title: Physiological and pharmacological properties of a modified Brooke ileostomy: justification for retaining the most distal ileum.

text: PURPOSE The traditional Brooke ileostomy removed the last 8-15 cm of the ileum due to concern of occurrence of terminal ileal Crohn's disease, vide infra the ileocolic sphincter was removed. Retaining all the terminal ileum has the potential of retaining the ileocolic sphincter. Our aim was to investigate whether a high-pressure zone existed within the last few centimetres of the ileum and its response to pharmacological stimuli. METHODS A balloon manometry catheter was introduced into the stoma of 16 patients who had formation of an end ileostomy (ileocolic sphincter retained, ICS). Recordings were made at 1 cm intervals from the meatus in order to identify the maximum intra-luminal resting and intra-abdominal pressure. At the point of maximum resting pressure, the response to phenylephrine (10% gel) and glyceryl trinitrate (GTN) (0.2% paste) was recorded. Results were recorded using an Ohmeda Oestiva 5 manometry system (in millimeter of mercury) and data were analysed using ANOVA. Results were compared with 13 historical controls (ileocolic sphincter removed). RESULTS There was no significant difference in resting intra-abdominal pressure between the two groups (historical controls 8.5 ± 3.0 mmHg; ICS 9.0 ± 3.2 mmHg), p = NS. The maximum resting intra-luminal pressure in ICS patients exceeded historical controls 16 ± 2.9 vs 10.0 ± 2.5 mmHg, p < 0.001. In ICS patients, phenylephrine increased the resting pressure to 26.0 ± 3.5 mmHg, p < 0.001. In historical controls, the pressure remained unchanged, 12 ± 4.7 mmHg, p = NS. Subsequent addition of GTN to both groups lowered maximum intra-luminal pressure to pre-study values, 10 ± 4.2 mmHg (ICS) and 7 ± 3.5 mmHg (controls), p = NS. CONCLUSION Retention of the ileocolic sphincter in a modified Brooke ileostomy preserves a physiological high-pressure zone, the properties of which can be modified by pharmacological agents.


title: Drug treatment options for the 2019-new coronavirus (2019-nCoV).

text: As of January 22, 2020, a total of 571 cases of the 2019-new coronavirus (2019-nCoV) have been reported in 25 provinces (districts and cities) in China. At present, there is no vaccine or antiviral treatment for human and animal coronavirus, so that identifying the drug treatment options as soon as possible is critical for the response to the 2019-nCoV outbreak. Three general methods, which include existing broad-spectrum antiviral drugs using standard assays, screening of a chemical library containing many existing compounds or databases, and the redevelopment of new specific drugs based on the genome and biophysical understanding of individual coronaviruses, are used to discover the potential antiviral treatment of human pathogen coronavirus. Lopinavir /Ritonavir, Nucleoside analogues, Neuraminidase inhibitors, Remdesivir, peptide (EK1), abidol, RNA synthesis inhibitors (such as TDF, 3TC), anti-inflammatory drugs (such as hormones and other molecules), Chinese traditional medicine, such ShuFengJieDu Capsules and Lianhuaqingwen Capsule, could be the drug treatment options for 2019-nCoV. However, the efficacy and safety of these drugs for 2019- nCoV still need to be further confirmed by clinical experiments.


title: Morphological and biochemical characterization of the membranous hepatitis C virus replication compartment.

text: Like all other positive-strand RNA viruses, hepatitis C virus (HCV) induces rearrangements of intracellular membranes that are thought to serve as a scaffold for the assembly of the viral replicase machinery. The most prominent membranous structures present in HCV-infected cells are double-membrane vesicles (DMVs). However, their composition and role in the HCV replication cycle are poorly understood. To gain further insights into the biochemcial properties of HCV-induced membrane alterations, we generated a functional replicon containing a hemagglutinin (HA) affinity tag in nonstructural protein 4B (NS4B), the supposed scaffold protein of the viral replication complex. By using HA-specific affinity purification we isolated NS4B-containing membranes from stable replicon cells. Complementing biochemical and electron microscopy analyses of purified membranes revealed predominantly DMVs, which contained viral proteins NS3 and NS5A as well as enzymatically active viral replicase capable of de novo synthesis of HCV RNA. In addition to viral factors, co-opted cellular proteins, such as vesicle-associated membrane protein-associated protein A (VAP-A) and VAP-B, that are crucial for viral RNA replication, as well as cholesterol, a major structural lipid of detergent-resistant membranes, are highly enriched in DMVs. Here we describe the first isolation and biochemical characterization of HCV-induced DMVs. The results obtained underline their central role in the HCV replication cycle and suggest that DMVs are sites of viral RNA replication. The experimental approach described here is a powerful tool to more precisely define the molecular composition of membranous replication factories induced by other positive-strand RNA viruses, such as picorna-, arteri- and coronaviruses.


title: The Association Between Serum Uric Acid Level and Prognosis in Critically Ill Patients, Uric Acid as a Prognosis Predictor.

text: BACKGROUND Uric acid is synthesized from xanthine via xanthine oxidase as an end-product of purine metabolism. Uric acid is a major non-enzymatic antioxidant in the blood, and it exerts a protective action on vitamin C. There are a limited number of ICU studies related to uric acid, which is a valuable prognostic biomarker. This study aimed to evaluate the utility of uric acid as a biomarker in predicting the outcomes of critically ill patients. METHODS This prospective, multi-centered cohort study included 128 patients from two different intensive care units who met the study inclusion criteria between May 2017 and October 2017. Study inclusion criteria were first admission to the ICU, age > 18 years, and ICU stay > 24 hours. In each patient, baseline serum uric acid levels were measured after acute interventions, prior to the initiation of the treatment process. RESULTS When comparing the last uric acid levels of patients, the median last uric acid levels in the non-survival and survival groups were significantly different (p = 0.001). A last uric acid level > 4.5 mg/dL was associated with a 2.638 times higher risk (relative risk) for mortality. According to ROC analysis, a cutoff value of 1.5 for the ratio between the last two uric acid levels had a sensitivity of 0.21 and a specificity of 0.96 for predicting mortality. A 1.5-fold increase in the uric acid level yielded a positive predictive value of 92.6% and a negative predictive value of 65.2% for predicting mortality. The median uric level in the patient subset with ARDS, was significantly higher than those without ARDS (p = 0.001). CONCLUSIONS Results of this study indicate that a time-dependent increase in uric acid levels can be used as an important biomarker for predicting mortality in critically ill patients; further, uric acid levels should possibly be included in the current mortality risk scoring systems. In addition, elevation of uric acid, a simple, inexpensive, and readily available biomarker, may provide guidance in the diagnostic stage and in predicting clinical outcomes of patients with sepsis or ARDS.


title: Feline lectin activity is critical for the cellular entry of feline infectious peritonitis virus.

text: Feline infectious peritonitis is a lethal disease of felids caused by systemic infection with a feline coronavirus. Here, we report identification and analysis of the feline homologue to the human lectin DC-SIGN and show that it is a coreceptor for virulent strains of serotype 1 and serotype 2 feline coronaviruses.


title: Comparison of dopamine and norepinephrine in the treatment of shock.

text: BACKGROUND Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about whether one agent is superior to the other. METHODS In this multicenter, randomized trial, we assigned patients with shock to receive either dopamine or norepinephrine as first-line vasopressor therapy to restore and maintain blood pressure. When blood pressure could not be maintained with a dose of 20 microg per kilogram of body weight per minute for dopamine or a dose of 0.19 microg per kilogram per minute for norepinephrine, open-label norepinephrine, epinephrine, or vasopressin could be added. The primary outcome was the rate of death at 28 days after randomization; secondary end points included the number of days without need for organ support and the occurrence of adverse events. RESULTS The trial included 1679 patients, of whom 858 were assigned to dopamine and 821 to norepinephrine. The baseline characteristics of the groups were similar. There was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P=0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001). A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1044 patients with septic shock or the 263 with hypovolemic shock (P=0.03 for cardiogenic shock, P=0.19 for septic shock, and P=0.84 for hypovolemic shock, in Kaplan-Meier analyses). CONCLUSIONS Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events. (ClinicalTrials.gov number, NCT00314704.)


title: Prevalence of respiratory pathogens during two consecutive respiratory syncytial virus seasons at a tertiary medical care center.

text: AIM To determine the etiological profiles of lower respiratory tract infection (LRI) in neonates during respiratory syncytial virus(RSV) season, and to define the clinical features of RSV-related infection and others. METHODS The retrospective study included newborn infants who were hospitalized for LRI during the two consecutive RSV seasons, and then tested for possible etiological agent by multiplex real-time polymerase chain reaction. All relevant data were reviewed, and the clinical characteristics of RSV-related infection were compared to those of others. RESULTS Of 224 patients, 160 (71 %) were positive for at least one potentially causative agent. Of them, 65 % had RSV, and 15 % had more than on ecausative agent (co-infection). The RSV group had more the findings of respiratory distress (p< 0.01), abnormal chest radiography (p< 0.01), need for intensive care (p< 0.01), and duration of oxygen requirement (p< 0.01) but less fever on admission and duration of antibiotic use (for both, p< 0.01), and no longer hospital stay. Need of intensive care nursery was more common in patients with co-infection than others (25 % vs. 6.5 %, p< 0.01). CONCLUSIONS This study highlighted that RSV was the most frequent agent in neonates hospitalized for LRI during the season, with a more severe clinical course than other detected pathogens. The disease severity of RSV infection may have seemed to be increased by the presence of coinfection and abnormal chest radiography.


title: Osteoarthritis year 2012 in review: clinical.

text: Epidemiologic and clinical research in osteoarthritis (OA) continues to focus on analytic and descriptive epidemiology, and the role of both nonpharmacologic and pharmacologic therapies in the management of OA, respectively. A systematic literature review was conducted using PubMed for the period between September 1, 2011 and March 31, 2012. Selected articles in these areas are discussed in this narrative review article.


Annex #1 as of 8 June 2020 to: Management of SARS-CoV-2 infection: recommendations of the Polish Association of Epidemiologists and Infectiologists as of March 31, 2020.


title: Exploration of adherence and patient experiences with DOACs one year after switching from vitamin-K antagonists- insights from the switching study.

text: BACKGROUND Current UK and European guidelines recommend anticoagulated patients prescribed warfarin with time in therapeutic range (TTR) <65% be considered for DOAC therapy. There has been considerable concern that adherence with DOACs may be poor compared with warfarin. Little is known about the patient experience of switching from warfarin to DOAC and how patients manage their DOAC long term. Our aim was to conduct focus groups exploring patient's previous experiences with warfarin, their current experience with DOACs, their adherence to DOACs and the long-term service provision they envisage. METHODS Patients enrolled on the Switching Study who had been switched from warfarin to a DOAC >1year previously were invited to participate in focus groups. Two focus groups for atrial fibrillation (AF) and two for secondary prevention of venous thromboembolism (VTE) patients were held at anticoagulation clinics in South London, UK. Data was analysed using framework analysis to extract dominant themes. RESULTS Five VTE patients and 15 AF patients attended the focus groups. Dominant themes that emerged were: indication specific anticoagulation prioritisation, warfarin as a necessary inconvenience, DOACs as the anticoagulant of choice, concerns regarding DOAC monitoring, high adherence to DOACs and desire for long-term access to specialist anticoagulation services. DISCUSSION VTE patients prioritised anticoagulation over other therapies whereas AF patients did not. All participants reported high levels of adherence to DOACs. Patients derived confidence from long-term management in specialist anticoagulation clinics stating a preference to be managed in such a service.


Dramatic presentation of acquired TTP associated with COVID-19.


title: Overall codon usage pattern of enterovirus 71.

text: Hand, foot, and mouth disease (HFMD) is a systemic illness in children and is usually caused by enterovirus 71 (EV71). To provide new insights into the genetic features of EV71 and the relationship between the overall codon usage pattern of this virus and that of humans, values for relative synonymous codon usage (RSCU), effective number of codons (ENC), codon adaptation index (CAI), and nucleotide composition were calculated and analyzed. The relationship between ENC values and (G+C)₃% suggests that, although nucleotide composition plays an important role in shaping the overall codon usage pattern of this virus, other factors also affect this pattern. In addition, the negative correlation between the CAI value and (G+C)₃% suggests that the secondary structure of the EV71 coding sequence caused by its nucleotide composition can affect gene expression. Moreover, there was no significant correlation between ENC and CAI, suggesting that gene expression does not play a role in shaping the overall codon usage pattern of EV71. The overall codon usage pattern of the EV71 virus is only partly similar to the general codon pattern of human, suggesting that, although EV71 has co-evolved with humans for extended periods, mutation pressure played an important role in shaping the virus's overall codon usage pattern. These results revealed that the EV71 virus has developed a subtle strategy during evolution for adapting to environmental changes in its host cells solely by means of mutation pressure.


Coronavirus is spreading under the radar in US homeless shelters.


title: Community acquired respiratory and gastrointestinal viral infections: challenges in the immunocompromised host.

text: PURPOSE OF REVIEW Newer molecular diagnostic techniques have advanced the field of clinical microbiology and infectious diseases, particularly with respect to characterizing the role that community acquired viruses play in the clinical course and outcomes of the immunocompromised host. This review will examine recent studies describing the impact of adenovirus, rhinovirus, hepatitis E and norovirus in the course of solid organ and stem cell transplant recipients, as well as their epidemiology and implications for infection prevention and control. RECENT FINDINGS Adenovirus transmission is poorly understood; recent studies increasingly point to reactivation of latent infection in the immunocompromised host. Rhinovirus shedding can persist for weeks after acute viral infection, complicating hospital infection control policies. Hepatitis E is increasingly recognized as a potential pathogen in the stem cell and solid organ transplant population, and should be considered in the work-up for unexplained liver function test abnormalities. Similar to rhinovirus, norovirus shedding from the gastrointestinal tract may persist for months in the immunocompromised host; infected patients are at a higher risk for transmitting norovirus compared with infected healthcare workers. SUMMARY Additional studies are needed, particularly with respect to transmission, for these community acquired viral infections, which often have devastating consequences in the immunocompromised patient population.


Point-of-care ultrasound in COVID-19 pandemic.


title: Alloplastic adjuncts in breast reconstruction.

text: BACKGROUND There has been an increasing role of acellular dermal matrices (ADMs) and synthetic meshes in both single- and two-stage implant/expander breast reconstruction. Numerous alloplastic adjuncts exist, and these vary in material type, processing, storage, surgical preparation, level of sterility, available sizes and cost. However, there is little published data on most, posing a significant challenge to the reconstructive surgeon trying to compare and select the most suitable product. The aims of this systematic review were to identify, summarize and evaluate the outcomes of studies describing the use of alloplastic adjuncts for post-mastectomy breast reconstruction. The secondary aims were to determine their cost-effectiveness and analyze outcomes in patients who also underwent radiotherapy. METHODS Using the PRSIMA 2009 statement, a systematic review was conducted to find articles reporting on the outcomes on the use of alloplastic adjuncts in post-mastectomy breast reconstruction. Multiple databases were searched independently by three authors (Cabalag MS, Miller GS and Chae MP), including: Ovid MEDLINE (1950 to present), Embase (1980 to 2015), PubMed and Cochrane Database of Systematic Reviews. RESULTS Current published literature on available alloplastic adjuncts are predominantly centered on ADMs, both allogeneic and xenogeneic, with few outcome studies available for synthetic meshes. Outcomes on the 89 articles, which met the inclusion criteria, were summarized and analyzed. The reported outcomes on alloplastic adjunct-assisted breast reconstruction were varied, with most data available on the use of ADMs, particularly AlloDerm(®) (LifeCell, Branchburg, New Jersey, USA). The use of ADMs in single-stage direct-to-implant breast reconstruction resulted in lower complication rates (infection, seroma, implant loss and late revision), and was more cost effective when compared to non-ADM, two-stage reconstruction. The majority of studies demonstrated inferior outcomes in ADM assisted, two-stage expander-to-implant reconstruction compared to non-ADM use. Multiple studies suggest that the use of ADMs results in a reduction of capsular contracture rates. Additionally, the reported beneficial effects of ADM use in irradiated tissue were varied. CONCLUSIONS ADM assisted two-stage breast reconstruction was associated with inferior outcomes when compared to non-ADM use. However, alloplastic adjuncts may have a role in single stage, direct-to-implant breast reconstruction. Published evidence comparing the long-term outcomes between the different types of adjuncts is lacking, and further level one studies are required to identify the ideal product.


title: Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study.

text: Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log (des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment.


title: COVID-19: the wrong target for healthcare liability claims

text: Regrettably, after a first moment of appreciation and praise of the citizens for healthcare personnel facing COVID 19 pandemia, numerous episodes of actions taken against them on the issue of their legal liability followed. Impelling is to start an argumentation on this problem that aims to establish a shared conduct in dealing with them. The authors propose a basis for discussion on which to begin a constructive debate.


title: ACE2 the Janus-faced protein - from cardiovascular protection to severe acute respiratory syndrome-coronavirus and COVID-19.

text: Angiotensin converting enzyme 2 (ACE2) is the major enzyme responsible for conversion of Ang II into Ang-(1-7). It also acts as the receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2, which causes Coronavirus Disease (COVID)-19. In recognition of the importance of ACE2 and to celebrate 20 years since its discovery, the journal will publish a focused issue on the basic science and (patho)physiological role of this multifunctional protein.


title: SARS-CoV-2 Infection in Febrile Neonates.

text: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in pediatric patients are mild or asymptomatic. However, infants have emerged at higher risk of hospitalization and severe outcomes in pediatric coronavirus disease 2019 (COVID-19). We report a case series of four full term neonates hospitalized with fever and found to have SARS-CoV-2 infection with a spectrum of illness severities. Two neonates required admission to the intensive care unit for respiratory insufficiency and end organ involvement. Half of the patients were found to have a co-infection. One neonate received antiviral therapy with remdesivir and is, to our knowledge, the youngest patient to receive this drug for COVID-19. All neonates had favorable outcomes.


title: Minimally invasive surgical management of a second trimester pregnancy in a rudimentary uterine horn.

text: BACKGROUND Pregnancy in a rudimentary uterine horn is a rare form of ectopic pregnancy with a high risk of rupture. Management usually involves excision of the rudimentary horn. If diagnosed after the first trimester, it has been managed in the past by laparotomy. CASE A primigravid woman was found on routine ultrasound to have a rudimentary horn pregnancy. The diagnosis was confirmed on MRI, and a thin uterine wall was demonstrated. Management comprised fetal injection of potassium chloride followed by complete laparoscopic excision of the rudimentary horn at 16 weeks' gestation. CONCLUSION Laparoscopic management of a mid-trimester rudimentary horn pregnancy is feasible, but expert radiological characterization is required for optimal surgical planning.


title: Coronavirus Disease among Persons with Sickle Cell Disease, United States, March 20-May 21, 2020.

text: Sickle cell disease (SCD) disproportionately affects Black or African American persons in the United States and can cause multisystem organ damage and reduced lifespan. Among 178 persons with SCD in the United States who were reported to an SCD-coronavirus disease case registry, 122 (69%) were hospitalized and 13 (7%) died.


Safety Signal for the Simple Double Ablation Regimen When Using the Barrx 360 Express Radiofrequency Ablation Balloon Catheter.


title: Gastric plication for morbid obesity: a systematic review.

text: BACKGROUND Gastric plication is a new bariatric procedure. Controversies exist regarding this emerging surgery. We herein present a comprehensive review of the literature regarding gastric plication approach. METHODS Advanced Pub Med search combining the MeSH terms "Gastric plication", OR "Gastric greater curvature plication" yielded 213 abstracts. Abstracts were screened for articles in English and articles on human subjects yielding 130. Further searches revealed 121 titles to be unrelated to gastric plication. The remaining nine abstracts were analyzed for their full texts. Two articles were excluded because, one was a commentary on another article, and the other was a released ASMBS policy on gastric plication. In the end, there were seven articles published on gastric plication. RESULTS A total of 307 patients had undergone gastric plication. The mean operative time range was 40 to 150 min. The median length of hospital stay ranged between 1.3 and 1.9 days. In respect to excess weight loss (EWL), at 6 months, it ranged from 54 to 51 %, while at 12 months 67-53.4 %. The longest follow-up was 3 years with a mean of 57 % EWL. CONCLUSION Laparoscopic gastric plication is still in its infancy. Prospective randomized studies comparing gastric plication to other well established bariatric procedures are needed to prove the reliability and metabolic effectiveness of such new procedure.


title: Perineal sigmoidopexy utilizing transanal endoscopic microsurgery (TEM) to treat full thickness rectal prolapse: a feasibility trial in porcine and human cadaver models.

text: BACKGROUND Perineal approaches for rectal prolapse repair have low complication rates but high recurrence rates, while abdominal approaches that include sigmoidopexy have lower recurrence rates but higher complication rates. To optimize both recurrence and complication rates, we developed a novel procedure that uses transanal endoscopic microsurgery (TEM) to perform a sigmoidopexy via a perineal approach. METHODS We created a rectal prolapse model in six swine and two human cadavers using a previously published technique. The rectum was mobilized and eviscerated transanally. After marking the planned point of sigmoid transection, the rectum was returned to the peritoneal cavity. A TEM proctoscope was inserted transanally alongside the rectum, and the lateral sigmoid colon walls were sutured to the sacrum. The sigmoid colon was then transected where previously planned, and a primary sigmoid anastomosis was performed. Total operative time, sigmoidopexy operative time, and suture security were measured and compared to standard rectosigmoidectomy and abdominal sigmoidopexy times. RESULTS No sigmoid colon, iliac vessel, bladder, or ureteral injuries occurred. At least two sigmoidopexy sutures were secure on inspection in all animals and human cadavers, with increasing success of secure suture placement as experience increased. Operative length was similar to traditional abdominal sigmoidopexy. CONCLUSIONS TEM sigmoidopexy is technically feasible. This approach has the potential to reduce the recurrence rate associated with perineal approaches alone, but further study is needed to confirm this hypothesis.


title: Palliative care interventions in intensive care unit patients - a systematic review protocol.

text: BACKGROUND Even though data suggest that palliative care (PC) improves patient quality of life, caregiver burden, cost, and intensive care unit (ICU) length of stay, integration of PC in the ICU is far from being universally accepted. Poor understanding of what PC provides is one of the barriers to the widespread implementation of their services in ICU. Evidence suggests that the availability of specialist PC is lacking in most European countries and provided differently depending on geographical location. The aim of this systematic review is to compare the numbers and types of PC interventions and gauge their impact on stakeholder outcomes and ICU resource utilisation. METHODS We will undertake a systematic review of the published peer-reviewed journal articles; our search will be carried out MEDLINE, Embase, Cochrane, CINAHL, and PsycINFO. The search strategy will include variations in the term 'palliative care' and 'intensive care'. All studies with patient populations undergoing palliative care interventions will be selected. Only full-text articles will be considered, and conference abstracts excluded. There will be no date restrictions on the year of publications or on language. The primary aim of the present study is to compare the numbers and types of PC interventions in ICU and their impact on stakeholder (patient, family, clinician, other) outcomes. Reporting of findings will follow the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. DISCUSSION This review will provide insight into the implementation of palliative care in ICU, elucidate differences between countries and health systems, reveal most effective models, and contribute to identifying research priorities to improve outcomes. SYSTEMATIC REVIEW REGISTRATION International Prospective Register of Systematic reviews PROSPERO ( CRD42018094315 ).


title: A total laparoscopic approach reduces the infertility rate after ileal pouch-anal anastomosis: a 2-center study.

text: OBJECTIVE To assess the infertility rate after laparoscopic ileal pouch-anal anastomosis (IPAA). BACKGROUND Total proctocolectomy with IPAA is known to be associated with postoperative infertility in open surgery, which may be caused by pelvic adhesions affecting the fallopian tubes. However, fertility after laparoscopic IPAA has never been assessed. METHODS All patients who underwent a total laparoscopic IPAA between 2000 and 2011 and were aged 45 years or less at the time of operation and 18 years or more at the time of data collection were included. The patients answered a fertility questionnaire by telephone. All demographic and perioperative data were prospectively collected. The results were compared with those of controls undergoing laparoscopic appendectomy. RESULTS Sixty-three patients were included. The mean age at the time of surgery was 31 ± 9 years (range 14-44). IPAA was performed for ulcerative colitis in 73% of the cases and familial adenomatous polyposis in 17%. The mean follow-up after IPAA was 68 ± 33 months (range 6-136). Fifty-six patients answered the questionnaire (89%). Half of them already had a child before IPAA. Fifteen patients attempted pregnancy after IPAA, of which 11 (73%) were able to conceive, resulting in 10 ongoing pregnancies and 1 miscarriage. The global infertility rate was 27%. There was no difference in fertility over time compared with the 14 controls who attempted pregnancy during the same period (90% vs 86% at 36 months, P = 0.397). CONCLUSIONS The infertility rate appears to be lower after laparoscopic IPAA than after open surgery.


Covid-19: NHS will restart some paused services this week.


Re: "Maxillofacial Trauma Management During COVID-19: Multidisciplinary Recommendations," by Edwards et al. and "A Guide to Facial Trauma Triage and Precautions in the COVID-19 Pandemic" by Hsieh et al.


title: Hyperglycemia, oxidative and nitrosative stress affect antiviral, inflammatory and apoptotic signaling of cultured thymocytes.

text: A high prevalence of various infectious diseases is reported in diabetic patients, which may suggest impaired innate immunity against different pathogen-associated molecular patterns. This study investigated the effects of hyperglycemia, oxidative stress (H(2)O(2)), nitric oxide (NO) and peroxynitrite (ONOO(-)) on the modulation of antiviral (MDA-5, IRF-3 and phospho-IRF-3), inflammatory (NF-kappaB) and pro/anti-apoptotic molecules (Bax and Bcl-2) in BALB/c mice thymocytes. Each of the experimental conditions, except the weakest NO concentration, resulted in down-regulation of MDA-5, IRF-3 and phospho-IRF-3. In contrast, each of the experimental conditions elicited up-regulation of NF-kappaB, Bcl-2 and Bax. These results suggest that hyperglycemia, oxidative and nitrosative stress may contribute to the reduced immunity of the host by altering the MDA-5/IRF-3/phosphoIRF-3 axis, as well as contributing to the mechanisms of inflammatory reaction via increased NF-kappaB, and to augmented turnover rate of thymocyte cells via Bcl2/Bax up-regulation.


Covid-19: doctors in final trimester of pregnancy should avoid direct patient contact.


title: Treatment of intracranial aneurysms using the pipeline flow-diverter embolization device: a single-center experience with long-term follow-up results.

text: BACKGROUND AND PURPOSE Flow-diverting devices now offer a new treatment alternative for cerebral aneurysms. We present the results of a large single-center series of patients treated with the PED, including long-term follow-up. MATERIALS AND METHODS Between November 2008 and September 2011, sidewall aneurysms with a wide neck (≥4 mm) or unfavorable dome-neck ratio (≤1.5); large/giant, fusiform, dissecting, blister-like, and recurrent sidewall aneurysms; aneurysms at difficult angles; and aneurysms in which a branch was originating directly from the sac were treated with the PED. Patients were premedicated with dual antiplatelet medications. Data, including demographics, aneurysm features, clinical presentation, complications, results, and follow-up information, for up to 2 years are presented. RESULTS Two hundred fifty-one aneurysms in 191 patients were treated. Of these, 96 (38.3%) were large or giant (≥10 mm). In 34/251 (13.5%), PEDs were used for retreatment. Adjunctive coiling was performed in 11 aneurysms (2.1%). The mean number of devices per aneurysm was 1.3. One aneurysm ruptured in the fourth month posttreatment (0.5%), and symptomatic in-construct stenosis was detected in 1 patient (0.5%) treated with percutaneous transarterial angioplasty. Any event rate was 27/191 (14.1%), with a permanent morbidity of 1% and mortality of 0.5%. Control angiography was available in 182 (95.3%) patients with 239 (95.2%) aneurysms. In 121 aneurysms (48.2%), 1- to 2-year control angiography was available. The aneurysm occlusion rate was 91.2% in 6 months, increasing to 94.6%. CONCLUSIONS Use of the PED is safe, efficacious, and durable in cerebral aneurysm treatment, with low morbidity-mortality and high occlusion rates as confirmed with mid- to long-term control angiography.


title: Mechanical Thrombectomy Using the Trevo ProVue in 50 Consecutive Patients with Anterior Circulation Stroke: A Single-Center Experience after Approval of the Stent Retriever in Japan.

text: Mechanical thrombectomy using the stent retriever has been proven to be effective for select patients with acute ischemic stroke. We evaluated our early experience using the device after its approval in 2014 in Japan, with a special emphasis on the occlusion site. Fifty consecutive endovascular revascularization procedures for treating anterior acute large vessel occlusion were performed using the Trevo ProVue as the first-line device at our institute between April 2015 and March 2016. Focusing on the involvement of the M1-M2 bifurcation with deployment or retrieval of the stent retriever, we regarded the middle cerebral artery M1 mid-portion as the boundary and divided the cases into proximal (n = 26) and distal (n = 24) groups. We assessed the overall clinical outcome and compared the outcome between the two groups. Among 50 patients (median age, 80 years; National Institutes of Health Stroke Scale score (NIHSS) score, 20), successful (modified Thrombolysis in Cerebral Infarction score (TICI) 2b or 3) or complete revascularization (TICI 3) was achieved in 41 patients (82%; 88% in the proximal group vs 75% in the distal group, P = 0.28) and in 27 patients (54%; 73% vs 33%, P = 0.01), respectively. Symptomatic intracranial hemorrhage occurred in three patients (6%; 4% vs 8%, P = 0.60). A good outcome (mRS score 0 to 2) was obtained in 25 patients at 90 days (50%; 54% vs 46%, P = 0.78). Mechanical thrombectomy using the Trevo ProVue was safe and effective in patients with acute cerebral artery occlusion, especially for proximal occlusions. The efficacy of the procedure for distal occlusions was somewhat inferior to those for proximal occlusions, which might be resolved by next generation devices.


Transanal minimally invasive surgery (TAMIS) versus transanal endoscopic microsurgery (TEM): is one better than the other?


title: Health Equity, Social Policy, and Promoting Recovery from COVID-19.

text: The COVID-19 pandemic has revealed starkly and publicly the close interconnections between social and economic inequality, health equity, and population health. To better understand what social policies would best promote population health, economic recovery, and preparedness for future pandemics, we must look both upstream and abroad for inspiration. In this essay, I argue for a suite of near-term and longer-term interventions, including universal health insurance and paid sick leave, upgraded wage insurance policies, tax reform, investments in parental leave, child care, and education, and upgraded government record systems. Policies that equalize the distribution of the social determinants of health and promote social solidarity will also improve population health and economic performance and allow us to confront future pandemics more successfully.


title: Drug-regulatable cancer cell death induced by BID under control of the tissue-specific, lung cancer-targeted TTS promoter system.

text: Gene therapy and virotherapy are among the approaches currently being used to treat lung cancer. The success of cancer gene therapy depends on treatments where different types of tumors can be selectively targeted and destroyed without affecting normal cells and tissue. Previously, we described a promoter system (TTS) that we designed that is specifically targeted to lung cancer cells but which does not affect other types of cells including stem cells. In our study, we have enhanced the utility of the TTS system by inserting the pro-apoptotic gene BH3 domain interacting death agonist (Bid) into the TTS promoter system (TTS/Bid) to create a drug regulatable lung cancer-specific gene therapy. A recombinant adenoviral vector was used to introduce TTS/Bid (Ad-TTS/Bid) into lung cancer cells. BID expression and apoptosis occurred in A549 pulmonary adenocarcinoma cells but little Bid expression or apoptosis occurred in MCF7 breast cancer cells or in normal human lung fibroblasts. The use of cisplatin enhanced the processing of full length BID to t-BID which significantly increased lung cancer-specific cell death. In in vivo experiments, intraperitonal injection of cisplatin enhanced the antitumor effects of the vector in a lung cancer xeno-graft mouse model. Moreover, dexamethasone effectively suppressed exogenous BID expression and the antitumor effect of Ad-TTS/Bid both in vitro and in vivo. Here, we describe the efficacy of the use of cisplatin and dexamethasone with the anti lung cancer promoter system (Ad-TTS/Bid) for a safe and effective gene therapy against advanced lung cancer.


title: Robotic laparoendoscopy single site surgery: a transdisciplinary review.

text: BACKGROUND Recent developments in minimal invasive surgery have led to laparoendoscopic single site surgery (LESS). This new approach has great potential but remains technically challenging. In order to relieve these difficulties many authors have adapted robotic technology to single site surgery. Numerous approaches have been developed and there is no real consensus. METHODS A transdisiplinary systematic review of the literature and analysis of the techniques were performed using PubMed up to 31 December 2011. RESULTS A total of 41 publications were found and included. Seven used the da Vinci Single Site Instrumentation (Intuitive Surgical, Sunnyvale, CA, USA) whereas others used various access devices including: GelPort/GelPOINT (Applied Medical, Rancho Santa Margarita, CA, USA) and a glove technique. CONCLUSIONS The technical feasibility of robotic LESS is established for numerous and various procedures. However, each kind of procedure requires a customized selection from among the da Vinci new platform, glove technique or GelPort/GelPOINT as well as instrument crossing with respect to minimal distances.


title: Peptide receptor radionuclide therapy for neuroendocrine tumors in Germany: first results of a multi-institutional cancer registry.

text: Peptide receptor radionuclide therapy is an effective treatment option for patients with well-differentiated somatostatin receptor-expressing neuroendocrine tumors. However, published data result mainly from retrospective monocentric studies. We initiated a multi-institutional, prospective, board-reviewed registry for patients treated with peptide receptor radionuclide therapy in Germany in 2009. In five centers, 297 patients were registered. Primary tumors were mainly derived from pancreas (117/297) and small intestine (80/297), whereas 56 were of unknown primary. Most tumors were well differentiated with median Ki67 proliferation rate of 5% (range 0.9-70%). Peptide receptor radionuclide therapy was performed using mainly yttrium-90 and/or lutetium-177 as radionuclides in 1-8 cycles. Mean overall survival was estimated at 213 months with follow-up between 1 and 230 months after initial diagnosis, and 87 months with follow-up between 1 and 92 months after start of peptide receptor radionuclide therapy. Median overall survival was not yet reached. Subgroup analysis demonstrated that best results were obtained in neuroendocrine tumors with proliferation rate below 20%. Our results indicate that peptide receptor radionuclide therapy is an effective treatment for well- and moderately differentiated neuroendocrine tumors irrespective of previous therapies and should be regarded as one of the primary treatment options for patients with somatostatin receptor-expressing neuroendocrine tumors.


title: Duration of Dual Antiplatelet Therapy in Patients with CKD and Drug-Eluting Stents: A Meta-Analysis.

text: BACKGROUND AND OBJECTIVES Whether prolonged dual antiplatelet therapy (DAPT) is more protective in patients with CKD and drug-eluting stents compared with shorter DAPT is uncertain. The purpose of this meta-analysis was to examine whether shorter DAPT in patients with drug-eluting stents and CKD is associated with lower mortality or major adverse cardiovascular event rates compared with longer DAPT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A Medline literature research was conducted to identify randomized trials in patients with drug-eluting stents comparing different DAPT duration strategies. Inclusion of patients with CKD was also required. The primary outcome was a composite of all-cause mortality, myocardial infarction, stroke, or stent thrombosis (definite or probable). Major bleeding was the secondary outcome. The risk ratio (RR) was estimated using a random-effects model. RESULTS Five randomized trials were included (1902 patients with CKD). Short DAPT (≤6 months) was associated with a similar incidence of the primary outcome, compared with 12-month DAPT among patients with CKD (48 versus 50 events; RR, 0.93; 95% confidence interval [95% CI], 0.64 to 1.36; P=0.72). Twelve-month DAPT was also associated with a similar incidence of the primary outcome compared with extended DAPT (≥30 months) in the CKD subgroup (35 versus 35 events; RR, 1.04; 95% CI, 0.67 to 1.62; P=0.87). Numerically lower major bleeding event rates were detected with shorter versus 12-month DAPT (9 versus 13 events; RR, 0.69; 95% CI, 0.30 to 1.60; P=0.39) and 12-month versus extended DAPT (9 versus 12 events; RR, 0.83; 95% CI, 0.35 to 1.93; P=0.66) in patients with CKD. CONCLUSIONS Short DAPT does not appear to be inferior to longer DAPT in patients with CKD and drug-eluting stents. Because of imprecision in estimates (few events and wide confidence intervals), no definite conclusions can be drawn with respect to stent thrombosis.


title: Do Not Forget Afghanistan in Times of COVID-19: Telemedicine and the Internet of Things to Strengthen Planetary Health Systems.

text: Health care does not always take place in a setting of peace, prosperity, and social order, a point that is often overlooked in quotidian medical practice. This has become most evident with the current COVID-19 pandemic by the new coronavirus that is wreaking havoc across the planet. Health care providers are facing unprecedented challenges to intervene on numerous nonlinear uncertainties in science and society as the pandemic evolves. In Afghanistan, health care delivery is already a major crosscutting challenge. Although efforts to rebuild the health care systems in Afghanistan have been made (Acerra et al.), both acute and chronic illnesses remain as major medical and critical governance gaps to be remedied. In addition, health care facilities and medical equipment are not adequate in the country. There is a need for medical and scientific expertise to clinically and sociologically contextualize and interpret diagnostic tests as well as drugs and vaccines that will be deployed in the coming months as part of the planetary collective response to the COVID-19 pandemic. In a time of pandemic and facing a novel infectious pathogen, health care workers are in need of planetary scale consultation and support. Even creating a small consultation network using mobile applications might offer improved health outcomes. The Internet of Things and digital health ought to be considered in concert with telemedicine as part of an effective pandemic response.


title: Comparison of continence outcomes of early catheter removal on postoperative day 2 and 4 after laparoscopic radical prostatectomy: a randomized controlled trial.

text: BACKGROUND The optimal timing of catheter removal following laparoscopic radical prostatectomy (LRP) has not yet been determined. This prospective study was designed to compare the efficacy and safety of catheter removal on postoperative day (POD) 2 versus POD 4 after LRP and its impact on urinary continence outcomes. METHODS One hundred and thirteen patients underwent LRP and were prospectively randomized into two groups: group 1 (n = 57) had the urinary catheter removed on POD 2 while group 2 (n = 56) had the catheter removed on POD 4. The urine loss ratio (ULR) was defined as the weight of urine loss in the pad divided by the daily micturition volume. Continence was defined as a pad-free status. RESULTS No significant differences were observed in clinical features between groups 1 and 2. Acute urinary retention (AUR) after catheter removal occurred in 21 patients (18.6%) (13 (22.8%) in group 1 and 8 (14.3%) in group 2 (p = 0.244). The first-day mean ULR values were 1.16 ± 4.95 in group 1 and 1.02 ± 3.27 in group 2 (p = 0.870). The last-day mean ULR values were 0.57 ± 1.60 in group 1 and 2.78 ± 15.49 in group 2 (p = 0.353). Continence rates at 3, 6, 9, and 12 months were 21.8, 41.1, 58.0, and 71.4% in group 1 and 34.5, 66.0, 79.2, and 83.7% in group 2 (p = 0.138, 0.009, 0.024, and 0.146, respectively). In AUR cases, continence rates at 3, 6, 9, and 12 months were 0, 23.1, 38.5, and 54.5% in group 1 and 37.5, 75.0, 87.5, and 87.5% in group 2 (p = 0.017, 0.020, 0.027, and 0.127, respectively). A multivariate analysis identified AUR after catheter removal on POD 2 as the only predictive factor for incontinence 6 and 9 months after LRP (p = 0.030 and 0.018, respectively). CONCLUSIONS Our results demonstrated that early catheter removal on POD 2 after LRP may increase the risk of incontinence. TRIAL REGISTRATION The study was registered as Clinical trial: (UMIN000014944); registration date: 12 March 2012.


title: Evaluating and Improving the Performance of Three 1-D Lake Models in a Large Deep Lake of the Central Tibetan Plateau.

text: The ability of FLake, WRF-Lake, and CoLM-Lake models in simulating the thermal features of Lake Nam Co in Central Tibetan Plateau has been evaluated in this study. All the three models with default settings exhibited distinct errors in the simulated vertical temperature profile. Then model calibration was conducted by adjusting three (four) key parameters within FLake and CoLM-Lake (WRF-Lake) in a series of sensitive experiments. Results showed that each model's performance is sensitive to the key parameters and becomes much better when adjusting all the key parameters relative to tuning single parameter. Overall, setting the temperature of maximum water density to 1.1 °C instead of 4 °C in the three models consistently leads to improved vertical thermal structure simulation during cold seasons; reducing the light extinction coefficient in FLake results in much deeper mixed layer and warmer thermocline during warm seasons in better agreement with the observation. The vertical thermal structure can be clearly improved by decreasing the light extinction coefficient and increasing the turbulent mixing in WRF-Lake and CoLM-Lake during warm seasons. Meanwhile, the modeled water temperature profile in warm seasons can be significantly improved by further replacing the constant surface roughness lengths by a parameterized scheme in WRF-Lake. Further intercomparison indicates that among the three calibrated models, FLake (WRF-Lake) performs the best to simulate the temporal evolution and intensity of temperature in the layers shallower (deeper) than 10 m, while WRF-Lake is the best at simulating the amplitude and pattern of the temperature variability at all depths.


title: Universal Access to Healthcare: The Case of South Africa in the Comparative Global Context of the Late Anthropocene Era.

text: Much current global debate - as well as a great deal of political rhetoric - about global health and healthcare is characterised by a renewed emphasis on the goal of universal access throughout the world. While this goal has been achieved to varying extents in the United Kingdom, Canada and many countries in Europe, even within those countries where national health systems have long been in place, the pervasive shift in emphasis from health as a social value to health as a commodity within a capitalist market civilization is eroding the commitment to equitable access to healthcare. Against this background the challenge is much greater in low- and middle-income countries that lag behind - especially if aspirations to universal access go beyond primary care. The challenges of achieving greater equity in access to health and in health outcomes, in a middle-income country like South Africa, illustrate the magnitude of the tensions and gaps that need to be traversed, given the vast differences between healthcare provided in the private and public sectors. Understandably the concept of National Health Insurance (NHI) in South Africa has widespread support. The strategies for how a successful and effective NHI could be implemented, over what time-frame and what it covers are, however, very controversial issues. What tends to be ignored is that sustainable improvement in health in South Africa, and elsewhere, is not determined merely by medical care but more especially by social structures intimately linked to deeply entrenched local and global social, economic and political forces and inequalities. While seldom openly addressed, some of these forces are explicated in this article to supplement views elsewhere, although most have elided emphasis on the pervasive effects of the global political economy on the provisioning and practising of health and healthcare everywhere on our planet.


title: Neuroendovascular Fellowship Training: Self-Assessment of a Program Accredited by the Committee on Advanced Subspecialty Training.

text: The University at Buffalo's neuroendovascular fellowship is one of the longest running fellowship programs in North America. The burgeoning neurointerventional workforce and the rapid growth in the neurointerventional space on the heels of groundbreaking clinical trials prompted us to assess the fellowship's academic impact and its graduates' perceptions and productivity. An anonymized web-based survey was sent to all former neuroendovascular fellows with specific questions pertaining to current practice, research and funding, and perceptions about the fellowship's impact on their skills, competitiveness, and compensation. Additionally, the h-index was calculated to assess the academic productivity of each graduated fellow. Among 50 former fellows, 42 (84%) completed the survey. The fellows came from various countries, ethnic backgrounds, and specialties including neurosurgery (n = 39, 93%), neurology (n = 2, 5%), and neuroradiology (n = 1, 2%). Twenty (48%) respondents were currently chairs or directors of their practice. Most (n = 30, 71%) spent at least 10% of their time on research activities, with 27 (64%) receiving research funding. The median h-index of all 50 former fellows was 14. The biggest gains from the fellowship were reported to be improvement in endovascular skills (median = 10 on a scale of 0-10 [highest]) and increase in competitiveness for jobs in vascular neurosurgery (median = 10), followed by increase in academic productivity (median = 8), and knowledge of vascular disease (median = 8). In an era with open calls for moratoriums on endovascular fellowships, concerns over market saturation, and pleas to improve training, fellowship programs perhaps merit a more objective assessment. The effectiveness of a fellowship program may best be measured by the academic impact and leadership roles of former fellows.


title: One Health: parasites and beyond.

text: The field of parasitism is broad, encompassing relationships between organisms where one benefits at the expense of another. Traditionally the discipline focuses on eukaryotes, with the study of bacteria and viruses complementary but distinct. Nonetheless, parasites vary in size and complexity from single celled protozoa, to enormous plants like those in the genus Rafflesia. Lifecycles range from obligate intracellular to extensive exoparasitism. Examples of parasites include high-profile medical and zoonotic pathogens such as Plasmodium, veterinary pathogens of wild and captive animals and many of the agents which cause neglected tropical diseases, stretching to parasites which infect plants and other parasites (e.g. Kikuchi et al. 2011; Hotez et al. 2014; Blake et al. 2015; Hemingway, 2015; Meekums et al. 2015; Sandlund et al. 2015). The breadth of parasitology has been matched by the variety of ways in which parasites are studied, drawing upon biological, chemical, molecular, epidemiological and other expertise. Despite such breadth bridging between disciplines has commonly been problematic, regardless of extensive encouragement from government agencies, peer audiences and funding bodies promoting multidisciplinary research. Now, progress in understanding and collaboration can benefit from establishment of the One Health concept (Zinsstag et al. 2012; Stark et al. 2015). One Health draws upon biological, environmental, medical, veterinary and social science disciplines in order to improve human, animal and environmental health, although it remains tantalizingly difficult to engage many relevant parties. For infectious diseases traditional divides have been exacerbated as the importance of wildlife reservoirs, climate change, food production systems and socio-economic diversity have been recognized but often not addressed in a multidisciplinary manner. In response the 2015 Autumn Symposium organized by the British Society for Parasitology (BSP; https://www.bsp.uk.net/home/) was focused on One Health, running under the title 'One Health: parasites and beyond…'. The meeting, held at the Royal Veterinary College (RVC) in Camden, London from September 14th to 15th, drew upon a blend of specialist parasitology reinforced with additional complementary expertise. Scientists, advocates, policy makers and industry representatives were invited to present at the meeting, promoting and developing One Health understanding with relevance to parasitology. The decision to widen the scope of the meeting to non-parasitological, but informative topics, is reflected in the diversity of the articles included in this special issue. A key feature of the meeting was encouragement of early career scientists, with more than 35% of the delegates registered as students and 25 posters.


title: Inflammatory Cell Infiltration of Adrenals in COVID-19.

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was originated in November-December 2019 in Wuhan, China, and has rapidly spread around the world causing severe health and socioeconomical damage to the entire civilization. The key feature of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is upper respiratory tract infection, which may be complicated by bilateral pneumonia. Angiotensin converting enzyme 2 (ACE2) has been identified as a key host factor, required for virus entry into cells. Interestingly, ACE2 is expressed not only in the respiratory system, but also in the other organs and systems including adrenal glands. Here we provide the first description of the pathomorphological changes in adrenal glands in patients with severe COVID-19 characterized by perivascular infiltration of CD3+ and CD8+ T-lymphocytes. Due to the central role of the adrenals in the stress response of the organism, this finding is of potential clinical relevance, because infection with the SARS-CoV-2 virus might critically impair adrenal function under pathophysiological conditions.


title: Imported Arbovirus Infections in Spain, 2009-2018.

text: To determine the epidemiologic and clinical characteristics of patients in Spain with imported arbovirus infections, we analyzed 22,655 records from a collaborative network for January 2009-December 2018. Among 861 arbovirus infections, 845 were monoinfections (456 [53%] dengue, 280 [32.5%] chikungunya, 109 [12.7%] Zika) and 16 (1.8%) were co-infections. Most patients were travelers (56.3%) or immigrants returning to Spain after visiting friends or relatives (31.3%). Median patient age was 37 years; most (62.3%) were women and some (28.6%) had received pretravel advice. Only 12 patients were immunosuppressed. Six cases (all dengue monoinfections, none in immunosuppressed patients) were severe. Since 2014, nondengue arbovirus infections increased; until 2016, chikungunya and Zika were most common. Imported arbovirus infections (mostly dengue) were frequently diagnosed, although increased chikungunya and Zika virus infections coincided with their introduction and spread in the Americas. A large proportion of cases occurred in women of childbearing age, some despite receipt of pretravel advice.


title: Relationship between ACE-inhibitors, ARBs and SARS-CoV-2 infection: where are we?

text: SARS-CoV-2 is spreading rapidly all over the world. The case fatality rate seems higher in cardiovascular disease and hypertension. Other comorbidities do not seem to confer the same risk, therefore the understanding of the relationship between infection and cardiovascular system could be a crucial point for the fight against the virus. A great interest is currently directed towards the angiotensin 2 converting enzyme (ACE 2) which is the SARS-CoV-2 receptor and creates important connections between the virus replication pathway, the cardiovascular system and blood pressure. All cardiovascular conditions share an imbalance of the renin angiotensin system (RAAS) in which ACE 2 plays a central role. In the last few days, much confusion has appeared about the management of therapy with angiotensin converting enzyme inhibitors (ACE-i) and angiotensin receptor blockers (ARBs) in infected patients and in those at risk of critical illness in case of infection. In this article we will try to reorder the major opinions currently emerging on this topic.


The COVID-19 vaccine development landscape.


title: "Awake Veno-arterial Extracorporeal Membrane Oxygenation" in Pediatric Cardiogenic Shock: A Single-Center Experience.

text: In pediatric patients with acute refractory cardiogenic shock (CS), extracorporeal membrane oxygenation (ECMO) remains an established procedure to maintain adequate organ perfusion. In this context, ECMO can be used as a bridging procedure to recovery, VAD or transplantation. While being supported by ECMO, most centers tend to keep their patients well sedated and supported by invasive ventilation. This may be associated with an increased risk of therapy-related morbidity and mortality. In order to optimize clinical management in pediatric patients with ECMO therapy, we report our strategy of veno-arterial ECMO (VA-ECMO) in extubated awake and conscious patients. We therefore present data of six of our patients with CS, who were treated by ECMO being awake without continuous analgosedation and invasive ventilation. Of these six patients, four were <1 year and two >14 years of age. Median time on ECMO was 17.4 days (range 6.9-94.2 days). Median time extubated, while receiving ECMO support was 9.5 days. Mean time extubated was 78 % of the total time on ECMO. Three patients reached full recovery of cardiac function on "Awake-VA-ECMO," whereas the other three were successfully bridged to destination therapy (VAD, heart transplantation, withdrawal). Four out of our six patients are still alive. Complications related to ECMO therapy (i.e., severe bleeding, site infection or dislocation of cannulas) were not observed. We conclude that "Awake-VA-ECMO" in extubated, spontaneously breathing conscious pediatric patients is feasible and safe for the treatment of acute CS and can be used as a "bridging therapy" to recovery, VAD implantation or transplantation.


title: Bedside placement of peritoneal dialysis catheters - a single-center experience from Hungary.

text: Objectives: The successful implantation of peritoneal dialysis (PD) catheters is a critical skill procedure with the potential to impact both the short- and long-term success of renal replacement therapy and the patients' survival. Methods: We retrospectively reviewed our single-center experience with nephrologist-placed minimally invasive, double-cuffed PD catheters (PDCs). Results: The recruitment period was March 2014 through December 2015. The follow-up period lasted until 2016. The mean age of the subjects was 60 ± 18 years and indications for the PD were diuretic resistant acutely decompensated chronic heart failure in seven patients (47%) and end-stage renal disease in eight (53%) patients. Comorbid conditions included diabetes (27%), ischemic heart disease (47%), advanced liver failure (27%), and a history of hypertension (73%). The cohort had a high mortality with five subjects only in severe heart failure group (33%) passing away during the index hospitalization; of the rest, two (13%) had heart transplantation, three (20%) changed modality to hemodialysis, and only five (33%) continued with maintenance PD beyond 1 month. Acute technical complications within the first month were infrequent: one catheter (6%) had drainage problems and one (6%) was lost due to extrusion. There were no serious complications (e.g., organ damage, peritonitis, etc.). Conclusions: In selected cases, particularly in severe diuretic refractory heart failure, PDC placement placed by a nephrologist is feasible with a low rate of complications even in a low-volume center setting. The catheters we placed were all functioning with only minor complications and PD could be started immediately.


title: Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial.

text: The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia-reperfusion injury. We present the first patients transplanted using a normothermic machine perfusion (NMP) device that transports and stores an organ in a fully functioning state at 37°C. In this Phase 1 trial, organs were retrieved using standard techniques, attached to the perfusion device at the donor hospital, and transported to the implanting center in a functioning state. NMP livers were matched 1:2 to cold-stored livers. Twenty patients underwent liver transplantation after NMP. Median NMP time was 9.3 (3.5-18.5) h versus median cold ischaemia time of 8.9 (4.2-11.4) h. Thirty-day graft survival was similar (100% NMP vs. 97.5% control, p = 1.00). Median peak aspartate aminotransferase in the first 7 days was significantly lower in the NMP group (417 IU [84-4681]) versus (902 IU [218-8786], p = 0.03). This first report of liver transplantation using NMP-preserved livers demonstrates the safety and feasibility of using this technology from retrieval to transplantation, including transportation. NMP may be valuable in increasing the number of donor livers and improving the function of transplantable organs.


title: Hormone replacement therapy after surgery for epithelial ovarian cancer.

text: BACKGROUND Women who have undergone surgical treatment for epithelial ovarian cancer (EOC) may develop menopausal symptoms due to immediate loss of ovarian function following surgery and chemotherapy. Women may experience vasomotor symptoms, sleep disturbance, difficulty concentrating, sexual dysfunction, vaginal symptoms and accelerated osteoporosis. Although hormone replacement therapy (HRT) is the most effective treatment to relieve these symptoms, its safety has been questioned for women with EOC. OBJECTIVES To assess the safety and efficacy of HRT for menopausal symptoms in women surgically treated for EOC. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 6), MEDLINE via Ovid (1946 to 12 June 2019) and Embase via Ovid (1980 to 2019, week 23). We also handsearched conference reports and trial registries. There was no language restriction. SELECTION CRITERIA We included randomized controlled trials (RCTs) with participants of any age and menopausal status who had undergone surgery for EOC and, after diagnosis and treatment, used any regimen and duration of HRT compared with placebo or no hormone therapy. We also included trials comparing different regimens or duration of administration of HRT. DATA COLLECTION AND ANALYSIS Two review authors independently identified studies that met the inclusion criteria. They used Covidence to extract study characteristics, outcome data and to assess methodological quality of the included studies. MAIN RESULTS Our search strategy identified 2617 titles, of which 2614 titles were excluded. Three studies, involving 350 women, met our inclusion criteria. Two of the studies included pre and postmenopausal women, and the third only included premenopausal women. The overall age range of those women included in the studies was 20 to 89.6 years old, with a median follow-up ranging from 31.4 months to 19.1 years. The geographical distribution of participants included Europe, South Africa and China. All stages and histological subtypes were included in two of the studies, but stage IV disease had been excluded in the third. The three included studies used a variety of HRT regimens (conjugated oestrogen with or without medroxyprogesterone and with or without nylestriol) and HRT administrations (oral, patch and implant), In all studies, the comparisons were made versus women who had not received HRT. The studies were at low or unclear risk of selection and reporting bias, and at high risk of performance, detection and attrition bias. The certainty of the evidence was low for overall survival and progression-free survival, and very low for quality-of-life assessment, incidence of breast cancer, transient ischaemic attack (TIA), cerebrovascular accident (CVA) and myocardial infarction (MI). Meta-analysis of these studies showed that HRT may improve overall survival (hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.54 to 0.93; 350 participants, 3 studies; low-certainty evidence). Quality-of-life assessment by use of the EORTC-C30 questionnaire was performed only in one study. We are uncertain whether HRT improves or reduces quality of life as the certainty of the evidence was assessed as very low (mean difference (MD) 13.67 points higher, 95% CI 9.26 higher to 18.08 higher; 1 study; 75 participants; very low-certainty evidence). Likewise, HRT may make little or no difference to progression-free survival (HR 0.76, 95% CI 0.57 to 1.01; 275 participants, 2 studies; low-certainty evidence). We are uncertain whether HRT improves or reduces the incidence of breast cancer (risk ratio (RR) 2.00, 95% CI 0.19 to 21.59; 225 participants, 2 studies; very low-certainty evidence); TIA (RR 5.00, 95% CI 0.24 to 102.42; 150 participants, 1 study; very low-certainty evidence); CVA (RR 0.67, 95% CI 0.11 to 3.88; 150 participants, 1 study; very low-certainty evidence); and MI (RR 0.20, 95% CI 0.01 to 4.10; 150 participants, 1 study; very low-certainty evidence). The incidence of gallstones was not reported in the included studies. AUTHORS' CONCLUSIONS Hormone replacement therapy may slightly improve overall survival in women who have undergone surgical treatment for EOC, but the certainty of the evidence is low. HRT may make little or no difference to quality of life, incidence of breast cancer, TIA, CVA and MI as the certainty of the evidence has been assessed as very low. There may be little or no effect of HRT use on progression-free survival. The evidence in this review is limited by imprecision and incompleteness of reported relevant outcomes and therefore the results should be interpreted with caution. Future well-designed RCTs are required as this is an important area to women experiencing menopausal symptoms following surgical treatment for ovarian cancer, especially as doctors are often reluctant to prescribe HRT in this scenario. The evidence in this review is too limited to support or refute that HRT is very harmful in this population.


title: Accuracy and precision of non-invasive cardiac output monitoring devices in perioperative medicine: a systematic review and meta-analysis†.

text: Cardiac output (CO) measurement is crucial for the guidance of therapeutic decisions in critically ill and high-risk surgical patients. Newly developed completely non-invasive CO technologies are commercially available; however, their accuracy and precision have not recently been evaluated in a meta-analysis. We conducted a systematic search using PubMed, Cochrane Library of Clinical Trials, Scopus, and Web of Science to review published data comparing CO measured by bolus thermodilution with commercially available non-invasive technologies including pulse wave transit time, non-invasive pulse contour analysis, thoracic electrical bioimpedance/bioreactance, and CO2 rebreathing. The non-invasive CO technology was considered acceptable if the pooled estimate of percentage error was <30%, as previously recommended. Using a random-effects model, sd, pooled mean bias, and mean percentage error were calculated. An I2 statistic was also used to evaluate the inter-study heterogeneity. A total of 37 studies (1543 patients) were included. Mean CO of both methods was 4.78 litres min−1. Bias was presented as the reference method minus the tested methods in 15 studies. Only six studies assessed the random error (repeatability) of the tested device. The overall random-effects pooled bias (limits of agreement) and the percentage error were −0,13 [−2.38 , 2.12] litres min−1 and 47%, respectively. Inter-study sensitivity heterogeneity was high (I2=83%, P<0.001). With a wide percentage error, completely non-invasive CO devices are not interchangeable with bolus thermodilution. Additional studies are warranted to demonstrate their role in improving the quality of care.


title: Safety and efficacy of aneurysm treatment with WEB: results of the WEBCAST study.

text: OBJECT WEB is an innovative intrasaccular treatment for intracranial aneurysms. Preliminary series have shown good safety and efficacy. The WEB Clinical Assessment of Intrasaccular Aneurysm Therapy (WEBCAST) trial is a prospective European trial evaluating the safety and efficacy of WEB in wide-neck bifurcation aneurysms. METHODS Patients with wide-neck bifurcation aneurysms for which WEB treatment was indicated were included in this multicentergood clinical practices study. Clinical data including adverse events and clinical status at 1 and 6 months were collected and independently analyzed by a medical monitor. Six-month follow-up digital subtraction angiography was also performed and independently analyzed by a core laboratory. Success was defined at 6 months as complete occlusion or stable neck remnant, no worsening in angiographic appearance from postprocedure, and no retreatment performed or planned. RESULTS Ten European neurointerventional centers enrolled 51 patients with 51 aneurysms. Treatment with WEB was achieved in 48 of 51 aneurysms (94.1%). Adjunctive implants (coils/stents) were used in 4 of 48 aneurysms (8.3%). Thromboembolic events were observed in 9 of 51 patients (17.6%), resulting in a permanent deficit (modified Rankin Scale [mRS] Score 1) in 1 patient (2.0%). Intraoperative rupture was not observed. Morbidity (mRS score > 2) and mortality were 2.0% (1 of 51 patients, related to rupture status on entry to study) and 0.0% at 1 month, respectively. Success was achieved at 6 months in 85.4% of patients treated with WEB: 23 of 41 patients (56.1%) had complete occlusion, 12 of 41 (29.3%) had a neck remnant, and 6 of 41 (14.6%) had an aneurysm remnant. CONCLUSIONS The WEBCAST study showed good procedural and short-term safety of aneurysm treatment with WEB and good 6-month anatomical results.


title: Percutaneous radiofrequency ablation for spinal osteoid osteoma and osteoblastoma.

text: PURPOSES We sought to verify the efficacy and safety of RFA in spinal OO and osteoblastomas (OB) (Enneking Stage 2, S2). METHODS We retrospectively reviewed patients treated in our hospital. Surgical resection was indicated for Enneking Stage 3 OB. RFA indications for spinal OO and OB (S2) were no neurological deficits, complete bone cortex around the lesion on computed tomography (CT), and cerebrospinal fluid between a lesion and the spinal cord/nerve root on magnetic resonance imaging. Abundant cerebrospinal fluid (more than 1.0 mm) between the lesion and nerve root/spinal cord was preferred to prevent neurological damage by heat. Otherwise, surgery was recommended. The minimum follow-up was 24 months. RESULTS Ten patients were treated with CT-guided percutaneous RFA, including three with OB and seven with OO. No patients had neurological deficits or scoliosis. In OO patients, the average visual analog scale (VAS) scores were 7.6/10 (range 6-10) before RFA. In OB cases, the VAS scores were 8, 7, and 9 before RFA. Nine patients had a one-stage biopsy and then RFA, and one patient had a two-stage procedure (biopsy before RFA). The average RFA time for OO was 10 min (range 4-12). In the three OB cases, the RFA time was 12, 12, and 24 min. The time of the whole produce was 98 min (range 65-130 min). All 10 patients were followed-up. The average follow-up time of OO was 46.6 months (range 24-66). Six patients were free of pain, except one who suffered occasional pain with VAS 2/10. The three OB cases were free of pain at 24, 26, and 26 months. CONCLUSION CT-guided percutaneous RFA is a safe and effective treatment for spinal OO and S2 OB, especially in lesions with no neurological deficits and intact cortical bone. Cerebrospinal fluid around the lesion is an appropriate indication for percutaneous RFA.


title: Perioperative fluid therapy: a statement from the international Fluid Optimization Group.

text: BACKGROUND Perioperative fluid therapy remains a highly debated topic. Its purpose is to maintain or restore effective circulating blood volume during the immediate perioperative period. Maintaining effective circulating blood volume and pressure are key components of assuring adequate organ perfusion while avoiding the risks associated with either organ hypo- or hyperperfusion. Relative to perioperative fluid therapy, three inescapable conclusions exist: overhydration is bad, underhydration is bad, and what we assume about the fluid status of our patients may be incorrect. There is wide variability of practice, both between individuals and institutions. The aims of this paper are to clearly define the risks and benefits of fluid choices within the perioperative space, to describe current evidence-based methodologies for their administration, and ultimately to reduce the variability with which perioperative fluids are administered. METHODS Based on the abovementioned acknowledgements, a group of 72 researchers, well known within the field of fluid resuscitation, were invited, via email, to attend a meeting that was held in Chicago in 2011 to discuss perioperative fluid therapy. From the 72 invitees, 14 researchers representing 7 countries attended, and thus, the international Fluid Optimization Group (FOG) came into existence. These researches, working collaboratively, have reviewed the data from 162 different fluid resuscitation papers including both operative and intensive care unit populations. This manuscript is the result of 3 years of evidence-based, discussions, analysis, and synthesis of the currently known risks and benefits of individual fluids and the best methods for administering them. RESULTS The results of this review paper provide an overview of the components of an effective perioperative fluid administration plan and address both the physiologic principles and outcomes of fluid administration. CONCLUSIONS We recommend that both perioperative fluid choice and therapy be individualized. Patients should receive fluid therapy guided by predefined physiologic targets. Specifically, fluids should be administered when patients require augmentation of their perfusion and are also volume responsive. This paper provides a general approach to fluid therapy and practical recommendations.


title: Impact of age and comorbidity on treatment of non-small cell lung cancer recurrence following complete resection: A nationally representative cohort study.

text: OBJECTIVE Older patients with non-small cell lung cancer (NSCLC) are less likely to receive guideline-recommended treatment at diagnosis, independent of comorbidity. However, national data on treatment of postoperative recurrence are limited. We evaluated the associations between age, comorbidity, and other patient factors and treatment of postoperative NSCLC recurrence in a national cohort. MATERIALS AND METHODS We randomly selected 9001 patients with surgically resected stage I-III NSCLC in 2006-2007 from the National Cancer Data Base. Patients were followed for 5 years or until first NSCLC recurrence, new primary cancer, or death, whichever came first. Perioperative comorbidities, first recurrence, treatment of recurrence, and survival were abstracted from medical records and merged with existing registry data. Factors associated with active treatment (chemotherapy, radiation, and/or surgery) versus supportive care only were analyzed using multivariable logistic regression. RESULTS Median age at initial diagnosis was 67; 69.7% had >1 comorbidity. At 5-year follow-up, 12.3% developed locoregional and 21.5% developed distant recurrence. Among patients with locoregional recurrence, 79.5% received active treatment. Older patients (OR 0.49 for age >75 compared with <55; 95% CI 0.27-0.88) and those with substance abuse (OR 0.43; 95% CI 0.23-0.81) were less likely to receive active treatment. Women (OR 0.62; 95% CI 0.43-0.89) and patients with symptomatic recurrence (OR 0.69; 95% CI 0.47-0.99) were also less likely to receive active treatment. Among those with distant recurrence, 77.3% received active treatment. Older patients (OR 0.42 for age >75 compared with <55; 95% CI 0.26-0.68) and those with any documented comorbidities (OR 0.59; 95% CI 0.38-0.89) were less likely to receive active treatment. CONCLUSION Older patients independent of comorbidity, patients with substance abuse, and women were less likely to receive active treatment for postoperative NSCLC recurrence. Studies to further characterize these disparities in treatment of NSCLC recurrence are needed to identify barriers to treatment.


title: Video-assisted thoracoscopic surgery lobectomy for lung cancer is associated with a lower 30-day morbidity compared with lobectomy by thoracotomy.

text: OBJECTIVES Lung cancer is the most common cause of cancer-related deaths worldwide. Survival is highly dependent on surgery. Video-assisted thoracoscopic surgery (VATS) is increasingly chosen over open thoracotomy (OT) because of the possible benefits of the minimally invasive approach. Consequently, our aim was to compare the 30-day morbidity and mortality for lung cancer patients operated by VATS lobectomy or lobectomy by OT. METHOD Data were obtained from prospective national and regional databases, including patients who underwent lobectomy for lung cancer in the eastern part of Denmark from 1 January 2005 to 31 December 2011. All patients operated before 2009 were re-staged according to the latest International Association for the Study of Lung Cancer lung cancer classification. Patient characteristics, comorbidities, pathology and operative data were assessed using an independent samples t-test, Pearson's χ(2), Fisher's exact test and Mann-Whitney test. Morbidity was assessed using multinomial logistic regression adjusted for gender, age, cancer stage, forced expiratory volume in 1 s (FEV1), year of surgery and Charlson comorbidity score. RESULTS In total, 1379 patients underwent lobectomy, 785 patients via VATS and 594 patients via thoracotomy. The two groups were similar in gender and FEV1. The patients operated by VATS were older (P < 0.001), and had a lower Charlson comorbidity score (P = 0.034), higher frequency of adenocarcinomas (P < 0.001) and lower cancer stage (P < 0.001). Among the VATS patients, 285 (36.3%) and among the thoracotomy patients, 288 (48.5%) had minor complications (P < 0.001); and 157 (20.0%) VATS patients and 212 (35.7%) thoracotomy patients had major complications (P < 0.001). The 30-day mortality rate was 1% in the VATS group and 1.5% in the thoracotomy group (P = 0.47). Multinomial logistic regression analysis showed that the prevalence of both minor [odds ratio (OR) = 1.51; 95% confidence interval (Cl) = 1.18-1.96] and major complications (OR = 1.91, 95% Cl = 1.44-2.53) was significantly higher for patients who underwent lobectomy via thoracotomy compared with VATS. CONCLUSION Patients undergoing lobectomy via VATS were less likely to have at least one minor complication within the first 30 postoperative days and less likely to have at least one major complication, compared with patients operated by thoracotomy. These findings remained after adjusting for gender, age, FEV1, cancer stage, year of surgery and Charlson comorbidity score.


title: Considering grief in mental health outcomes of COVID-19.

text: The novel coronavirus disease of 2019 (COVID-19) pandemic has created challenging circumstances for the physical and mental health of individuals across the United States. This commentary addresses the role of grief in mental health outcomes relating to the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Lung Base Findings of Coronavirus Disease (COVID-19) on Abdominal CT in Patients With Predominant Gastrointestinal Symptoms.

text: OBJECTIVE. This series of patients presented to the emergency department (ED) with abdominal pain, without the respiratory symptoms typical of coronavirus disease (COVID-19), and the abdominal radiologist was the first to suggest COVID-19 infection because of findings in the lung bases on CT of the abdomen. CONCLUSION. COVID-19 infection can present primarily with abdominal symptoms, and the abdominal radiologist must suggest the diagnosis when evaluating the lung bases for typical findings.


title: Clinical evaluation of self-collected saliva by RT-qPCR, direct RT-qPCR, RT-LAMP, and a rapid antigen test to diagnose COVID-19.

text: Background: The clinical performance of six molecular diagnostic tests and a rapid antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were clinically evaluated for the diagnosis of coronavirus disease 2019 (COVID-19) in self-collected saliva.Methods: Saliva samples from 103 patients with laboratory-confirmed COVID-19 (15 asymptomatic and 88 symptomatic) were collected on the day of hospital admission. SARS-CoV-2 RNA in saliva was detected using a quantitative reverse-transcription polymerase chain reaction (RT-qPCR) laboratory-developed test (LDT), a cobas SARS-CoV-2 high-throughput system, three direct RT-qPCR kits, and reverse-transcription loop mediated isothermal amplification (RT-LAMP). The viral antigen was detected by a rapid antigen immunochromatographic assay.Results: Of the 103 samples, viral RNA was detected in 50.5-81.6% of the specimens by molecular diagnostic tests and an antigen was detected in 11.7% of the specimens by the rapid antigen test. Viral RNA was detected at a significantly higher percentage (65.6-93.4%) in specimens collected within 9 d of symptom onset compared to that of specimens collected after at least 10 d of symptom onset (22.2-66.7%) and that of asymptomatic patients (40.0-66.7%).Conclusions: Self-collected saliva is an alternative specimen option for diagnosing COVID-19. LDT RT-qPCR, cobas SARS-CoV-2 high-throughput system, direct RT-qPCR except for one commercial kit, and RT-LAMP showed sufficient sensitivity in clinical use to be selectively used according to clinical settings and facilities. The rapid antigen test alone is not recommended for initial COVID-19 diagnosis because of its low sensitivity.


title: Identification of Mycobacterium genavense natural infection in a domestic ferret.

text: A 6-y-old neutered male ferret ( Mustela putorius furo) was presented because of a 1-mo history of progressive weight loss, chronic cough, and hair loss. On clinical examination, the animal was coughing, slightly depressed, moderately hypothermic, and had bilateral epiphora. Thoracic radiography was suggestive of severe multinodular interstitial pneumonia. Abdominal ultrasound examination revealed hepatosplenomegaly and mesenteric and pancreaticoduodenal lymphadenopathy. Fine-needle aspiration of the pancreaticoduodenal lymph node, followed by routine Romanowsky and Ziehl-Neelsen stains, revealed numerous macrophages containing myriad acid-fast bacilli, leading to identification of mycobacteriosis. Autopsy and histologic examination confirmed the presence of disseminated, poorly defined, acid-fast, bacilli-rich granulomas in the pancreaticoduodenal and mesenteric lymph nodes, intestines, and lungs. Destaining of May-Grünwald/Giemsa-stained slides with alcohol, and then restaining with Ziehl-Neelsen, revealed acid-fast rods and avoided repeat tissue sampling without affecting the Ziehl-Neelsen stain quality and cytologic features. Tissue samples were submitted for a PCR assay targeting the heat shock protein gene ( hsp65) and revealed 100% homology with Mycobacterium genavense. We emphasize the use of special stains and PCR for identification of this potential zoonotic agent.


title: Extraction of an incisor embedded within the nasal cavity in two guinea pigs.

text: Oral examination of two guinea pigs revealed that the unilateral incisor was absent. On radiographic examination, the incisor was identified within the nasal cavity in both patients. Under anesthesia in both patients, the skin was incised from the nostril to 1.5 cm proximal, and the premaxilla and part of the maxilla were exposed. The bone was removed using a surgical drill, and the incisor was exposed in the nasal cavity. The root was grasped with forceps and carefully extracted as it was degraded and very fragile. Diagnosis was easy using oral and radiographic examination. In guinea pig patients where an incisor is absent on oral examination, this condition should be considered.


title: Neural Control Adaptation to Motor Noise Manipulation.

text: Antagonistic muscular co-activation can compensate for movement variability induced by motor noise at the expense of increased energetic costs. Greater antagonistic co-activation is commonly observed in older adults, which could be an adaptation to increased motor noise. The present study tested this hypothesis by manipulating motor noise in 12 young subjects while they practiced a goal-directed task using a myoelectric virtual arm, which was controlled by their biceps and triceps muscle activity. Motor noise was increased by increasing the coefficient of variation (CV) of the myoelectric signals. As hypothesized, subjects adapted by increasing antagonistic co-activation, and this was associated with reduced noise-induced performance decrements. A second hypothesis was that a virtual decrease in motor noise, achieved by smoothing the myoelectric signals, would have the opposite effect: co-activation would decrease and motor performance would improve. However, the results showed that a decrease in noise made performance worse instead of better, with no change in co-activation. Overall, these findings suggest that the nervous system adapts to virtual increases in motor noise by increasing antagonistic co-activation, and this preserves motor performance. Reducing noise may have failed to benefit performance due to characteristics of the filtering process itself, e.g., delays are introduced and muscle activity bursts are attenuated. The observed adaptations to increased noise may explain in part why older adults and many patient populations have greater antagonistic co-activation, which could represent an adaptation to increased motor noise, along with a desire for increased joint stability.


title: Diagnosis of Lymphoid Lesions in Limited Samples: A Guide for the General Surgical Pathologist, Cytopathologist, and Cytotechnologist.

text: Objectives Advances in interventional techniques allow obtaining samples from most body sites through minimally invasive procedures that yield limited samples. We provide practical guidelines for diagnosis of lymphoid lesions in these samples. Methods Guidelines for selection of biopsy site and triage of the specimen according to results of rapid on-site evaluation (ROSE), and description of the advantages and limitations of currently available ancillary studies are described, based on the experience of the authors, complemented by a comprehensive review of the literature. Results Five diagnostic categories are observed at ROSE: (1) preponderance of small cells, (2) large cells, (3) mixed small and large cells, (4) blast-like cells, and (5) rare large pleomorphic cells. Detailed description of the diagnostic work-up and subsequent classification for each of these groups is provided. Conclusions A definitive diagnosis of lymphoid neoplasms in limited samples is possible in most cases through correlation of morphology, ancillary studies, and clinical scenario.


title: Flocked nasal swab versus nasopharyngeal aspirate in adult emergency room patients: similar multiplex PCR respiratory pathogen results and patient discomfort.

text: Fifty adult emergency room patients with symptoms of respiratory tract infections or acute onset of extreme fatigue were sampled by both nasopharyngeal aspirate (NPA) and flocked nasal swab (fNS). Respiratory agents were detected by a qualitative influenza PCR and an 18-valent multiplex PCR in 20 of 29 patients with a clinical diagnosis of respiratory tract infection, and in 3 of 21 without such a diagnosis. PCR detected influenza A and B in NPA samples from 11 patients and in fNS samples from 10 patients. Little or no discomfort was perceived by 60% of the patients when sampled by NPA and by 66% when sampled by fNS. We conclude that NPA and fNS were equally sensitive for detection of respiratory agents by multiplex PCR, and the two sampling methods did not differ significantly regarding discomfort perceived by patients (p = 0.171, Wilcoxon signed rank test). Hence less invasive sampling by fNS might be preferable in certain settings and situations.


Obesity, overweight and survival in critically ill patients with SARS-CoV-2 pneumonia: is there an obesity paradox? Preliminary results from Italy.


The precarious position of postdocs during COVID-19.


title: Effectiveness of open-label losartan/hydrochlorothiazide combination therapy in Asian patients with hypertension not controlled with ACE inhibitor or ARB monotherapy.

text: Antihypertensive efficacy and safety of losartan/hydrochlorothiazide (HCTZ) combinations have not been adequately studied in Asians. In this open-label, 12-week study in seven Asian areas, patients on monotherapy with angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) but not at blood pressure (BP) goal (sitting diastolic BP (SiDBP) <90 mm Hg in non-diabetics and <80 mm Hg in diabetics) were switched to losartan 50 mg/HCTZ 12.5 mg. At 4 and 8 weeks, the therapy for patients not at goal BP was titrated to losartan 100 mg/HCTZ 12.5 mg and to losartan 100 mg/HCTZ 25 mg, respectively. Data analysis included 430 patients with mean (s.d.) age 53.0 (10.1) years and 51.9% of the female gender. After 8 weeks (primary end point; titration up to losartan 100 mg/HCTZ 12.5 mg), 73.5% (95% confidence interval (CI): 69.0-77.6) of patients reached BP goal; 63.4 and 78.1% of patients reached BP goal at 4 weeks (titration up to losartan 50 mg/HCTZ 12.5 mg) and at 12 weeks (titration up to losartan 100 mg/HCTZ 25 mg). The mean changes from baseline (95% CI) in sitting systolic BP and SiDBP at 8 weeks were -16.7 (-18.0 to -15.4) mm Hg and -12.1 (-12.9 to -11.4) mm Hg, respectively. Clinical and laboratory adverse experiences (AEs) were reported in 27.5 and 21.0% of patients, respectively. Nine patients were discontinued because of drug-related clinical AEs. Switching Asian patients currently not at BP goal with ARB or ACEI monotherapy to a losartan/HCTZ combination achieved BP goal in the majority of patients. Losartan/HCTZ combinations were generally well tolerated.


title: Contribution of intraoperative neuromonitoring to the identification of the external branch of superior laryngeal nerve.

text: OBJECTIVE We evaluated the contribution of intraoperative neuromonitoring to the visual and functional identification of the external branch of the superior laryngeal nerve. MATERIAL AND METHODS The prospectively collected data of patients who underwent thyroid surgery with intraoperative neuromonitoring for external branch of the superior laryngeal nerve exploration were assessed retrospectively. The surface endotracheal tube-based Medtronic NIM3 intraoperative neuromonitoring device was used. The external branch of the superior laryngeal nerve function was evaluated by the cricothyroid muscle twitch. In addition, contribution of external branch of the superior laryngeal nerve to the vocal cord adduction was evaluated using electromyographic records. RESULTS The study included data of 126 (female, 103; male, 23) patients undergoing thyroid surgery, with a mean age of 46.2±12.2 years (range, 18-75 years), and 215 neck sides were assessed. Two hundred and one (93.5%) of 215 external branch of the superior laryngeal nerves were identified, of which 60 (27.9%) were identified visually before being stimulated with a monopolar stimulator probe. Eighty-nine (41.4%) external branch of the superior laryngeal nerves were identified visually after being identified with a probe. Although 52 (24.1%) external branch of the superior laryngeal nerves were identified with a probe, they were not visualized. Intraoperative neuromonitoring provided a significant contribution to visual (p<0.001) and functional (p<0.001) identification of external branch of the superior laryngeal nerves. Additionally, positive electromyographic responses were recorded from 160 external branch of the superior laryngeal nerves (74.4%). CONCLUSION Intraoperative neuromonitoring provides an important contribution to visual and functional identification of external branch of the superior laryngeal nerves. We believe that it can not be predicted whether the external branch of the superior laryngeal nerve is at risk or not and the nerve is often invisible; thus, intraoperative neuromonitoring may routinely be used in superior pole dissection. Glottic electromyography response obtained via external branch of the superior laryngeal nerve stimulation provides quantifiable information in addition to the simple visualization of the cricothyroid muscle twitch.


Characteristics of SARS-CoV-2 isolated from asymptomatic carrier in Tokyo.


Peptide-based in vivo delivery agents for oligonucleotides and siRNA.