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INTRODUCTION: The nose and throat are areas of high viral load, which could place otolaryngologists at an even higher risk for COVID-19 than other health-care workers. OBJECTIVE: To investigate the prevalence of antibodies against SARS-CoV-2 in otorhinolaryngologists in southern Brazil, its relationship to demographic data, professional practice and reported symptoms of COVID-19, and compare it with official data on other health-care workers of the state and the general population in the same period. METHODS: In this cross-sectional multicenter study, otolaryngologists actively practicing officially registered in Rio Grande do Sul were screened for IgM and IgG antibodies against SARS-CoV-2 from August 1 to September 15, 2020. A questionnaire was also applied. RESULTS: We screened 358 (80.1%) of 447 actively practicing otolaryngologists (195 [54.5%] male; mean [SD] age, 47.77 [13.57] years; range, 26-84 years). Twenty-three were positive for IgM and/or IgG (6.4%). This result was significantly associated with reports of infected household contacts (19/315 negatives and 8/23 positives; p 

Background The impact of postero-anterior and medio-lateral mitral valve (MV) tethering patterns on outcomes in patients undergoing transcatheter edge-to-edge repair (M-TEER) for secondary mitral regurgitation (SMR) is unknown. Methods The ratio of the posterior to anterior MV leaflet angle (PLA/ALA) in MV segment 2 was defined as postero-anterior tethering asymmetry. Medio-lateral tethering asymmetry was assessed as the ratio of the medial (segment 3) to lateral (segment 1) MV tenting area. We used receiver-operating characteristics and a Cox regression model to identify cut-off values of asymmetric anteroposterior and medio-lateral tethering for prediction of 2 year all-cause mortality after TMVR. Results Among 178 SMR patients, postero-anterior tethering was asymmetric in 67 patients (37.9%, PLA/ALA ratio > 1.54). Asymmetric medio-lateral tethering (tenting area ratio > 1.49) was observed in 49 patients (27.5%). M-TEER reduced MR to ≤ 2 + in 92.1% of patients; MR reduction was less effective in the presence of asymmetric postero-anterior tethering (p = 0.02). A multivariable Cox regression model identified both types of asymmetric MV tethering to be associated with increased all-cause 2-year mortality (postero-anterior tethering asymmetry: HR = 2.77, CI 1.43–5.38; medio-lateral tethering asymmetry: HR = 2.90, CI 1.54–5.45; p Conclusions Asymmetric postero-anterior and medio-lateral MV tethering patterns are associated with increased 2-year mortality in patients undergoing M-TEER for SMR. A detailed echocardiographic analysis of MV anatomy may help to identify patients who profit most from M-TEER. Graphical abstract

BACKGROUND: Diverticulitis is a complication of the common condition, diverticulosis. Uncomplicated diverticulitis has traditionally been treated with antibiotics, as diverticulitis has been regarded as an infectious disease. Risk factors for diverticulitis, however, may suggest that the condition is inflammatory rather than infectious which makes the use of antibiotics questionable. OBJECTIVES: The objectives of this systematic review were to determine if antibiotic treatment of uncomplicated acute diverticulitis affects the risk of complications (immediate or late) or the need for emergency surgery. SEARCH METHODS: For this update, a comprehensive systematic literature search was conducted in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov and WHO International Clinical Trial Registry Platform on February 2021. SELECTION CRITERIA: Randomised controlled trials (RCTs), including all types of patients with a radiologically confirmed diagnosis of left‐sided uncomplicated acute diverticulitis. Comparator and interventions included antibiotics compared to no antibiotics, placebo, or to any other antibiotic treatment (different regimens, routes of administration, dosage or duration of treatment). Primary outcome measures were complications and emergency surgery. Secondary outcomes were recurrence, late complications, elective colonic resections, length of hospital stay, length to recovery of symptoms, adverse events and mortality. DATA COLLECTION AND ANALYSIS: Two authors performed the searches, identification and assessment of RCTs and data extraction. Disagreements were resolved by discussion or involvement of the third author. Authors of trials were contacted to obtain additional data if needed or for preliminary results of ongoing trials. The Cochrane Collaboration's tool for assessing risk of bias was used to assess the methodological quality of the identified trials. The overall quality of evidence for outcomes was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Effect estimates were extracted as risk ratios (RRs) with 95% confidence intervals. Random‐effects meta‐analyses were performed with the Mantel‐Haenzel method. MAIN RESULTS: The authors included five studies. Three studies compared no antibiotics to antibiotics; all three were original RCTs of which two also published long‐term follow‐up information. For the outcome of short‐term complications there may be little or no difference between antibiotics and no antibiotics (RR 0.89; 95% CI 0.30 to 2.62; 3 studies, 1329 participants; low‐certainty evidence). The rate of emergency surgery within 30 days may be lower with no antibiotics compared to antibiotics (RR 0.47; 95% CI 0.13, 1.71; 1329 participants; 3 studies; low‐certainty evidence). However, there is considerable imprecision due to wide confidence intervals for this effect estimate causing uncertainty which means that there may also be a benefit with antibiotics. One of the two remaining trials compared single to double compound antibiotic therapy and, due to wide confidence intervals, the estimate was imprecise and indicated an uncertain clinical effect between these two antibiotic regimens (RR 0.70; 95% CI 0.11 to 4.58; 51 participants; 1 study; low‐certainty evidence). The last trial compared short to long intravenous administration of antibiotics and did not report any events for our primary outcomes. Both trials included few participants and one had overall high risk of bias. Since the first publication of this systematic review, an increasing amount of evidence supporting the treatment of uncomplicated acute diverticulitis without antibiotics has been published, but the total body of evidence is still limited. AUTHORS' CONCLUSIONS: The evidence on antibiotic treatment for uncomplicated acute diverticulitis suggests that the effect of antibiotics is uncertain for complications, emergency surgery, recurrence, elective colonic resections, and long‐term complications. The quality of the evidence is low. Only three RCTs on the need for antibiotics are currently available. More trials are needed to obtain more precise effect estimates.

Background Receptor activator of NF kappa B (RANK) and its ligand have an essential role in T-cell regulation and the development of bone metastases. The role of RANK expression in muscle-invasive bladder cancer (MIBC) is unknown. Objective To assess the relevance of RANK expression in patients with MIBC. Design, setting, and participants Expression of RANK was assessed via immunohistochemistry of benign urothelium, MIBC tissue, and lymph node metastases from 153 patients undergoing radical cystectomy. Expression data from The Cancer Genome Atlas (TCGA) cohort were analyzed for potential associations with molecular subtypes and outcome. Outcome measurements and statistical analysis RANK expression was correlated with clinical and pathological parameters and to individual data for the clinical course of MIBC. Results and limitations Expression of RANK was significantly higher in both primary tumors (p = 0.02) and lymph node metastases (p = 0.01) compared to normal urothelium. In tumor tissue, RANK expression was significantly lower in patients with locally advanced disease and lymph node involvement compared to those with organ-confined disease (p = 0.0009) and node-negative MIBC (p = 0.0002). In univariable and multivariable analyses, high expression of RANK was associated with a longer time to recurrence (p = 0.0005 and 0.01) and better cancer-specific (p = 0.0004 and 0.007) and overall survival (p = 0.002 and 0.04). High expression of RANK was associated with better outcome for patients with luminal infiltrated tumors in the TCGA cohort. Conclusions RANK expression is increased in bladder cancer tissue compared to benign urothelium, with higher expression in organ-defined compared to locally advanced disease. High RANK expression indicates a favorable prognosis in MIBC. The prognostic role differs in tumors of different molecular subtypes. Patient summary Expression of a protein involved in bone turnover regulation (RANK) is higher in bladder cancer tissue than in benign bladder tissue. However, high levels of RANK on tumor cells indicate favorable prognosis for patients with bladder cancer that invades the muscle layer of the bladder.

Context Episodic breathlessness is characterized by increased breathlessness intensity, and it is burdensome for patients. A vicious cycle of breathlessness-anxiety/panic-breathlessness leads to emergencies that can rarely be alleviated by drugs. Non-pharmacological interventions seem to be beneficial: Can a brief cognitive and behavioral intervention help patients to better manage episodic breathlessness? Objectives To evaluate the feasibility, safety, acceptability, and potential effects of a brief cognitive and behavioral intervention for the management of episodic breathlessness. Methods Between February 2019 and February 2020, 49 patients with life-limiting diseases suffering from episodic breathlessness were enrolled in the single-arm phase II study. The baseline assessment was followed by the 1- to 2-hour intervention. In weeks two, four, and six after the intervention, the outcomes (main outcome of potential effects: mastery of breathlessness) were assessed, and in week six, a qualitative interview, and the final assessment took place. A mixed-methods approach was used to evaluate mainly the feasibility, including interviewing informal carers. Results 46/49 patients (24 female; 36 with COPD; mean age: 66.0 years) participated in the baseline assessment, 38 attended the intervention, 32 completed the final assessment, and 22 were interviewed. Study procedures and the intervention were feasible and mainly well accepted and patients did not experience burdens caused by it (28/32). In the interviews, patients described a positive change in their competencies in managing episodic breathlessness and feelings of anxiety during the episode. Mastery of breathlessness improved after the intervention. Conclusion The brief cognitive and behavioral intervention and the study procedures are feasible, safe, and well accepted. We can describe a change for better management of episodic breathlessness in patients after the intervention, still, this needs to be evaluated in a Phase III trial for inclusion in the management of episodic breathlessness. Key message The brief cognitive and behavioral intervention shows a positive change in the management of episodic breathlessness in patients with life-limiting diseases by reducing panic and anxiety in breathlessness episodes and promoting a feeling of competence in managing the episodes. It is safe, feasible, and acceptable.

Background: Since facial paralysis is a dynamic condition, the analysis of still photographs is not sufficient for measurement of facial reanimation outcomes. This study aimed at evaluating an arti...

Aim: We aimed to study gender-specific differences in patients who underwent left atrial appendage closure (LAAC). Materials & methods: A total of 201 consecutive patients who underwent LAAC were enrolled. The EQ-5D-3L questionnaire was employed before and 3 months post-LAAC to study the quality of life. Results: Women had a higher score for Anxiety/Depression before implantation. Three months after LAAC, both groups showed a significant improvement in mobility, self-care and usual activities. The female gender had a significant improvement in health state 3 months after implantation than their male counterparts. Conclusion: Our data shows an improvement in mobility, self-care, usual activities and the overall health state in all patients after LAAC. This potential improvement, most likely caused by the discontinuation of oral anticoagulants, should be considered an indication for LAAC.

Background Vascular and bleeding complications are common after transcatheter aortic valve implantation (TAVI) and are associated with worse outcomes. The plug-based Manta (M) vascular closure device (VCD) is a novel option to achieve haemostasis for large-bore arterial access sites. Objective We aimed to compare vascular and bleeding complications between the M-VCD and the established suture-based Perclose ProGlide (P)-VCD. Methods From February to September 2019 a total of 578 patients underwent transfemoral TAVI at a single high-volume centre. Access site closure was performed using M-VCD in 195 patients (33.7%) and P-VCD in 383 patients (66.3%). We assessed vascular and access site-related complications as well as bleeding events according to the Valve Academic Research Consortium-2 definition. Results Overall vascular complications occurred less frequently in the M-VCD group (10.7% vs. 19.0%, p = 0.011) driven by a significantly lower rate of major vascular events (2.0% vs. 6.5%, p = 0.025). Access site-related complications were significantly less frequent in the M-VCD cohort (10.7% vs. 16.6%, p = 0.048). The M-VCD was associated with significantly lower rates of major (0.5% vs. 4.4%, p = 0.009) and life-threatening bleeding (0% vs. 2.3%, p = 0.032). In multivariable analysis, the use of M-VCD was the only independent predictor of vascular complications (odds ratio 0.54, 95% confidence interval 0.32–0.91, p = 0.022). Conclusions The M-VCD was associated with a reduction of vascular and access-site complications as well as severe bleeding after transfemoral TAVI compared to the P-VCD in this observational study.

Purpose No clear consensus exists on how to routinely assess the integrity of the colorectal anastomosis prior to ileostomy reversal. The objective of this study was to evaluate the accuracy of contrast enema, endoscopic procedures, and digital rectal examination in rectal cancer patients in this setting. Methods A systematic literature search was performed. Studies assessing at least one index test for which a 2 × 2 table was calculable were included. Hierarchical summary receiver operating characteristic curves were calculated and used for test comparison. Paired data were used where parameters could not be calculated. Methodological quality was assessed with the QUADAS-2 tool. Results Two prospective and 11 retrospective studies comprising 1903 patients were eligible for inclusion. Paired data analysis showed equal or better results for sensitivity and specificity of both endoscopic procedures and digital rectal examination compared to contrast enema. Subgroup analysis of contrast enema according to methodological quality revealed that studies with higher methodological quality reported poorer sensitivity for equal specificity and vice versa. No case was described where a contrast enema revealed an anastomotic leak that was overseen in digital rectal examination or endoscopic procedures. Conclusions Endoscopy and digital rectal examination appear to be the best diagnostic tests to assess the integrity of the colorectal anastomosis prior to ileostomy reversal. Accuracy measures of contrast enema are overestimated by studies with lower methodological quality. Synopsis of existing evidence and risk–benefit considerations justifies omission of contrast enema in favor of endoscopic and clinical assessment. Trial registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019107771

Objectives To analyze the ability of machine-learning (ML)-based computed tomography (CT)-derived fractional flow reserve (CT-FFR) to further improve the diagnostic performance of coronary...

BACKGROUND: Research shows that surgery patients who have undergone Roux-en-Y gastric bypass (RYGB) are at increased risk for an alcohol use disorder (AUD). However, the mechanisms through which this increased risk is incurred are poorly understood. A host of variables have been proposed as potentially causal in developing AUDs, but empirical examination of many of these variables in human samples is lacking. OBJECTIVES: Our objective was to examine the extent to which alcohol pharmacokinetics (PK), the rewarding effects of alcohol, and the relationship between these variables change from before to after weight loss surgery. SETTING: Large healthcare facility in the Midwest United States METHODS: Thirty-four participants completed assessments prior to, and one year after, RYGB. They completed laboratory sessions and provided data on the PK of alcohol and the extent to which alcohol was reinforcing to them at each timepoint. RESULTS: Findings show that the PK effects of alcohol (p

STUDY OBJECTIVES: We determined the relationship of cardiovascular risk factors, cardiovascular diseases, nocturnal blood pressure (NBP), and NBP fluctuations (NBPFs) with the severity of obstructive sleep apnea (OSA). We also investigated the effect of short-term continuous positive airway pressure therapy on NBP parameters. METHODS: This retrospective study included 548 patients from our cardiac clinic with suspected OSA. Patients underwent polysomnography and continuous NBP measurement using the pulse transit time. According to their apnea-hypopnea index (AHI), patients were subclassified as controls (AHI < 5 events/h), mild (AHI 5 to < 15 events/h), moderate (AHI 15 to < 30 events/h), and severe OSA (AHI ≥ 30 events/h); 294 patients received continuous positive airway pressure therapy. RESULTS: Analysis of covariance showed that NBP and the frequency of NBPFs were the highest in severe followed by moderate and mild OSA (all P < .001). Multivariable regression analysis revealed a significant association of NBPFs with AHI, body mass index, systolic NBP, and lowest SpO(2). The severity of OSA is also associated with the frequency of obesity, hypertension, diabetes mellitus, atrial fibrillation, heart failure (all P < .001), and coronary artery disease (P = .035). Short-term continuous positive airway pressure decreased the frequency of NBPFs in all OSA groups and the systolic NBP in severe and moderate but not in mild OSA. CONCLUSIONS: The severity of OSA is associated with an increase in NBP and NBPFs. Continuous positive airway pressure reduces NBP parameters already after the first night. In addition to BP, the diagnosis and therapy of NBPFs should be considered in patients with OSA. CLINICAL TRIAL REGISTRATION: Registry: German Clinical Trials Register; Name: Nocturnal blood pressure and nocturnal blood pressure fluctuations associated with the severity of obstructive sleep apnea; URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00024087; Identifier: DRKS00024087. CITATION: Picard F, Panagiotidou P, Tammen A-B, et al. Nocturnal blood pressure and nocturnal blood pressure fluctuations: the effect of short-term CPAP therapy and their association with the severity of obstructive sleep apnea. J Clin Sleep Med. 2022;18(2):361–371.

Background: Transcatheter aortic valve replacement is an established treatment option for patients with severe symptomatic aortic stenosis and is most commonly performed through the transfemoral access route. Percutaneous access site closure can be achieved using dedicated plug-based or suture-based vascular closure device (VCD) strategies, but randomized comparative studies are scarce. Methods: The CHOICE-CLOSURE trial (Randomized Comparison of Catheter-based Strategies for Interventional Access Site Closure during Transfemoral Transcatheter Aortic Valve Implantation) is an investigator-initiated, multicenter study, in which patients undergoing transfemoral transcatheter aortic valve replacement were randomly assigned to vascular access site closure using either a pure plug-based technique (MANTA, Teleflex) with no additional VCDs or a primary suture-based technique (ProGlide, Abbott Vascular) potentially complemented by a small plug. The primary end point consisted of access site– or access-related major and minor vascular complications during index hospitalization, defined according to the Valve Academic Research Consortium-2 criteria. Secondary end points included the rate of access site– or access-related bleeding, VCD failure, and time to hemostasis. Results: A total of 516 patients were included and randomly assigned. The mean age of the study population was 80.5±6.1 years, 55.4% were male, 7.6% of patients had peripheral vascular disease, and the mean Society of Thoracic Surgeons score was 4.1±2.9%. The primary end point occurred in 19.4% (50/258) of the pure plug-based group and 12.0% (31/258) of the primary suture-based group (relative risk, 1.61 [95% CI, 1.07–2.44], P =0.029). Access site– or access-related bleeding occurred in 11.6% versus 7.4% (relative risk, 1.58 [95%CI: 0.91–2.73], P =0.133) and device failure in 4.7% versus 5.4% (relative risk, 0.86, [95% CI, 0.40–1.82], P =0.841) in the respective groups. Time to hemostasis was significantly shorter in the pure plug-based group (80 [32–180] versus 240 [174–316] seconds, P Conclusions: Among patients treated with transfemoral transcatheter aortic valve replacement, a pure plug-based vascular closure technique using the MANTA VCD is associated with a higher rate of access site– or access-related vascular complications but a shorter time to hemostasis compared with a primary suture-based technique using the ProGlide VCD. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04459208.

Biallelic mutations of the CEBPA gene (CEBPAbi) define a distinct entity associated with favorable prognosis; however, the role of monoallelic mutations (CEBPAsm) is poorly understood. We retrospectively analyzed 4708 adults with acute myeloid leukemia (AML) who had been recruited into the Study Alliance Leukemia trials, to investigate the prognostic impact of CEBPAsm. CEBPA mutations were identified in 240 patients (5.1%): 131 CEBPAbi and 109 CEBPAsm (60 affecting the N-terminal transactivation domains [CEBPAsmTAD] and 49 the C-terminal DNA-binding or basic leucine zipper region [CEBPAsmbZIP]). Interestingly, patients carrying CEBPAbi or CEBPAsmbZIP shared several clinical factors: they were significantly younger (median, 46 and 50 years, respectively) and had higher white blood cell (WBC) counts at diagnosis (median, 23.7 × 109/L and 35.7 × 109/L) than patients with CEBPAsmTAD (median age, 63 years, median WBC 13.1 × 109/L; P < .001). Co-mutations were similar in both groups: GATA2 mutations (35.1% CEBPAbi; 36.7% CEBPAsmbZIP vs 6.7% CEBPAsmTAD; P < .001) or NPM1 mutations (3.1% CEBPAbi; 8.2% CEBPAsmbZIP vs 38.3% CEBPAsmTAD; P < .001). CEBPAbi and CEBPAsmbZIP, but not CEBPAsmTAD were associated with significantly improved overall (OS; median 103 and 63 vs 13 months) and event-free survival (EFS; median, 20.7 and 17.1 months vs 5.7 months), in univariate and multivariable analyses. Additional analyses revealed that the clinical and molecular features as well as the favorable survival were confined to patients with in-frame mutations in bZIP (CEBPAbZIP-inf). When patients were classified according to CEBPAbZIP-inf and CEBPAother (including CEBPAsmTAD and non-CEBPAbZIP-inf), only patients bearing CEBPAbZIP-inf showed superior complete remission rates and the longest median OS and EFS, arguing for a previously undefined prognostic role of this type of mutation.

Cardiac magnetic resonance (CMR) imaging provides valuable prognostic information in patients with ST-elevation myocardial infarction (STEMI). The peri-infarct zone (PIZ) is a potential marker for post-infarction risk stratification. The aim of this study was to assess the prognostic impact of PIZ in a large multicenter STEMI-trial.The study population consisted of 704 consecutive patients undergoing CMR within 10 days after STEMI to assess established parameters of myocardial injury and additionally the extent of PIZ. The primary clinical endpoint was major adverse cardiac events (MACE) consisting of death, re-infarction and new congestive heart failure within 1 year after infarction.The median heterogeneous PIZ-volume in the overall population was 14 ml (interquartile range [IQR] 7 to 24 ml). Male sex, infarct size, and left ventricular ejection fraction were identified as independent predictors of larger PIZ alterations. Patients with MACE had a significantly larger PIZ volume compared to patients without adverse events (21 ml [IQR 12 to 35 ml] versus 14 ml [IQR 7 to 23 ml]; p = 0.001). In stepwise multivariable Cox regression analysis, PIZ median (14 ml) emerged as an independent predictor of MACE (hazard ratio [HR] 2.84; 95% confidence interval [CI] 1.34 to 6.00; p = 0.006) in addition to the Thrombolysis In Myocardial Infarction (TIMI) risk score (HR 1.53; 95% CI 1.19 to 1.53; p 0.001). Addition of PIZ to a CMR risk model comprising LVEF, infarct size and microvascular obstruction resulted in net reclassification improvement of 0.46 (0.19-0.73, p 0.001).In this currently largest prospective, multicenter CMR study assessing PIZ, the extent of PIZ emerged as an independent predictor of MACE and a potential novel marker for optimized risk stratification in STEMI patients. ClinicalTrials.gov: NCT00712101.

Purpose This trial was conducted to investigate the clinical equivalence of the proposed biosimilar FYB201 and reference ranibizumab in patients with treatment-naive, subfoveal choroidal neovascularization caused by neovascular age-related macular degeneration (nAMD). Design This was a prospective, multicenter, evaluation-masked, parallel-group, 48-week, phase III randomized study. Participants A total of 477 patients were randomly assigned to receive FYB201 (n = 238) or reference ranibizumab (n = 239). Methods Patients received FYB201 or ranibizumab 0.5 mg by intravitreal injection in the study eye every four weeks. Main Outcome Measures The primary end point was change from baseline in best corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 8 weeks prior to the third monthly intravitreal injection. Biosimilarity of FYB201 to its originator was assessed via a two-sided equivalence test, with an equivalence margin in BCVA of 3 ETDRS letters. Results BCVA improved in both groups, with a mean improvement of +5.1 (FYB201) and +5.6 (reference ranibizumab) ETDRS letters at week 8. The analysis of covariance (ANCOVA) least squares mean difference for the change from baseline between FYB201 and reference ranibizumab was –0.4 ETDRS letters with a 90% confidence interval (CI) of –1.6 to 0.9. Primary end point was met as the 90% CI was within the predefined equivalence margin. Adverse events were comparable between treatment groups. Conclusions FYB201 is biosimilar to reference ranibizumab in terms of clinical efficacy and ocular and systemic safety in the treatment of patients with nAMD.

Objective The aim of this survey was to describe existing perioperative care standards and best practices in the Netherlands and Belgium. Design An online survey was followed up by an in-depth personal interview. The main outcomes were the existing standards of perioperative care for patients undergoing cardiac surgery. Setting The online survey and subsequent interviews were targeted to one representative in the intensive care unit (ICU), cardiac surgery, and anesthesiology department from each cardiac surgical center in the Netherlands and Belgium. Participants A representative intensive care physician, cardiac surgeon, and cardiac anesthesiologist. Interventions None. Measurements and Main Results The response rate was 60% (71% for the Netherlands, and 44% in Belgium). Agreement across centers was found for discontinuation of proton-pump inhibitors (80%) and avoiding intra- and postoperative (92%) nonsteroidal antiinflammatory drugs. Additionally, 98% of respondents stated that physiotherapy should be started immediately in the ICU. Major divergence was found for elements such as the discontinuation of angiotensin-converting enzyme inhibitors (55%) or the postoperative use of chest support vests (44%). Conclusions The authors demonstrated a wide range of different local protocols. Strategies differed among disciplines, hospitals, and countries. This emphasized the need for the implementation of a more universal protocol to further reduce variance and improve recovery practices. This nationwide survey was the first of its kind simultaneously studying best practices for cardiac surgery through the entire care pathway at the advent of Enhanced Recovery After Surgery (ERAS) Cardiac implementation. A multinational randomized controlled trial to test the implementation of an evidence-based ERAS Cardiac protocol is the next step to pave the way for further outcome improvements in this high-risk population.

PURPOSE: To determine the interreader agreement for incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) and their related features in age-related macular degeneration (AMD). DESIGN: Interreader agreement study. PARTICIPANTS: Twelve readers from 6 reading centers. METHODS: After formal training, readers qualitatively assessed 60 OCT B-scans from 60 eyes with AMD for 9 individual features associated with early atrophy and performed 7 different annotations to quantify the spatial extent of OCT features within regions of interest. The qualitative and quantitative features were used to derive the presence of iRORA and cRORA and also in an exploratory analysis to examine if agreement could be improved using different combinations of features to define OCT atrophy. MAIN OUTCOME MEASURES: Interreader agreement based on Gwet's first-order agreement coefficient (AC1) for qualitatively graded OCT features and classification of iRORA and cRORA, and smallest real difference (SRD) for quantitatively graded OCT features. RESULTS: Substantial or better interreader agreement was observed for all qualitatively graded OCT features associated with atrophy (AC1 = 0.63-0.87), except for RPE attenuation (AC1 = 0.46) and disruption (AC1 = 0.26). The lowest SRD for the quantitatively graded horizontal features was observed for the zone of choroidal hypertransmission (± 190.8 μm). Moderate agreement was found for a 3-category classification of no atrophy, iRORA, and cRORA (AC1 = 0.53). Exploratory analyses suggested a significantly higher level of agreement for a 3-category classification using (1) no atrophy; (2) presence of inner nuclear layer and outer plexiform layer subsidence, or a hyporeflective wedge-shaped band, as a less severe atrophic grade; and (3) the latter plus an additional requirement of choroidal hypertransmission of 250 μm or more for a more severe atrophic grade (AC1 = 0.68; P = 0.013). CONCLUSIONS: Assessment of iRORA and cRORA, and most of their associated features, can be performed relatively consistently and robustly. A refined combination of features to define early atrophy could further improve interreader agreement.

BACKGROUND: The US Food and Drug Administration warned that exposure of pregnant women to general anaesthetics may impair fetal brain development. This review systematically evaluates the evidence underlying this warning. METHODS: PubMed, EMBASE, and Web of Science were searched from inception until April 3, 2020. Preclinical and clinical studies were eligible. Exclusion criteria included case reports, in vitro models, chronic exposures, and exposure only during delivery. Meta-analyses were performed on standardised mean differences. The primary outcome was overall effect on learning/memory. Secondary outcomes included markers of neuronal injury (apoptosis, synapse formation, neurone density, and proliferation) and subgroup analyses. RESULTS: There were 65 preclinical studies included, whereas no clinical studies could be identified. Anaesthesia during pregnancy impaired learning and memory (standardised mean difference -1.16, 95% confidence interval -1.46 to -0.85) and resulted in neuronal injury in all experimental models, irrespective of the anaesthetic drugs and timing in pregnancy. Risk of bias was high in most studies. Rodents were the most frequently used animal species, although their brain development differs significantly from that in humans. In a minority of studies, anaesthesia was combined with surgery. Monitoring and strict control of physiological homeostasis were below preclinical and clinical standards in many studies. The duration and frequency of exposure and anaesthetic doses were often much higher than in clinical routine. CONCLUSION: Anaesthesia-induced neurotoxicity during pregnancy is a consistent finding in preclinical studies, but translation of these results to the clinical situation is limited by several factors. Clinical observational studies are needed. PROSPERO REGISTRATION NUMBER: CRD42018115194. ispartof: BRITISH JOURNAL OF ANAESTHESIA vol:126 issue:6 pages:1128-1140 ispartof: location:England status: published

Aims The aim of this pooled sub-analysis of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) and Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial was to compare the clinical outcome of patients with acute myocardial infarction complicated by cardiogenic shock treated either with clopidogrel or the newer, more potent ADP-receptor antagonists prasugrel or ticagrelor. Methods and results For the current analysis the primary endpoint was 1-year mortality and the secondary safety endpoint was moderate or severe bleedings until hospital discharge with respect to three different ADP-receptor antagonists. 856 patients were eligible for analysis. Of these, 507 patients (59.2%) received clopidogrel, 178 patients (20.8%) prasugrel and 171 patients (20.0%) ticagrelor as acute antiplatelet therapy. The adjusted rate of mortality after 1-year did not differ significantly between prasugrel and clopidogrel (hazard ratio [HR]: 0.81, 95% confidence interval [CI] 0.60–1.09, padj = 0.17) or between ticagrelor and clopidogrel treated patients (HR: 0.86, 95% CI 0.65–1.15, padj = 0.31). In-hospital bleeding events were significantly less frequent in patients treated with ticagrelor vs. clopidogrel (HR: 0.37, 95% CI 0.20 -0.69, padj = 0.002) and not significantly different in patients treated with prasugrel vs. clopidogrel (HR: 0.73, 95% CI 0.43 -1.24, padj = 0.24). Conclusion This pooled sub-analysis is the largest analysis on safety and efficacy of three oral ADP-receptor antagonists and shows that acute therapy with either clopidogrel, prasugrel or ticagrelor is no independent predictor of 1-year mortality. Treatment with ticagrelor seems independently associated with less in-hospital moderate and severe bleeding events compared to clopidogrel. This finding might be due to selection bias and should be interpreted with caution. Graphic abstract

Background In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted. Study Design The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke. Conclusions The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock.

The purpose of this paper was to evaluate the impact of proportionality of secondary mitral regurgitation (SMR) in a large real-world registry of transcatheter edge-to-edge mitral valve repair (TMVr) BACKGROUND: Differences in the outcomes of recent randomized trials of TMVr for SMR may be explained by the proportionality of SMR severity to left ventricular (LV) volume.The ratio of pre-procedural effective regurgitant orifice area (EROA) to LV end-diastolic volume (LVEDV) was retrospectively assessed in patients undergoing TMVr for severe SMR between 2008 and 2019 from the EuroSMR registry. A recently proposed SMR proportionality scheme was adapted to stratify patients according to EROA/LVEDV ratio in 3 groups: MR-dominant (MD), MR-LV-co-dominant (MLCD), and LV-dominant (LD). All-cause mortality was assessed as a primary outcome, secondary heart failure (HF) outcomes included hospitalization for HF (HHF), New York Heart Association (NYHA) functional class, N-terminal pro-B-type natriuretic peptide (NT-proBNP), 6-min-walk distance, quality of life and MR grade.A total of 1,016 patients with an EROA/LVEDV ratio were followed for 22 months after TMVr. MR was reduced to grade ≤2+ in 92%, 96%, and 94% of patients (for MD, MLCD, and LD, respectively; p = 0.18). After adjustment for covariates including age, sex, diabetes, kidney function, body surface area, LV ejection fraction, and procedural MR reduction (grade ≤2+), adjusted rates of 2-year mortality in MD patients did not differ from those for MLCD patients (17% vs. 18%, respectively), whereas it was higher in LD patients (23%; p = 0.02 for comparison vs. MD+MLCD). The adjusted first HHF rate differed between groups (44% in MD, 56% in MLCD, 29% in LD; p = 0.01) as did the adjusted time for first death or HHF rate (66% in MD, 82% in MLCD, 68% in LD; p = 0.02). Improvement of NYHA functional class was seen in all groups (p 0.001). Values for 6-min-walk distances, quality of life and NT-proBNP improved in most patients.MD and MLCD patients had a comparable, adjusted 2-year mortality rate after TMVr which was slightly better than that of LD patients. Patients treated with TMVr had symptomatic improvement regardless of EROA/LVEDV ratio.

Acute upper limb ischemia is considered a vascular emergency. These events are mostly thromboembolic and are often detected in patients with atrial fibrillation (AF). Surgical thrombectomy and percutaneous mechanical thrombectomy are the usual methods to treat this medical emergency. In this case, we report the case of a 75-years old woman with a history of AF who initially presented to our center because of syncope resulting from Torsades de pointes due to a known long-QT syndrome. Those episodes were treated adequately from the implanted ICD. In addition to the symptoms of syncope, the patient also noted symptoms of right upper-limb ischemia. Using duplex sonography, we noticed a thrombotic occlusion at the level of the axillary artery. Using femoral access, we performed an antegrade angiography of the axillary artery, which confirmed a fresh thrombotic occlusion. The initially performed thrombus aspiration wasn't successful, and the decision was made to use an ekosonic endovascular system (Ekosonic ™ Endovascular System, Boston Scientific, EKOS) catheter to perform catheter-directed thrombolysis. Locally, 10 mg Actilyse were administrated. Then an EKOS Catheter was delivered to the occlusion area and was placed for 6 h. Symptoms of ischemia were resolved, and the angiographic control showed normal flow in the axillary artery. The patient was discharged without any local deficits of the right hand.

Background/Objectives Older patients admitted to cardiac care units often suffer functional decline. We evaluated whether a nurse-led geriatric co-management program leads to better functional status at hospital discharge. Design A quasi-experimental before-and-after study was performed between September 2016 and December 2018, with the main endpoint at hospital discharge and follow-up at 6 months. Setting Two cardiac care units of the University Hospitals Leuven. Participants One hundred and fifty-one intervention and 158 control patients aged 75 years or older admitted for acute cardiovascular disease or transcatheter aortic valve implantation. Intervention A nurse from the geriatrics department performed a comprehensive geriatric assessment within 24 h of admission. The cardiac care team and geriatrics nurse drafted an interdisciplinary care plan, focusing on early rehabilitation, discharge planning, promoting physical activity, and preventing geriatric syndromes. The geriatrics nurse provided daily follow-up and coached the cardiac team. A geriatrician co-managed patients with complications. MEASUREMENTS The primary outcome was functional status measured using the Katz Index for independence in activities of daily living (ADL; one-point difference was considered clinically relevant). Secondary outcomes included the incidence of ADL decline and complications, length of stay, unplanned readmissions, survival, and quality of life. RESULTS The mean age of patients was 85 years. Intervention patients had better functional status at hospital discharge (8.9, 95% CI = 8.7-9.3 versus 9.5, 95% CI = 9.2-9.9; p = 0.019) and experienced 18% less functional decline during hospitalization (25% vs. 43%, p = 0.006). The intervention group experienced significantly fewer cases of delirium and obstipation during hospitalization, and significantly fewer nosocomial infections. At 6-month follow-up, patients had significantly better functional status and quality of life. There were no differences regarding length of stay, readmissions, or survival. CONCLUSION This first nurse-led geriatric co-management program for frail patients on cardiac care units was not effective in improving functional status, but significantly improved secondary outcomes. Onderzoeksraad, KU Leuven, Grant/Award Number: REF22/15/028 Deschodt, M (corresponding author), UZ, Dept Gerontol & Geriatr, AGSF, Herestr 49 Box 7003 35, B-3000 Leuven, Belgium. mieke.deschodt@kuleuven.be

Purpose The aim was to analyze the incidence and survival of patients living with HIV (PLWH) with head and neck squamous cell carcinoma (HNSCC) and to compare with a control group of HIV-negative HNSCC patients. Methods Clinicopathological data and predictors for overall survival (OS) and disease-free survival (DFS) were investigated (2009–2019). Results 50 of 5151 HNSCC patients (0.97%) were PLWH, and 76% were smokers. Age ≤ 60 years, HIV-PCR ≤ 50 copies, CD4 cells ≤ 200/mm3, cART treatment, T and UICC classification, oral cavity and nasal/paranasal sinuses, and therapy were significantly associated with OS in univariate analysis. In the multivariate analysis, only age and HIV-PCR independently predicted OS. The OS of the 50 PLWH was not significantly altered compared with the 5101 HIV-negative controls. However, OS and DFS were significantly inferior in advanced tumor stages of PLWH compared with an age-matched control group of 150 HIV-negative patients. Conclusions PLWH were diagnosed with HNSCC at a significantly younger age compared to HIV-negative patients. Taking into account patient age at initial diagnosis, both OS and DFS rates in PLWH are significantly worse compared with a matched control group of HIV-negative patients in advanced tumor stages UICC III/IV. The prognosis (OS) is improved when taking cART treatment, the HIV viral load is undetectable and CD4 count is high.

ZusammenfassungDie Veränderungen zur Klassifizierung schizophrener Psychosen in der Revision der ICD (International Classification of Diseases) gehen nicht mit einer grundsätzlichen Veränderung der bekannten Konzepte einher. Die Beurteilung der psychiatrischen Voraussetzungen der Schuldfähigkeit wird kaum beeinflusst. Die Aufgabe der Subtypen der Schizophrenie ist jedoch möglicherweise mit der Gefahr verbunden, dass die besonderen und individuellen Verläufe bei Betroffenen mit schizophrenen Psychosen in ihrem Variantenreichtum nicht mehr bekannt sein und wahrgenommen werden. Dies ist insbesondere problematisch in Fällen, in denen die psychotische Erkrankung nicht in dem weit verbreiteten und bekannten Phänomen „paranoid-halluzinatorisches Syndrom“ mündet, sondern eher mit Verhaltensauffälligkeiten einhergeht oder mit Veränderungen des Affektes, sprich den hebephrenen Verläufen. Die forensische Psychiatrie ist gefordert, das Wissen um solche Verläufe aktiv zu fördern, um jugendliche Straftäter, bei denen Psychopathologie mit „normalen“ Besonderheiten der Entwicklung verschränkt ist, adäquat als im Sinne der §§ 20 und 21 StGB „krankhaft seelisch gestört“ zu identifizieren und ihre sachgerechte forensisch-psychiatrische Beurteilung zu gewährleisten.

Introduction: This retrospective analysis assessed geographic atrophy (GA) progression in fellow eyes from the Proxima B trial intermediate age-related macular degeneration (iAMD) subcohort using high-resolution multimodal imaging anchored on optical coherence tomography (OCT). Methods: Thirty-two patients from the Proxima B iAMD subcohort were assessed; all had GA with no macular neovascularization (MNV) in the contralateral eye. Imaging data, including color fundus photography, fluorescein angiography, near-infrared reflectance, fundus autofluorescence (FAF), and spectral-domain OCT, were obtained. Features preceding progression/conversion to advanced AMD (drusen, reticular pseudodrusen [RPD], MNV, incomplete/complete retinal pigment epithelium and outer retinal atrophy [iRORA/cRORA]) were assessed. Results: Of 30 fellow eyes with available follow-up images, 12 converted to GA (FAF), 2 converted to MNV, and 16 were nonconverters during the review period (median: 17.8 months). iRORA/cRORA features (present in all converters at baseline) were identified on OCT in eyes that progressed to GA. Median time interval from iRORA to cRORA and from cRORA to GA was 7 months each. GA development/progression was either drusen- or RPD-associated (n = 6 each). Eyes with baseline RPD showed faster GA progression versus eyes with drusen (1.49 vs. 0.38 mm2/year). Conclusions: RPD presence was associated with rapid GA lesion enlargement and may provide an early indication of faster GA progression.

BACKGROUND: Ocular surface diseases (OSDs), including conjunctivitis and blepharitis, are common in atopic dermatitis (AD) patients, but the magnitude and patient characteristics are unclear.OBJECTIVES: To examine the prevalence of OSDs in adults with AD and identify patient characteristics and risk factors.METHODS: We designed a cross-sectional questionnaire-based survey and sent it via a secure public mail to all adult Danes with a hospital diagnosis of AD (ICD-10 code L20.x) registered in the National Patient Register (n=16,718) between 2000-2019 and 7,044 (42%) participated. Primary outcomes were OSDs and severity according to Ocular Surface Disease Index (OSDI). Adjusted odds ratios (aOR) were calculated with 95% confidence intervals (CIs) using logistic regression models.RESULTS: Respondents were mostly females and middle-aged (67.4%, mean [SD] age, 39.0 [15.5] years). Based on Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) 49% had mild AD, 35% moderate, 10% severe and in 6% AD was inactive. 44.3% reported physician-diagnosed asthma bronchiale and 55.8% rhinitis. The lifetime prevalence of OSDs was 66.6% for conjunctivitis, 63.5% for hordeolum, 11.0% for blepharitis, 9.7% for keratitis, 2.0% for pterygium, 1.5% for symblepharon, 1.1% for keratoconus and 12.7% reported current conjunctivitis. Factors associated with lifetime occurrence of conjunctivitis included mild, moderate, and severe AD (aOR=1.48 [95% CI, 1.02-2.14], aOR=1.73 [95% CI, 1.19-2.53], aOR=2.17 [95% CI, 1.42-3.21]), asthma bronchiale and rhinitis (aOR=1.76 [95% CI, 1.49-2.07]), childhood-onset of AD (aOR=1.34 [95% CI, 1.16-1.56]) and systemic AD treatment (aOR=1.27 [95% CI, 1.08-1.50]). Use of soft and hard contact lenses (aOR=2.15 [95% CI, 1.65-2.80], aOR=3.35 [95% CI, 1.62-6.92]) were associated with lifetime occurrence of keratitis. Moderate and severe AD, asthma bronchiale and rhinitis were also associated with a higher OSDI level.CONCLUSIONS: This study identified important patient factors associated with OSDs. Clinicians should be attentive of ocular signs and symptoms in AD patients and ask about these.

By applying multivariate regression to 2020 survey data from four Tehran hospitals, we measure eight recognized sources of Coronavirus disease 2019 (COVID-19) pandemic-related anxiety among 723 healthcare workers (HCWs) with diverse sociodemographic characteristics employed across different hospital areas and positions. The most prominent anxiety source identified is the risk of workplace COVID-19 contraction and transmission to family, followed by uncertainty about organizational support for personal and family needs in the event of worker infection. A supplemental qualitative analysis of 68 respondents in the largest hospital identifies four additional anxiety sources, namely, health, finances, workload, and leadership. This evidence of the multifaceted nature of anxiety sources among HCWs highlights the differentiated approaches that hospital policymakers must take to combat anxiety.

Introduction Visceral artery aneurysms (VAA) are a rare entity of arterial aneurysms with the imminent threat of rupture. The impact of cancer and chemotherapy on the growth of VAAs is unknown. Patients and methods A retrospective dual center cohort study of patients with concomitant VAA and different types of cancer was conducted and the impact of various chemotherapeutic agents on VAA growth was studied by sequential CT analysis. For comparison, a non-cancer all comer cohort with VAAs and no cancer was studied to compare different growth rates. The primary endpoint was aneurysm progress or regression >1.75 mm. Chi-Square Test, Fisher's-Exact-Test and Mann-Whitney test was used for statistical comparison. Results In the 17-year-period from January 2003 to March 2020, 59 patients with 30 splenic artery aneurysms, 14 celiac trunk aneurysms, 11 renal artery aneurysms and 4 other VAA and additional malignancy were identified. 20% of patients suffered from prostate cancer, the rest were heterogeneous. The most prevalent chemotherapies were alkylating agents (23%), antimetabolites (14%) and mitose inhibitors (10%). 8 patients had relevant growth of their VAA and one patient showed diameter regression (average growth rate 0.1±0.5mm/year). 29 patients with 14 splenic, 11 RAAs (seven right) and 4 celiac trunk aneurysms were available in the non-cancer comparison cohort (average growth rate 0.5±0.9mm/year, p=0.058). However, the growth rate of patients receiving operative treatment for relevant VAA growth was significantly higher (p=0.004). Conclusion VAAs grow rarely, and rather slow. Cancer and/or chemotherapy do not significantly influence the annual growth rate. Additional control examinations seem unnecessary.

Background To examine published data and assess evidence relating to safety and efficacy of surgical management of symptomatic pineal cysts without hydrocephalus (nhSPC), we performed a systematic review of the literature and meta-analysis. Methods Following the PRISMA guidelines, we searched Pubmed and SCOPUS for all reports with the query ‘Pineal Cyst’ AND ‘Surgery’ as of March 2021, without constraints on study design, publication year or status (PROSPERO_CRD:42,021,242,517). Assessment of 1537 hits identified 26 reports that met inclusion and exclusion criteria. Results All 26 input studies were either case reports or single-centre retrospective cohorts. The majority of outcome data were derived from routine physician-recorded notes. A total of 294 patients with surgically managed nhSPC were identified. Demographics: Mean age was 29 (range: 4–63) with 77% females. Mean cyst size was 15 mm (5–35). Supracerebellar-infratentorial approach was adopted in 90% of cases, occipital-transtentorial in 9%, and was not reported in 1%. Most patients were managed by cyst resection (96%), and the remainder by fenestration. Mean post-operative follow-up was 35 months (0–228). Presentation: Headache was the commonest symptom (87%), followed by visual (54%), nausea/vomit (34%) and vertigo/dizziness (31%). Other symptoms included focal neurology (25%), sleep disturbance (17%), cognitive impairment (16%), loss of consciousness (11%), gait disturbance (11%), fatigue (10%), ‘psychiatric’ (2%) and seizures (1%). Mean number of symptoms reported at presentation was 3 (0–9). Outcomes: Improvement rate was 93% (to minimise reporting bias only consecutive cases from cohort studies were considered, N = 280) and was independent of presentation. Predictors of better outcomes were large cyst size (OR = 5.76; 95% CI: 1.74–19.02) and resection over fenestration (OR = 12.64; 3.07–52.01). Age predicted worse outcomes (OR = 0.95; 0.91–0.99). Overall complication rate was 17% and this was independent of any patient characteristics. Complications with long-term consequences occurred in 10 cases (3.6%): visual disturbance (3), chronic incisional pain (2), sensory disturbance (1), fatigue (1), cervicalgia (1), cerebellar stroke (1) and mortality due to myocardial infarction (1). Conclusions Although the results support the role of surgery in the management of nhSPCs, they have to be interpreted with a great deal of caution as the current evidence is limited, consisting only of case reports and retrospective surgical series. Inherent to such studies are inhomogeneity and incompleteness of data, selection bias and bias related to assessment of outcome carried out by the treating surgeon in the majority of cases. Prospective studies with patient-reported and objective outcome assessment are needed to provide higher level of evidence.

Hypoglossal nerve stimulation (HGNS) has evolved as a novel and effective therapy for patients with moderate-to-severe obstructive sleep apnea. Despite positive published outcomes of HGNS, there exist uncertainties regarding proper patient selection, surgical technique, and the reporting of outcomes and individual factors that impact therapy effectiveness. According to current guidelines, this therapy is indicated for select patients, and recommendations are based on the Stimulation Therapy for Apnea Reduction or STAR trial. Ongoing research and physician experiences continuously improve methods to optimize the therapy. An understanding of the way in which airway anatomy, obstructive sleep apnea phenotypes, individual health status, psychological conditions, and comorbid sleep disorders influence the effectiveness of HGNS is essential to improve outcomes and expand therapy indications. This article presents discussions on current evidence, future directions, and research gaps for HGNS therapy from the 10th International Surgical Sleep Society expert research panel. CITATION: Suurna MV, Jacobowitz O, Chang J, et al. Improving outcomes of hypoglossal nerve stimulation therapy: current practice, future directions and research gaps. Proceedings of the 2019 International Sleep Surgery Society Research Forum. J Clin Sleep Med. 2021;17(12):2477–2487.

Background and Purpose: The aim of this study was to examine whether sphingosine-1-phosphate (S1P) levels in patients with acute stroke are associated with stroke severity and outcome. Methods: In a prospective stroke cohort (MARK-STROKE), 374 patients with acute ischemic stroke or transient ischemic attack were enrolled (mean age: 67.9±13.0 years, sex: 64.7% male), and serum-S1P at admission was analyzed with tandem mass spectrometry. In addition to cross-sectional analyses, 79 adverse events (death, stroke, myocardial infarction, rehospitalization) were recorded in 270 patients during follow-up. Regression analyses were adjusted for age, sex, low-density lipoprotein cholesterol, and vascular risk factors. Results were validated in an independent stroke cohort with 219 patients with acute ischemic stroke (CIRCULAS). Results: Low serum-S1P was associated with higher National Institutes of Health Stroke Scale score at admission and with anterior circulation nonlacunar infarcts determined by multivariate regression analyses. During a follow-up of 294±170 days, patients with S1P in the lowest tertile (P =0.048 for trend). In adjusted Cox regression analysis, the lowest S1P tertile was associated with a worse outcome after stroke (hazard ratio, HR 0.51 [95% confidence interval 0.28–0.92]). Results were confirmed in an independent cohort, ie, low S1P levels were associated with higher National Institutes of Health Stroke Scale, larger infarct volumes and worse outcome after 90 days (β-coefficient: –0.03, P =0.026; β-coefficient: −0.099, P =0.009 and odds ratio 0.52 [0.28–0.96], respectively). Conclusions: Our findings imply a detrimental role of low S1P levels in acute stroke and therefore underpin the therapeutic potential of S1P-mimics.

The contribution of veno-venous (VV) extracorporeal membrane oxygenation (ECMO) to systemic oxygen delivery is determined by the ratio of total extracorporeal blood flow (Q˙EC) to cardiac output (Q˙). Thermodilution-based measurements of Q˙ may be compromised by blood recirculating through the ECMO (recirculation fraction; Rf). We measured the effects of Q˙EC and Rf on classic thermodilution-based measurements of Q˙ in six anesthetized pigs. An ultrasound flow probe measured total aortic blood flow (Q˙A0) at the aortic root. Rf was quantified with the ultrasound dilution technique. Q˙EC was set to 0-125% of Q˙A0 and Q˙ was measured using a pulmonary artery catheter (PAC) in healthy and lung injured animals. PAC overestimated Q˙ (Q˙Pa) at all Q˙EC settings compared to Q˙A0. The mean bias between both methods was 2.1 L/min in healthy animals and 2.7 L/min after lung injury. The difference between Q˙Pa and Q˙A0 increased with an Q˙EC of 75-125%/Q˙A0 compared to QEC

WDR45-related neurodevelopmental disorder (NDD) is a clinically-heterogenous congenital disorder of macroautophagy/autophagy. The natural history of this ultra-orphan disease remains incompletely understood, leading to delays in diagnosis and lack of quantifiable outcome measures. In this cross-sectional study, we model quantitative natural history data for WDR45-related NDD using a standardized analysis of 160 published cases, representing the largest cohort to date. The primary outcome of this study was survival. Age at disease onset, diagnostic delay and geographic distribution were quantified as secondary endpoints. Our tertiary aim was to explore and quantify the spectrum of WDR45-related phenotypes. Survival estimations showed low mortality until 39 years of age. Median age at onset was 10 months, with a median diagnostic delay of 6.2 years. Geographic distribution appeared worldwide with clusters in North America, East Asia, Western Europe and the Middle East. The clinical spectrum was highly variable with a bi-phasic evolution characterized by early-onset developmental and epileptic encephalopathy during childhood followed by a progressive dystonia-parkinsonism syndrome along with cognitive decline during early adulthood. Female individuals showed milder disease severity. The majority of pathogenic WDR45 variants were predicted to result in a loss of WDR45 expression, without clear genotype-phenotype associations. Our results provide clinical and epidemiological data that may facilitate an earlier diagnosis, enable anticipatory guidance and counseling of affected families and provide the foundation for endpoints for future interventional trials. Abbreviations: BPAN: beta-propeller protein-associated neurodegeneration; CNS: central nervous system; DEE: developmental and epileptic encephalopathy; MRI: magnetic resonance imaging; NBIA: neurodegeneration with brain iron accumulation; NDD: neurodevelopmental disorder; NGS: next-generation sequencing; WDR45/WIPI4: WD repeat domain 45

Background Sepsis and inflammation can cause intensive care unit‐acquired weakness (ICUAW). Increased interleukin‐6 (IL‐6) plasma levels are a risk factor for ICUAW. IL‐6 signalling involves the glycoprotein 130 (gp130) receptor and the JAK/STAT‐pathway, but its role in sepsis‐induced muscle wasting is uncertain. In a clinical observational study, we found that the IL‐6 target gene, SOCS3, was increased in skeletal muscle of ICUAW patients indicative for JAK/STAT‐pathway activation. We tested the hypothesis that the IL‐6/gp130‐pathway mediates ICUAW muscle atrophy. Methods We sequenced RNA (RNAseq) from tibialis anterior (TA) muscle of cecal ligation and puncture‐operated (CLP) and sham‐operated wildtype (WT) mice. The effects of the IL‐6/gp130/JAK2/STAT3‐pathway were investigated by analysing the atrophy phenotype, gene expression, and protein contents of C2C12 myotubes. Mice lacking Il6st, encoding gp130, in myocytes (cKO) and WT controls, as well as mice treated with the JAK2 inhibitor AG490 or vehicle were exposed to CLP or sham surgery for 24 or 96 h. Results Analyses of differentially expressed genes in RNAseq (≥2‐log2‐fold change, P

Background Sacral insufficiency fractures (SIFs) are fractures related to reduced bone strength. In a previous study, we noticed that many patients with SIF had undergone total hip arthroplasty (THA). Therefore, the purpose of the present study was to research the localization of clinically apparent SIFs in relation to unilateral THA as well as the influence of unilateral THA on bone mineral density changes in the sacrum. Methods In this retrospective study, 171 patients with SIFs were screened for unilateral THA. In the group of patients with SIF and THA, the rate of SIF ipsilateral and contralateral to the side of the THA was determined. In a second cohort of 39 THA patients with healthy bone, changes in bone mineral density at the sacral alae ipsilateral and contralateral to the THA were analyzed by use of computed tomography immediately postoperatively and at the 1-year follow-up. Results Of the 171 patients with SIF, 50 (40 female; mean age, 79 years; range, 54 to 101 years) were previously treated with THA. Of the 50, 31 patients were treated with unilateral THA. The proportion of patients with an SIF contralateral to the THA was 42% (13 of 31) and ipsilateral to the THA was 19% (6 of 31). Twelve patients had bilateral SIFs. The mean age of the THA group without SIF was 62 years (range, 49 to 79 years); 17 were female. The median bone mineral density decreased significantly (p = 0.023), from 35.0 to 13.0 HU, at the sacral ala contralateral to the THA, whereas the decrease of ipsilateral bone mineral density, from 24.0 to 17.0 HU, was not significant (p = 0.361). Conclusions The proportion of patients with an SIF contralateral to a THA was twice as high as that of patients with an SIF ipsilateral to a THA. These findings are supported by the second cohort's decrease in bone mineral density at the sacral ala contralateral to the THA at 1 year after surgery. We conclude that THA can lead to spatially different remodeling of the sacrum, possibly affecting the development of SIFs. Level of evidence Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Aims: Primary aim was to determine survival of a cemented acetabular component with bulk roof autograft with a minimum of 12 years follow-up. The secondary aim was to determine the clinical outcome. Methods: A cohort of 62 consecutive patients (74 hips) undergoing cemented total hip arthroplasty with acetabular bulk roof autograft for acetabular dysplasia were retrospectively identified. The group consisted of 57 female patients (67 hips) and 5 male patients (7 hips) with a mean age at operation of 45 years. No patient was lost to follow-up, however 9 patients died had during the study period. The Oxford Hip Score (OHS), Forgotten Joint Score (FJS), EuroQol 5-Dimensional Score (EQ-5D), Short Form (SF-12) physical score and patient satisfaction were used to assess clinical outcome for patients with a surviving prosthesis. Results: The median follow-up was 16.6 (13.4–19.1) years. 6 revisions were performed during the follow-up period, all of which were due to aseptic loosening of the acetabular component. The all-cause Kaplan Meier survival rate for the acetabular component was 99% at 10 years, 95% at 15 years and 83% at 20 years. Neither age, gender, femoral osteotomy or polyethylene (UHMW vs. cross-linked) were significant predictors of aseptic revision of the acetabular component. There were no case of graft resorption and all grafts were radiologically incorporated. 45 patients were available for functional assessment at a mean follow-up of 18.2 years. The mean OHS was 37.8, FJS was 55.7, EQ5D was 0.73, and SF-12 physical component was 43.2. No patient was dissatisfied, with 2 patients reporting a neutral satisfaction, 7 stating they were satisfied and the remaining 36 were very satisfied. Conclusions: A cemented acetabular component with bulk roof autograft for dysplasia offers excellent survival with good to excellent functional outcome with high patient satisfaction in the medium- to long-term.

Benign tumors of the eyelids are manifold. They can severely impair the anatomical unit of upper and lower eyelid, which basically serves to protect the eyeball. Furthermore, they can induce reduction of visual acuity or cause a subjectively more or less strong aesthetic disturbance of appearance. Patients may visit the ophthalmologist by themselves or referred by a dermatologist or a general practitioner. Therefore, knowledge of the clinical signs and symptoms of benign tumors are mandatory to discriminate against malign tumors or to identify possible associated disease. In this article, the incidence, clinic, risk factors, symptomatology, histopathologic features, and probabilities of malignant transformation and recurrence of the most common benign eyelid tumors are presented. Objective of this article is to illustrate when to do further work-up to rule out systemic disease and when to do biopsy to rule out malignancy. Finally, the publication is giving an outlook on the use of artificial intelligence to diagnose lid tumors in the future.

Objective To assess in a cross-sectional study the impact of including dental professionals in the multidisciplinary treatment team of head and neck squamous cell carcinoma (HNSCC) patients on the long-term oral health status. Materials and methods Oral health status, dental care behaviours, and oral health–related quality of life were assessed based on a clinical and radiographic examination, interview, and medical records in patients treated for HNSCC ≥ 6 months ago. This patient group (‘cohort 2’) was treated in a multidisciplinary treatment team including dental professionals and compared to a group of HNSCC patients previously treated at the same university, but without dental professionals included in the multidisciplinary treatment team (‘cohort 1’). Results Cohort 2 consisted of 34 patients, who had received a dental check-up and if necessary, treatment by dental professionals prior to the initiation of cancer treatment. This cohort showed significantly improved oral hygiene habits and a better periodontal health status compared to cohort 1. However, cohort 2 still presented high demand for treatment due to active carious lesions; only a few, statistically insignificant improvements were detected compared to cohort 1. Conclusion Including dental professionals in the multidisciplinary treatment team of HNSCC patients has a positive impact on patient oral health status—primarily in terms of periodontal disease—6 months and longer after finishing cancer therapy. Clinical relevance A team-based approach including dental professionals specialised in head and neck cancer improves oral health status.

The aim of this review was to determine whether smartphone applications are reliable and valid to measure range of motion (RoM) in lower extremity joints. A literature search was performed up to October 2020 in the databases PubMed and Cochrane Library. Studies that reported reliability or validity of smartphone applications for RoM measurements were included. The study quality was assessed with the QUADAS-2 tool and baseline information, validity and reliability were extracted. Twenty-five studies were included in the review. Eighteen studies examined knee RoM, whereof two apps were analysed as having good to excellent reliability and validity for knee flexion (“DrGoniometer”, “Angle”) and one app showed good results for knee extension (“DrGoniometer”). Eight studies analysed ankle RoM. One of these apps showed good intra-rater reliability and excellent validity for dorsiflexion RoM (“iHandy level”), another app showed excellent reliability and moderate validity for plantarflexion RoM (“Coach’s Eye”). All other apps concerning lower extremity RoM had either insufficient results, lacked study quality or were no longer available. Some apps are reliable and valid to measure RoM in the knee and ankle joint. No app can be recommended for hip RoM measurement without restrictions.

Objective Psychosocial factors are known to predict chronic pain, and the use of complementary and integrative health (CIH) therapies to address pain is emerging among the military population. However, conflicting results on pain outcomes warrant additional research. This study aimed to 1) evaluate the benefit of adding a CIH pain management program to standard rehabilitative care (SRC), as compared with SRC alone, as a precursor to an intensive functional restoration (FR) program; 2) identify factors that predict improvement in pain outcomes after treatment; and 3) determine the proportion of participants who experience a clinically meaningful response. Design Pragmatic randomized controlled clinical trial. Participants were randomized to a 3-week course of either SRC alone or SRC+CIH (stage 1), followed by a 3- to 6-week course of FR (stage 2). Subjects Active duty service members with chronic pain. Methods Participants completed either SRC alone or SRC+CIH (stage 1), followed by a course of FR (stage 2). Patient-reported and provider-determined outcomes were collected at baseline, after stage 1, and after stage 2. A covariance pattern model with an unstructured residual covariance matrix was used to compare treatment arms while accounting for dependency due to repeated measurements. Results A total of 210 service members participated. Most were in the Army (82%) and were male (84%). Participants randomized to the SRC+CIH intervention had greater improvement in the pain impact score than did those in the SRC-alone group. Predictors of outcomes were baseline impact score, anger, depression, and educational status. Conclusions This study found that military service members with the highest pain impact benefit the most from interdisciplinary pain care.

OBJECTIVES AND METHODS Intracranial hemorrhage (ICH) in acute myeloid leukemia (AML) patients is a major concern due to the increased risk of mortality. Few studies have examined ICH specifically in newly diagnosed AML patients receiving intensive induction chemotherapy (IC) and prophylactic platelet transfusions during thrombocytopenia

Aims Left atrial strain (LAS) and skeletal muscle endurance demonstrate a linear relationship to peak VO2. Less is known about the relationship between central (cardiac) and peripheral (muscle endurance) limitations of exercise capacity in patients with heart failure (HF). We investigated this relationship using novel cardiac markers such as LAS and left atrial ejection fraction (LAEF). Methods We analysed echocardiographic measurements, cardiopulmonary exercise testing, and isokinetic muscle function in 55 subjects with HF and controls (17 heart failure with preserved ejection fraction -HFpEF, 18 heart failure with reduced ejection fraction-HFrEF and 20 healthy controls). Results Patients with reduced LAEF showed reduced peak VO2: 14.3±3.5 vs. 18.5±3.5 ml/min/kg, p=0.003 and reduced muscle endurance (RME): 64.3±23.9 vs. 88.5±32.3 Nm/kg, p=0.028. Patients with reduced LAS showed similar results. Neither left ventricular global longitudinal strain (LVGLS) nor left atrial volume index (LAVI) were associated with RME. The area under the curve of LAS and LAEF in patients with HF in association with RME were (0.76 vs. 0.80) with 95% confidence interval (CI) (0.59–0.96, p=0.012 vs. 0.63–0.98, p=0.006, respectively). Peak torque of the left leg was associated with E/LAS (E: early diastolic) in patients with HFpEF (r=−0.6, p=0.020). Endurance of the left leg was associated with LAEF (r=0.79, p=0.001) in patients with HFrEF. Conclusion LAS/LAEF are potential cardiac markers in demonstrating the link between cardiac and peripheral limitations of exercise capacity. Thus, integrating LAS/LAEF in the evaluation of exercise intolerance in patients with HF could be useful. Funding Acknowledgement Type of funding sources: None.

Introduction While overcrowding of emergency departments was often reported in the recent years, during the early phase of the pandemic, a reduction in patient numbers was seen. The aim of the current study was to describe the orthopedic trauma patient cohort presenting to the emergency department (ED) during the early pandemic period as compared to the cohort from the analogue time period 2019. Materials and methods A single-center case–control study was performed. All the consecutive orthopedic trauma patients > 12 years presenting to the ED were included. Patients in the same time period in 2019 served as the control group. Results Compared to 2019, in 2020, 33% less patients presented in the emergency department. Patients treated in 2020 were significantly older, significantly more often brought to ED by emergency medical services and significantly more often admitted. The number of fractures and diagnoses requiring surgical treatment decreased only slightly and the proportion of these patients among all the patients was significantly higher during the pandemic than in the control period. Furthermore, a higher percentage of polytrauma patients could be found in 2020 as well. Analysis of Manchester Triage System showed significantly less not urgent patients in 2020. Conclusion The present study shows a significant decline in the number of patients treated in the ED during the pandemic period but at the same time almost identical numbers of patients with fractures or diagnoses requiring surgical treatment. In the context of an overall decline in patient numbers, a stronger concentration on level 1 trauma centers seems to be evident during the pandemic.

BACKGROUND Genetics of sudden cardiac deaths (SCD) remains frequently undetected. Genetic analysis is recommended in undefined selected cases in the 2021 ERC-guideline. The emergency medical service and physicians (EMS) may play a pivotal role for unraveling SCD by saving biomaterial for later molecular autopsy. Since for high-throughput DNA-sequencing (NGS) high quality genomic DNA is needed. We investigated in a prospective proof-of-concept study the role of the EMS for the identification of genetic forms of SCDs in the young. METHODS We included patients aged 1-50 years with need for cardiopulmonary resuscitation attempts (CPR). Cases with non-natural deaths were excluded. In two German counties with 562,904 residents 39,506 services were analysed. Paired end panel-sequencing was performed, and variants were classified according to guidelines of the American College of Medical Genetics (ACMG). RESULTS 769 CPR-attempts were recorded (1.95% of all EMS-services; CPR-incidence 68/100,000). In 103 cases CPR were performed in patients

Venous thromboembolism is a significant source of morbidity and mortality worldwide. Catheter-directed thrombolytics is the primary treatment used to relieve critical obstructions, though its efficacy varies based on the thrombus composition. Non-responsive portions of the specimen often remain in situ, which prohibits mechanistic investigation of lytic resistance or the development of diagnostic indicators for treatment outcomes. In this study, thrombus samples extracted from venous thromboembolism patients were analyzed ex vivo to determine their histological properties, susceptibility to lytic therapy, and imaging characteristics. A wide range of thrombus morphologies were observed, with a dependence on age and etymology of the specimen. Fibrinolytic inhibitors including PAI-1, alpha 2-antiplasmin, and TAFI were present in samples, which may contribute to the response venous thrombi to catheter-directed thrombolytics. Finally, a weak but significant correlation was observed between the response of the sample to lytic drug and its magnetic microstructure assessed with a quantitative MRI sequence. These findings highlight the myriad of changes in venous thrombi that may promote lytic resistance, and imaging metrics that correlate with treatment outcomes.

Objectives\udThe aim of this study was to define the variability of maximal wall thickness (MWT) measurements across modalities and predict its impact on care in patients with hypertrophic cardiomyopathy (HCM).\ud\udBackground\udLeft ventricular MWT measured by echocardiography or cardiovascular magnetic resonance (CMR) contributes to the diagnosis of HCM, stratifies risk, and guides key decisions, including whether to place an implantable cardioverter-defibrillator (ICD).\ud\udMethods\udA 20-center global network provided paired echocardiographic and CMR data sets from patients with HCM, from which 17 paired data sets of the highest quality were selected. These were presented as 7 randomly ordered pairs (at 6 cardiac conferences) to experienced readers who report HCM imaging in their daily practice, and their MWT caliper measurements were captured. The impact of measurement variability on ICD insertion decisions was estimated in 769 separately recruited multicenter patients with HCM using the European Society of Cardiology algorithm for 5-year risk for sudden cardiac death.\ud\udResults\udMWT analysis was completed by 70 readers (from 6 continents; 91% with >5 years’ experience). Seventy-nine percent and 68% scored echocardiographic and CMR image quality as excellent. For both modalities (echocardiographic and then CMR results), intramodality inter-reader MWT percentage variability was large (range –59% to 117% [SD ±20%] and –61% to 52% [SD ±11%], respectively). Agreement between modalities was low (SE of measurement 4.8 mm; 95% CI 4.3 mm-5.2 mm; r = 0.56 [modest correlation]). In the multicenter HCM cohort, this estimated echocardiographic MWT percentage variability (±20%) applied to the European Society of Cardiology algorithm reclassified risk in 19.5% of patients, which would have led to inappropriate ICD decision making in 1 in 7 patients with HCM (8.7% would have had ICD placement recommended despite potential low risk, and 6.8% would not have had ICD placement recommended despite intermediate or high risk).\ud\udConclusions\udUsing the best available images and experienced readers, MWT as a biomarker in HCM has a high degree of inter-reader variability and should be applied with caution as part of decision making for ICD insertion. Better standardization efforts in HCM recommendations by current governing societies are needed to improve clinical decision making in patients with HCM.