings in long-term disability. In October of 2005, an increased DRG payment to hospitals for alteplase-treated stroke patients was introduced. We sought to describe the trends in the cost of alteplase over time, in comparison to trends in hospital reimbursement in the United States. METHODS Using publicly available information on the Centers for Medicare and Medicaid Services (CMS) website (www.cms.gov), we obtained CMS quarterly payment amounts between January 1, 2005, and October 1, 2014, for alteplase, listed as alteplase recombinant, per mg. CMS payment amounts are the manufacturer's average sales price+6% until April 2014, when it was lowered to +4.3%. Estimates for DRG base payments were calculated within the Medicare Provider and Analysis Review (MEDPAR) for fiscal years 2006 (DRG 559) and 2013 (MS DRGs 61, 62, and 63) as (DRG relative weights)×(standardized operating and capital amount). The consumer price index was also queried for all prescription drugs, urban areas, during the same study period as reference. RESULTS The CMS payment amount for alteplase per milligram was $30.50 in January 2005 and $64.30 in October 2014. Trends in the CMS payment amounts for alteplase increased by 111% between 2005 and 2014. The consumer price index for all prescription drugs increased by 30.2% in the same time frame. The base payment for alteplase-treated stroke admissions was $11 173 in 2006 and $12 064 in 2013, an 8% increase. CONCLUSIONS We found a striking increase in the cost of alteplase over the last decade, with a 100 mg vial now with a CMS payment of ≈$6400, a >100% increase over 10 years. During the same time frame, the DRG base payment to hospitals increased by only 8%, and alteplase cost increased from 27% of the payment in 2006 to 53% in 2013. Researchers and stroke physicians should be aware of these changes in drug costs and their impact on cost-effectiveness analyses.


title: The Application of Mobile Telehealth System to Facilitate Patient Information Presentation and Case Discussion.

text: Background: Most secondary transmission of COVID-19 is occurring in a hospital setting. To decrease person-to-person contact, health care providers have built many isolation wards. However, out-of-hospital professionals cannot access patient information, which has greatly reduced the efficiency of treatment; it is inconvenient for health care professionals to issue a case discussion with professionals from other wards. This article mainly introduces a mobile telehealth system (MTS) applied to facilitate patient information presentation and case discussion. Materials and Methods: The MTS searches patient information, which is stored in hospital intranet, and uses five modules to display patient information. By a request/response module and a real-time interaction module, we successfully conducted case discussions. In addition, we took measures in three areas to prevent patient information leakage. Results: The system uses mobile collaboration technology to present patient information and support case discussion. MTS was officially launched for 37 days, during which it has been used 3,061 times. Conclusions: The building of the MTS not only provides convenience and benefit for health care professionals, but also reduces person-to-person contact.


title: US variant porcine epidemic diarrhea virus: histological lesions and genetic characterization.

text: Porcine epidemic diarrhea virus (PEDV) was first recognized in pigs in the United States (US) in May 2013. Since then, the virus has spread to over 30 states and caused significant economic losses in the US swine industry due to the high mortality in newborn piglets less than 2 weeks of age. A mild-variant strain OH851 of PEDV in the US was first reported in January 2014. Here, we report histological changes in the small intestines of five piglets infected with the variant strain OH851 of PEDV. The lesions observed were milder, compared to the US classical strain of PEDV. Our study, for the first time, reports the histological lesions caused by the variant PEDV OH851 strain from a field case. In addition, genomic characterization demonstrated that US variant PEDV is more closely related to European-like strains in the first 1170 nt of the 5' spike gene but to US classical PEDV strains in the remaining genome, suggesting that the variant PEDV strain may derive from a recombinant event between the US classical and European-like PEDV strains.


title: Tracheal intubation with channeled vs. non-channeled videolaryngoscope blades.

text: Study objective Videolaryngoscopes can be fitted either with channeled or non-channeled blades, which may result in a different performance and success of tracheal intubation. We investigated the characteristics of the two different blade types of the commercially available KingVision™ videolaryngoscope. Design A prospective, randomized, single center investigation study in a urological operation unit of a tertiary hospital. Subjects and Methods Forty adult patients undergoing elective urological surgery in general anaesthesia with tracheal intubation were randomly allocated into group 1 (channeled videolaryngoscopy, n = 20) and group 2 (non-channeled videolaryngoscopy, n = 20). We measured the times from laryngoscope insertion to recognize the glottis and to conclude tracheal intubation. The number of laryngoscopy/intubation attempts and the degree of visual glottis exposure on a visual analog scale from 0 (glottis not visible) to 10 (glottis fully visible) was assessed. The lowest SpO2 value during airway management was recorded. Results There was no statistically significant difference in biometric data between the 2 groups. The time from the laryngoscope insertion to glottis recognition with the non-channeled blades was 5 (4-8) s as compared to the channeled ones with 11 (7-14) s (median and range; p = 0.01). Intubation duration was shorter with the channeled blades 17 (12-27) s vs. 29 (25-51) s (median and range; p < 0.001). Number of laryngoscopy/intubation attempts, grades for glottis visibility, intubation difficulty were not different. The lowest SpO2 was 98% in both groups. Conclusions Videolaryngoscopic glottis recognition time was longer and the total time to secure the airway was shorter with the channeled blades.


A Strategy for Improving U.S. Health Care Delivery - Conducting More Randomized, Controlled Trials.


Spinal Manipulative Therapy for Low Back Pain-Reply.


title: Fortifier and cream improve fat delivery in continuous enteral infant feeding of breast milk.

text: Premature and high-risk infants require accurate delivery of nutrients to promote appropriate growth. Continuous enteral feeding methods may result in significant fat and micronutrient loss. This study evaluated fat loss in enteral nutrition using current strategies for providing high-risk infants fortified human milk (HM). The fat content of HM was measured by IR analyzer in a simulated feeding system using the Kangaroo epumpTM and the MedFusionTM 2010 pump. Comparisons in fat loss were made between HM, HM supplemented with donor HM-derived fortifier Prolacta+H2MFTM (H2MF), and HM supplemented with H2MF and donor HM-derived cream ProlactCRTM (cream). When using the Kangaroo epumpTM, the addition of H2MF and cream to HM increased fat delivery efficiency from 75.0%±1.2% to 83.7%±1.0% (p<0.0001). When using the MedFusionTM 2010 pump, the addition of H2MF to HM increased fat delivery efficiency from 83.2%±2.8% to 88.8%±0.8% (p<0.05), and the addition of H2MF and cream increased fat delivery efficiency to 92.0%±0.3% (p<0.01). The addition of H2MF and cream to HM provides both the benefits of bioactive elements from mother's milk and increased fat delivery, making the addition of H2MF and cream an appropriate method to improve infant weight gain.


title: Epidemic curve and reproduction number of COVID-19 in Iran.

text: COVID-19 was first reported in Iran on 19 February, 2020. We estimated the initial basic reproduction number to be 4.86. With increasingly stringent public health measures, the effective reproduction number declined to below 1 after 2 months.


title: Do evidence summaries increase policy-makers' use of evidence from systematic reviews: A systematic review protocol.

text: BACKGROUND Systematic reviews are important for decision-makers. They offer many potential benefits but are often written in technical language, are too long, and do not contain contextual details which makes them hard to use for decision-making. There are many organizations that develop and disseminate derivative products, such as evidence summaries, from systematic reviews for different populations or subsets of decision-makers. This systematic review will assess the effectiveness of systematic review summaries on increasing policymakers' use of systematic review evidence and to identify the components or features of these summaries that are most effective. METHODS/DESIGN We will include studies of policy-makers at all levels as well as health-system managers. We will include studies examining any type of "evidence summary," "policy brief," or other products derived from systematic reviews that present evidence in a summarized form. The primary outcomes are the following: (1) use of systematic review summaries decision-making (e.g., self-reported use of the evidence in policy-making, decision-making) and (2) policy-maker understanding, knowledge, and/or beliefs (e.g., changes in knowledge scores about the topic included in the summary). We will conduct a systematic review of randomized controlled trials (RCTs), non-randomized controlled trials (NRCTs), controlled before-after studies (CBA), and interrupted time series (ITS) studies. DISCUSSION The results of this review will inform the development of future systematic review summaries to ensure that systematic review evidence is accessible to and used by policy-makers making health-related decisions.


title: The Effects of Community Home Visit and Peer Group Nutrition Intervention Delivery Platforms on Nutrition Outcomes in Low and Middle-Income Countries: A Systematic Review and Meta-Analysis.

text: Weak delivery systems reduce the potential of evidence-supp orted interventions to improve nutrition. We synthesized the evidence for the effectiveness of nutrition-specific intervention delivery platforms for improving nutrition outcomes in low and middle-income countries (LMIC). A systematic literature search for studies published from 1997 to June 2018 resulted in the inclusion of 83 randomized controlled trials (RCTs), quasi-randomized, and controlled before-after studies across a variety of delivery platforms. In this paper, we report on meta-analysed outcomes for community health worker (CHW) home visits and mother/peer group delivery platforms. Compared to care as usual, CHW home visits increased early initiation of breastfeeding (EIBF) (OR: 1.50; 95% CI: 1.12, 1.99; n = 10 RCTs) and exclusive breastfeeding (EBF) (OR: 4.42; 95% CI: 2.28, 8.56; n = 9 RCTs) and mother/peer groups were effective for improving children's minimum dietary diversity (OR: 2.34; 95% CI: 1.17, 4.70; n = 4) and minimum meal frequency (OR: 2.31; 95% CI: 1.61, 3.31; n = 3). Pooled estimates from studies using both home visit and group platforms showed positive results for EIBF (OR: 2.13; 95% CI: 1.12, 4.05; n = 9), EBF (OR: 2.43; 95% CI: 1.70, 3.46; n = 12), and < 5 wasting (OR: 0.77; 95% CI: 0.67, 0.89; n = 4). Our findings underscore the importance of interpersonal community platforms for improving infant and young child feeding practices and children's nutritional status in LMICs.


title: Netrin-1 dampens pulmonary inflammation during acute lung injury.

text: RATIONALE Acute lung injury (ALI) is an inflammatory disorder characterized by hypoxemia and diffuse infiltration of neutrophils into the alveolar space. The migration and extravasation of neutrophils is guided through positive guidance cues, such as chemokines. Recent work has identified the neuronal guidance protein netrin-1 to be a negative guidance cue for leukocyte migration and to hold antiinflammatory potential. OBJECTIVES To test the role of pulmonary netrin-1 during ALI. METHODS Pulmonary netrin-1 expression was evaluated during acute inflammation in vitro and in vivo; the netrin-1 promoter was studied using pGL4 luciferase reporter. ALI was induced through LPS inhalation and mechanical ventilation in wild-type, Ntn1(+/-), and A2BAR(-/-) animals. Exogenous netrin-1 was used to evaluate its impact on pulmonary inflammation. MEASUREMENTS AND MAIN RESULTS Wild-type animals demonstrated repression of pulmonary netrin-1 after LPS inhalation. In vitro studies confirmed the repression of netrin-1. Studies in the putative netrin-1 promoter identified a nuclear factor-kappaB-dependent mechanism to be involved in this repression. Ntn1(+/-) animals demonstrated increased inflammatory changes after LPS inhalation compared with Ntn1(+/+) animals. Reconstitution with netrin-1 dampened the infiltration of neutrophils and cytokine production in the alveolar space. This effect was dependent on the adenosine 2b receptor. The importance of netrin-1 for the control of pulmonary inflammation could be corroborated in a model of ventilator-induced lung injury. CONCLUSIONS Pulmonary netrin-1 levels are repressed during ALI. This results in pronounced pulmonary damage, an increased infiltration of neutrophils, and increased pulmonary inflammation. Exogenous netrin-1 significantly dampens the extent of ALI through the adenosine 2B receptor.


title: Reliability and validity of the Symptoms of Depression Questionnaire (SDQ).

text: Current measures for major depressive disorder focus primarily on the assessment of depressive symptoms, while often omitting other common features. However, the presence of comorbid features in the anxiety spectrum influences outcome and may effect treatment. More comprehensive measures of depression are needed that include the assessment of symptoms in the anxiety-depression spectrum. This study examines the reliability and validity of the Symptoms of Depression Questionnaire (SDQ), which assesses irritability, anger attacks, and anxiety symptoms together with the commonly considered symptoms of depression. Analysis of the factor structure of the SDQ identified 5 subscales, including one in the anxiety-depression spectrum, with adequate internal consistency and concurrent validity. The SDQ may be a valuable new tool to better characterize depression and identify and administer more targeted interventions.


Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.


title: A prospective, randomized, single-blind comparison of laparoscopic versus open sigmoid colectomy for diverticulitis.

text: OBJECTIVE The aim of this study was to compare open and laparoscopic sigmoid resection for diverticulitis with the patient and the nursing staff blinded to the surgical approach. METHODS A total of 113 patients scheduled for an elective sigmoidectomy were randomized to receive either a conventional open (54 patients) or a laparoscopic (59 patients) approach. Postoperatively, an opaque wound dressing was applied and left in place for 4 days, and patients from both groups were managed similarly. The primary endpoints for analysis were (1) postoperative pain; (2) duration of postoperative ileus; and (3) duration of hospital stay (ClinicalTrials.gov, number NCT 00453830). RESULTS The median duration of procedure was 165 minutes (range, 90-285) in the laparoscopy group and 110 minutes (range, 70-210) in the open group (P < 0.0001). The median delay between surgery and first bowel movement was 76 (range, 31-163) hours in the laparoscopy group versus 105 (range, 53-175) hours in the open group (P < 0.0001). The median score for maximal pain (assessed by a visual analog scale) was 4 (range, 1-10) in the laparoscopy group and 5 (range, 1-10) in the open group (P = 0.05). Finally, the median duration of hospital stay was 5 days (range, 4-69) in the laparoscopy group versus 7 days (range, 5-17) in the open group (P < 0.0001). CONCLUSION Laparoscopic sigmoid resection is associated with a 30% reduction in duration of postoperative ileus and hospital stay; by comparison, benefits in terms of postoperative pain appear less impressive, when the patient is blinded to the surgical technique.


title: Association of follow-up infarct volume with functional outcome in acute ischemic stroke: a pooled analysis of seven randomized trials.

text: BACKGROUND Follow-up infarct volume (FIV) has been recommended as an early indicator of treatment efficacy in patients with acute ischemic stroke. Questions remain about the optimal imaging approach for FIV measurement. OBJECTIVE To examine the association of FIV with 90-day modified Rankin Scale (mRS) score and investigate its dependency on acquisition time and modality. METHODS Data of seven trials were pooled. FIV was assessed on follow-up (12 hours to 2 weeks) CT or MRI. Infarct location was defined as laterality and involvement of the Alberta Stroke Program Early CT Score regions. Relative quality and strength of multivariable regression models of the association between FIV and functional outcome were assessed. Dependency of imaging modality and acquisition time (≤48 hours vs >48 hours) was evaluated. RESULTS Of 1665 included patients, 83% were imaged with CT. Median FIV was 41 mL (IQR 14-120). A large FIV was associated with worse functional outcome (OR=0.88(95% CI 0.87 to 0.89) per 10 mL) in adjusted analysis. A model including FIV, location, and hemorrhage type best predicted mRS score. FIV of ≥133 mL was highly specific for unfavorable outcome. FIV was equally strongly associated with mRS score for assessment on CT and MRI, even though large differences in volume were present (48 mL (IQR 15-131) vs 22 mL (IQR 8-71), respectively). Associations of both early and late FIV assessments with outcome were similar in strength (ρ=0.60(95% CI 0.56 to 0.64) and ρ=0.55(95% CI 0.50 to 0.60), respectively). CONCLUSIONS In patients with an acute ischemic stroke due to a proximal intracranial occlusion of the anterior circulation, FIV is a strong independent predictor of functional outcome and can be assessed before 48 hours, oneither CT or MRI.


title: Challenges in providing oral and dental health services in COVID-19 pandemic.

text: Coronavirus disease (COVID-19) pandemic has rendered the world completely unaware and off-balance. Most of the countries of the world are in a lockdown of varying severity to break the chain of transmission. Many non-essential healthcare practices have been shut down to impose social distancing against a population whose slogan has been freedom of movement. Several healthcare providers have also been caught off guard. Many are not well-versed in the use of transmission-based safeguards, and the dental community, is no different. In this article, we identify the challenges faced by the oral and dental care providers, whose procedures generate a significant amount of aerosol, which can be a significant source of disease transmission within the community. It further describes the dynamics of aerosol spread and various strategies to minimise aerosol generation. Guidelines for the delivery of emergency dental treatment are formulated based on different guidelines from various international dental associations and organisations.


title: Importance of repeat angiography in the diagnosis of iatrogenic anterior cerebral artery territory pseudoaneurysm following endoscopic sinus surgery.

text: Iatrogenic intracranial pseudoaneurysm formation and rupture are rare complications following endoscopic sinus surgery. Given the propensity for devastating neurologic injury after a relatively routine procedure, swift diagnosis and treatment is essential. The authors present a patient who experienced bifrontal intracranial hemorrhage and subarachnoid hemorrhage due to a ruptured iatrogenic frontopolar artery pseudoaneurysm caused during routine endoscopic sinus surgery. The pseudoaneurysm was not present on initial angiograms but became apparent radiographically 19 days after the endoscopic procedure. Endovascular treatment consisted of coil and Onyx embolization for sacrifice of the parent vessel proximal to the lesion. Early recognition of iatrogenic intracranial vascular injury is important to allow for rapid treatment. Initial radiographic studies may be unreliable in excluding the presence of a pseudoaneurysm so delayed repeat angiographic assessment is necessary, particularly in the presence of a high index of clinical suspicion. Endovascular techniques may provide an effective and safe option for the treatment of iatrogenic anterior cerebral artery distribution pseudoaneurysms.


title: Strategies to enhance the distribution of nanotherapeutics in the brain.

text: Convection enhanced delivery (CED) provides a powerful means to bypass the blood-brain barrier and drive widespread distribution of therapeutics in brain parenchyma away from the point of local administration. However, recent studies have detailed that the overall distribution of therapeutic nanoparticles (NP) following CED remains poor due to tissue inhomogeneity and anatomical barriers present in the brain, which has limited its translational applicability. Using probe NP, we first demonstrate that a significantly improved brain distribution is achieved by infusing small, non-adhesive NP via CED in a hyperosmolar infusate solution. This multimodal delivery strategy minimizes the hindrance of NP diffusion imposed by the brain extracellular matrix and reduces NP confinement within the perivascular spaces. We further recapitulate the distributions achieved by CED of this probe NP using a most widely explored biodegradable polymer-based drug delivery NP. These findings provide a strategy to overcome several key limitations of CED that have been previously observed in clinical trials.


title: Wound complications in 1145 consecutive transumbilical single-incision laparoscopic procedures.

text: OBJECTIVE To evaluate the wound complication rate in patients undergoing transumbilical single-incision laparoscopic (SIL) surgery. BACKGROUND SIL surgery claims to be less invasive than conventional laparoscopy. Small SIL series have raised concerns toward a higher wound complication rate related to the transumbilical incision. METHODS In a 44-month period, 1145 consecutive SIL procedures were included. The outcomes were assessed according to the intention-to-treat analysis principle. All procedures were followed for a minimum of 6 months postoperatively, and wound complications were recorded as bleeding, infection (superficial/deep), or hernia. Patients were classified as having a wound complication or not. For all comparisons, significance level was set at P<0.05. RESULTS Pure transumbilical SIL surgery was completed in 92.84%, and additional trocars were used in 7.16%. After a median follow-up of 22.1 (range, 7.67-41.11) months, 29 wound complications (2.53%) had occurred [bleeding 0%/infection 1.05% (superficial 0.9%/deep 0.17%)/early-onset hernia 0.09%/late-onset hernia 1.40%, respectively]. Factors associated with complications were higher patient body mass index (28.16±4.73 vs 26.40±4.68 kg/m; P=0.029), longer skin incisions (3.77±1.62 vs 2.96±1.06 cm; P=0.012), and multiport SIL versus single-port SIL (8.47% vs 2.38%; P=0.019) in complicated versus uncomplicated procedures. Furthermore, a learning curve effect was noted after 500 procedures (P=0.015). CONCLUSIONS With transumbilical SIL surgery, the incidence of wound complications is acceptable low and is further reduced once the learning curve has been passed.


title: CSF fistulas after transsphenoidal pituitary surgery--a solved problem?

text: OBJECTIVE Transsphenoidal surgery has been the gold standard for intra- and suprasellar lesions as well as some extrasellar pathologies for more than 40 years. This approach, with proper surgical expertise, is very safe with a low morbidity and mortality rate. However, as with every surgical treatment, complications can occur and may result in serious consequences for the patient. The goal of this article is to focus on cerebrospinal fluid (CSF) fistulas after transsphenoidal surgery and discuss possible risk factors and treatment options, including less common procedures in persistent CSF fistulas. METHODS Over a period of 24 months, 339 consecutive patients underwent a total of 363 transsphenoidal surgeries for different pathologies in our institution. There were 282 patients with pituitary adenomas and 57 patients with nonadenomateous lesions. RESULTS CSF fistulas occurred in total of six patients (1.77%), most frequently after surgery for nonadenomateous lesions (7%). The rate was only 0.7% after surgery for pituitary adenomas. In three patients, a simple resurgery with repacking of the sella using muscle, fat, and fibrin glue was performed. All three patients received a lumbar drainage for 5 days as well. All three patients had recurrent CSF fistulas despite surgical repair, requiring multiple resurgeries. In two patients, the implantation of a ventriculoperitoneal (vp) shunt with programmable valve for continuous lowering of the CSF pressure was required. In both patients, the vp shunt was explanted 2 to 3 months after the last proven rhinorrhea. Out of the 339, 2 patients developed meningitis due to CSF fistulas (0.59%). CONCLUSIONS CSF fistulas continue to present a problem after transsphenoidal surgery and require sophisticated technical measures to treat this complication. Failure after repair can occur and necessitates more intense treatment modalities. The usage of the transsphenoidal approach in other skull base lesions leads to higher rates of CSF fistulas and subsequently higher frequency of meningitis.


Management of rheumatic diseases in the time of covid-19 pandemic: perspectives of rheumatology practitioners from India.


title: [What to do about the deceased in suspected, probable and confirmed COVID-19 cases].

text: The SARS-CoV-2 beta-coronavirus outbreak, which first appeared in Wuhan, China, in late 2019, was declared a pandemic by the World Health Organization on March 11, 2020. The first confirmed case of COVID-19 was reported in Hungary on 4 March 2020, and the first patient infected with a new type of coronavirus died on 15 March. At the time of the deceased's death, there was no central, uniform directive clarifying the range of precautions required or providing a clear description of the safe handling of the corpse. Transporting the dead to a pathology department, storing them, possibly dissecting them, and then placing them in their final resting place, how these raise countless questions. The current legislation on communicable diseases and actions on the dead does not provide sufficient information on the performance of tasks after the death of a COVID-19 infected patient. On March 19, the national chief medical officer suspended the autopsies, except for forensic autopsies, but transportation and storage remained a problem. Although on March 21, 2020, the Department of Pathology of the Health Professional College of the Ministry of Human Resources issued a formal procedure, the recommendations contained therein represent a narrower spectrum of literature and need to be supplemented in several places. Unfortunately, data on post-mortem procedures are also under-represented in the international literature, given their importance. Another problem is that in the articles written for the treatment of the victims of crisis situations caused by epidemics, the available algorithms take into account different organizational and resource possibilities in addition to the legal environment different from Hungary, which circumstances make domestic adaptation significantly more difficult. In our article, in addition to the literature review, we formulate suggestions and recommendations for healthcare professionals involved in the treatment of COVID-19 suspected, probable and confirmed patients, as well as potentially affected pathology departments, which increase the safety of providers. * Orv Hetil. 2020; 161 (17): 713-722.


title: Corticospinal-Evoked Responses from the Biceps Brachii during Arm Cycling across Multiple Power Outputs.

text: Background: We examined corticospinal and spinal excitability across multiple power outputs during arm cycling using a weak and strong stimulus intensity. Methods: We elicited motor evoked potentials (MEPs) and cervicomedullary motor evoked potentials (CMEPs) in the biceps brachii using magnetic stimulation over the motor cortex and electrical stimulation of corticospinal axons during arm cycling at six different power outputs (i.e., 25, 50, 100, 150, 200 and 250 W) and two stimulation intensities (i.e., weak vs. strong). Results: In general, biceps brachii MEP and CMEP amplitudes (normalized to maximal M-wave (Mmax)) followed a similar pattern of modulation with increases in cycling intensity at both stimulation strengths. Specifically, MEP and CMEP amplitudes increased up until ~150 W and ~100 W when the weak and strong stimulations were used, respectively. Further increases in cycling intensity revealed no changes on MEP or CMEP amplitudes for either stimulation strength. Conclusions: In general, MEPs and CMEPs changed in a similar manner, suggesting that increases and subsequent plateaus in overall excitability are likely mediated by spinal factors. Interestingly, however, MEP amplitudes were disproportionately larger than CMEP amplitudes as power output increased, despite being initially matched in amplitude, particularly with strong stimulation. This suggests that supraspinal excitability is enhanced to a larger degree than spinal excitability as the power output of arm cycling increases.


title: Individualizing propofol dosage: a multivariate linear model approach.

text: In the last decades propofol became established as an intravenous agent for the induction and maintenance of both sedation and general anesthesia procedures. In order to achieve the desired clinical effects appropriate infusion rate strategies must be designed. Moreover, it is important to avoid or minimize associated side effects namely adverse cardiorespiratory effects and delayed recovery. Nowadays, to attain these purposes the continuous propofol delivery is usually performed through target-controlled infusion (TCI) systems whose algorithms rely on pharmacokinetic and pharmacodynamic models. This work presents statistical models to estimate both the infusion rate and the bolus administration. The modeling strategy relies on multivariate linear models, based on patient characteristics such as age, height, weight and gender along with the desired target concentration. A clinical database collected with a RugLoopII device on 84 patients undergoing ultrasonographic endoscopy under sedation-analgesia with propofol and remifentanil is used to estimate the models (training set with 74 cases) and assess their performance (test set with 10 cases). The results obtained in the test set comprising a broad range of characteristics are satisfactory since the models are able to predict bolus, infusion rates and the effect-site concentrations comparable to those of TCI. Furthermore, comparisons of the effect-site concentrations for dosages predicted by the proposed Linear model and the Marsh model for the same target concentration is achieved using Schnider model and a factorial design on the factors (patients characteristics). The results indicate that the Linear model predicts a dosage profile that is faster in leading to an effect-site concentration closer to the desired target concentration.


title: Endovascular reconstruction of vertebral artery occlusion prior to basilar thrombectomy in a series of six patients presenting with acute symptomatic basilar thrombosis.

text: INTRODUCTION AND PURPOSE Symptomatic acute basilar thrombosis is associated with a high mortality rate. Aggressive endovascular management has led to survival rates of 35-50%. We report the largest series of endovascular reconstruction of occluded dominant vertebral arteries prior to basilar thrombectomy. MATERIALS AND METHODS A prospective database since August 2010 of all neuroendovascular interventions was mined for patients undergoing basilar artery thrombolysis from which a group with vertebral artery reconstruction was selected. Patient charts were retrospectively reviewed for relevant clinical, technical, and outcome data. RESULTS From August 2010 to September 2012, six patients were identified who underwent vertebral reconstruction prior to basilar thrombectomy. Patients ranged in age from 42 to 57 years (mean 51 years). Mean time from symptoms until recanalization was approximately 6 h. Angiographic Thrombolysis in Cerebral Infarction IIB reconstitution of the basilar trunk was achieved in all cases. There were no technical complications. Two patients had care withdrawn secondary to massive completed brainstem infarction and poor neurological status post intervention. Three patients are now independent at 12, 14, and 31 months, respectively. One patient, after a follow-up of only 8 months, has achieved a modified Rankin Scale score of 3. CONCLUSIONS Complete vertebral occlusion below a basilar thrombus can be recanalized prior to thrombectomy. In this case series, 100% of the acutely occluded vertebral arteries could be opened using either anterograde or retrograde access. However, basilar thrombosis continues to be a devastating illness, with one-third of the patients in this series dying of progressive infarction despite angiographic patency of the large conduit vessels with technical complications.


title: Innate receptors and cellular defense against pulmonary infections.

text: In the United States, lung infections consistently rank in the top 10 leading causes of death, accounting for >50,000 deaths annually. Moreover, >140,000 deaths occur annually as a result of chronic lung diseases, some of which may be complicated by an infectious process. The lung is constantly exposed to the environment and is susceptible to infectious complications caused by bacterial, viral, fungal, and parasitic pathogens. Indeed, we are continually faced with the threat of morbidity and mortality associated with annual influenza virus infections, new respiratory viruses (e.g., SARS-CoV), and lung infections caused by antibiotic-resistant "ESKAPE pathogens" (three of which target the lung). This review highlights innate immune receptors and cell types that function to protect against infectious challenges to the respiratory system yet also may be associated with exacerbations in chronic lung diseases.


title: INCIDENTAL FINDINGS SUGGESTIVE OF COVID-19 IN ASYMPTOMATIC PATIENTS UNDERGOING NUCLEAR MEDICINE PROCEDURES IN A HIGH PREVALENCE REGION.

text: Infection with the novel coronavirus SARS-CoV-2 may remain asymptomatic, leading to under-recognition of the related disease, COVID-19, and to incidental findings in nuclear imaging procedures performed for standard clinical indications. Here, we report about our local experience in a region with high COVID-19 prevalence and dynamically increasing infection rates. Methods: Within the 8 day period of March 16-24, 2020, hybrid imaging studies of asymptomatic patients who underwent 18F-FDG-PET/CT or 131I-SPECT/CT for standard oncologic indications at our institution in Brescia, Italy, were analyzed for findings suggestive of COVID-19. Presence, radiological features and metabolic activity of interstitial pneumonia were identified, correlated with subsequent short-term clinical course and described in a case series. Results: Six of 65 patients (9%) that underwent PET/CT for various malignancies showed unexpected signs of interstitial pneumonia on CT and elevated regional FDG-avidity. Additionally, 1 of 12 patients who received radioiodine for differentiated thyroid carcinoma also showed interstitial pneumonia on SPECT/CT. 5/7 patients had subsequent proof of COVID-19 by RT-PCR. The remaining 2 patients were not tested immediately but underwent quarantine and careful monitoring. Conclusion: Incidental findings suggestive of COVID-19 may not be infrequent in hybrid imaging of asymptomatic patients, in regions with expansive spread of SARS-CoV-2. Nuclear medicine services should prepare accordingly.


title: Operational considerations and challenges of biochemistry laboratories during the COVID-19 outbreak: an IFCC global survey.

text: Objectives The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on COVID-19 conducted a global survey to understand how biochemistry laboratories manage the operational challenges during the coronavirus disease 2019 (COVID-19) pandemic. Materials and methods An electronic survey was distributed globally to record the operational considerations to mitigate biosafety risks in the laboratory. Additionally, the laboratories were asked to indicate the operational challenges they faced. Results A total of 1210 valid submissions were included in this analysis. Most of the survey participants worked in hospital laboratories. Around 15% of laboratories restricted certain tests on patients with clinically suspected or confirmed COVID-19 over biosafety concerns. Just over 10% of the laboratories had to restrict their test menu or services due to resource constraints. Approximately a third of laboratories performed temperature monitoring, while two thirds of laboratories increased the frequency of disinfection. Just less than 50% of the laboratories split their teams. The greatest reported challenge faced by laboratories during the COVID-19 pandemic is securing sufficient supplies of personal protective equipment (PPE), analytical equipment, including those used at the point of care, as well as reagents, consumables and other laboratory materials. This was followed by having inadequate staff, managing their morale, anxiety and deployment. Conclusions The restriction of tests and services may have undesirable clinical consequences as clinicians are deprived of important information to deliver appropriate care to their patients. Staff rostering and biosafety concerns require longer-term solutions as they are crucial for the continued operation of the laboratory during what may well be a prolonged pandemic.


Reply to Tognù et al: regional anesthesia for proximal humerus surgery during COVID-19 pandemic.


title: An unexpected cause of pericardial effusion.

text: We present a case of pericardial effusion due to embolization of a fragment of an inferior vena cava (IVC) filter, with subsequent perforation of the right ventricle. This is a rare and unexpected cause of pericardial effusion. Fracture or embolization of IVC filters is a relatively uncommon complication, but these events may have serious clinical implications. Although IVC filters are often placed with the intent of removal, the device in many patients is never removed. The long-term implications of IVC filter placement must be kept in mind when making decisions about device placement and subsequent removal.


title: Variability is adaptability…also during weaning!

text: Heart rate variability in the frequency domain can now be obtained at the bedside in the ICU. Promising data suggest that it may help to characterize a patient response to a spontaneous breathing trial. Refinement of the analysis could even help to predict the outcome of extubation or at least help to detect early patients at risk of failure. It is possible that combining this type of analysis, the breathing pattern variability, and other objective indices could help clinicians in the decision-making process of weaning and extubation.


title: Correction of retractile penis with subcutaneous soft silicone penile implant.

text: We report a novel solution for patients suffering from adult acquired retractile penis. Three patients complained of retractile penis (when standing) and/or prepubic recession. Physical examination confirmed the shaft of the penis was buried with only the glans visible. All three patients reported lower levels of self-confidence, self-esteem, and sexual confidence prior to their procedure. The three patients received surgical treatment with the insertion of a subcutaneous soft silicone penile implant and two of the three also received removal of the suprapubic fat pad. Over one year post operatively, the penile shaft and glans was visible and appeared natural. All patients reported an increase in self-confidence and self-esteem. The insertion of a subcutaneous soft silicone penile implant may prove to be a viable solution to reverse retractile penis and to increase patient quality of life when compared to more invasive current surgical treatments.


title: Principled decisions and virtuous care: an ethical assessment of the Siaarti guidelines for allocating intensive care resources.

text: This article sets forth ethical principles for responding to extraordinary circumstances in which the demand for medical care threatens to overwhelms available resources, as in the COVID-19 pandemic. In light of these principles, the author then assesses the ethics of the SIAARTI guidelines for rationing ICU beds and ventilators under such circumstances.


title: Early Secondary Prevention in Transient Ischemic Attack (TIA) and Minor Stroke.

text: PURPOSE OF REVIEW The purpose of this study was to review recent literature on the early secondary prevention in transient ischemic attack (TIA) and minor stroke. RECENT FINDINGS The result of Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events and the secondary analysis of Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) have shown that treatment with clopidogrel and aspirin for 21 days reduced the risk of recurrent stroke with no significant increase in bleeding risk. Triple antiplatelet therapy with aspirin, clopidogrel, and dipyridamole resulted in a significant increase in major (including fatal) bleeding with no significant reduction in the recurrent stroke or TIA. The early treatment of patients with TIA or minor stroke with clopidogrel and aspirin for 21 days was effective in reducing the risk of recurrent stroke with no significant increase in bleeding risk. Most stroke guidelines have been updated to reflect this recommendation.


Commentary: treatment of femoropopliteal in-stent restenosis for patients with diabetes: do we have an answer to the DEBATE?


title: Typhus Group Rickettsiosis, Texas, USA, 2003-2013.

text: We characterized the epidemiology of typhus group rickettsiosis in Texas, USA. During 2003-2013, a total of 1,762 cases were reported to the state health department. The number of diagnosed cases and geographic expansion increased over time. Physician awareness is critical to diagnose and effectively treat rickettsial infections.


title: Intraoperative awareness risk, anesthetic sensitivity, and anesthetic management for patients with natural red hair: a matched cohort study.

text: PURPOSE The red-hair phenotype, which is often produced by mutations in the melanocortin-1 receptor gene, has been associated with an increase in sedative, anesthetic, and analgesic requirements in both animal and human studies. Nevertheless, the clinical implications of this phenomenon in red-haired patients undergoing surgery are currently unknown. METHODS In a secondary analysis of a prospective trial of intraoperative awareness, red-haired patients were identified and matched with five control patients, and the relative risk for intraoperative awareness was determined. Overall anesthetic management between groups was compared using Hotelling's T(2) statistic. Inhaled anesthetic requirements were compared between cohorts by evaluating the relationship between end-tidal anesthetic concentration and the bispectral index with a linear mixed-effects model. Time to recovery was compared using Kaplan-Meier analysis, and differences in postoperative pain and nausea/vomiting were evaluated with Chi square tests. RESULTS A cohort of 319 red-haired patients was matched with 1,595 control patients for a sample size of 1,914. There were no significant differences in the relative risk of intraoperative awareness (relative risk = 1.67; 95% confidence interval 0.34 to 8.22), anesthetic management, recovery times, or postoperative pain between red-haired patients and control patients. The relationship between pharmacokinetically stable volatile anesthetic concentrations and bispectral index values differed significantly between red-haired patients and controls (P < 0.001), but without clinical implications. CONCLUSION There were no demonstrable differences between red-haired patients and controls in response to anesthetic and analgesic agents or in recovery parameters. These findings suggest that perioperative anesthetic and analgesic management should not be altered based on self-reported red-hair phenotype.


title: Endoscopic diverticulotomy using Ligasure™.

text: INTRODUCTION Endoscopic treatment of Zenker diverticulum is considered feasible, effective and safe. The use of the Ligasure™ vessel sealer provides adequate and quick dissection of tissue, achieving effective haemostasis. PATIENTS AND METHODS Retrospective, descriptive study of all patients with Zenker diverticulum who were treated by endoscopic diverticulotomy using Ligasure™. The procedure was performed in the endoscopy unit under deep sedation controlled by the endoscopist. Patients were subsequently admitted for observation and, after discharge, were followed-up in the outpatient clinic. RESULTS Eight patients, 5 women and 3 men, mean age 78±15 years, 25% ASA I, 36% ASA II, 14% ASA III and 25% ASA IV. Main symptom: dysphagia. Diverticula size: 1-7cm. Technical success: 100%. COMPLICATIONS one patient with upper gastrointestinal bleeding. Average stay: 24h. Seven patients: asymptomatic; one patient with partial improvement, requiring repeat endoscopic intervention. Surgery and morbidity and mortality: 0%. CONCLUSION The treatment of Zenker diverticulum by endoscopic diverticulotomy using the Ligasure™ vessel sealer is highly effective, fast and safe, and could be considered the treatment of choice.


title: [Position Paper for the State of the Art Application of Respiratory Support in Patients with COVID-19 - German Respiratory Society].

text: Against the background of the pandemic caused by infection with the SARS-CoV-2, the German Society for Pneumology and Respiratory Medicine (DGP e.V.), in cooperation with other associations, has designated a team of experts in order to answer the currently pressing questions about therapy strategies in dealing with COVID-19 patients suffering from acute respiratory insufficiency (ARI).The position paper is based on the current knowledge that is evolving daily. Many of the published and cited studies require further review, also because many of them did not undergo standard review processes.Therefore, this position paper is also subject to a continuous review process and will be further developed in cooperation with the other professional societies.This position paper is structured into the following five topics:1. Pathophysiology of acute respiratory insufficiency in patients without immunity infected with SARS-CoV-22. Temporal course and prognosis of acute respiratory insufficiency during the course of the disease3. Oxygen insufflation, high-flow oxygen, non-invasive ventilation and invasive ventilation with special consideration of infectious aerosol formation4. Non-invasive ventilation in ARI5. Supply continuum for the treatment of ARIKey points have been highlighted as core statements and significant observations. Regarding the pathophysiological aspects of acute respiratory insufficiency (ARI), the pulmonary infection with SARS-CoV-2 COVID-19 runs through three phases: early infection, pulmonary manifestation and severe hyperinflammatory phase.There are differences between advanced COVID-19-induced lung damage and those changes seen in Acute Respiratory Distress Syndromes (ARDS) as defined by the Berlin criteria. In a pathophysiologically plausible - but currently not yet histopathologically substantiated - model, two types (L-type and H-type) are distinguished, which correspond to an early and late phase. This distinction can be taken into consideration in the differential instrumentation in the therapy of ARI.The assessment of the extent of ARI should be carried out by an arterial or capillary blood gas analysis under room air conditions and must include the calculation of the oxygen supply (measured from the variables of oxygen saturation, the Hb value, the corrected values of the Hüfner number and the cardiac output). In principle, aerosols can cause transmission of infectious viral particles. Open systems or leakage systems (so-called vented masks) can prevent the release of respirable particles. Procedures in which the invasive ventilation system must be opened, and endotracheal intubation must be carried out are associated with an increased risk of infection.The protection of personnel with personal protective equipment should have very high priority because fear of contagion must not be a primary reason for intubation. If the specifications for protective equipment (eye protection, FFP2 or FFP-3 mask, gown) are adhered to, inhalation therapy, nasal high-flow (NHF) therapy, CPAP therapy or NIV can be carried out according to the current state of knowledge without increased risk of infection to the staff. A significant proportion of patients with respiratory failure presents with relevant hypoxemia, often also caused by a high inspiratory oxygen fraction (FiO2) including NHF, and this hypoxemia cannot be not completely corrected. In this situation, CPAP/NIV therapy can be administered under use of a mouth and nose mask or a respiratory helmet as therapy escalation, as long as the criteria for endotracheal intubation are not fulfilled.In acute hypoxemic respiratory insufficiency, NIV should be performed in an intensive care unit or in a comparable unit by personnel with appropriate expertise. Under CPAP/NIV, a patient can deteriorate rapidly. For this reason, continuous monitoring with readiness to carry out intubation must be ensured at all times. If CPAP/NIV leads to further progression of ARI, intubation and subsequent invasive ventilation should be carried out without delay if no DNI order is in place.In the case of patients in whom invasive ventilation, after exhausting all guideline-based measures, is not sufficient, extracorporeal membrane oxygenation procedure (ECMO) should be considered to ensure sufficient oxygen supply and to remove CO2.


Age at Diagnosis as a Relative Contraindication for Intervention in Facial Nonmelanoma Skin Cancer.


title: A history of pediatric anesthesia: a tale of pioneers and equipment.

text: The history of pediatric anesthesia is fascinating in terms of how inventive anesthesiologists became over time to address the needs for advances in surgery. We have many pioneers and heroes. We hope you will enjoy this brief overview and that we have not left out any of the early contributors to our speciality. Obviously there is insufficient space to include everyone.


title: Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events.

text: The popularity of adipose-derived cell therapy has increased over the last decade, and the number of studies published annually is growing. However, concerns regarding safety in the setting of previous malignancy or the use of allogeneic cells have been raised. We therefore aimed to systematically review all clinical studies using adipose-derived cell therapy to identify reported adverse events with a special focus on risk of thromboembolic, immunological, and oncological safety concerns. Our systematic search resulted in 70 included studies involving more than 1,400 patients that were treated with adipose-derived cell therapy. Safety assessment method was not described in 32 of the included studies. For studies involving systemic or cardiac administration, one case of pulmonary thromboembolism and cases of both myocardial and cerebral infarctions were described. In the setting of allogeneic cell therapy studies, where the production of specific antibodies toward donor cells was examined, it was noted that 19%-34% of patients develop antibodies, but the consequence of this is unknown. With regard to oncological safety, only one case of breast cancer recurrence was identified out of 121 patients. Adipose-derived cell therapy has so far shown a favorable safety profile, but safety assessment description has, in general, been of poor quality, and only adverse events that are looked for will be found. We encourage future studies to maintain a strong focus on the safety profile of cell therapy, so its safeness can be confirmed. Stem Cells Translational Medicine 2017;6:1786-1794.


title: Increasing similarity in the dynamics of influenza in two adjacent subtropical Chinese cities following the relaxation of border restrictions.

text: The drivers of influenza seasonality remain heavily debated, especially in tropical/subtropical regions where influenza activity can peak in winter, during the rainy season, or remain constant throughout the year. We compared the epidemiological and evolutionary patterns of seasonal influenza epidemics in Hong Kong and Shenzhen, two adjacent cities in subtropical southern China. This comparison represents a unique natural experiment, as connectivity between these two cities has increased over the past decade. We found that, whilst summer influenza epidemics in Shenzhen used to peak 1-3 months later than those in Hong Kong, the difference decreased after 2005 (P<0.0001). Phylogenetic analysis revealed that influenza isolates from Shenzhen have become genetically closer to those circulating in Hong Kong over time (P = 0.045). Furthermore, although Shenzhen isolates used to be more distant from the global putative source of influenza viruses than isolates from Hong Kong (P<0.001), this difference has narrowed (P = 0.02). Overall, our study reveals that influenza activities show remarkably distinct epidemiological and evolutionary patterns in adjacent subtropical cities and suggests that human mobility patterns can play a major role in influenza dynamics in the subtropics.


Breastfeeding and Respiratory Antivirals: Coronavirus and Influenza.


title: Is it time for the 4th P in nurse practitioner education? Physical assessment, pharmacology, pathophysiology, and procedures: A systematic review.

text: BACKGROUND AND PURPOSE Nurse practitioners (NPs) perform diagnostic and clinical procedure skills in the acute, specialty, urgent, and primary care settings. Nurse practitioners surveyed on readiness for practice report a lack of confidence and education preparation for performing selected advanced diagnostic and skills. As NPs gain independent, full practice scope, it is imperative advanced diagnostic and procedure skills used in practice are taught in nurse practitioner curriculum. The purpose of this review is to document a systematic review of the literature, answering the following question: Among primary care NPs, does current program curriculum align with current procedures and skills in theclinical setting? METHODS PubMed, Cochrane, Scopus, CINAHL, and Embase were searched between inception and 2018 using the search terms "advanced practice nursing, clinical competence, diagnostic techniques or procedures, and primary health care." Following the preferred reporting items for systematic reviews and meta-analysis guidelines, nine articles were included in the synthesis. CONCLUSION There is scant research regarding NP educational preparation of skills and procedures. Study findings indicate that programs are not teaching all the procedures deemed important. Education should promote improved congruence between the skills and procedures taught in program curricula and those used in clinical practice. IMPLICATIONS FOR PRACTICE It is critical to complete an education practice survey measuring skill and procedure preparation and competency at graduation. Survey results will determine whether skill and procedure guidelines are indicated for NP education. A recommendation may include minimal skills and procedure for all nurse practitioner curricula.


Covid-19: Trust withdraws guidance that doctors need not put "covid-19" on death certificates.


title: Ileocecal Anastomosis Type Significantly Influences Long-Term Functional Status, Quality of Life, and Healthcare Utilization in Postoperative Crohn's Disease Patients Independent of Inflammation Recurrence.

text: OBJECTIVES Anastomotic reconstruction following intestinal resection in Crohn's disease (CD) may employ side-to-side anastomosis (STSA; anti-peristaltic orientation) or end-to-end anastomosis (ETEA). Our aim was to determine the impact of these two anastomotic techniques on long-term clinical status in postoperative CD patients. METHODS We performed a comparative effectiveness study of prospectively collected observational data from consented CD patients undergoing their first or second ileocolonic bowel resection and re-anastomosis between 2008 and 2012, in order to assess the association between anastomosis type and 2-year postoperative quality of life (QoL), healthcare utilization, disease clinical or endoscopic recurrence, use of medications, and need for repeat resection. RESULTS One hundred and twenty eight postoperative CD patients (60 STSA and 68 ETEA) were evaluated. At 2 years postoperatively, STSA patients had higher rates of emergency department visits (33.3% vs. 14.7%; P=0.01), hospitalizations (30% vs. 11.8%; P=0.01), and abdominal computed tomography scans (50% vs. 13.2%; P<0.001) with lower QoL (mean short inflammatory bowel disease questionnaire 47.9 vs. 53.4; P=0.007). There was no difference among the two groups in the 30 day surgical complications and 2-year patterns of disease activity, CD medication requirement, endoscopic recurrence, and need for new surgical management (all P > 0.05). CONCLUSIONS At 2 years postoperatively, CD patients with ETEA demonstrated better QoL and less healthcare utilization compared with STSA, despite having similar patterns of disease recurrence and CD treatment. These findings suggest that surgical reconstruction of the bowel as an intact tube (ETEA) contribute to improved functional and clinical status in patients with CD.


Medtronic subsidiary pays $17m to settle allegations of kickbacks to US doctors.


title: Chikungunya virus envelope-specific human monoclonal antibodies with broad neutralization potency.

text: Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics in Africa and Asia. Infection by CHIKV is often characterized by long-lasting, incapacitating arthritis, and some fatal cases have been described among elderly and newborns. Currently, there is no available vaccine or specific treatment against CHIKV. Blood B cells from a donor with history of CHIKV infection were activated, immortalized, amplified, and cloned. Two human mAbs against CHIKV, 5F10 and 8B10, were identified, sequenced, and expressed in recombinant form for characterization. In a plaque reduction neutralization test, 5F10 and 8B10 show mean IC(50) of 72 and 46 ng/ml, respectively. Moreover, both mAbs lead to a strong decrease in extracellular spreading of infectious viral particles from infected to uninfected cells. Importantly, the mAbs neutralize different CHIKV isolates from Singapore, Africa, and Indonesia, as well as O'nyong-nyong virus, but do not recognize other alphaviruses tested. Both mAbs are specific for the CHIKV envelope: 5F10 binds to the E2 glycoprotein ectodomain and 8B10 to E1 and/or E2. In conclusion, these two unique human mAbs strongly, broadly, and specifically neutralize CHIKV infection in vitro and might become possible therapeutic tools against CHIKV infection, especially in individuals at risk for severe disease. Importantly, these mAbs will also represent precious tools for future studies on host-pathogen interactions and the rational design of vaccines against CHIKV.