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International audience; Background - Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD). Objectives - This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients. Methods - Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression. Results - A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non-HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p

We examined the characteristics of individuals with biomarker evidence of tauopathy but without β-amyloid (Aβ) (A-T+) in relation to individuals with (A+T+) and without (A-T-) evidence of Alzheimer’s disease (AD). We included 561 participants with Aβ and tau PET from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We compared A-T- (n = 316), A-T+ (n = 63), and A+T+ (n = 182) individuals on demographics, amyloid, tau, hippocampal volumes, and cognition. A-T+ individuals were low on apolipoprotein E ɛ4 prevalence (17%) and had no evidence of subtly elevated brain Aβ within the negative range. The severity of tau deposition, hippocampal atrophy, and cognitive dysfunction in the A-T+ group was intermediate between A-T- and A+T+ (all p < 0.001). Tau uptake patterns in A-T+ individuals were heterogeneous, but approximately 29% showed tau deposition in the medial temporal lobe only, consistent with primary age-related tauopathy and an additional 32% showed a pattern consistent with AD. A-T+ individuals also share other features that are characteristic of AD such as cognitive impairment and neurodegeneration, but this group is heterogeneous and likely reflects more than one disorder.

Nonalcoholic steatohepatitis (NASH) is common in patients with obesity. Liver biopsy (LB) can be routinely or selectively performed during bariatric surgery to identify patients with NASH.Patients undergoing bariatric surgery between 2016 and 2020 at our institution were identified. Chart review identified patients undergoing concurrent LB. LB results were compared between patients undergoing routine LB and selective LB. Patient demographics and postoperative outcomes were compared between those who received LB and those who did not (non-LB). In the LB cohort, preoperative characteristics of patients with NASH were compared to those without NASH, and multivariable regression was used to identify predictors of NASH.Two thousand three hundred ninety-three patients were identified, of which 400 (16.7%) had liver biopsies (LB) and 1,993 (83.3%) did not (non-LB). Three hundred thirty LB were performed routinely, and 70 were selective. Compared to selective LB, routine LB identified significantly higher rates of steatosis (83.6% vs. 4.5%, p 0.01), periportal inflammation (67.0% vs. 3.2%, p 0.01), fibrosis (65.8% vs. 2.1%, p 0.01), and NASH (10.9% vs. 1.5%, p 0.01). There were no differences in postoperative complications, blood transfusions, readmissions, or reoperations between LB and non-LB. On multivariable regression, highest BMI 40 (OR 2.85, 95% CI 1.43-5.67) and insulin-dependent diabetes (OR 4.83, 95% CI 1.70-13.69) were associated with a higher odds of NASH, while Black race was associated with lower odds (OR 0.25, 95% CI 0.09-0.65).Routine liver biopsies during bariatric surgery identify higher rates of advanced NAFLD compared to selective biopsies, and can be safely performed without an increased risk of postoperative complications.

Psychiatric disorders are frequently found in both patients with PNES and DRE, making the differential diagnosis even more complex. The aim of this study was to analyze and compare psychiatric aspects and the quality of life in patients with psychogenic non-epileptic seizures (PNES) and drug resistant epilepsy (DRE).Patients admitted to video-electroencephalograpy (VEEG) unit with confirmed PNES and DRE were included. Demographical characteristics, psychiatric diagnosis according to SCID I and II of DSM IV, pharmacological treatment, general functioning measured with GAF (Global assessment of functionality), quality of life (QoL) using QlesQSF (Quality of Life Enjoyment and Satisfaction Questionnaire Short Form) and depression severity using BDI II (Beck depression inventory), were compared between the groups. Non-parametric tests, chi square test, and logistic regression were used for statistical analysis.148 patients consecutively admitted to VEEG were included (DRE n = 97; PNES n = 51). Somatization disorder (RR: 13.02, 95% CI: 1.23-137.39, p = 0.03) and a history of trauma (RR: 8.66, 95% CI: 3.21-23.31, p = 0.001) were associated with PNES. The QlesQ score and the GAF score were lower with a higher prevalence of suicide attempts in the PNES group (p 0.01). A negative correlation was observed between the severity of depression and the quality of life (DRE r = - 0.28, p = 0.013; PNES r = - 0.59, p = 0.001).Higher psychiatric comorbidity with poorer QoL were found in PNES patients compared to DRE. However, depression comorbidity negatively affected the QoL in both groups. Future studies based on illness perception will be orientated to complete this analysis.

Despite the expansion of available in vitro laboratory tests at a rate far exceeding that of dermatologic pharmaceuticals, the existing literature is dominated by discussion of the latter. With the advent of numerous new tests, it can be difficult for practicing dermatologists to stay up-to-date on the available options, methodologies, and recommendations for when to order one test over another. Understanding the inherent strengths and weaknesses of these options is necessary to inform appropriate ordering and proper interpretation of the results. The first article in this continuing medical education series summarizes information on methodology, test characteristics, and limitations of several in vitro laboratory tests used for the work up of undifferentiated patients suspected of having dermatologic autoimmune diseases and it provides a general guide to ordering these tests.

The skin often provides initial clues of hypercoagulability with features such as livedo reticularis, livedo racemosa, retiform purpura, necrosis, and ulcerations. Because these cutaneous manifestations are nonspecific, laboratory testing is often needed to evaluate for underlying causes of hypercoagulability. Importantly, these disorders are reported to be the most common mimicker, resulting in an erroneous diagnosis of pyoderma gangrenosum. Understanding inherent properties of, and indications for, available tests is necessary for appropriate ordering and interpretation of results. Additionally, ordering of these tests in an indiscriminate manner may lead to inaccurate results, complicating the interpretation and approach to management. This second article in this continuing medical education series summarizes information on methodology, test characteristics, and limitations of several in vitro laboratory tests used for the work up of hypercoagulability and vasculopathic disease as it pertains to dermatologic disease.

To review bedside diagnostic techniques in the modern dermatologic landscape. Microscopy has been a commonly used bedside technique for the diagnosis of various fungal, parasitic, and bacterial infections. Tzanck smears are another useful technique often used for diagnosing herpesvirus lesions, but evidence shows that its use could be expanded to include other conditions as well. Wood’s light fluorescence is a simple non-invasive technique that has often been utilized to diagnose various bacterial, fungal, and pigmentation disorders, although its list of uses has not been exhausted. Cellophane tape scraping can provide a scalpel-free alternative to traditional scrapings. With the ever-decreasing costs of technologies such as PCR, swabbing for PCR may become a more common method of diagnosing more infectious skin pathologies. Bedside diagnostic techniques in dermatology are a useful adjunct to the dermatologic physical exam to confirm a diagnosis rapidly, affordably, and accurately.

BACKGROUND: Amyloid-β (Aβ) likely plays a primary role in Alzheimer’s disease pathogenesis, but longitudinal Aβ, tau, and neurodegeneration (A/T/N) measurements in the same individuals have rarely been examined to verify the temporal dynamics of these biomarkers. METHODS: In this study, we investigated the temporal ordering of Aβ, tau, and neurodegeneration using longitudinal biomarkers in nondemented elderly individuals. A total of 395 cognitively unimpaired individuals and 204 individuals with mild cognitive impairment (320 [53%] were female) were classified into 8 A±/T±/N± categories according to the abnormal (+)/normal (−) status of Aβ ((18)F-florbetapir or (18)F-florbetaben) positron emission tomography (PET), (18)F-flortaucipir PET, and adjusted hippocampal volume (aHCV). Follow-up Aβ PET, tau PET, and aHCV measurements at 0.6 to 4.1 years were available for 35% to 63% of the sample. Baseline Aβ, tau, and aHCV were compared between different A/T/N profiles. We investigated the associations of baseline and longitudinal Aβ, tau, and neurodegeneration in relation to one another continuously. RESULTS: Among T− participants, tau was higher for A+/T−/N− individuals compared with the A−/T−/N− group (p = .02). Among N− participants, neurodegeneration was worse among A+/T+/N− individuals compared with the A−/T−/N− group (p = .001). High baseline Aβ was associated (p < .001) with subsequent tau increase and high baseline tau was associated (p = .002) with subsequent aHCV decrease, whereas high tau and low aHCV at baseline were not associated with subsequent Aβ increase. CONCLUSIONS: These findings define a sequence of pathological events in Alzheimer’s disease that support a current model of Alzheimer’s disease pathogenesis in which Aβ appears early, followed by deposition of abnormal tau aggregates and subsequent neurodegeneration.

De-differentiated chondrosarcoma (DDCS) is an extremely aggressive tumor of the bone characterized by a high-grade, non-chondroid sarcoma adjacent to a low- or intermediate-grade chondrosarcoma. Adequate tumor sampling demonstrating the biphasic features is necessary to make an accurate diagnosis. The diagnosis may be challanging as histopathology may mimic other neoplasms. We present a case of 76-year-old woman with a history of breast cancer who presented with a pathologic non-displaced fracture. A bone biopsy demonstrated a high-grade neoplasm composed of pleomorphic spindled and epithelioid cells with focal expression of AE1/3 and GATA3, most likely consistent with metastatic breast carcinoma. After a difficult clinical course, the tumor was resected demonstrating a similar morphology to her prior biopsy, as well as an area of a low-grade cartilaginous neoplasm consistent with chondrosarcoma. The biphasic tumor alongside a low-grade chondrosarcoma allowed for a diagnosis of DDCS. Several days after her procedure, the patient developed violaceous nodules overlying and surrounding the surgical site. Skin biopsy demonstrated a malignant epithelioid neoplasm with identical histomorphologic features identical to her prior bone resection. Given the location of the skin lesions directly within the surgical site right after resection, the clinical-pathological picture was that of sarcomatosis cutis by iatrogenic cutaneous implantation. This article is protected by copyright. All rights reserved.

While interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc), there remains a paucity of predictive markers to assess disease progression. We previously demonstrated that adipose tissue metabolism and adipokine homeostasis is dysregulated in SSc. The present study was undertaken to determine the association and predictive ability of the novel adipokine C1q/tumor necrosis factor-related protein 9 (CTRP9) for SSc-associated ILD.We performed a retrospective longitudinal study utilizing the Northwestern Scleroderma Program Patient Registry and Biorepository. Serum levels of CTRP9 were measured in 110 SSc patients at baseline, and demographic, clinical, and pulmonary function test data were collected in 12-month intervals to 48 months. Longitudinal trajectory of forced vital capacity percent predicted (FVC%) was used as a primary outcome measure. We utilized a mixed model to compare trajectories of lung function by CTRP9 groups and performed latent trajectory analysis to accommodate for heterogeneity.In cross-sectional analysis, elevated circulating CTRP9 was associated with significantly lower FVC% at baseline (72% ± 17 versus 80% ± 18; P = 0.02) and 48 months (68 ± 19 versus 84 ± 18; P = 0.001). In mixed model analysis, high CTRP9 was associated with worse lung function but not with a different trajectory (P = 0.23). In contrast, low CTRP9 identified patients with stability of lung disease with reasonable accuracy (sensitivity 73%). Latent trajectory analysis confirmed the association of lower CTRP9 with higher FVC%.Higher circulating CTRP9 associated with worse pulmonary function, while low CTRP9 identified patients with lung disease stability over time. These findings suggest that CTRP9 may be a potential biomarker in SSc-associated ILD.

How does the time of day of a practice session affect learning of a new motor sequence in the elderly? Participants practiced a given finger tapping sequence either during morning or evening hours. All participants robustly improved performance speed within the session concurrent with a reorganization of the tapping pattern of the sequence. However, evening-trained participants showed additional gains overnight and at 1 wk posttraining; moreover, evening training led to a further reorganization of the tapping pattern offline. A learning experience preceding nocturnal sleep can lead to a task-specific movement routine as an expression of novel “how to” knowledge in the elderly.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the United States population. This guideline addresses important clinical questions that arise in psoriasis management and care and provides recommendations based on the available evidence. The treatment of psoriasis with topical agents and with alternative medicine will be reviewed, emphasizing treatment recommendations and the role of dermatologists in monitoring and educating patients regarding benefits as well as risks that may be associated. This guideline will also address the severity assessment methods of psoriasis in adults.

Renata Sokolik,1,* Milena Iwaszko,2,* Jerzy Świerkot,1 Barbara Wysoczańska,2 Lucyna Korman,1 Piotr Wiland,1 Katarzyna Bogunia-Kubik2 1Department of Rheumatology and Internal Medicine, Wrocław Medical University, Wrocław, Poland; 2Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland*These authors contributed equally to this workCorrespondence: Milena IwaszkoHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, Wrocław 53-114, PolandTel +48 71 3709960Fax +48 71 3371382Email milena.iwaszko@hirszfeld.plIntroduction: The purpose of the study was to investigate whether single-nucleotide polymorphisms (SNPs) IL-6 − 174 G/C and IL-6R Asp358Ala are associated with susceptibility to psoriatic arthritis (PsA) or affect response to treatment with methotrexate (MTX).Patients and Methods: Seventy-four patients diagnosed with PsA and qualified for MTX treatment were enrolled to the study. The control group consisted of 120 healthy individuals. Polymorphisms IL-6 − 174 G/C and IL-6R Asp358Ala were genotyped using a polymerase chain reaction (PCR) amplification employing LightSNiP assays.Results: A significant association between the IL-6 − 174 CC genotype and an improved clinical outcome of MTX therapy was observed. A good response was more frequently observed among PsA patients bearing the IL-6 − 174 CC genotype than patients with the GC or GG genotypes (P = 0.007). On the other hand, patients carrying the IL-6 − 174 GC genotype less frequently responded to MTX treatment as compared to patients with other genotypes (P = 0.006). With respect to the IL-6R Asp358Ala SNP, there were no significant differences in genotype and allelic frequencies in relation to clinical outcome of MTX treatment. No association was found between the IL-6 − 174 G/C or IL-6R Asp358Ala SNPs and PsA susceptibility.Conclusion: Results from this study provide evidence that the IL-6 − 174 G/C polymorphism might influence efficacy of MTX treatment.Keywords: psoriatic arthritis, methotrexate treatment, IL-6 − 174G/C polymorphism, IL-6R Asp358Ala polymorphism

Introduction . For modern people stress is an inevitable part of their life. Unfortunately, it is often assumed that stress is just a transient nervous tension that does not require treatment. This delusion only exacerbates the situation: one stressful situation is replaced by another, and the state of health is constantly deteriorating, and the psychosomatic disorders develop that have various clinical manifestations. Stress also aggravates the course of an existing pathology, and the presence of pathology is in itself a powerful stress factor. It should also be noted that stress is often accompanied by somatic dysfunctions for which osteopathic correction is effective. It is also impossible to imagine a modern person without dorsopathies, often associated with a sedentary lifestyle. Today, approximately 45 % of dorsopathies are in the cervical spine, of which 41.3 % of patients have cervicocranialgia. This pathology is characterized by frequent recurrence and progression, especially in people of the most working age, and it causes a high medical and social significance of cervicocranialgia. Frequent anomalies of the craniocervical zone, extensive fascial, visceral and muscle connections at the regional and global level, participation in the membrane system of mutual tension of the dura mater and suture structures of the skull — all this necessitates an integrated approach to the treatment of patients with cervicocranialgia, including osteopathic correction. All of the above allowed us to suggest that osteopathic correction may influence stress levels in patients with cervicocranialgia. The goal of research — to study the effect of osteopathic correction on the level of stress in patients with cervicocranialgia in a state of severe psychological stress. Materials and methods . The study involved 24 patients suffering from cervicocranialgia, characterized by prolonged exposure to severe psychological stress and high levels of cortisol in the blood. The study participants were divided into a control (12 people) and an experimental (12 people) group by the method of simple randomization using a random number generator. Participants in both groups received standard drug treatment for cervicocranialgia: non-steroidal anti-inflammatory drugs, B vitamins, muscle relaxants, angioprotectors and microcirculation correctors. The participants in the experimental group additionally received osteopathic correction. In both groups, before and after the course of treatment, the patients’ osteopathic status was assessed, the stress level was assessed using the PSM-25 psychological stress scale, and the morning blood cortisol level was measured. The obtained results were processed by methods of parametric and nonparametric statistics. Results . It was found that both the standard drug treatment of patients suffering from cervicocranialgia and the complex treatment with the use of osteopathic correction contribute to a statistically significant decrease in the level of cortisol in the blood (p

Urea cycle disorders (UCDs), including OTC deficiency (OTCD), are life-threatening diseases with a broad clinical spectrum. Early diagnosis and initiation of treatment based on a newborn screening (NBS) test for OTCD with high specificity and sensitivity may contribute to reduction of the significant complications and high mortality. The efficacy of incorporating orotic acid determination into routine NBS was evaluated. Combined measurement of orotic acid and citrulline in archived dried blood spots from newborns with urea cycle disorders and normal controls was used to develop an algorithm for routine NBS for OTCD in Israel. Clinical information and genetic confirmation results were obtained from the follow-up care providers. About 1147986 newborns underwent routine NBS including orotic acid determination, 25 of whom were ultimately diagnosed with a UCD. Of 11 newborns with OTCD, orotate was elevated in seven but normal in two males with early-onset and two males with late-onset disease. Orotate was also elevated in archived dried blood spots of all seven retrospectively tested historical OTCD patients, only three of whom had originally been identified by NBS with low citrulline and elevated glutamine. Among the other UCDs emerge, three CPS1D cases and additional three retrospective CPS1D cases otherwise reported as a very rare condition. Combined levels of orotic acid and citrulline in routine NBS can enhance the detection of UCD, especially increasing the screening sensitivity for OTCD and differentiate it from CPS1D. Our data and the negligible extra cost for orotic acid determination might contribute to the discussion on screening for proximal UCDs in routine NBS.

Background Infections related to intravenous drug use and opioid use disorders (OUDs) are increasing nationwide. Endocarditis is a recognized complication of intravenous drug use, and inpatient treatment typically focuses on infection management without attention to underlying addiction. Objective A comprehensive intervention for inpatients with infective endocarditis and intravenous drug use was implemented by a multidisciplinary team at a large midwestern hospital. The team included behavioral health/addiction medicine, infectious disease, pain medicine, cardiothoracic surgery, pharmacy, and nursing to address the OUD while managing the infection. The intervention was assessed by measuring the initiation of medication-assisted treatment and endocarditis-related readmissions. Methods Patients were identified from the medical records using discharge diagnosis codes for OUDs and infective endocarditis. In addition to medical management of infective endocarditis, the multidisciplinary intervention included early involvement of addiction medicine and the pain management at the time of admission. Patient interventions included education, motivational interviewing, behavioral health engagement, collaborative pain management, individual/family therapy, medication evaluation, and initiation of medication-assisted treatment. Caregivers were also educated on OUDs and ways to support patients undergoing interventions. Results Both the historical control group (N = 37) and the intervention group (N = 33) were comparable in age, gender, race, marital status, psychiatric history, and smoking but differed by employment status, religious affiliation, and use of psychiatric medications. At discharge, 18.9% of the control group and 54.5% in the intervention group were initiated on medication-assisted treatment for OUDs. No differences in readmission rates were found. Conclusion Multidisciplinary teams for treating inpatients with intravenous drug use and infective endocarditis are feasible and can increase the uptake of OUD-specific treatment.

BACKGROUND Infective endocarditis (IE) results in substantial morbidity and mortality in people who inject drugs (PWID). AIMS To describe the burden of IE and its outcomes in PWID. METHODS Retrospective cohort study of adults admitted to a tertiary referral centre in Melbourne, Australia, with IE due to injection drug use from 1997 to 2015. RESULTS Ninety-seven PWID with 127 episodes of IE were identified with a median acute inpatient stay of 37 days (1-84). Admission to an intensive care unit was required in 67/127 (53%) episodes. Twenty-seven percent (34/127) of episodes occurred in patients with a previous episode of endocarditis. One third (43/127, 34%) of episodes involved left-sided cardiac valves. Antimicrobial treatment was completed in 88 (70%) episodes. Valve surgery was performed in 25/127 (20%) episodes. Predictors of surgery in univariable analysis were left-sided cardiac involvement (risk ratio (RR) 6.0), severe valvular regurgitation (RR 2.6) and cardiac failure (RR 2.2) (all P

Healthcare workers are at increased risk of occupational transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report 2 instances of healthcare workers contracting SARS-CoV-2 despite no known breach of personal protective equipment. Additional specific equipment cleaning was initiated. Viral genomic sequencing supported this transmission hypothesis and our subsequent response.

OBJECTIVE Connective tissue disease (CTD)-associated pulmonary arterial hypertension (PAH) is the second most common etiology of PAH and carries a poor prognosis. Recently, it has been shown that female human tumor necrosis factor (TNF)-transgenic (Tg) mice die of cardiopulmonary disease by 6 months of age. This study was undertaken to characterize this pathophysiology and assess its potential as a novel model of CTD-PAH. METHODS Histologic analysis was performed on TNF-Tg and wild-type (WT) mice to characterize pulmonary vascular and right ventricular (RV) pathology (n = 40 [4-5 mice per group per time point]). Mice underwent right-sided heart catheterization (n = 29) and micro-computed tomographic angiography (n = 8) to assess vascular disease. Bone marrow chimeric mice (n = 12), and anti-TNF-treated mice versus placebo-treated mice (n = 12), were assessed. RNA sequencing was performed on mouse lung tissue (n = 6). RESULTS TNF-Tg mice displayed a pulmonary vasculopathy marked by collagen deposition (P < 0.001) and vascular occlusion (P < 0.001) with associated RV hypertrophy (P < 0.001) and severely increased RV systolic pressure (mean ± SD 75.1 ± 19.3 mm Hg versus 26.7 ± 1.7 mm Hg in WT animals; P < 0.0001). TNF-Tg mice had increased α-smooth muscle actin (α-SMA) staining, which corresponded to proliferation and loss of von Willebrand factor (vWF)-positive endothelial cells (P < 0.01). There was an increase in α-SMA-positive, vWF-positive cells (P < 0.01), implicating endothelial-mesenchymal transition. Bone marrow chimera experiments revealed that mesenchymal but not bone marrow-derived cells are necessary to drive this process. Treatment with anti-TNF therapy halted the progression of disease. This pathology closely mimics human CTD-PAH, in which patient lungs demonstrate increased TNF signaling and significant similarities in genomic pathway dysregulation. CONCLUSION The TNF-Tg mouse represents a novel model of CTD-PAH, recapitulates key disease features, and can serve as a valuable tool for discovery and assessment of therapeutics.

BackgroundAlzheimer’s disease (AD)-related tauopathy can be measured with CSF phosphorylated tau (pTau) and tau PET. We aim to investigate the associations between these measurements and their relative ability to predict subsequent disease progression.MethodsIn 219 cognitively unimpaired and 122 impaired Alzheimer’s Disease Neuroimaging Initiative participants with concurrent amyloid-β (Aβ) PET (18F-florbetapir or18F-florbetaben),18F-flortaucipir (FTP) PET, CSF measurements, structural MRI, and cognition, we examined inter-relationships between these biomarkers and their predictions of subsequent FTP and cognition changes.ResultsThe use of a CSF pTau/Aβ40ratio eliminated positive associations we observed between CSF pTau alone and CSF Aβ42in the normal Aβ range likely reflecting individual differences in CSF production rather than pathology. Use of the CSF pTau/Aβ40ratio also increased expected associations with Aβ PET, FTP PET, hippocampal volume, and cognitive decline compared to pTau alone. In Aβ+ individuals, abnormal CSF pTau/Aβ40only individuals (26.7%) were 4 times more prevalent (p 40mediates the association between Aβ PET and FTP PET accumulation, but FTP PET is more closely linked to subsequent cognitive decline than CSF pTau/Aβ40.ConclusionsTogether, these findings suggest that CSF pTau/Aβ40may be a superior measure of tauopathy compared to CSF pTau alone, and CSF pTau/Aβ40enables detection of tau accumulation at an earlier stage than FTP among Aβ+ individuals.

Background: Active surveillance (AS) of small, low-risk papillary thyroid cancers (PTCs) is increasingly being considered. There is limited understanding of why individuals with low-risk PTC may choose AS over traditional surgical management. Methods: We present a mixed-methods analysis of a prospective observational real-life decision-making study regarding the choice of thyroidectomy or AS for management of localized, low-risk PTCs

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world's population. In this guideline, we focus the discussion on systemic, nonbiologic medications for the treatment of this disease. We provide detailed discussion of efficacy and safety for the most commonly used medications, including methotrexate, cyclosporine, and acitretin, and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch on a number of other medications, including fumaric acid esters (used outside the United States) and therapies that are no longer widely used for the treatment of psoriasis (ie, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus).

More data are needed to characterize the perceptions of dermatology by nondermatologist physicians in order to address how current perceptions may be improved. Residency program directors of 21 medical specialties were contacted by e-mail and directed to a survey created with Research Electronic Data Capture software. Data from survey responses were collated and analyzed. A total of 80 residency program directors completed the survey. Physicians who worked more frequently with dermatologists were more likely to describe dermatologists positively. Most physicians believed dermatologists manage skin conditions, but fewer knew that they also manage hair, nail, or mucosal conditions. Cross-specialty collaboration between nondermatologists and dermatologists is associated with positive perceptions of dermatology. Further collaboration could provide the opportunity to educate physicians regarding the conditions treated by dermatologists and how their expertise may benefit patient care.

IntroductionBCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19.Methods and analysisThis international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood samples. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections.Ethics and disseminationEthical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system.Trial registrationClinicalTrials.gov NCT04327206

The Choosing Wisely Canada campaign raises awareness amongst physicians and patients regarding unnecessary or inappropriate tests and treatments. Using an online survey, members of the Pediatric Otolaryngology Subspecialty Group within the Canadian Society of Otolaryngology – Head & Neck Surgery developed a list of nine evidence based recommendations to help physicians and patients make treatment decisions regarding common pediatric otolaryngology presentations: (1) Don’t routinely order a plain film x-ray in the evaluation of nasal fractures; (2) Don’t order imaging to distinguish acute bacterial sinusitis from an upper respiratory infection; (3) Don’t place tympanostomy tubes in most children for a single episode of otitis media with effusion of less than 3 months duration; (4) Don’t routinely prescribe intranasal/systemic steroids, antihistamines or decongestants for children with uncomplicated otitis media with effusion; (5) Don’t prescribe oral antibiotics for children with uncomplicated tympanostomy tube otorrhea or uncomplicated acute otitis externa; (6) Don’t prescribe codeine for post-tonsillectomy/adenoidectomy pain relief in children; (7) Don’t administer perioperative antibiotics for elective tonsillectomy in children; (8) Don’t perform tonsillectomy for children with uncomplicated recurrent throat infections if there have been fewer than 7 episodes in the past year, 5 episodes in each of the past 2 years, or 3 episodes in each of the last 3 years; and (9) Don’t perform endoscopic sinus surgery for uncomplicated pediatric chronic rhinosinusitis prior to failure of maximal medical therapy and adenoidectomy.

Background Humoral responses to COVID-19 vaccines in hemodialysis patients can direct vaccination policy. Methods We compared 409 COVID-19 naïve hemodialysis patients from 13 hemodialysis units in Israel to 148 non-dialysis dependent COVID-19 naïve controls. Twenty-four previously infected (anti-nucleocapsid positive) hemodialysis patients were analyzed separately. Blood samples were obtained ≥ 14 days post vaccination (BNT162b2) to assess seroconversion-rates and titers of anti-S and neutralizing antibodies. Results Median time from vaccination to blood sample collection was 82 (IQR 64–87) and 89 (IQR 68–96) days, for hemodialysis patients and controls, respectively. Seroconversion rates were lower in hemodialysis patients compared to controls for both anti-S and neutralizing antibodies (89% and 77% vs. 99.3%, respectively, P, Graphical Abstract Graphical Abstract

The primary objective of this study is to detect biomarkers and develop models that enable the identification of clinically significant prostate cancer and to understand the biologic implications of the genes involved. Peripheral blood samples (1018 patients) were split chronologically into independent training (n = 713) and validation (n = 305) sets. Whole transcriptome RNA sequencing was performed on isolated phagocytic CD14+ and non-phagocytic CD2+ cells and their gene expression levels were used to develop predictive models that correlate to adverse pathologic features. The immune-transcriptomic model with the highest performance for predicting adverse pathology, based on a subtraction of the log-transformed expression signals of the two cell types, displayed an area under the curve (AUC) of the receiver operating characteristic of 0.70. The addition of biomarkers in combination with traditional clinical risk factors (age, serum prostate-specific antigen (PSA), PSA density, race, digital rectal examination (DRE), and family history) enhanced the AUC to 0.91 and 0.83 for the training and validation sets, respectively. The markers identified by this approach uncovered specific pathway associations relevant to (prostate) cancer biology. Increased phagocytic activity in conjunction with cancer-associated (mis-)regulation is also represented by these markers. Differential gene expression of circulating immune cells gives insight into the cellular immune response to early tumor development and immune surveillance.

Background Universal screening has been proposed as a strategy to identify asymptomatic individuals infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mitigate transmission. Aim To investigate the rate of positive tests among pregnant women in Melbourne, Australia. Methods We performed a cross-sectional prevalence study at three maternity hospitals (one tertiary referral hospital and two secondary maternities) in Melbourne, Australia. SARS-CoV-2 testing was offered to all pregnant women attending face-to-face antenatal visits and to those attending the hospital with symptoms of possible coronavirus disease, between 6th and 19th of May 2020. Testing was performed by multiplex-tandem polymerase chain reaction (PCR) on combined oropharyngeal and nasopharyngeal swabs. The primary outcome was the proportion of positive SARS-CoV-2 tests. Findings SARS-CoV-2 testing was performed in 350 women, of whom 19 had symptoms of possible COVID-19. The median maternal age was 32 years (IQR 28–35 years), and the median gestational age at testing was 33 weeks and four days (IQR 28 weeks to 36 weeks and two days). All 350 tests returned negative results (p = 0%, 95% CI 0–1.0%). Conclusion In a two-week period of low disease prevalence, the rate of asymptomatic coronavirus infection among pregnant women in Australia during the study period was negligible, reflecting low levels of community transmission.

Japanese encephalitis (JE) virus is a mosquito-borne flavivirus endemic throughout Asia. Incidence in non-endemic countries is rare, with an estimate of less than one case per one million travelers. Most human JE infections are asymptomatic or cause a mild, nonspecific febrile illness. Neurological involvement, if present, is usually severe and associated with high mortality or ongoing neurological sequelae in survivors. Ocular manifestations are rare with JE, but uveitis has been described to be associated with other flavivirus infections, including West Nile virus. We report the first probable case of JE chorioretinitis acquired by a 45-year-old Australian traveler to Bali. This case highlights the importance of a detailed ocular examination when there is clinical suspicion of JE.

No abstract available.

Cel: W publikacji omówiono skutki działania promieniowania jonizującego na organizm ludzki. W przeświadczeniu autorów przedstawienie problematyki zdarzeń radiacyjnych od strony skutków napromieniowania pozwoli na lepsze przygotowanie na wypadek ich wystąpienia, a w konsekwencji bezpieczniejsze działanie w trakcie tego zagrożenia. Wprowadzenie: Coraz szersze zastosowanie materiałów promieniotwórczych i urządzeń wytwarzających promieniowanie jonizujące w wielu obszarach naszego życia niesie za sobą ryzyko narażenia na działanie niebezpiecznych dla zdrowia dawek promieniowania. Dawki te mogą być generowane wskutek uszkodzenia źródeł promieniowania lub postępowania z nimi w nieodpowiedni sposób. Nie można również wykluczyć narażeń wynikających z intencjonalnego wykorzystania materiałów promieniotwórczych w działaniach kryminalnych lub terrorystycznych. Narażenie na promieniowanie jonizujące może wywołać negatywne skutki zdrowotne – zarówno u ofiar zdarzenia radiacyjnego, jak i u ratowników udzielających ofiarom pomocy. Istniejące zagrożenia wymagają więc odpowiedniego przygotowania medycznych służb ratowniczych. Jednym z elementów tych przygotowań jest poznanie specyfiki zagrożeń radiacyjnych, w tym źródeł promieniowania, mechanizmu działania poszczególnych form promieniowania jonizującego, a także rodzaju obrażeń radiacyjnych, które wywołują. Metodologia: W artykule przedstawiono właściwości promieniowania jonizującego, najbardziej istotne z punktu widzenia ratownictwa medycznego. Omówiono zagadnienia związane z kontaktem ze źródłem promieniowania, skażenia zewnętrznego i wewnętrznego, pomiaru wielkości ekspozycji i dawek pochłoniętych oraz zaprezentowano wzajemne zależności pomiędzy nimi. Szczegółowo opisano mechanizm bezpośredniego i pośredniego działania promieniowania jonizującego na struktury komórkowe (DNA, mRNA, błony cytoplazmatyczne) enzymy wewnątrzkomórkowe. Przedstawiono konsekwencje zdrowotne dla organizmu w postaci uszkodzeń ostrych (deterministycznych) i zmian późnych (stochastycznych). Wnioski: Szczególną uwagę zwrócono na ostry zespół radiacyjny (ang. Acute Radiation Syndrome, ARS). Szczegółowo omówiono zależność poszczególnych postaci ARS od wielkości pochłoniętej dawki. Przedstawiono każdą z faz ARS: wstępną, utajoną, rozwiniętych objawów i zdrowienia (śmierci) oraz czas ich wystąpienia, długość trwania i moment zakończenia. Scharakteryzowano mechanizm uszkodzenia poszczególnych narządów i układów. Wskazano najczęstsze objawy, ich nasilenie i przyczyny zagrożenia życia w poszczególnych postaciach ARS. Obok skutków ogólnoustrojowych opisano zmiany miejscowe pod postacią radiacyjnego zespołu skórnego (ang. Cutaneous Radiation Syndrome, CSR). Purpose: The effects of ionising radiation on the human body has been discussed. The authors believe that the understanding of the radiation incidents from the perspective of its effects is crucial for better preparation, and therefore safer and more effective responses to incidents involving such threats. Introduction: The increasing use of radioactive materials and radiation producing devices in many areas of our lives carries the risk of exposure to high doses of radiation being hazardous to our health due to possible damage to radiation sources or improper handling. Exposure resulting from the intentional use of radioactive materials for criminal or terrorist purposes cannot be excluded, either. Exposure to ionising radiation may cause adverse health effects both to victims of a radiation incident and for rescuers providing emergency care. Such threats require the proper preparation of emergency medical services (EMS). Part of these preparations is to examine the specifics of radiation hazards, including radiation sources, the mechanism of injury of ionising radiation and the type of radiation damage. Methodology: The publication presents the properties of ionising, corpuscular and electromagnetic types of radiation, which are the most important from EMS’s perspective. The dangers of contact with a radiation source, the problem of external and internal contamination, the estimation of the amount of absorbed radiation were discussed, and the interrelationships between them were presented. The mechanism of direct and indirect action of ionising radiation on cell structures (DNA, mRNA, cytoplasmic membranes) and intracellular enzymes was thoroughly discussed. The authors presented health consequences of radiation for the body in the form of acute (deterministic) lesions and late (stochastic) lesions. Conclusions: Particular attention was paid to acute radiation syndrome (ARS). The dependence of ARS on the amount of absorbed radiation was discussed in detail. Four stages of ARS were presented: initial, latent, manifest illness and recovery (or death) as well as the time of their onset, duration and end. The mechanism of damage to individual organs and systems was also analysed. The most common symptoms, their severity, and causes of life-threatening conditions, resulting from radiation damage in particular syndromes of ARS, were indicated. In addition to systemic effects, local changes in the form of Cutaneous Radiation Syndrome (CSR) were discussed.

Psoriasis is a chronic, multisystem, inflammatory disease that affects approximately 1% of children, with onset most common during adolescence. This guideline addresses important clinical questions that arise in psoriasis management and provides evidence-based recommendations. Attention will be given to pediatric patients with psoriasis, recognizing the unique physiology, pharmacokinetics, and patient-parent-provider interactions of patients younger than 18 years old. The topics reviewed here mirror those discussed in the adult guideline sections, excluding those topics that are irrelevant to, or lack sufficient information for, pediatric patients.

Summary Background Psoriasis is a chronic, systemic immune‐mediated disease characterized by development of erythematous, indurated, scaly, pruritic and often painful skin plaques. Psoriasis pathogenesis is driven by proinflammatory cytokines and psoriasis is associated with increased risk for comorbidities, including, but not limited to, psoriatic arthritis, cardiovascular disease, diabetes mellitus, obesity, inflammatory bowel disease and nonalcoholic fatty liver disease compared with the general population. Objectives To explore the pathophysiological relationship between psoriasis and its common comorbidities and discuss the need for new treatment paradigms that include strategies to reduce systemic inflammation in patients with moderate‐to‐severe psoriasis. Methods This narrative review summarizes the published evidence related to the ability of biological therapies to ameliorate the consequences of systemic inflammation in patients with psoriasis. Results Current evidence suggests that preventing damage associated with inflammation, and preventing development of future inflammatory damage and comorbidities, may be a potentially achievable treatment goal for many patients with moderate‐to‐severe plaque psoriasis when biological therapies are utilized early in the disease. Encouraging data from recent studies suggest that the loftier goal of reversing existing inflammatory damage and improving signs and symptoms of inflammatory comorbidities could also possibly be attainable. Conclusions Results from ongoing prospective studies regarding the effects of biologics on markers of systemic inflammation in patients with psoriasis will strengthen the clinical evidence base that can be used to inform treatment decisions for patients with moderate‐to‐severe psoriasis. What's already known about this topic? Psoriasis is a systemic inflammatory disease and treatments are needed to optimize patient outcomes. What does this study add? This review discusses new psoriasis treatment paradigms that may potentially reduce effects of systemic inflammation.Evidence demonstrating that biological treatment may prevent or reverse inflammatory damage associated with psoriasis comorbidities is reviewed., Linked Comment: https://doi.org/10.1111/bjd.18456

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 3.2% of the world's population. In this section of the guidelines of care for psoriasis, we will focus the discussion on ultraviolet (UV) light-based therapies, which include narrowband and broadband UVB, UVA in conjunction with photosensitizing agents, targeted UVB treatments such as with an excimer laser, and several other modalities and variations of these core phototherapies, including newer applications of pulsed dye lasers, intense pulse light, and light-emitting electrodes. We will provide an in-depth, evidence-based discussion of efficacy and safety for each treatment modality and provide recommendations and guidance for the use of these therapies alone or in conjunction with other topical and/or systemic psoriasis treatments.

Resumo Objetivo O objetivo do presente trabalho é relatar as características clínicas de pacientes pediátricos com diagnóstico de osteocondroma retroescapular submetidos a tratamento cirúrgico, entre os anos de 2003 e 2017. Métodos Série de casos, analítica, descritiva e retrospectiva de sete pacientes com diagnóstico de osteocondroma retroescapular. Resultados A média de idade dos pacientes analisados foi de 9,5 anos, sendo 71% deles do sexo masculino. O tempo médio entre o início dos sintomas e o procedimento cirúrgico foi de 1,2 anos. Aproximadamente 71% dos pacientes apresentaram osteocondroma na escápula direita, e 57,1% dos casos foram classificados como sésseis. Ao exame clínico, observou-se pseudoescápula alada em 85,7%, crepitação em 71,4%, e queixa de dor em 42,9% dos pacientes. Conclusão A escápula alada pode ter diferentes etiologias, dentre elas o osteocondroma retroescapular. O conhecimento sobre anatomia funcional e semiologia ortopédica somado à correta sistematização da abordagem dos tumores ósseos consiste na base para o correto diagnóstico diferencial e tratamento adequado.

Background: Memorial Sloan Kettering Cancer Center (MSK) created the MSK Cancer Alliance in 2014, a dynamic and bidirectional collaboration with high-quality community providers to enhance access to state-of-the-art cancer care close to home. Hartford HealthCare Cancer Institute (HHC), joined the MSK Cancer Alliance as the first member in 2014. Research suggests that bone marrow transplant (BMT) is an underutilized definitive therapy (Yao et al, Biol Blood Bone Marrow Transplant 2013) for patients with hematologic malignancies and the timing of a referral for transplant has significant impact on patient outcomes (National Marrow Donor Program, available at: https://bethematchclinical.org/transplant-indications-and-outcomes/additional-outcomes/timing-impact-on-outcomes/). MSK and HHC developed the BMT Shared Care program to improve access to transplant, ensure BMT specialist consults for appropriate candidates occur during initial treatment planning, reduce burdensome travel for patients by facilitating care locally, and enhance seamless coordination between local oncologists and BMT providers from initial consult through post-transplant care. Methods: To achieve these goals, MSK and HHC physicians, nurses, and staff created a program that includes: HHC hiring a BMT nurse, who trained for 4 weeks at MSK, and works with MSK counterparts to create a streamlined referral process, pretransplant care at HHC, and travel logistics to MSK; MSK and HHC physicians hold virtual tumor boards to jointly evaluate patients and provide BMT consults at the optimal time; onsite lectures and observer-ships focused on advances in BMT, supportive care, and management of complications like graft versus host disease, leading to the integration of additional clinical services like infectious disease and dermatology; and research, including an MSK clinical trial open at HHC to identify and understand barriers to transplant in the community for patients with newly diagnosed or relapsed acute leukemia. Results: Since November 2015, HHC has referred 86 patients for BMT consult through this Shared Care program, with 35 patients transplanted or receiving immune effector cells (IEC) to date. Conclusions: The BMT Shared Care program effectively facilitates the referral and transplant of appropriate patients while allowing them to receive much of their pre- and post-transplant care in their local communities. Collaboration between BMT nurse coordinators and robust physician engagement are essential to this program. Future opportunities include expanding the use of telemedicine, enhancing electronic data sharing, quantifying and analyzing patient satisfaction, and expanding BMT research at HHC.

We tested how observation of a skilled pattern of planar movements can assist in the learning of a new motor skill, which otherwise requires rigorous long-term practice to achieve fast and smooth performance. Sixty participants performed a sequence of planar hand movements on pre-test, acquisition, post-test and 24 h post-training blocks, under 1 of 4 conditions: an observation group (OG), a slowed observation group (SOG), a random motion control group (RMCG) and a double physical training control group (DPTCG). The OG and SOG observed an expert model’s right hand performing the study task intermittently throughout acquisition, RMCG observed random dots movement instead of a model. Participants in the DPTCG received extra physical practice trials instead of the visually observed trials. Kinematic analysis revealed that only in conditions with observation of an expert model there was an instant robust improvement in motor planning of the task. This step-wise improvement was not only persistent in post-training retests but was also apparently implicit and subject to further incremental improvements in movement strategy over the period of 24 hours. The rapid change in motor strategy was accompanied by a transient within-session increase in spatial error for the observation groups, but this went away by 24 h post-training. We suggest that observation of hand movements of an expert model coaligned with self-produced movements during training can significantly condense the time-course of ecologically relevant drawing/writing skill mastery.

ObjectiveHigh-intensity interval training (HIIT) is a safe and feasible form of exercise. The aim of this meta-analysis was to investigate the mental health effects of HIIT, in healthy populations and those with physical illnesses, and to compare the mental health effects to non-active controls and other forms of exercise.DesignRandom effects meta-analyses were undertaken for randomised controlled trials (RCTs) comparing HIIT with non-active and/or active (exercise) control conditions for the following coprimary outcomes: mental well-being, symptoms of depression, anxiety and psychological stress. Positive and negative affect, distress and sleep outcomes were summarised narratively.Data sourcesMedline, PsycINFO, Embase and CENTRAL databases were searched from inception to 7 July 2020.Eligibility criteria for selecting studiesRCTs that investigated HIIT in healthy populations and/or those with physical illnesses and reported change in mental well-being, depression, anxiety, psychological stress, positive/negative affect, distress and/or sleep quality.ResultsFifty-eight RCTs were retrieved. HIIT led to moderate improvements in mental well-being (standardised mean difference (SMD): 0.418; 95% CI: 0.135 to 0.701; n=12 studies), depression severity (SMD: –0.496; 95% CI: −0.973 to −0.020; n=10) and perceived stress (SMD: −0.474; 95% CI: −0.796 to −0.152; n=4) compared with non-active controls, and small improvements in mental well-being compared with active controls (SMD:0.229; 95% CI: 0.054 to 0.403; n=12). There was a suggestion that HIIT may improve sleep and psychological distress compared with non-active controls: however, these findings were based on a small number of RCTs.ConclusionThese findings support the use of HIIT for mental health in the general population.Level of evidenceThe quality of evidence was moderate-to-high according to the Grading of Recommendations Assessment, Development and Evaluation) criteria.PROSPERO registration numberCRD42020182643

Enteropathy-associated T-cell lymphoma (EATL) is a tumor of intraepithelial T-lymphocytes arising in the small intestine. Based on the genetic profile, immunohistochemistry, and histology, EATL is divided into two subtypes. EATL type I occurs in individuals with celiac disease (CD) while EATL type II is a sporadic form that occurs in individuals without CD. Intensive chemotherapy and surgery are the mainstay treatment. However, despite the currently available treatment options, the five-year survival rate is only 9%. EATL presents as abdominal pain, nausea, or slow gastrointestinal bleeding. Severe bleeding leading to hemodynamic instability is rarely known in EATL. Therefore, we present a unique case of EATL who presented with acute and severe gastrointestinal bleeding with no prior history of CD.

Aim Thoracic outlet syndrome (TOS) is a condition that occurs when the cervical neuro-vascular bundle becomes compressed at one of the three narrow areas of the thoraco-cervico-axillary region. Conservative management is the first line of treatment. Patients who do not respond to conservative management should be treated surgically. The aim of this review is to present our experience with the surgical management of TOS in pediatric patients. Methods We retrospectively reviewed the outcomes of all patients with TOS operated at our Hospital between 2001 and 2020. We collected all demographic data, clinical features, imaging data, type of operation performed, intraoperative findings, complications and recurrence. Results We operated 9 patients within the study period. The median age at surgery was 14 (7 to 17) years. A transaxillary approach was used in 7 patients and a supraclavicular approach in 2. There was only one minor intraoperative complication (violation of the pleural space). There were no postoperative complications. The median length of stay was 3 (2 to 4) days. All patients were extubated in the operating room. Two patients developed symptoms on the contralateral side. One of these underwent a successful contralateral transaxillary Roos operation. The follow-up was 4 months to 20 years. All patients are asymptomatic. Conclusion We believe that the Roos operation is a safe and effective treatment with excellent long-term outcomes for children with TOS that fail conservative management.

Study question Does slow development of fresh transferred day 5 embryos lead to decreased implantation potential and birthweight? Summary answer Slow day 5 development was associated with reduced implantation potential when transferred fresh but the subsequent birthweight of the resulting baby was not impacted. What is known already Slow development of in vitro cultured cleavage stage embryos is associated with reduced blastocyst development and implantation rates. There is no current consensus regarding whether to transfer fresh slow developing day 5 embryos or to extend culture for a subsequent day with potential for cryopreservation. It is therefore important to understand the true prognosis of fresh transferred day 5 embryos at less advanced developmental stages. This would provide evidence based guidelines for the decision making process in regard to embryo transfer. Study design, size, duration This is a retrospective multi-center cohort study, including 1213 consecutive patients undergoing autologous oocyte in vitro fertilization (IVF) treatment during 2016-2019,with fresh transfer of a single day 5 embryo (selection based on developmental stage and inner cell mass and trophectoderm morphology if blastocyst was at the ≥expanding stage). Cycle data were collected from 4 associated private clinics, with repeat cycles of same patients excluded to avoid clustering effect at statistical analysis. Participants/materials, setting, methods Live birth and birthweight were followed up in all 1213 fresh day 5 SETs. Multiple regression (logistic or linear) was performed to investigate association between slow day 5 development (defined as ≤ early blastocyst) and (a)live birth, (b) birthweight, and (c) gestation-adjusted birthweight (Z score) to account for gestational age, gender and compared to embryos at ≥ expanded stage. Results were expressed as adjusted odds ratio (aOR) with 95% confidence interval (CI)or coefficients (β). Main results and the role of chance No implantation was achieved following single fresh transfer of day 5 embryos that failed to reach early blastocyst stage (n = 76) and were transferred as ≤ morula stage. Live birth rate was significantly lower following single day 5 fresh transfer of an early blastocyst (n = 237, 16%), in comparison to expanding (n = 329, 27%, P = 0.001), expanded(n = 392, 41%, P = 0.000), and hatching/hatched blastocysts (n = 169, 44%, P = 0.000). After adjusting for potential confounding factors including; maternal age, hours post insemination at day 5 assessment, number of oocytes collected, number of 2PN embryos, and number of embryos frozen; multiple logistic regression showed significantly reduced likelihood of live birth resulting from early blastocysts in reference to those at the expanding (aOR=0.584, 0.371-0.917, P = 0.020), expanded (aOR=0.322, 0.208-0.501, P = 0.000), or hatching/hatched stages (aOR=0.255, 0.147-0.443, P = 0.000). However, multivariate linear regression indicated that early blastocysts resulting in a live birth (n = 39) did not lead to altered birthweight (β=-9.091, P = 0.904; β=-34.960, P = 0.343; β=-26.074, P = 0.414; respectively) or Z score (β = 0.045, P = 0.706; β=-0.051, P = 0.426; β=-0.028, P = 0.506; respectively) in reference to the expanding (n = 90), expanded (n = 160), or hatching/hatched stages (n = 75). Limitations, reasons for caution The retrospective nature of this study does not allow controlling of unknown confounders. The 4 participating clinics are associated within the same network with shared protocols, therefore, results may not be generalized to other clinics with different settings. Wider implications of the findings The findings suggest no clinical value of fresh day 5 transfer of embryos ≤morula stage. Although early blastocysts implant at reduced rate, assuring birthweight outcomes suggest clinical value. Future studies intend to investigate slow growing day 5 fresh transfers versus embryos that were slow growing but transferred after day 6. Trial registration number NA

Objectives:To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission.Design:Pilot prospective multicenter surveillance study.Setting:The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals.Methods:All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data.Results:In total, 408 isolates were collected from 358 patients; 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%), and ESBL-Kp (7.6%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure.Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients).Conclusions:Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.

Introduction/Objectives Project ECHO COVID-19 was launched nationwide on March 4, 2020 to disseminate guidance about COVID-19 in a timely and scalable manner to meet the urgent needs of primary care settings, the first line of defense in a pandemic. Methods Data from post-session surveys were analyzed to assess participant satisfaction, knowledge gaps, change in knowledge, and anticipated changes in practice as a result of Project ECHO COVID-19. A content analysis was conducted of the 243 questions and concerns posted by over 2000 participants in the Question and Answer function of Zoom during the first 8 sessions (March 4-April 29, 2020). Results Of 5243 registrants, 49% attended at least one session. Respondents agreed or strongly agreed that didactic sessions (97%) and case presentations (96%) met their learning needs; 93% reported gaining new knowledge, and 88% would implement that knowledge. Only 32% and 53% of respondents anticipated changing workflows and adapting to telehealth, respectively, despite the need for both as the pandemic continued. The content analysis identified 3 categories: clinical operations (eg, testing, triage, telehealth, billing); patient care (diagnosis and treatment of COVID-19, management of high-risk vulnerable populations); and epidemiology (viral spread, implications for public health). Conclusions Care of vulnerable populations and clinical operations should be addressed when planning education and clinical interventions for public health crises. Adapting the Project ECHO model to be more scalable was an effective means of creating a community of practice among health professionals when evidence-based guidance was not available to manage the implications of a pandemic.