Diagnosis and management in Rubinstein-Taybi syndrome:first international consensus statement

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.</p

Diagnosis and management in Rubinstein-Taybi syndrome:first international consensus statement

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.</p

Motor, cognitive and mobility deficits in 1000 geriatric patients : protocol of a quantitative observational study before and after routine clinical geriatric treatment – the ComOn-study

© The Author(s). 2020 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). Methods: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. Discussion: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.info:eu-repo/semantics/publishedVersio

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Diagnosis and management in Rubinstein-Taybi syndrome: first international consensus statement

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care

Diagnosis and management in Rubinstein-Taybi syndrome: first international consensus statement

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care

Redefining the MED13L syndrome

Congenital cardiac and neurodevelopmental deficits have been recently linked to the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8-associated mediator complex that functions in transcriptional regulation through DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L variants cause transposition of the great arteries and intellectual disability (ID). Here, we report eight patients with predominantly novel MED13L variants who lack such complex congenital heart malformations. Rather, they depict a syndromic form of ID characterized by facial dysmorphism, ID, speech impairment, motor developmental delay with muscular hypotonia and behavioral difficulties. We thereby define a novel syndrome and significantly broaden the clinical spectrum associated with MED13L variants. A prominent feature of the MED13L neurocognitive presentation is profound language impairment, often in combination with articulatory deficits

High Diagnostic Value of a New Real-Time Pneumocystis PCR from Bronchoalveolar Lavage in a Real-Life Clinical Setting

Unnewehr M, Friederichs H, Bartsch P, Schaaf B. High Diagnostic Value of a New Real-Time Pneumocystis PCR from Bronchoalveolar Lavage in a Real-Life Clinical Setting. Respiration. 2016;92(3):144-149.Background: To diagnose Pneumocystis jirovecii pneumonia (PCP), PCR testing in bronchoalveolar lavage (BAL) fluid has recently become an alternative to immunofluorescence testing (IFT); however, its diagnostic accuracy is less clear. Objective: To analyze the diagnostic value of a new semiquantitative real-time PCR (RT-PCR) in BAL in a real-life clinical setting. Methods: Retrospective analysis of all RT-PCR results [semiquantitative: negative, weakly positive, and strongly positive; measured in cycle thresholds (Ct)] in BAL in the period between 2010 and 2014. The diagnosis of PCP was defined by clinical, radiological, and laboratory signs and by treatment initiation. Any positive PCR was compared with subsequent IFT. Results: Of 128 patient samples, 32 had PCP. There is a relevant correlation of high significance between positive PCR Ct and IFT (r = -0.7781, p 45) rules out PCP. A strongly positive PCR (Ct <31.5) confirms PCP. In these cases, the diagnostic value of the new method is at least equal to the IFT. A weakly positive PCR probably represents pneumocystis colonization and can occur under PCP treatment

Housing interventions for women experiencing intimate partner violence: a systematic review

Background Intimate partner violence (IPV) is the leading cause of women's homelessness. However, what works best to respond to the needs of women experiencing IPV and homelessness remains unclear. We aimed to systematically review the effects of housing interventions on the physical, psychosocial, and economic wellbeing of women experiencing IPV. Methods In this systematic review, we searched 15 electronic databases and conducted an extensive grey literature and hand reference search between Jan 29, 2020, and May 31, 2021. We included controlled quantitative studies of housing interventions (from emergency shelter to permanent supportive housing) that were reported in English, without time restrictions, and examined any physical, psychosocial, or economic outcomes among women experiencing IPV. We critically appraised included studies using the Cochrane Effective Practice and Organisation of Care criteria and extracted data using a piloted extraction form. We synthesised our results using harvest plots to summarise whether the weight of the evidence suggested benefits, disadvantages, or null effects; patterns by study quality; and evidence gaps. This study is registered with PROSPERO, CRD42020176705. Findings We screened 23 902 unique records and identified 34 eligible studies with quantitative data on the outcomes of housing interventions among women experiencing IPV. Most studies evaluated the outcomes of either shelter interventions (18 studies [53%]) or shelter plus some other programming (eight [24%]). The remaining eight studies evaluated longer-term housing solutions, including supportive housing (five studies [15%]), critical time interventions (one [3%]), transitional housing (one [3%]), and stay-at-home models (one [3%]). There was no cumulative evidence of disadvantages following any IPV-housing intervention. Evidence of benefits was strongest for mental health outcomes, intent to leave partner, perceived safety, and housing and partner-related stress. Included studies were at high risk of bias across most domains (eg, confounding). Interpretation There is promising evidence on the continuum of IPV-housing services for women, especially in terms of proximal outcomes, such as mental health, intent to leave partner, safety, and housing stress. However, more research of higher quality is needed, particularly on long-term housing solutions and from outside of the USA