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BACKGROUND: The majority of opioid overdose admissions in pediatric patients are associated with prescription opioids. Post-operative prescriptions are an addressable source of opioids in the household. This study aims to assess for sustained reduction in opioid prescribing after implementation of provider-based education at nine centers. METHODS: Opioid prescribing information was collected for pediatric patients undergoing umbilical hernia repair at nine centers between December 2018 and January 2019, one year after the start of an education intervention. This was compared to prescribing patterns in the immediate pre- and post-intervention periods at each of the nine centers. RESULTS: In the current study period, 29/127 (22.8%) patients received opioid prescriptions (median 8 doses) following surgery. There were no medication refills, emergency department returns or readmissions related to the procedure. There was sustained reduction in opioid prescribing compared to pre-intervention (22.8% vs 75.8% of patients, p

Background The aim of this study was to assess the inter- and intrarater reliability of a recently proposed scoring system for temporomandibular disorders (TMD), based upon radiological findings from magnetic resonance imaging (MRI). Materials and methods Patients with clinically suspected uni- or bilateral TMD, and subsequently conducted MRI examination of both temporomandibular joints, were included in this study. MRI data were independently evaluated by two experienced radiologists according to the DLJ scoring system proposed by Wurm et al., which includes assessment of the following categories: articular disk (prefix ‘D’), direction of disk luxation (prefix ‘L’), and osseous joint alterations (prefix ‘J’). Results 60 patients (49 female and 11 male) were eligible for analysis. No significant differences were found between both observers regarding ‘D’ and ‘L’ scores (p = 0.13 and p = 0.59, respectively). Significant differences were found for the assessment of subtle osseous changes (‘J0’ category: p = 0.041; ‘J1’ category: p = 0.018). Almost perfect intra- and interrater agreements were found for ‘D’ and ‘L’ categories (intrarater and interrater agreements for ‘D’: κ = 0.92 and κ = 0.84, respectively; intrarater and interrater agreements for ‘L’: κ = 0.93 and κ = 0.89, respectively). However, the assessment of ‘J’ categories revealed only moderate interrater agreement (κ = 0.49). Conclusion The DLJ scoring system based upon MRI findings is feasible for routine clinical TMD assessment, and may help to simplify interdisciplinary communication between radiologists and clinicians.

OBJECTIVE Chronic adhesive spinal arachnoiditis (SA) is a complex disease process that results in spinal cord tethering, CSF flow blockage, intradural adhesions, spinal cord edema, and sometimes syringomyelia. When it is focal or restricted to fewer than 3 spinal segments, the disease responds well to open surgical approaches. More extensive arachnoiditis extending beyond 4 spinal segments has a much worse prognosis because of less adequate removal of adhesions and a higher propensity for postoperative scarring and retethering. Flexible neuroendoscopy can extend the longitudinal range of the surgical field with a minimalist approach. The authors present a cohort of patients with severe cervical and thoracic arachnoiditis and myelopathy who underwent flexible endoscopy to address arachnoiditis at spinal segments not exposed by open surgical intervention. These observations will inform subsequent efforts to improve the treatment of extensive arachnoiditis. METHODS Over a period of 3 years (2017–2020), 10 patients with progressive myelopathy were evaluated and treated for extensive SA. Seven patients had syringomyelia, 1 had spinal cord edema, and 2 had spinal cord distortion. Surgical intervention included 2- to 5-level thoracic laminectomy, microscopic lysis of adhesions, and then lysis of adhesions at adjacent spinal levels performed using a rigid or flexible endoscope. The mean follow-up was 5 months (range 2–15 months). Neurological function was examined using standard measures. MRI was used to assess syrinx resolution. RESULTS The mean length of syringes was 19.2 ± 10 cm, with a mean maximum diameter of 7.0 ± 2.9 mm. Patients underwent laminectomies averaging 3.7 ± 0.9 (range 2–5) levels in length followed by endoscopy, which expanded exposure by an average of another 2.4 extra segments (6.1 ± 4.0 levels total). Endoscopic dissection of extensive arachnoiditis in the dorsal subarachnoid space proceeded through a complex network of opaque arachnoidal bands and membranes bridging from the dorsal dura mater to the spinal cord. In less severely problematic areas, the arachnoid membrane was transparent and attached to the spinal cord through multifocal arachnoid adhesions bridging the subarachnoid space. The endoscope did not compress or injure the spinal cord. CONCLUSIONS Intrathecal endoscopy allowed visual assessment and safe removal of intradural adhesions beyond the laminectomy margins. Further development of this technique should improve its effectiveness in opening the subarachnoid space and untethering the spinal cord in cases of extensive chronic adhesive SA.

Nivolumab and pembrolizumab, anti–programmed cell death protein 1 monoclonal antibodies, have revolutionized oncology but are expensive. Using an interventional pharmacoeconomic approach, these drugs can be administered less often to reduce costs and increase patient convenience while maintaining efficacy. Both drugs are good candidates for less frequent dosing because of long half-lives and no evidence of a relationship of dose to efficacy. Established population pharmacokinetic models for both nivolumab and pembrolizumab were used to simulate profiles for multiple dosing regimens on 1000 randomly generated virtual patients. Simulations were initially performed on standard dose regimens to validate these in silico predictions. Next, simulations of nivolumab 0.3 mg/kg every 3 weeks revealed that >95% of patients maintained ≥1.5 μg/mL at steady state, which was inferred as the minimum effective concentration (MEC) for both drugs. Various alternative dosing regimens were simulated for both drugs to determine which regimen(s) can maintain this MEC in >95% of patients. Extended dosing regimens of nivolumab 240 mg every 4 weeks and 480 mg every 8 weeks along with pembrolizumab 200 mg every 6 weeks were simulated, showing that >95% of patients maintained MEC or greater. These simulations demonstrate the potential to reduce drug exposure by at least 50%, thus substantially reducing patient visits (as well as costs), while maintaining equivalent efficacy. These models provide the scientific justification for an ongoing prospective randomized clinical trial comparing standard interval fixed dosing with extended interval fixed dosing, and ultimately an efficacy-driven comparative trial.

Purpose Abiraterone acetate, prescribed for metastatic prostate cancer, has enhanced absorption with food. This effect was exploited in a randomized trial which showed noninferiority of PSA decline for 250 mg abiraterone with a low-fat meal (LOW) compared to 1,000 mg abiraterone fasting (STD). Drug was obtained via patient insurance. Patient out-of-pocket costs and adherence were surveyed. Methods Trial participants were randomized to STD or LOW, and surveys of adherence and out-of-pocket costs were administered at baseline and just before coming off study (follow-up). Results Out-of-pocket costs were available from 20 of 36 STD and 21 of 36 LOW patients. Median out-of-pocket costs for a month of drug were $0 (LOW) and $5 (STD); mean costs were $43.61 (LOW) and $393.83 (STD). The two groups did not differ significantly (p = 0.421). Maximum out-of-pocket cost was $1,000 (LOW) and $4,000 (STD). Monthly out-of-pocket costs > $500 were found in 1 LOW and 5 STD patients. For adherence, only 11 STD and 19 LOW patients had questionnaires completed at both baseline and follow-up. STD adherence was 98.18% at baseline and 91.69% at follow-up, differing significantly (p = 0.0078). LOW adherence was 96.52% at baseline and 97.86% at follow-up, not differing significantly (p = 0.3511). Adherence did not correlate with demographics. At follow-up, increasing adherence correlated significantly with decreasing dose (p = 0.013; rho = - 0.458). Conclusions Out-of-pocket costs did not differ significantly in this limited analysis. Adherence was significantly different in STD as the trial progressed, which was not found in LOW. Trial registration ClinicalTrials.gov NCT01543776; registered March 5, 2012.

BackgroundThe association of periodontal disease with atherosclerotic cardiovascular diseases is well known, but not specifically with incident peripheral artery disease (PAD). Therefore, we studied the associations of periodontal disease with incident PAD in a population-based setting.MethodsAmong 9,793 participants (aged 53-75 years) without prevalent PAD, self-reported history of periodontal disease was ascertained. Of these, 5,872 participants underwent full-mouth examinations from which periodontal status was defined using the US Centers for Disease Control and Prevention-American Academy of Periodontology (CDC-AAP) definition. We quantified the association of periodontal disease with incident PAD (defined by hospital admission diagnosis or procedures) using multivariable Cox regression models.ResultsDuring a median follow-up of 20.1 years, 360 participants (3.6%) developed PAD. In models accounting for potential confounders including diabetes and smoking pack-years, there was higher hazard of PAD in participants with self-reported tooth loss because of periodontal disease (hazard ratio:1.54 [95% CI:1.20-1.98]), history of periodontal disease treatment (1.37 [1.05-1.80]), and periodontal disease diagnosis (1.38 [1.09-1.74]), compared to their respective counterparts. The clinical measure of periodontal disease (n=5,872) was not significantly associated with incident PAD in the fully adjusted model (e.g., 1.53 [0.94-2.50] in CDC-AAP-defined severe periodontal disease versus no disease).ConclusionWe observed a modest association of self-reported periodontal disease, especially when resulting in tooth loss, with incident PAD in the general population. Nonetheless, a larger study with the clinical measure of periodontal disease is warranted.

Purpose Even though obesity is a known risk factor for needing cholecystectomy, most research excludes patients with higher degrees of obesity. The aim of this retrospective study was to compare postoperative pain and analgesic consumption in obese patients, who underwent either transvaginal hybrid Natural Orifice Transluminal Endoscopic Surgery (NOTES) cholecystectomy (NC) or traditional laparoscopic cholecystectomy (LC). Methods Between 12/2008 and 01/2017, 237 NC were performed, of which 35 (14.8%) showed a body mass index (BMI) of 35 kg/m2 or more (obesity II and III according to the World Health Organization). Of these, procedural time, postoperative pain, analgesic requirements, and other early postoperative parameters were collected and compared with 35 matched LC patients from the same time period. Results There were no differences in the baseline characteristics between the two groups, but we found significant benefits for the hybrid NOTES technique in terms of less pain (P = 0.006), coherent with significantly less intake of peripheral (paracetamol; P = 0.005), and of centrally acting analgesics (piritramide; P = 0.047) within the first two-day post-surgery. We also found that those in the NC group had shorter hospital stays (P Conclusion With regard to postoperative pain and analgesic requirements and without an increase in postoperative complications, obese patients experience short-term benefits from the hybrid NOTES technique compared to traditional laparoscopic cholecystectomy.

Summary: Background: Galectin-3 (gal-3) is a β-galactoside-binding lectin associated tissue fibrosis and inflammation. There is limited understanding of the relationship between gal-3 and vascular health. Our aim was to assess the association between gal-3 and arterial stiffness in older adults. Methods: We conducted a cross-sectional study of 4275 participants (mean age of 75 years) from the Atherosclerosis Risk in Communities (ARIC) Study. Central arterial stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). We evaluated the association of gal-3 with cfPWV using multivariable linear regression. Results: The median (interquartile range) gal-3 concentration was 16.5 (13.8, 19.8) ng/mL and mean cfPWV was 1163±303 cm/s. Higher gal-3 concentration was associated with greater central arterial stiffness after adjustment for age, sex, race-center, heart rate, systolic blood pressure, anti-hypertensive medication use, and current smoking status (β=36.4 cm/s change in cfPWV per log unit change in gal-3; 95% CI: 7.2, 65.5, p=0.015). The association was attenuated after adjusting for additional cardiovascular risk factors (β=17.3, 95% CI: −14.4, 49.0). Conclusions: In community-dwelling older adults, gal-3 concentration was associated with central arterial stiffness, likely sharing common pathways with traditional cardiovascular risk factors.

Summary: Patients with peripheral arterial disease (PAD) are at very high risk of cardiovascular events, but risk factor management is usually suboptimal. This Joint Task Force from the European Atherosclerosis Society and the European Society of Vascular Medicine has updated evidence on the management on dyslipidaemia and thrombotic factors in patients with PAD. Guidelines recommend a low-density lipoprotein cholesterol (LDLC) goal of more than 50% reduction from baseline and

Background Both parental and neighbourhood socio-economic status (SES) are linked to poorer health independently of personal SES measures, but the biological mechanisms are unclear. Our objective was to examine these influences via epigenetic age acceleration (EAA)—the discrepancy between chronological and epigenetic ages. Methods We examined three USA-based [Coronary Artery Risk Disease in Adults (CARDIA) study, Fragile Families and Child Wellbeing Study (FFCWS) and Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS)] and one Mexico-based (Project Viva) cohort. DNA methylation was measured using Illumina arrays, personal/parental SES by questionnaire and neighbourhood disadvantage from geocoded address. In CARDIA, we examined the most strongly associated personal, parental and neighbourhood SES measures with EAA (Hannum’s method) at study years 15 and 20 separately and combined using a generalized estimating equation (GEE) and compared with other EAA measures (Horvath’s EAA, PhenoAge and GrimAge calculators, and DunedinPoAm). Results EAA was associated with paternal education in CARDIA [GEEs: βsome college = −1.01 years (−1.91, −0.11) and β Conclusions These findings suggest that EAA captures epigenetic impacts of paternal education independently of personal SES later in life. Longitudinal studies should explore these associations at different life stages and link them to health outcomes. EAA could be a useful biomarker of SES-associated health and provide important insight into the pathogenesis and prevention of chronic disease.

Purpose The quantitative detection of failure modes is important for making deep neural networks reliable and usable at scale. We consider three examples for common failure modes in image reconstruction and demonstrate the potential of uncertainty quantification as a fine-grained alarm system. Methods We propose a deterministic, modular and lightweight approach called Interval Neural Network (INN) that produces fast and easy to interpret uncertainty scores for deep neural networks. Importantly, INNs can be constructed post hoc for already trained prediction networks. We compare it against state-of-the-art baseline methods (MCDrop, ProbOut). Results We demonstrate on controlled, synthetic inverse problems the capacity of INNs to capture uncertainty due to noise as well as directional error information. On a real-world inverse problem with human CT scans, we can show that INNs produce uncertainty scores which improve the detection of all considered failure modes compared to the baseline methods. Conclusion Interval Neural Networks offer a promising tool to expose weaknesses of deep image reconstruction models and ultimately make them more reliable. The fact that they can be applied post hoc to equip already trained deep neural network models with uncertainty scores makes them particularly interesting for deployment.

To realize the potential of artificial intelligence in medical imaging, improvements in imaging capabilities are required, as well as advances in computing power and algorithms. Hybrid inorganic–organic metal halide perovskites, such as methylammonium lead triiodide (MAPbI3), offer strong X-ray absorption, high carrier mobilities (µ) and long carrier lifetimes (τ), and they are promising materials for use in X-ray imaging. However, their incorporation into pixelated sensing arrays remains challenging. Here we show that X-ray flat-panel detector arrays based on microcrystalline MAPbI3 can be created using a two-step manufacturing process. Our approach is based on the mechanical soft sintering of a freestanding absorber layer and the subsequent integration of this layer on a pixelated backplane. Freestanding microcrystalline MAPbI3 wafers exhibit a sensitivity of 9,300 µC Gyair–1 cm–2 with a μτ product of 4 × 10–4 cm2 V–1, and the resulting X-ray imaging detector, which has 508 pixels per inch, combines a high spatial resolution of 6 line pairs per millimetre with a low detection limit of 0.22 nGyair per frame.

Molecular mechanisms of malignant transformation in spinal cord gliomas are not well-understood. Our objective was to investigate genetic causes of malignant transformation in a primary spinal cord glioma. A 32-year-old female patient presented with bilateral lower extremity weakness and was diagnosed with a primary spinal cord glioma from T9 to T12, with a syrinx extending from the craniocervical junction to the conus. She underwent resection in 2006. Pathology showed an abundance of Rosenthal fibers, calcification and degenerative features consistent with a low-grade pilocytic astrocytoma. She presented in 2020 with tumor recurrence and underwent re-resection. Whole exome sequencing, DNA methylation profiling and immunohistochemistry were performed on her initial and recurrent tumor samples. Immunohistochemical profiling of her recurrent tumor showed pleomorphic cells with extensive necrosis consistent with a high-grade glioma. DNA methylation profiling showed that the initial tumor clustered with pilocytic astrocytomas, whereas the recurrent lesion clustered with anaplastic astrocytomas, confirming malignant transformation. Whole-exome sequencing showed interim acquisition of a rare fibroblast growth factor receptor-transforming acidic coiled-coil (FGFR1-TACC1) gene fusion. We report an FGFR1-TACC1 fusion associated with malignant transformation in a primary spinal cord glioma. Our study adds to growing reports of FGFR-TACC fusions, which are amenable to receptor tyrosine kinase inhibition.

We investigated the association between human herpesvirus 6 (HHV‐6) and mesial temporal sclerosis (MTS) in 87 patients who had surgery for drug‐resistant epilepsy. Fifty‐four had MTS, 22 focal cortical dysplasia (FCD), four tumors, three vascular malformations, and three a history of encephalitis. We extracted DNA from fresh brain tissue immediately after surgery and performed viral detection with quantitative real‐time polymerase chain reaction (PCR) or digital droplet PCR specific for HHV‐6A and HHV‐6B. Tissue was studied with standard clinical techniques, including hematoxylin and eosin, glial fibrillary acidic protein, and NeuN stains. Twenty‐nine of 54 patients with MTS, six of 23 with focal cortical dysplasia (FCD), and one of three with a history of encephalitis were positive for HHV‐6 (P

The aim of this retrospective study was to investigate the implementation of measures to prevent perioperative COVID-19 in thoracic surgery during the first wave of the COVID-19 pandemic 2020 allowing a continued surgical treatment of patients. The implemented preventive measures in patient management of the thoracic surgery department of the Asklepios Lung Clinic Munich-Gauting, Germany were retrospectively analyzed. Postoperative COVID-19 incidence before and after implementation of preventive measures was investigated. Patients admitted for thoracic surgical procedures between March and May 2020 were included in the study. Patient characteristics were analyzed. For the early detection of putative postoperative COVID-19 symptoms, typical post-discharge symptomatology of thoracic surgery patients was compared to non-surgical patients hospitalized for COVID-19. Thirty-five surgical procedures and fifty-seven surgical procedures were performed before and after implementation of the preventive measures, respectively. Three patients undergoing thoracic surgery before implementation of preventive measures developed a COVID-19 pneumonia post-discharge. After implementation of preventive measures, no postoperative COVID-19 cases were identified. Fever, dyspnea, dry cough and diarrhea were significantly more prevalent in COVID-19 patients compared to normally recovering thoracic surgery patients, while anosmia, phlegm, low energy levels, body ache and nausea were similarly frequent in both groups. Based on the lessons learned during the first pandemic wave, we here provide a blueprint for successful easily implementable preventive measures minimizing SARS-CoV-2 transmission to thoracic surgery patients perioperatively. While symptoms of COVID-19 and the normal postoperative course of thoracic surgery patients substantially overlap, we found dyspnea, fever, cough, and diarrhea significantly more prevalent in COVID-19 patients than in normally recovering thoracic surgery patients. These symptoms should trigger further diagnostic testing for postoperative COVID-19 in thoracic surgery patients. Ziel dieser retrospektiven Studie war die Untersuchung von Maßnahmen zur Prävention perioperativer COVID-19-Erkrankungen bei fortgesetztem Vollbetrieb der Thoraxchirurgie während der ersten Welle der COVID-19-Pandemie 2020. Es erfolgte eine retrospektive Analyse von eingesetzten Präventionsmaßnahmen in der Abteilung für Thoraxchirurgie der Asklepios Lungenklinik München-Gauting. Hierzu wurde die Inzidenz postoperativer COVID-19-Erkrankungen vor und nach der Einführung der Präventionsmaßnahmen ausgewertet. Patienten mit thoraxchirurgischen Operationen zwischen März und Mai 2020 wurden in die Studie eingeschlossen. Durch den Vergleich der postoperativen Symptome thoraxchirurgischer Patienten mit Symptomen von COVID-19-Patienten wurden spezifische Symptome zur Früherkennung der postoperativen COVID-19-Erkrankung identifiziert. Vor Einführung der Präventionsmaßnahmen erfolgten 35 thoraxchirurgische Operationen innerhalb von 22 Tagen während hoher COVID-19-Prävalenz im Einzugsgebiet der Klinik. Nach Einführung der Präventionsmaßnahmen erfolgten 57 thoraxchirurgische Eingriffe innerhalb von 54 Tagen. Vor Umsetzung der Präventionsmaßnahmen entwickelten 3 Patienten postoperativ eine COVID-19-Pneumonie. Nach Umsetzung zeigte sich kein postoperativer COVID-19-Fall. Fieber, Atemnot, trockener Husten und Durchfall waren bei an COVID-19 erkrankten Patienten signifikant häufiger als bei thoraxchirurgischen Patienten mit regelhaftem postoperativem Verlauf. Anosmie, Auswurf, Abgeschlagenheit, Gliederschmerzen und Übelkeit traten in beiden Gruppen ähnlich häufig auf. Basierend auf unseren Erfahrungen in der ersten Pandemiewelle bieten wir eine Blaupause für erfolgreiche, leicht umzusetzende präventive Maßnahmen zur Minimierung des Risikos für eine perioperative COVID-19-Erkrankung bei thoraxchirurgischen Patienten. Wir konnten zeigen, dass Symptome einer postoperativen COVID-19-Pneumonie teilweise schwer von klassischen postoperativen Beschwerden abgrenzbar sind. Postoperative Dyspnoe, Fieber, Husten und Diarrhöen traten jedoch signifikant häufiger bei COVID-19-Erkrankten als im postoperativen Verlauf thoraxchirurgischer Patienten auf und sollten daher differenzialdiagnostisch an eine postoperative COVID-19-Erkrankung denken lassen.

Chronic kidney disease (CKD) affects about 10% of all populations worldwide, with about 2 million people requiring dialysis. Although patients with CKD are at high risk of cardiovascular disease and events, they are often underrepresented or excluded in clinical trials, leading to important knowledge gaps about how to treat these patients. KDIGO (Kidney Disease: Improving Global Outcomes) convened the fourth clinical Controversies Conference on the heart, kidney and vasculature in Dublin, Ireland, in February 2020, entitled Central and Peripheral Arterial Diseases in Chronic Kidney Disease. A global panel of multidisciplinary experts from the fields of nephrology, cardiology, neurology, surgery, radiology, vascular biology, epidemiology, and health economics attended. The objective was to identify key issues related to the optimal detection, management, and treatment of cerebrovascular diseases, central aortic disease, renovascular disease, and peripheral artery disease in the setting of CKD. This report outlines the common pathophysiology of these vascular processes in the setting of CKD, describes best practices for their diagnosis and management, summarizes areas of uncertainty, addresses ongoing controversial issues, and proposes a research agenda to address key gaps in knowledge that, when addressed, could improve patient care and outcomes.

PURPOSE To evaluate the safety and efficacy of N-acetylmannosamine (ManNAc) in GNE myopathy, a genetic muscle disease caused by deficiency of the rate-limiting enzyme in N-acetylneuraminic acid (Neu5Ac) biosynthesis. METHODS We conducted an open-label, phase 2, single-center (NIH, USA) study to evaluate oral ManNAc in 12 patients with GNE myopathy (ClinicalTrials.gov NCT02346461). Primary endpoints were safety and biochemical efficacy as determined by change in plasma Neu5Ac and sarcolemmal sialylation. Clinical efficacy was evaluated using secondary outcome measures as part of study extensions, and a disease progression model (GNE-DPM) was tested as an efficacy analysis method. RESULTS Most drug-related adverse events were gastrointestinal, and there were no serious adverse events. Increased plasma Neu5Ac (+2,159 nmol/L, p

Anatomische Reposition dislozierter Frakturen mittels winkelstabiler Hakenplatte. Operative Revision symptomatischer Pseudarthrosen mit dem Ziel der knochernen Durchbauung. Dislozierte Frakturen des Processus styloideus ulnae mit Beteiligung der Fovea ulnaris. Kombinierte Frakturen mit Instabilitat des distalen Radioulnargelenks sowie symptomatische Pseudarthrosen. Undislozierte Frakturen des Processus styloideus ulnae sowie asymptomatische Pseudarthrosen. Dorsoradialer Zugang zur distalen Ulna zwischen dem 6. Strecksehnenfach und der Sehne des M. flexor carpi ulnaris. Darstellen der Fraktur/Pseudarthrose. Im Falle einer Pseudarthrose ausraumen und anfrischen der Frakturenden. Reposition erfolgt uber die Haken der Platte, ggf. zusatzliche Anlagerung autologer Spongiosa bei Pseudarthrosen. Fixierung der Platte uber das Gleitloch und anschliesendes Besetzen der winkelstabilen Schraubenlocher. Je nach Begleitverletzung Ruhigstellung in Unterarmgipsschiene fur 1 bis 2 Wochen. Aktive Bewegungsubungen der Finger ab dem 1. postoperativen Tag, ggf. Lymphdrainage. Nach knocherner Durchbauung Belastungsaufbau unter ergotherapeutischer Anleitung. Die knocherne Heilung konnte bei 100 % unserer Falle erreicht werden. Die operative Behandlung sowohl symptomatischer Pseudarthrosen als auch dislozierter Frakturen des Processus styloideus ulnae mittels winkelstabiler Hakenplatte hat sich in der Anwendung bewahrt.

Resistance to single-agent chemotherapy and molecularly targeted drugs prevents sustained efficacy of treatments. To address this challenge, combination drug treatments have been used to improve outcomes for patients. Potential toxicity of combination treatments is a major concern, however, and has led to the failure of several clinical trials in different cancers. The use of cell-based models of normal tissues in preclinical studies enables testing and identifying toxic effects of drug combinations and facilitates an informed decision-making process for advancing the treatments to animal models and clinical trials. Recently, we established that combinations of molecular inhibitors of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase-protein kinase B (PI3K/Akt) pathways effectively and synergistically inhibit growth of BRAFmut and KRASmut colorectal tumor spheroids by blocking feedback signaling of downstream kinase pathways. These pathways are important for cell proliferation, however, and their simultaneous inhibition may cause toxicity to normal cells. We used a cellular spheroid model to study toxicities of drug combinations to human bone marrow and colon. Our results indicated that MAPK and PI3K/Akt inhibitors used simultaneously were only moderately toxic to bone marrow cells but significantly more toxic to colon cells. Our molecular analysis of proliferative cell activities and housekeeping proteins further corroborated these results. Overall, our approach to identify toxic effects of combinations of cancer drugs to normal cells in three-dimensional cultures will facilitate more informed treatment selections for subsequent animal studies.

Aim: To explore the current practice of stakeholder engagement in clinical trials and its evaluation in North America (USA and Canada), DACH countries (Germany, Austria and Switzerland) and China. Participants & methods: We conducted a web-based, anonymous, international, cross-sectional online survey for clinical researchers. Data were analyzed using descriptive and explorative statistical analysis including analysis of variance and analysis of covariance. Results: Stakeholder engagement is more prominent and higher accepted among researchers in North America. Researchers in DACH countries have less knowledge of the stakeholder engagement method and are less likely to apply it. Conclusion: Stakeholder engagement is perceived very differently among participants from DACH countries, North America and China. For a broader acceptance and implementation institutional support and motivational conditions might be needed.

ARIC (Atherosclerosis Risk In Communities) initiated community-based surveillance in 1987 for myocardial infarction and coronary heart disease (CHD) incidence and mortality and created a prospective cohort of 15,792 Black and White adults ages 45 to 64 years. The primary aims were to improve understanding of the decline in CHD mortality and identify determinants of subclinical atherosclerosis and CHD in Black and White middle-age adults. ARIC has examined areas including health disparities, genomics, heart failure, and prevention, producing more than 2,300 publications. Results have had strong clinical impact and demonstrate the importance of population-based research in the spectrum of biomedical research to improve health.

Objective: Nonatherosclerotic outward remodeling of the large intracranial arteries may facilitate propagation of excessive aortic pulsatile energy into the cerebral microcirculation and has been associated with adverse cognitive outcomes. We sought to determine the relationship between central artery stiffness, brain arterial diameters, and white matter hyperintensity (WMH) volume in the general population of older adults. Approach and Results: We examined data from 1275 stroke-free participants of the ARIC (Atherosclerosis Risk in Communities) study (59% female, 30% Black, mean age 77 years) who underwent carotid-femoral pulse wave velocity (cf-PWV) testing and brain magnetic resonance imaging. A cf-PWV >12 m/s was considered elevated. Relationships between WMH and arterial diameters at the M1A1 segment of the middle and anterior cerebral arteries (whichever larger) were analyzed in the absence of artery-specific plaque, adjusting for intracranial volume and potential confounders. The average cf-PWV was 11.7 m/s and WMH volume was 11.2 cm 3 . Each 0.5 mm increment in M1A1 diameter was associated with 24% greater WMH volume in participants with elevated cf-PWV (exponentiated β=1.24 [95% CI, 1.12–1.36]), compared with a 10% greater WMH volume in participants without elevated cf-PWV (exponentiated β=1.10 [95% CI, 1.01–1.19]), P value for interaction=0.04. Conclusions: In this examination of older adults from the general population, larger, plaque-free arterial diameters in the middle cerebral circulation were associated with greater WMH volume, particularly among participants with elevated central artery stiffness. Strategies to reduce central artery stiffness may mitigate the association between cerebrovascular outward remodeling and microvascular damage.

Introduction Although pediatric surgeons have lower rates of burnout compared to other surgical subspecialists, they still struggle with work-home conflict, depersonalization, and emotional exhaustion. Prior surveys have measured career satisfaction and burnout, but none have identified factors that contribute to physician well-being or provided potential solutions. Methods Members of the American Pediatric Surgical Association were surveyed regarding sources of distress and institutional practices intended to promote well-being. Responses were analyzed using content analysis. Results There was a 31.5% response rate to the survey. The most frequently cited sources of distress were administrative issues (45.2%), work/life balance (42.3%), personal issues (18.8%), and relationships with coworkers (17.9%). In open-ended questions, other sources of distress included poor leadership, loss of autonomy, lack of support and mentorship, and patient complications. Successful wellness strategies included relief from clinical burden, substantive wellness programming, surgeon inclusion in administrative decision making, support after adverse events, appropriate compensation and benefits, and opportunities for career development in research, teaching, and clinical care. Conclusion Pediatric surgeons are affected by multiple sources of distress. Interventions that ameliorate stress in pediatric surgeons were identified and should be considered by local institutions and national organizations to promote well-being. Level of evidence n/a

The fascia thoracolumbalis (FTL) is an important component for stabilization and motion control of the lumbar spine. It coordinates the traction forces of the autochthonous muscles of the back (AM) and connects them to the muscles of the abdominal wall, shoulder, and buttocks.The aim of our study was to describe the assessment of the normal FTL and epimysium of the AM in MRI and to identify patterns associated with pathological changes in the lumbar spine.A total of 33 patients were retrospectively evaluated: 15 patients had no pathology at the lumbar spine; six patients had previous hemilaminectomy, three had spondylodesis, two had ventrolisthesis, and seven had scoliosis. The thickness of the FTL and EM was measured, and the adhesion of both structures was assessed.The fascial thickness at the levels of the lumbar vertebral bodies LVB 3 was 1.8, of LVB 4 it was 2.0, of LVB 5 it was 2.1, and at the sacral vertebra SVB 1 it was 1.8 mm. Fascial adhesions together with thickening of the EM occurred at the level of LVB 4 in 36% of the cases independently of the underlying disorder. Only thickening of the EM was seen in 48% of cases at the level of SVB 1. By contrast, adhesion of the FTL without epimysial changes occurred in 36% of cases at the level of LVB 3.Thickening and adhesions at the EM and FTL occurred both postoperatively and in the case of scoliosis. Furthermore, lipomatous and muscular herniation could be detected in the FTL postoperatively. Epimysial and fascial alterations may be imaging manifestations of chronic myofascial back pain and should be included in radiological assessments.HINTERGRUND: Die Fascia thoracolumbalis (FTL) ist eine wichtige Struktur für die Stabilisierung und Bewegungssteuerung der Lendenwirbelsäule (LWS). Sie koordiniert die Traktionskräfte der autochthonen Rückenmuskulatur und verbindet sie mit den Muskeln der Bauchwand, der Schulter und des Gesäßes. ZIEL: Ziel der vorliegenden Studie war es, die Beurteilung der normalen FTL und des Epimysiums (EM) der autochthonen Rückenmuskulatur in der Magnetresonanztomographie (MRT) zu beschreiben und dabei Muster zu erkennen, die mit pathologischen Veränderungen in der LWS einhergehen.Retrospektiv wurden die Daten von 33 Patienten ausgewertet: Bei 15 Patienten zeigten sich keine pathologischen Veränderungen im LWS-Bereich; bei 6 Patienten bestand ein Z. n. Hemilaminektomie, bei 3 lag eine Spondylodese vor, 2 wiesen eine Ventrolisthese und 7 eine Skoliose auf. Die Dicke der FTL und des EM wurden gemessen und die Adhäsion beider Strukturen ermittelt.Auf Höhe des Lendenwirbelkörpers 3 (LWK 3) lag die Fasziendicke bei 1,8 mm, auf Höhe von LWK 4 betrug sie 2,0 mm, bei LWK 5 war sie 2,1 mm und auf Höhe des Sakralwirbels 1 (SWK 1) 1,8 mm. Faszienadhäsionen in Kombination mit einer Verdickung des EM traten auf Höhe des LWK 4 in 36 % der Fälle auf, unabhängig von der zugrunde liegenden Erkrankung. Auf Höhe von SWK 1 wurde in 48 % der Fälle lediglich eine Verdickung des EM festgestellt. Dagegen trat auf Höhe des LWK 3 eine Adhäsion der FTL ohne EM-Veränderungen in 36 % der Fälle auf.Eine Verdickung und Adhäsionen des EM und der FTL zeigten sich sowohl postoperativ als auch bei Skoliose. Darüber hinaus wurde eine lipomatöse und muskuläre Herniation in der FTL postoperativ festgestellt. Epimysium- und Faszienveränderungen können sich bildgebend als Manifestationen chronischer myofaszialer Rückenschmerzen darstellen und sollten in die radiologische Beurteilung einfließen.

BACKGROUND AND AIMS: Previous community-based studies have demonstrated sex and race-based disparities in the risk of cardiovascular disease. We sought to examine the association of sex and race with incident peripheral artery disease (PAD) and critical limb ischemia (CLI) related hospitalizations. METHODS: In 13,451 Black and White ARIC participants without prevalent PAD at baseline (1987–89), we estimated the cumulative incidence of PAD- and CLI-related hospitalization over a median follow-up of 26 years. We quantified hazard ratios (HRs) using Cox models across four sex- and race-groups. PAD and CLI were defined by hospitalization discharge codes. RESULTS: The cumulative incidence of PAD-related hospitalization was higher in males than females in Whites (5.1% vs. 2.7%; p

The aim of this randomized controlled laboratory study was to evaluate the role of standardized protection, rest, ice (cryotherapy), compression and elevation (PRICE) therapy on microvascular blood flow in human skeletal muscle. Quantifiable contrast-enhanced ultrasound was used to analyze intramuscular tissue perfusion (ITP) of the rectus femoris (RF) and vastus intermedius (VI) muscles in 20 healthy athletes who were randomly assigned to PRICE or control groups. Baseline perfusion measurements (resting conditions, T0) were compared with cycling exercise (T1), intervention (PRICE or control, T2) and follow-up at 60 min post-intervention (T3). The 20 min PRICE intervention included rest, cryotherapy (3°C), compression (35 mm Hg) and elevation. After intervention, PRICE demonstrated a decrease of ITP in VI (–47%, p = 0.01) and RF (–50%, p = 0.037) muscles. At T3, an ongoing decreased ITP for the RF (p = 0.003) and no significant changes for the VI were observed. In contrast, the control group showed an increased ITP at T2 and no significant differences at T3. PRICE applied after exercise led to a down-regulation of ITP, and the termination of PRICE does not appear to be associated with a reactive hyperemia for at least 60 min after treatment.

Summary: Background: Peripheral artery disease presents an increasing healthcare burden worldwide. Day-case angioplasty in a secondary care setting can be a safe and effective means of meeting the growing demand for lower limb revascularisation. We evaluated the safety and efficacy of a day-case-based angioplasty service in a UK district general hospital. Patients and methods: Consecutive patients undergoing endovascular revascularisation between August 2018–February 2020 were analysed retrospectively. All patients were discussed at a multi-disciplinary (diabetic foot) team meeting following a day case algorithm. Patient and procedural characteristics, technical success, peri-procedural complications, and 30-day outcome of day-case angioplasties were compared with those requiring overnight stay or were hospitalized. Results: Fifty-seven percent of 138 patients were diabetic, mean age 75 ± 12 years, 95% had critical limb ischaemia (Fontaine III 12%, IV 83%), and baseline ankle brachial pressure index [ABPI] 0.40 ± 0.30. Sixty-three patients (45%) were treated as planned day cases, 21 (15%) required overnight admission for social indications. Fifteen (11%) were planned admissions with the need for sequential debridement procedures, and 39 (28%) were already hospitalised at the time of referral to the vascular service. The overall technical success was 92% and not successful procedures mainly occurred in patients > 80 years. The ABPI increased at the initial follow-up to 0.84 ± 0.18. Fifty-three percent required treatment of > 1 level, 80% included recanalisations of chronic total occlusions, and average total lesion length was 133 ± 90 mm. Closure devices were employed in all cases. There were no major peri-procedural complications. A single minor access-site related bleeding episode (0.8%) occurred, requiring 24 h observation in hospital. While significantly more wounds had closed in out-patients, the mortality, major amputation and target lesion revascularization did not differ between groups. Conclusions: Safe and effective day-case-based angioplasty can be provided in a secondary care setting for patients with critical limb ischaemia needing complex multi-level procedures.

To describe the occurrence of imaging-depicted sports-related injuries (bone, muscle, tendon, and ligament injuries) during the Rio 2016 Summer Paralympic Games. Descriptive data on all imaging examinations by using radiography, ultrasonography (US), and MRI were collected and retrospectively analyzed centrally by five musculoskeletal radiologists according to imaging modality, country of origin of the athletes, type of sport, type of disability, and type and location of injury. We report 109 injuries in 4378 athletes. A total of 382 radiologic examinations were performed in 261 athletes, including 118 (31%) radiographic, 22 (6%) US, and 242 (63%) MRI examinations. Para athletes from Africa had the highest utilization rate (20.1%, 67 out of 333). Athletes from Europe underwent the most examinations with 29 radiographic, 12 US, and 66 MRI examinations. The highest utilization rate of imaging modalities by sport was among Judo para athletes (16.7%, 22 out of 132). Most injuries were reported in athletics discipline (37.6%, 41 out of 109). Most injuries were also reported among para athletes with visual impairment (40 injuries, 36.7% of all injuries). Bone stress injuries were most common among para athletes with visual impairment (6 out of 7). Para athletes with visual impairment were also more prone to bone stress injuries than traumatic fractures, unlike para athletes with neurologic and musculoskeletal impairments. Imaging was used in 6.0% of para athletes. MRI comprised 63% of imaging utilization. Identification of patterns of injuries may help building future prevention programs in elite para athletes. • The highest imaging utilization rates were found among para athletes competing in Judo, sitting volleyball, powerlifting, and football. • Utilization of diagnostic imaging at the Rio 2016 Paralympic Games demonstrated similar trends to what was observed at the Rio 2016 Olympic Games. • Comparison of the rate of imaging-depicted injuries between Olympic and Paralympic athletes is limited due to inherent differences between the two athlete populations and the manner in which injury risk in the Paralympic athlete varies dependent on impairment type, which is not the case for the Olympic athlete.

Purpose Reported outcome after multiple staged surgical treatment of infected nonunion is scarce. We, therefore, asked: (1) What is the clinical outcome in infected nonunion patients after multiple staged revision surgery? (2) Are different pathogens evidenced after surgical treatment in patients who have undergone more or less surgeries? Methods All enrolled patients were surgically treated for long bone-infected nonunion between January 2010 and March 2018. Besides patients´ demographics outcome in terms of bony consolidation and major complications defined as death during inward treatment, amputation and recurrence of infection during follow-up of at least 12 months were assessed. Microbiological findings were assessed and compared between two groups with less than five versus five or more surgical revisions. Results Bone consolidation was achieved in 86% of the patients while complications such as femoral or transtibial amputation, recurrence of infection or even death during inpatient treatment could be evidenced in six patients (14%). In patients who underwent multiple-stage surgery for five or more times, germ changes and repeated germ detection was more common than in patients with less surgeries. Conclusions Surgical treatment of infected nonunions poses a high burden on the patients with major complications occurring in about 14% of the patients using a multiple staged treatment concept. Future prospective studies comparing outcomes after limited with multiple staged revision surgeries are necessary.

Purpose We conducted a retrospective observational study in order to identify negative effects of NOTES procedures (Natural Orifice Transluminal Endoscopic Surgery) with transvaginal specimen removal on pregnancy and delivery. Methods From the total population of 299 patients in our NOTES registry, we tried to contact the 121 patients who were of reproductive age (≤ 45 years) at the time of a transvaginal NOTES procedure. They were interviewed by telephone regarding their desire for children, post NOTES-operation pregnancies, and type of delivery using a structured questionnaire. The collected data was analyzed and compared with current data. Results We were able to contact 76 patients (follow-up rate: 62.8%) with a median follow-up of 77 months after surgery (33–129 months). Twenty of 74 participating patients had a desire for children (27.0%). One of them and another's male partner were diagnosed as infertile. Regarding the remaining 18 patients, 14 became pregnant, and three of them became pregnant twice. Considering these 17 pregnancies, there was one miscarriage (5.9%) and one twin birth (5.9%). On average, childbirth occurred 44 months after the NOTES procedure. With regard to the type of delivery, 10 vaginal births (58.8%) and 7 caesarean sections (41.2%) occurred. Thus, the rate of fulfilled desire for children was 77.8%. Compared with the literature, no difference to the normal course could be detected. Conclusion There is no sign that the transvaginal approach in Hybrid-NOTES, with removal of the specimen through the vagina, has a negative effect on conception, the course during pregnancy, or the type of delivery.

Background: Low levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the low physiologic range, surrogate markers for reduced liver metabolic function, are associated with cerebral hypometabolism, impairment in neurotransmitter production and synaptic maintenance, and a higher prevalence of dementia. It is unknown whether a prospective association exists between low liver enzyme levels and incident dementia. Objective: To determine whether low levels of ALT and AST are associated with higher risk of incident dementia. Methods: Plasma ALT and AST were measured on 10,100 study participants (mean age 63.2 years, 55% female, 22% black) in 1996–1998. Dementia was ascertained from comprehensive neuropsychological assessments, annual contact, and medical record surveillance. Cox proportional hazards regression was used to estimate the association. Results: During a median follow-up of 18.3 years (maximum 21.9 years), 1,857 individuals developed dementia. Adjusted for demographic factors, incidence rates of dementia were higher at the lower levels of ALT and AST. Compared to the second quintile, ALT values

Objective To characterize the longitudinal relationships between blood pressure measured over 24 years and arterial stiffness in late life measured as pulse wave velocity (PWV). Methods Carotid--femoral (cf) and femoral--ankle (fa) PWV were measured in 4166 adults at the visit 5 Atherosclerosis Risk in Communities study cohort examination (2011-2013). Participants were categorized into tertiles of PWV measurements. Blood pressure measurements were made at baseline (1987-1989), three subsequent triennial examinations, and visit 5. Results Partial correlation coefficients between visit 5 cfPWV and SBP ranged from 0.13 for visit 1 SBP to 0.32 for visit 5 SBP. For visit 5 faPWV, correlations were ∼0 for visits 1 to 4 SBP, but was 0.20 for visit 5 SBP. Over 24 years of follow-up, those with higher average SBP were more likely to fall in the middle and upper tertiles of visit 5 cfPWV. Average pulse pressure and mean arterial pressure over 24 years had similar but weaker associations with cfPWV tertiles. DBP had no clear association with cfPWV. Blood pressure measurements were positively associated with faPWV tertiles only cross-sectionally at visit 5. Conclusion Adult life-course measures of SBP, more so than mean arterial and pulse pressure, were associated with later life central arterial stiffness. By contrast, only contemporaneous measures of blood pressure were associated with peripheral arterial stiffness. Although arterial stiffness was only measured at later life, these results are consistent with the notion that elevated blood pressure over time is involved in the pathogenesis of arterial stiffening.

Background Short episodes of myocardial ischemia can protect from myocardial infarction. However, the role of endothelial β1 integrin in these cardioprotective ischemic events is largely unknown. Objective In this study we investigated whether endothelial β1 integrin is required for cardiac adaptation to ischemia and protection from myocardial infarction. Methods Here we introduced transient and permanent left anterior descending artery (LAD) occlusions in mice. We inhibited β1 integrin by intravenous injection of function-blocking antibodies and tamoxifen-induced endothelial cell (EC)-specific deletion of Itgb1. Furthermore, human ITGB1 was silenced in primary human coronary artery ECs using small interfering RNA. We analyzed the numbers of proliferating ECs and arterioles by immunohistochemistry, determined infarct size by magnetic resonance imaging (MRI) and triphenyl tetrazolium chloride staining, and analyzed cardiac function by MRI and echocardiography. Results Transient LAD occlusions were found to increase EC proliferation and arteriole formation in the entire myocardium. These effects required β1 integrin on ECs, except for arteriole formation in the ischemic part of the myocardium. Furthermore, this integrin subunit was also relevant for basal and mechanically induced proliferation of human coronary artery ECs. Notably, β1 integrin was needed for cardioprotection induced by transient LAD occlusions, and the absence of endothelial β1 integrin resulted in impaired growth of blood vessels into the infarcted myocardium and reduced cardiac function after permanent LAD occlusion. Conclusion We showed that endothelial β1 integrin is required for adaptation of the heart to cardiac ischemia and protection from myocardial infarction.

Introduction: Infectious complications represent a major cause of morbidity and mortality in hairy cell leukemia (HCL) patients. Due to the immunosuppressive nature of the disease, these patients are frequently affected by opportunistic infections and rare pathogens. Furthermore, cytotoxic chemotherapy might lead to poor or even fatal outcomes in the setting of an active infection. Case Presentation: We report the case of a 62-year-old HCL patient who presented with recurrent fever episodes, pancytopenia, and mediastinal lymphadenopathy. A treatment decision against purine analogs and for rituximab mono was made as lymph node tissue revealed disseminated Mycobacterium kansasii infection. Together with specific antimycobacterial treatment, rituximab mono led to complete hematologic remission after 6 months without aggravating the accompanying infection. Conclusion: Here, we demonstrate successful treatment of HCL with rituximab in a patient with concomitant disseminated M. kansasii infection.

Objective The aim of this study was to investigate the approach (open or laparoscopic) and mesh type (synthetic or biological) in ventral hernias in a clean setting.Summary of Background Data: The level of evidence on the optimal surgical approach and type of mesh in ventral hernia repair is still low. Methods Patients with a ventral abdominal hernia (diameter 4-10 cm) were included in this double-blind randomized controlled trial across 17 hospitals in 10 European countries. According to a 2 × 2-factorial design, patients were allocated to 4 arms (open retromuscular or laparoscopic intraperitoneal, with synthetic or Surgisis Gold biological mesh). Patients and outcome assessors were blinded to mesh type used. Major postoperative complication rate (hernia recurrence, mesh infection, or reoperation) within 3 years after surgery, was the primary endpoint in the intention-to-treat population. Results Between September 1st, 2005, and August 7th, 2009, 253 patients were randomized and 13 excluded. Six of 61 patients (9.8%) in the open synthetic mesh arm, 15 of 66 patients (22.7%) in the open biological mesh arm, 7 of 64 patients (10.9%) in the laparoscopic synthetic mesh arm and 17 of 62 patients (27.4%) in the laparoscopic biological mesh arm had a major complication. The use of biological mesh resulted in significantly more complications (P = 0.013), also after adjusting for hernia type, body mass index, and study site. The trial was prematurely stopped due to an unacceptable high recurrence rate in the biological mesh arms. Conclusions The use of Surgisis Gold biological mesh is not recommended for noncomplex ventral hernia repair. Trial registration This trial was registered at controlled-trials.com (ISRCTN34532248).

Background: Physical activity has been associated with longer chronic disease–free life expectancy, but specific cancer types have not been investigated. We examined whether leisure-time moderate-to-vigorous physical activity (LTPA) and television (TV) viewing were associated with life expectancy cancer-free. Methods: We included 14,508 participants without a cancer history from the Atherosclerosis Risk in Communities (ARIC) study. We used multistate survival models to separately examine associations of LTPA (no LTPA, Results: Compared with no LTPA, participants who engaged in LTPA ≥median had a greater life expectancy cancer-free from colorectal [men-2.2 years (95% confidence interval (CI), 1.7–2.7), women-2.3 years (95% CI, 1.7–2.8)], lung [men-2.1 years (95% CI, 1.5–2.6), women-2.1 years (95% CI, 1.6–2.7)], prostate [1.5 years (95% CI, 0.8–2.2)], and postmenopausal breast cancer [2.4 years (95% CI, 1.4–3.3)]. Compared with watching TV often/very often, participants who seldom/never watched TV had a greater colorectal, lung, and postmenopausal breast cancer-free life expectancy of ∼1 year. Conclusions: Participating in LTPA was associated with longer life expectancy cancer-free from colorectal, lung, prostate, and postmenopausal breast cancer. Viewing less TV was associated with more years lived cancer-free from colorectal, lung, and postmenopausal breast cancer. Impact: Increasing physical activity and reducing TV viewing may extend the number of years lived cancer-free.

Enhanced recovery after surgery (ERAS) protocols have been successfully implemented in several surgical fields; however, the application of ERAS in the pediatric population is still limited.The aim was to determine if implementation of an ERAS protocol can improve outcomes of laparoscopic sleeve gastrectomy (LSG) in adolescents.University Hospital, United States.A retrospective analysis of 112 adolescent patients who underwent LSG from February 2011 to July 2019 was conducted. An ERAS protocol was instituted in June 2016. Conventional care patients (n = 51) were compared with ERAS patients (n = 61). Comparisons were made using ΧThe 2 cohorts were similar in age, sex, race, number of co-morbidities, and preoperative body mass index. The volume of intraoperative fluid, intraoperative and postoperative opioids were significantly reduced in the ERAS group (P.0001). The number of ERAS elements received per patient increased from a median of 9 to 15 (P.0001). ERAS group had more discharges on postoperative day 1 (48% versus 6 %, respectively). Length of stay was significantly lower in the ERAS group (2.34 versus 2.04 median d, respectively). Difference was still significant after adjusting for age, sex, race/ethnicity, payor status, American Society of Anesthesiologists score, preoperative body mass index, and the duration of surgery (P.0001). There were no differences in postoperative complications and 30-day readmissions.An LSG ERAS protocol is associated with significant reduction in perioperative opioid use and length of stay with no increase in complications or readmission rates.

Since the publication of the updated German guideline in 2015, the recommendations for performing pelvic lymphadenectomy (LAE) in patients with vulvar cancer (VSCC) have changed considerably. The guideline recommends surgical lymph node staging in all patients with a higher risk of pelvic lymph node involvement. However, the current data do not allow the population at risk to be clearly defined, therefore, the indication for pelvic lymphadenectomy is still not clear. There are currently two published German patient populations who had pelvic LAE which can be used to investigate both the prognostic effect of histologically verified pelvic lymph node metastasis and the relation between inguinal and pelvic lymph node involvement. A total of 1618 patients with primary FIGO stage ≥ IB VSCC were included in the multicenter AGO CaRE-1 study (1998 – 2008), 70 of whom underwent pelvic LAE. During a retrospective single-center evaluation carried out at the University Medical Center Hamburg-Eppendorf (UKE), a total of 514 patients with primary VSCC treated between 1996 – 2018 were evaluated, 21 of whom underwent pelvic LAE. In both cohorts, around 80% of the patients who underwent pelvic LAE were inguinally node-positive, with a median number of three affected groin lymph nodes. There were no cases of pelvic lymph node metastasis without inguinal lymph node metastasis in either of the two cohorts. Between 33 – 35% of the inguinal node-positive patients also had pelvic lymph node metastasis; the median number of affected groin lymph nodes in these patients was high (> 4), and the maximum median diameter of the largest inguinal metastasis was > 40 mm in both cohorts. Pelvic lymph node staging and pelvic radiotherapy is therefore probably not necessary for the majority of node-positive patients with VSCC, as the relevant risk of pelvic lymph node involvement was primarily found in node-positive patients with high-grade disease. More, ideally prospective data collections are necessary to validate the relation between inguinal and pelvic lymph node involvement.

AIMS SAR247799 is a G-protein-biased sphingosine-1 phosphate receptor-1 (S1P1 ) agonist designed to activate endothelial S1P1 and provide endothelial-protective properties, while limiting S1P1 desensitization and consequent lymphocyte-count reduction associated with higher doses. The aim was to show whether S1P1 activation can promote endothelial effects in patients and, if so, select SAR247799 doses for further clinical investigation. METHODS Type-2 diabetes patients, enriched for endothelial dysfunction (flow-mediated dilation, FMD

State restrictions on nongovernmental organizations (NGOs) have become increasingly pervasive across the globe. Although this crackdown has been shown to have a negative impact on public funding flows, we know little about how it affects private philanthropy. How does information about crackdown abroad, as well as organizational attributes of nonprofits, affect individual donors’ willingness to donate internationally? Using a survey experiment, we find that learning about repressive NGO environments increases generosity in that already-likely donors are willing to donate substantially more to legally besieged nonprofits. This generosity persists when mediated by two organizational-level heuristics: NGO issue areas and main funding sources. We discuss the implications of our results on how nonprofits can use different framing appeals to increase fundraising at a time when traditional public donor funding to such organizations is decreasing.

The aim of this study was to develop an algorithm for automated estimation of patient height and weight during computed tomography (CT) and to evaluate its accuracy in everyday clinical practice. Depth images of 200 patients were recorded with a 3D camera mounted above the patient table of a CT scanner. Reference values were obtained using a calibrated scale and a measuring tape to train a machine learning algorithm that fits a patient avatar into the recorded patient surface data. The resulting algorithm was prospectively used on 101 patients in clinical practice and the results were compared to the reference values and to estimates by the patient himself, the radiographer and the radiologist. The body mass index was calculated from the collected values for each patient using the WHO formula. A tolerance level of 5 kg was defined in order to evaluate the impact on weight-dependent contrast agent dosage in abdominal CT. Differences between values for height, weight and BMI were non-significant over all assessments (p 0.83). The most accurate values for weight were obtained from the patient information (R² = 0.99) followed by the automated estimation via 3D camera (R² = 0.89). Estimates by medical staff were considerably less precise (radiologist: R² = 0.78, radiographer: R² = 0.77). A body-weight dependent dosage of contrast agent using the automated estimations matched the dosage using the reference measurements in 65 % of the cases. The dosage based on the medical staff estimates would have matched in 49 % of the cases. Automated estimation of height and weight using a digital twin model from 3D camera acquisitions provide a high precision for protocol design in computer tomography. · Machine learning can calculate patient-avatars from 3D camera acquisitions.. · Height and weight of the digital twins are comparable to real measurements of the patients.. · Estimations by medical staff are less precise.. · The values can be used for calculation of contrast agent dosage..· Geissler F, Heiß R, Kopp M et al. Personalized computed tomography - Automated estimation of height and weight of a simulated digital twin using a 3D camera and artificial intelligence. Fortschr Röntgenstr 2021; 193: 437 - 445. Ziel der Studie war es, einen Algorithmus zur Abschätzung von Größe und Gewicht der Patienten vor einer Computertomografie (CT) zu entwickeln und dessen Genauigkeit im klinischen Alltag zu evaluieren. Mit einer über dem Patiententisch montierten 3D-Kamera wurden Tiefenbilder von 200 Patienten aufgenommen und zusammen mit den Referenzwerten einer geeichten Waage und eines Maßbandes zum Trainieren eines maschinellen Lernalgorithmus verwendet. Dies erfolgte über die Anpassung eines Patienten-Avatars an die aufgenommenen Oberflächeninformationen. Der so entstandene automatische Algorithmus wurde dann prospektiv im klinischen Alltag an 101 Patienten angewandt und die Ergebnisse mit den gemessenen Referenzwerten, den Patientenangaben sowie den Schätzwerten durch das technische und ärztliche Personal verglichen. Der Body-Mass-Index wurde aus den erhobenen Werten für jeden Patienten mit der WHO-Formel berechnet. Um die Auswirkungen auf die Kontrastmittelmenge bei gewichtsabhängiger Dosierung abschätzen zu können, wurde eine Toleranz von 5 kg definiert. Die Unterschiede zwischen den erhobenen Werten für Größe, Gewicht und BMI waren für alle Methoden nicht signifikant (p 0,83). Die genauesten Werte für das Gewicht wurden aus der Patientenangabe (R² = 0,99), gefolgt von der automatischen Erfassung über die 3D-Kamera (R² = 0,89), erzielt. Abschätzungen durch das medizinische Personal waren deutlich ungenauer (Radiologe: R² = 0,78; MTRA: R² = 0,77). Eine gewichtsabhängige Kontrastmitteldosierung mit den Werten der automatischen Abschätzung wäre im Vergleich zur Dosierung anhand der Referenzmessungen in 65 % der Fälle identisch gewesen. Analog wären bei einem Vorgehen basierend auf Schätzwerten des Personals 49 % der Patienten identisch dosiert worden. Die automatisierte Abschätzung von Größe und Gewicht mit einer 3D-Kamera kann durch ein digitales Zwillingsmodell mit hoher Präzision für die Untersuchungsplanung in der Computertomografie verwendet werden. · Patienten-Avatare können durch maschinelles Lernen aus 3D-Kameraaufnahmen berechnet werden.. · Die Größe und das Gewicht der digitalen Zwillinge sind mit den realen Messwerten der Patienten vergleichbar.. · Schätzungen durch medizinisches Personal sind weniger genau.. · Die Werte können zur Berechnung der Kontrastmitteldosis verwendet werden..· Geissler F, Heiß R, Kopp M et al. Personalized computed tomography – Automated estimation of height and weight of a simulated digital twin using a 3D camera and artificial intelligence. Fortschr Röntgenstr 2021; 193: 437 – 445.

This article investigates the use of iterative prototyping to facilitate interdisciplinary collaboration in the design and development of an innovative self-fit modular hearing aid. The de...

BD MAX MDR-TB assay is a new molecular platform for the detection of Mycobacterium tuberculosis complex (MTBC) in clinical specimens and simultaneous detection of resistance towards isoniazid and rifampicin. In this study, we assessed its diagnostic accuracy using pre-characterized MTBC-culture negative (n=257), smear-negative / MTBC-culture positive (n=93), and smear-positive / MTBC-culture positive (n=153) respiratory specimens. Compared to culture, overall sensitivity and specificity of BD MAX MDR-TB were 86.6% and 100%, respectively; sensitivities for smear-positive and smear-negative samples were 100% and 64.5%, respectively. Sensitivity and specificity for isoniazid and rifampicin resistance were 58.3% (biased low due to sample collection strategy in low prevalence setting), 99.3%, 100%, and 98.2%, respectively, compared to phenotypic drug resistance testing and 100%, 99.4%, 100% and 99.4%, respectively, compared to Genotype MTBDRplus. In conclusion, BD MAX MDR-TB is an accurate assay for the diagnostic detection of MTBC in respiratory samples and its resistance toward the most important anti-TB drugs isoniazid and rifampicin. Due to its medium to high throughput, good validity and ease of use, the assay will be of great benefit for medium-size to large TB diagnostic centers.

Die Polyarthrose der Hand und der Finger ist keine exklusive Erkrankung des fortgeschrittenen Lebensalters. Verletzungen und Unfalle fuhren zu sekundaren Veranderungen an der Handwurzel und den Fingergelenken. Die Therapie umfasst konservative, interventionelle und operative Ansatze. Das primare Ziel der konservativen Therapie ist der Erhalt der Beweglichkeit und der funktionellen Kapazitat. Neben dem motorisch-funktionellen Training umfasst die Ergotherapie neben Gelenkschutz und Selbsthilfetraining die gezielte Unterstutzung der individualisierten Therapie durch erforderliche Orthesen. Bei persistierenden Einschrankungen und Schmerzen, die durch konservative und interventionelle Masnahmen nicht ausreichend therapierbar sind, kann eine operative Versorgung in Erwagung gezogen werden. Diese kann dann zu einer Verbesserung der Gesamtsituation der Hand beitragen, soweit alle anderen Therapieoptionen ausgeschopft sind und der Leidensdruck des Patienten das Ausmas des Eingriffes rechtfertigt. Polyarthrosis of the hand and fingers is not an exclusive disease of advanced age. Injuries and accidents lead to secondary changes in the wrist, and finger joints. The therapy includes conservative, interventional and surgical options. The primary goal of conservative therapy is to maintain mobility and function of the hand. In addition to motor-functional training, occupational therapy includes joint protection and self-help training, as well as targeted support of the individualized therapy with splints and braces. In cases of persistent limitations and pain that cannot be sufficiently treated by conservative and interventional therapies, surgical treatment can be considered. This can then help to improve the overall situation of the hand, provided that all other therapy options have been exhausted and the patient’s level of suffering justifies the extent of the intervention.

Context: Foam rolling (FR) has been developed into a popular intervention and has been established in various sports disciplines. However, its effects on target tissue, including changes in stiffness properties, are still poorly understood. Objective: To investigate muscle-specific and connective tissue-specific responses after FR in recreational athletes with different FR experience. Design: Case series. Setting: Laboratory environment. Participants: The study was conducted with 40 participants, consisting of 20 experienced (EA) and 20 nonexperienced athletes (NEA). Intervention: The FR intervention included 5 trials per 45 seconds of FR of the lateral thigh in the sagittal plane with 20 seconds of rest between each trial. Main Outcome Measures: Acoustic radiation force impulse elastosonography values, represented as shear wave velocity, were obtained under resting conditions (t0) and several times after FR exercise (0 min [t1], 30 min [t2], 6 h [t3], and 24 h [t4]). Data were assessed in superficial and deep muscle (vastus lateralis muscle; vastus intermedius muscle) and in connective tissue (iliotibial band). Results: In EA, tissue stiffness of the iliotibial band revealed a significant decrease of 13.2% at t1 (P ≤ .01) and 12.1% at t3 (P = .02). In NEA, a 6.2% increase of stiffness was found at t1, which was not significantly different to baseline (P = .16). For both groups, no significant iliotibial band stiffness changes were found at further time points. Also, regarding muscle stiffness, no significant changes were detected at any time for EA and NEA (P > .05). Conclusions: This study demonstrates a significant short-term decrease of connective tissue stiffness in EA, which may have an impact on the biomechanical output of the connective tissue. Thus, FR effects on tissue stiffness depend on the athletes’ experience in FR, and existing studies have to be interpreted cautiously in the context of the enrolled participants.

OBJECTIVEBotulinum toxin serotype A (BoNT/A) was reported to raise the seizure threshold when injected into the seizure focus of a kindled rodent model. Delivering BoNT/A to the nonhuman primate (NHP) central nervous system via convection-enhanced delivery (CED) has not been performed. The objective of this study was to determine the toxicity and distribution characteristics of CED of BoNT/A into the NHP hippocampus and cisterna magna.METHODSEscalating BoNT/A doses were delivered by CED into the NHP hippocampus (n = 4) and cisterna magna (n = 5) for behavioral and histological assessment and to determine the highest nonlethal dose (LD0) and median lethal dose (LD50). Hippocampal BoNT/A was coinfused with Gd-albumin, a surrogate MRI tracer. Gd-albumin and radioiodinated BoNT/A (125I-BoNT/A) were coinfused into the hippocampus of 3 additional NHPs to determine BoNT/A distribution by in vivo MRI and postmortem quantitative autoradiography. Scintillation counting of CSF assessed the flow of 125I-BoNT/A from the hippocampus to CSF postinfusion.RESULTSLD0 and LD50 were 4.2 and 18 ng/kg, and 5 and > 5 ng/kg for the NHP hippocampus and cisterna magna, respectively. Gd-albumin and 125I-BoNT/A completely perfused the hippocampus (155–234 mm3) in 4 of 7 NHPs. Fifteen percent of BoNT/A entered CSF after hippocampal infusion. The MRI distribution volume of coinfused Gd-albumin (VdMRI) was similar to the quantitative autoradiography distribution of 125I-BoNT/A (VdQAR) (mean VdMRI = 139.5 mm3 [n = 7]; VdQAR = 134.8 mm3 [n = 3]; r = 1.00, p < 0.0001). No infusion-related toxicity was identified histologically except that directly attributable to needle placement.CONCLUSIONSGd-albumin accurately tracked BoNT/A distribution on MRI. BoNT/A did not produce CNS toxicity. BoNT/A LD0 exceeded 10-fold the dose administered safely to humans for cosmesis and dystonia.