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Posttreatment evaluation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma currently relies on esophagogastroduodenoscopy with histological assessment of biopsies. Overexpression of the G protein–coupled C-X-C chemokine receptor type 4 (CXCR4) has been previously observed in MALT lymphoma. The aim of this prospective study was to evaluate positron emission tomography (PET) with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow up biopsies for assessment of residual disease (noncomplete remission [CR]) after first-line Helicobacter pylori eradication. Forty-six post–H pylori eradication [68Ga]Pentixafor–PET/magnetic resonance imaging (MRI) examinations of 26 gastric MALT lymphoma patients, and 20 [68Ga]Pentixafor–PET/MRI examinations of 20 control group patients without lymphoma, were analyzed. In the MALT lymphoma group, time-matched gastric biopsies were used as reference standard and showed CR in 6 cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive values of [68Ga]Pentixafor–PET for detection of residual gastric MALT lymphoma at follow-up were 97.0%, 95.0%, 100.0%, 100.0%, and 92.9%, respectively. Maximum and mean PET standardized uptake values showed moderate correlation with immunohistochemistry-based CXCR4+ cell counts, with correlation coefficients of r = 0.51 and r = 0.52 (P = .008 and P = .006). In summary, CXCR4 imaging with [68Ga]Pentixafor–PET may represent a promising test for assessment of residual gastric MALT lymphomas after H pylori eradication.

Introduction To improve quality across levels of care, we developed a standardized care pathway (SCP) integrating palliative and oncology services for hospitalized and home-dwelling palliative cancer patients in a rural region. Methods A multifaceted implementation strategy was directed towards a combination of target groups. The implementation was conducted on a system level, and implementation-related activities were registered prospectively. Adult patients with advanced cancer treated with non-curative intent were included and interviewed. Healthcare leaders (HCLs) and healthcare professionals (HCPs) involved in the development of the SCP or exposed to the implementation strategy were interviewed. In addition, HCLs and HCPs exposed to the implementation strategy answered standardized questionnaires. Hospital admissions were registered prospectively. Results To assess the use of the SCP, 129 cancer patients were included. Fifteen patients were interviewed about their experiences with the patient-held record (PHR). Sixty interviews were performed among 1320 HCPs exposed to the implementation strategy. Two hundred and eighty-seven HCPs reported on their training in and use of the SCP. Despite organizational cultural differences, developing an SCP integrating palliative and oncology services across levels of care was feasible. Both HCLs and HCPs reported improved quality of care in the wake of the implementation process. Two and a half years after the implementation was launched, 28% of the HCPs used the SCP and 41% had received training in its use. Patients reported limited use and benefit of the PHR. Conclusion An SCP may be a usable tool for integrating palliative and oncology services across care levels in a rural region. An extensive implementation process resulted in improvements of process outcomes, yet still limited use of the SCP in clinical practice. HCLs and HCPs reported improved quality of cancer care following the implementation process. Future research should address mandatory elements for usefulness and successful implementation of SCPs for palliative cancer patients. Supplementary Information The online version contains supplementary material available at 10.1007/s40487-021-00176-y., Plain language summary When a patient has incurable cancer, it is beneficial to introduce palliative care early in the disease trajectory along with anti-cancer treatment. A standardized care pathway is a method to improve quality and reduce variation in healthcare. It can promote integrated healthcare services in palliative care, e.g. by specifying action points when the patient’s situation is changing. In this study, a standardized care pathway for cancer patients with palliative care needs was developed in a rural region of Norway. The pathway focused on patients’ needs and symptoms and on smooth transition between levels of care. An educational program and an information strategy were developed to ensure implementation. To evaluate the implementation, all activity regarding the implementation process was registered. Cancer patients and healthcare professionals were interviewed and answered questionnaires. One thousand three hundred and twenty healthcare professionals were exposed to the implementation strategy. One hundred and twenty-nine cancer patients were followed up according to the standardized care pathway. Despite different perspectives of care, it was feasible to develop a standardized care pathway for palliative cancer patients across care settings. A paper-based patient-held record was only found to be useful by a limited number of patients. An extensive implementation process was completed and resulted in improvements regarding healthcare professionals’ experience with the quality of cancer care in the region, but limited use of the care pathway in clinical practice. Further research should identify the most important elements for usefulness and successful implementation of the care pathway. Supplementary Information The online version contains supplementary material available at 10.1007/s40487-021-00176-y.

BACKGROUND Tenolysis is an established treatment for flexor tendon adhesions at the hand. Concomitant finger nerve injuries with incomplete reinnervation may negatively influence outcomes. This study investigates the impact of finger nerve injuries on outcomes of flexor tendon tenolysis. METHODS A retrospective pair-matched study was conducted, including patients undergoing tenolysis for flexor tendon adhesion after primary repair of isolated superficial and deep flexor tendon injury and both finger nerves (test group [TG]). These were compared with patients (control group [CG]) with similar injuries without affection of nerves and pair-matched in age, zone of injury and follow-up. Patients' demographics, finger sensitivity, total active range of motion (TAM) before and after tenolysis and complications were retrieved. RESULTS For both study groups, 10 patients each were included in this study. There were no significant differences regarding patients' demographics and follow-up. Mean follow-up was 37 (CG) and 41 (TG) months. Total active range of motion was preoperatively 81 ± 47° (CG) and 68 ± 54° (TG) and reached postoperatively 125 ± 57° (CG) and 79 ± 43° (TG). Hence, TAM improvement was significantly higher in patients without nerve damage (58 ± 16 vs 21 ± 11%; P > 0.05). Tendon ruptures occurred significantly more frequent in patients with nerve injury (n = 0.4 ± 0.52) compared with patients of the CG (n = 0; P < 0.05). CONCLUSIONS This study shows that finger nerve injury with incomplete recovery after combined flexor tendon and nerve injuries of the finger negatively influences the outcomes of flexor tendon tenolysis.

Background Lymphovascular invasion (VI) is an established prognostic marker for many cancers including bladder cancer. There is a paucity of data regarding whether the prognostic significance of lymphatic invasion (LVI) differs from blood vessel invasion (BVI). The aim was to examine LVI and BVI separately using immunohistochemistry (IHC), and investigate their associations with clinicopathological characteristics and prognosis. A secondary aim was to compare the use of IHC with assessing VI on standard HAS (hematoxylin-azophloxine-saffron) sections without IHC. Methods A retrospective, population –based series of 292 invasive bladder cancers treated with radical cystectomy (RC) with curative intent at Vestfold Hospital Trust, Norway were reviewed. Traditional histopathological markers and VI based on HAS sections were recorded. Dual staining using D2–40/CD31 antibodies was performed on one selected tumor block for each case. Results The frequency of LVI and BVI was 32 and 28%, respectively. BVI was associated with features such as higher pathological stages, positive regional lymph nodes, bladder neck involvement and metastatic disease whereas LVI showed weaker or no associations. Both BVI and LVI independently predicted regional lymph node metastases, LVI being the slightly stronger factor. BVI, not LVI predicted higher pathological stages. BVI showed reduced recurrence free (RFS) and disease specific (DSS) survival in uni-and multivariable analyses, whereas LVI did not. On HAS sections, VI was found in 31% of the cases. By IHC, 51% were positive, corresponding to a 64% increased sensitivity in detecting VI. VI assessed without IHC was significantly associated with RFS and DSS in univariable but not multivariable analysis. Conclusions Our findings indicate that BVI is strongly associated with more aggressive tumor features. BVI was an independent prognostic factor in contrast to LVI. Furthermore, IHC increases VI sensitivity compared to HAS.

Obesity is associated with increasing cardiometabolic morbidity and mortality rates worldwide. Not everyone with obesity, however, develops metabolic complications. Brown adipose tissue (BAT) has been suggested to be a promoter of leanness and metabolic health. To date, little is known about the prevalence and metabolic function of BAT in people with severe obesity, a population at high cardiometabolic risk. In this cross-sectional study, we included 40 individuals with World Health Organization class II-III obesity (BMI ≥35 kg/m2). Using a 150-min personalized cooling protocol and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography, cold-activated BAT was detectable in 14 of the participants (35%). Cold-induced thermogenesis was significantly higher in participants with detectable BAT compared with those without. Notably, individuals with obesity and active BAT had 28.8% lower visceral fat mass despite slightly higher total fat mass compared with those without detectable BAT 18F-FDG uptake. The lower amount of visceral fat mass was accompanied by lower insulin resistance and systemic inflammation and improved nonalcoholic fatty liver disease parameters, all adjusted for age, sex, and percent body fat. Contrary to previous assumptions, we show here that a significant fraction of individuals with severe obesity has active BAT. We found that decreased BAT 18F-FDG uptake was not associated with adiposity per se but with higher visceral fat mass. In summary, active BAT is linked to a healthier metabolic phenotype in obesity.

Seit 2015 stellen Immuncheckpointinhibitoren neue Optionen in der Therapie des fortgeschrittenen nichtkleinzelligen Lungenkarzinoms dar. Bislang mangelt es an Studien, die den Gebrauch dieser Arzneimittel im realen Versorgungsgeschehen in Deutschland beschreiben. Beschreibung der Anwendung von Nivolumab, Pembrolizumab und Atezolizumab bei Personen mit Lungenkrebs im Langsschnitt, basierend auf deutschen Versichertendaten. Anhand einer Stichprobe (~5.6 Millionen Versicherte) aus der pharmakoepidemiologischen Forschungsdatenbank GePaRD wurde eine retrospektive Kohortenstudie durchgefuhrt. Eingeschlossen wurden Patienten mit Lungenkrebs ab der erstmaligen Abgabe von Nivolumab, Pembrolizumab oder Atezolizumab nach deren jeweiliger Zulassung fur Lungenkrebs (Kohorteneintritt). Die Beobachtungszeit endete spatestens am 31.12.2018. Die Kohorte wurde – stratifiziert nach Wirkstoff, der zum Kohorteneintritt gefuhrt hat – beschrieben. Insgesamt wurden 2764 Personen mit Lungenkrebs eingeschlossen (Kohorteneintritt mit Nivolumab: 1787; Pembrolizumab: 869; Atezolizumab: 108). Fur Nivolumab, Pembrolizumab bzw. Atezolizumab betrug die Zeit zwischen der Lungenkrebsdiagnose und der erstmaligen Abgabe (Kohorteneintritt) im Median 13, 4 bzw. 11 Monate. Fur Nivolumab betrug das mediane Gesamtuberleben ab Kohorteneintritt 7,4 Monate (Manner/Frauen: 6,3/8,9 Monate) und die 12-Monats-Uberlebenswahrscheinlichkeit 38 % (Manner/Frauen: 34 %/42 %), fur Pembrolizumab waren es 12,3 Monate (Manner/Frauen: 10,6/14,5 Monate) und 50 % (Manner/Frauen: 47 %/54 %). Die Ergebnisse liefern einen ersten Einblick in die Anwendung von Immuncheckpointinhibitoren in der Therapie von Lungenkrebs nach deren Zulassung in Deutschland. Das im Vergleich zu den Zulassungsstudien niedrigere Gesamtuberleben konnte auf eine weniger selektive Anwendung dieser Arzneimittel im realen Versorgungsgeschehen hinweisen.

ZusammenfassungHintergrund. Eltern stehen im Rahmen der eigenen Impfung und der Kinderimpfung mit einem COVID-19-Vakzin vor einer Impfentscheidung. Zum aktuellen Zeitpunkt gibt es keine (vollständige) Impfempfehlung.Fragestellung. Die Studie untersucht die Impfbereitschaft von Eltern minderjähriger Kinder und Personen ohne minderjährige Kinder, wobei insbesondere Geschlechtsunterschiede überprüft werden.Methoden. Die Studie basiert auf einer Zufallsstichprobe (Telefon-Survey, n = 2014, Erhebung zwischen 12.11.2020 und 10.12.2020). Die Auswertung stützt sich insbesondere auf die Teilstichprobe von Personen mit minderjährigen Kindern im Haushalt (n = 461).Ergebnisse. Eltern weisen durchgängig eine geringere Impfbereitschaft mit einem COVID-19-Vakzin auf als Befragte ohne minderjährige Kinder (54,1 % vs. 71,1 %). Väter weisen eine stärker ausgeprägte eigene Impfbereitschaft auf als Mütter. Darüber hinaus sind Männer eher als Frauen bereit, das eigene Kind mit einem COVID-19-Vakzin impfen zu lassen.Schlussfolgerungen. Bei Eltern und insbesondere Müttern ist eine erhebliche Fehleinschätzung von Impfrisiken und häufiger Glaube an Impfverschwörungstheorien zu beobachten. Empfohlen werden anschauliche und leicht verständliche Informationen über die Wirkung und Nebenwirkungen der Impfung mit einem COVID-19-Vakzin durch zuständige Institutionen und Ärzte.

Claudia Börnhorst,1 Tammo Reinders,1 Wolfgang Rathmann,2 Brenda Bongaerts,2 Ulrike Haug,1 Vanessa Didelez,1 Bianca Kollhorst1 1Leibniz Institute for Prevention Research and Epidemiology – BIPS, Department of Biometry and Data Management, Bremen, Germany; 2Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, GermanyCorrespondence: Bianca KollhorstLeibniz Institute for Prevention Research and Epidemiology – BIPS, Department of Biometry and Data Management, Achterstr. 30, Bremen, 28359, GermanyTel +49 421 21856980Email kollhorst@leibniz-bips.dePurpose: Investigating intended or unintended effects of sustained drug use is of high clinical relevance but remains methodologically challenging. This feasibility study aims to evaluate the usefulness of the parametric g-formula within a target trial for application to an extensive healthcare database in order to address various sources of time-related biases and time-dependent confounding.Patients and Methods: Based on the German Pharmacoepidemiological Research Database (GePaRD), we estimated the pancreatic cancer incidence comparing two hypothetical treatment strategies for type 2 diabetes mellitus (T2DM), i.e., (A) sustained metformin monotherapy vs (B) combination therapy with DPP-4 inhibitors after one year metformin monotherapy. We included 77,330 persons with T2DM who started metformin therapy at baseline between 2005 and 2011. Key aspects for avoiding time-related biases and time-dependent confounding were the emulation of a target trial over a 7-year follow-up period and application of the parametric g-formula.Results: Over the 7-year follow-up period, 652 out of the 77,330 study subjects had a diagnosis of pancreatic cancer. Assuming no unobserved confounding, we found evidence that the metformin/DPP-4i combination therapy increased the risk of pancreatic cancer compared to a sustained metformin monotherapy (risk ratio: 1.47; 95% bootstrap CI: 1.07– 1.94). The risk ratio decreased in sensitivity analyses addressing protopathic bias.Conclusion: While protopathic bias could not fully be ruled out, and computational challenges necessitated compromises in the analysis, the g-formula and target trial emulation proved useful: Self-inflicted biases were avoided, observed time-varying confounding was adjusted for, and the estimated risks have a clear causal interpretation.Keywords: target trial emulation, electronic health data, parametric g-formula, time-related bias, time-dependent confounding, type-2 diabetes mellitus

There is limited experience with facial re-transplantation (fRT). We report on the management of facial re-transplantation in a facial vascularized composite allotransplant recipient following irreversible allograft loss 88 months after the first transplant. Chronic antibody mediated rejection and recurrent cellular rejection resulted in a deteriorated first allograft and the patient underwent retransplantation. We summarize the events between the two transplantations, focusing on the final rejection episode. We describe the surgical technique of facial re-transplantation, the immunological and psychosocial management, and the six-month post-operative outcomes. Removal of the old allograft and inset of the new transplant were done in one operation. The donor and recipient were a good immunological match. The procedure was technically complex, requiring more proximal arterial anastomoses and an interposition vein graft. During the first and second transplantation the facial nerve was coapted at the level of the branches. There was no hyperacute rejection in the immediate postoperative phase. Outcomes six months postoperatively are promising. We provide proof-of-concept that facial re-transplantation is a viable option for patients who suffer irreversible facial vascularized composite allograft loss.

PURPOSE: Patients with pneumonia often present to the emergency department and require prompt diagnosis and treatment. Clinical decision support systems for the diagnosis and management of pneumonia are commonly utilized in emergency departments to improve patient care. The purpose of this study is to investigate whether a deep learning model for detecting radiographic pneumonia and pleural effusions can improve functionality of a clinical decision support system for pneumonia management (ePNa) operating in 20 emergency departments. MATERIALS AND METHODS: In this retrospective cohort study, a dataset of 7,434 prior chest radiographic studies from 6,551 emergency department patients was used to develop and validate a deep learning model to identify radiographic pneumonia, pleural effusions, and evidence of multilobar pneumonia. Model performance was evaluated against three radiologists’ adjudicated interpretation and compared to performance of the natural language processing of radiology reports used by ePNa. RESULTS: The deep learning model achieved an area under the receiver operating characteristic curve of 0.833 (95% CI 0.795, 0.868) for detecting radiographic pneumonia, 0.939 (95% CI 0.911, 0.962) for detecting pleural effusions, and 0.847 (95% CI 0.800, 0.890) for identifying multilobar pneumonia. On all three tasks, the model achieved higher agreement with the adjudicated radiologist interpretation compared to ePNa. CONCLUSIONS: A deep learning model demonstrated higher agreement with radiologists than the ePNa clinical decision support system in detecting radiographic pneumonia and related findings. Incorporating deep learning models into pneumonia clinical decision support systems could enhance diagnostic performance and improve pneumonia management.

Purpose More long-term follow-up studies beyond 10 years after secondary sphincteroplasty for obstetric damage are warranted. This prospective study aimed to compare reported data on incontinence and satisfaction in a cohort of such patients examined at short-, long-, and very long-term follow-up. Methods Twenty out of 33 obstetric patients (61%) operated with secondary anterior overlapping sphincteroplasty during February 1996 to April 2004 were evaluated preoperatively and at short-, long-, and very long-term follow-up. Anal incontinence was scored by a combination of Wexner’s and St. Mark’s incontinence scores. The patients also reported degree of treatment satisfaction. Results Twenty patients were examined preoperatively and after a median (range) of 5 (2–62), 102 (64–162), and 220 (183–278) months. Corresponding incontinence scores were 11.5 (5–18), 5.5 (1–17) (p p > 0.05), and 12.0. (1–18) (p > 0.05). With increasing follow-up times, patients reporting a better outcome were 75%, 65%, and 45%. At very long-term follow-up patients, reports were more dismal than expected in those also reporting improved incontinence cores. Incontinence scores did not improve in patients with neuropathy (n = 5) or patients (n = 5) with more than 10 years of symptoms. Conclusion Initial improvement of anal incontinence attenuated with time, in particular from short- to long-term follow-up. Patients with neuropathy experienced no improvement of incontinence. Beyond stoma formation, in compliant patients, one should consider other treatment options like sacral nerve stimulation and neosphincter formation.

Die Anzahl der Revisionseingriffe in der Kniegelenkendoprothetik nimmt deutlich zu. Damit mussen zunehmend auch komplexe Knochendefekte adaquat versorgt werden. Zur Therapieplanung eignet sich die Anderson-Orthopaedic-Research-Institute(AORI)-Klassifikation. Das zentrale Ziel ist hier die sichere Fixation der Komponenten. Dabei werden sowohl femoral als auch tibial drei Fixationszonen, epi-, meta- und diaphysar, unterschieden. Es sollte immer eine Fixation in zwei dieser Zonen angestrebt werden, um eine vorzeitige aseptische Lockerung zu vermeiden. Neben der Rekonstruktion der Epiphyse sollte daher immer zusatzlich eine Fixation diaphysar oder v. a. metaphysar erfolgen, insbesondere bei hoheren Kopplungsgraden. Moderne metaphysare Verankerungsmoglichkeiten sind Sleeves und Cones. Sleeves sind stufenformige Titankonstrukte, die sich aufgrund ihrer festen Verbindung mit dem Implantat durch eine sehr gute Kraftubertragung und eine exzellente Rotationsstabilitat auszeichnen. Sleeves sind fur zentrale Defekte mit weitgehend erhaltener zirkumferenter Kortikalis als zementfreie Verankerungsoption geeignet. Beim Vorliegen eines peripheren kortikalen Defektes stellen Cones eine gute Alternative dar. Cones sind aus Tantalum oder Titan bestehende Rekonstruktionskomponenten, die, im Gegensatz zu Sleeves, keine direkte Verbindung mit dem Implantat aufweisen, sondern eine Augmentation des ossaren Lagers ermoglichen. Die Implantation der Prothesenkomponente erfolgt dann zementiert. Fur die diaphysare Verankerung stehen zementierte oder zementfreie Schafte zur Verfugung. Die Wahl ist hierbei sowohl von der Art der metaphysaren Verankerungsoption, Sleeve oder Cone, sowie von weiteren Faktoren wie dem Vorliegen von anatomischen Varianten, Deformation oder Osteoporose abhangig.

Objective Preconception and prenatal carrier screening is designed to provide reproductive risk information, but carriers for some autosomal recessive or X-linked conditions also have personal health risks. This study investigated the prevalence of and inclusion of personal health implications in pre- and post-test counseling. Methods Twelve genetic conditions with personal health risks for carriers included on carrier screening panels but not otherwise screened routinely were identified (e.g., Gaucher disease with Parkinson's disease risk). A retrospective review was performed of patients with a positive carrier screen for one of these conditions at our center from 2012-2019. Results Of 6,147 individuals that had carrier screening for one of the twelve conditions, 96 (1.56%) did not report a known family history and screened positive for one of the conditions. Testing was ordered largely by reproductive endocrinologists (51.0%) and genetic counselors (35.4%). Most individuals did not receive pre- (96.8%) or post-test (64.6%) counseling about personal health risks. Post-test counseling was performed principally by genetic counselors (97.1%). For carriers of conditions with guidelines for specialist referral, most individuals (75.9%) were referred. Conclusion Expanded genetic carrier screening increasingly identifies individuals with personal health implications, but patients are frequently not counseled before or after testing. These findings stress the importance of developing guidelines for practitioners about expanded carrier screening counseling and follow-up. This article is protected by copyright. All rights reserved.

ispartof: PRENATAL DIAGNOSIS vol:41 issue:10 pages:1222-1232 ispartof: location:England status: published

There is a common, well-known and established recommendation to excise burn wounds within 24-72 h in order to mitigate the systemic inflammatory and immunomodulatory response, shorten length of hospitalization through early grafting and optimize patient survival. Despite this apparent consensus, surprisingly few systematic studies have evaluated the actual adherence to this practice and its implications on patient outcomes. In this registry study, we sought to objectify the current status of early burn wound excision, its influencing factors and impact on patient outcomes for all German burn centers.The German burn registry ('Deutsches Verbrennungsregister') was queried for 3 consecutive years for all patients, who received at least one surgical intervention. Patients were stratified based on whether the first surgical procedure was performed early (EE, within 72 h) or late (LE, after 72 h) post-burn. Descriptive statistics and univariate regressions were performed to quantify fraction of EE vs. LE and to evaluate factors which might favor one over the other (i.e. age, inhalation injury, burn severity by total body surface area (TBSA), scald vs. other burns, obesity, time of admission). Key patient outcomes were analyzed for each group (i.e. mortality, length of hospitalization, number of surgeries) and multifactorial regression analyses were carried out to model the impact of EE on mortality. Statistical significance was accepted at p 0.05.After initial screening, 1494 complete records were included for final analysis and were stratified into EE and LE. Only 670 (44%) underwent EE within 72 h. Increasing TBSA burned (i.e. [TBSA 30%]: 53.8% EE, [TBSA 30%]: 43.5% EE, p 0.01) and admission on a weekday between Sunday and Wednesday were associated with higher probability of EE (51.5% EE) versus Thursday to Sunday (37.3%, p 0.001). Age, inhalation injury, cause of burn, and obesity had no effect on EE vs. LE. Patients with EE had significantly shorter median lengths of hospitalization (EE: 18 d, LE: 21 d, p 0.01). The median number of operations was comparable for both groups. Gross mortality appeared higher in the EE group, but turned out to be comparable to LE after correction for age, TBSA and sex in multifactorial regression analysis.Despite apparent consensus among burn physicians, early excision of burn wounds is performed in less than 50% of cases in German burn centers. The relationship of EE to TBSA burned is expected and clinically sound, while a dependence on admission weekday raises administrative and infrastructural questions, especially when patients who receive EE have significantly shorter hospital stays. More analyses from other burn repositories are needed to compare and benchmark the international status quo of early burn wound excision.

Ziel Die Studie untersucht die Impfbereitschaft mit einem COVID-19-Vakzin an einer Zufallsstichprobe der Gesamtbevolkerung und deren Determinanten (wahrgenommene Risiken einer Erkrankung, wahrgenommene Nebenwirkungen und allgemeine Einstellung zu Impfungen, Vertrauen in Institutionen, soziostrukturelle Faktoren, Einfluss sozialer Bezugsgruppen). Methodik Telefonische Ein-Themen-Bevolkerungsbefragung zur Impfbereitschaft (n=2014) vor der Zulassung eines COVID-19-Vakzins in Deutschland im November/Dezember 2020. Ergebnisse Die Impfbereitschaft liegt bei etwa 67% und steigt mit dem Anteil der impfbereiten Freunde und Bekannten und dem Vertrauen gegenuber dem Robert-Koch-Institut, bei Zugehorigkeit zu einer Risikogruppe und der Erwartung gefahrlicher Konsequenzen bei einer Erkrankung. Erfahrungen mit einer Infektion bei den Befragten oder in ihrer sozialen Bezugsgruppe erhohen die Impfbereitschaft. Manner haben eine erhohte Impfbereitschaft. Bei hoherem Schulbildungsniveau zeigt sich (mit Ausnahme der Personen mit Fachhochschulreife) durchgangig eine hohere Impfneigung. Eine Uberschatzung der Wahrscheinlichkeit ernsthafter Nebenwirkungen bei Grippeimpfungen senkt die Impfbereitschaft gegen COVID-19. Auffallig ist der Befund einer erheblichen Uberschatzung der Haufigkeit von ernsthaften Impfnebenwirkungen bei Influenza-Impfungen. Schlussfolgerungen Es werden Implikationen fur eine zielgruppenadaquate Informationskampagne und Risikokommunikation abgeleitet. Bestrebungen zur Forderung der Impfbereitschaft der Bevolkerung sollten insbesondere benachteiligte Bevolkerungsgruppen in den Fokus nehmen.

Initial reports of a clinical response in patients treated with the radioligand [177Lu]-PSMA-617 for castration-resistant prostate cancer (CRPC) are promising, despite known inter- and intrapatient heterogeneity. In metastatic CRPC, we examined the association of baseline immunohistochemical (IHC) expression of prostate-specific membrane antigen (PSMA) in a single lesion and responsiveness to [177Lu]-PSMA-617 therapy, measured as the PSMA maximum standardized uptake value (SUVmax). Between 2015 and 2020, 19 patients with multiple metastases underwent single-lesion biopsy, [68Ga]-PSMA positron emission tomography (PET) imaging, and treatment with [177Lu]-PSMA-617. A monoclonal anti-PSMA antibody was used to semiquantitatively assess PSMA IHC in the biopsy specimen. Imaging evaluation of the biopsied single lesion and overall response was performed according to Positron Emission Tomography Response Criteria in Solid Tumors. The PSMA IHC histoscore correlated positively with pretreatment same-site PSMA SUVmax (rs = 0.6). Nine patients had imaging after three cycles of [177Lu]-PSMA-617 and were included in the lesion-specific analysis. Of these, five patients (55.6%) had an SUVmax response at the biopsy site, but three experienced overall progression. The histoscore was unable to predict the lesion-specific change in SUVmax (95% confidence interval [CI] −44.2 to 69.2) or PSA (95% CI−125.2 to 17.2). There was no correlation between single-lesion SUVmax and overall progression (rs = 0.1) on [68Ga]-PSMA PET imaging. Additional studies need to interrogate the clinical consequence of PSMA expression heterogeneity in metastases and the association with response to [177Lu]-PSMA-671. Patient summary Treatment with a radioactive binding molecule called [177Lu]-PSMA-617 for men with prostate cancer resistant to castration (CRPC) is showing promise. We investigated the association between the presence of PSMA protein in metastatic lesions at biopsy and response to [177Lu]-PSMA-617 among men with metastatic CRPC. We found that assessment of PSMA presence at biopsy is not a reliable predictor of response to [177Lu]-PSMA-617. Additional studies are needed to better determine which CRPC metastatic sites will respond to this therapy.

Background Facial vascularized composite allotransplantation (fVCA) represents a reconstructive approach that enables superior improvements in functional and esthetic restoration compared to conventional craniomaxillofacial reconstruction. Outcome reports of fVCA are usually limited to short-term follow-up or single-center experiences. We merge scientific literature on reported long-term outcome data to better define the risks and benefits of fVCA. Methods We conducted a systematic review of PubMed/MEDLINE databases in accordance with PRISMA guidelines. English full-text articles providing data on at least 1 unique fVCA patient, with ≥ 3 years follow-up, were included. Results The search yielded 1812 articles, of which 28 were ultimately included. We retrieved data on 23 fVCA patients with mean follow-up of 5.3 years. More than half of the patients showed improved quality of life, eating, speech, and motor and sensory function following fVCA. On average, the patients had 1 acute cell-mediated rejection and infectious episode per year. The incidence rates of acute rejection and infectious complications were high within first year posttransplant but declined thereafter. Sixty-five percent of the patients developed at least 1 neoplastic and/or metabolic complication after transplantation. Chronic vascular rejection was confirmed in 2 patients, leading to allograft loss after 8 and 9 years. Two patient deaths occurred 3.5 and 10.5 years after transplant due to suicide and lung cancer, respectively. Conclusions Allograft functionality and improvements in quality of life suggest a positive risk-benefit ratio for fVCA. Recurrent acute rejection episodes, chronic rejection, immunosuppression related complications, and heterogeneity in outcome reporting present ongoing challenges in this field.

Background The presentation of medical topics in the cinema can greatly influence the public’s understanding and perception of a medical field, with regard to the doctors and surgeons, medical diagnosis, and treatment and outcome expectations. This study aims to evaluate the representation of plastic surgery in commercial films that include a character with a link to plastic surgery, either as a patient or surgeon. Methods The international film databases Internet Movie Database (IMDb), The American Film Institute (AFI), and British Film Institute (BFI) were searched from 1919 to 2019 to identify feature-length films with a link to plastic surgery. Movies were visualized and analyzed to identify themes, and the portrayal of plastic surgery was rated negative or positive, and realistic or unrealistic. Results A total of 223 films were identified from 1919 to 2019, produced across 19 countries. Various genres were identified including drama (41), comedy (25), and crime (23). A total of 172 patient characters and 57 surgeon characters were identified as major roles, and a further 102 surgeons as minor roles. Disparities were noted in presentation of surgeons, both in terms of race and gender, with the vast majority of surgeons being white and male. In total only 11 female surgeons were portrayed and only one black surgeon. Thirteen themes emerged: face transplantation, crime, future society, surgeon mental status, body dysmorphic disorder, vanity, anti-aging, race, reconstructive surgery, deformity, scarring, burns, and gender transitioning. The majority of films (146/223) provide an unrealistic view of plastic surgery, painted under a negative light (80/146). Only 20 films provide a positive realistic image (24/77). Conclusions There exists a complicated relationship between plastic surgery and its representation on film. Surgical and aesthetic interventions are portrayed unrealistically, with surgeons and patients presented negatively, perpetuating stigma, particularly with regard to cosmetic surgery. Cinema is also characterized by lack of representation of female and non-white surgeons. Recruitment of surgeons as technical advisors would help present a more realistic, representative view, without necessarily sacrificing creativity. Level of evidence: Not ratable.

Objectives To examine associations between preoperative fear-avoidance model (FAM) risk subgroup status and patient expectation of surgical success with postoperative outcomes at 6 and 12 months after anterior cruciate ligament reconstruction (ACLR). Design Cohort study. Setting Academic medical center. Participants 54 patients (25 females) undergoing unilateral ACLR. Main outcome measures Cluster analysis distinguished FAM risk subgroups based on preoperative fear of movement/reinjury, self-efficacy, and pain catastrophizing. Preoperative expectation for surgical success was assessed with a numeric rating scale. Six and 12-month outcomes included Subjective Patient Outcomes for Return to Sport, Knee Injury and Osteoarthritis Outcome Score (KOOS) sports/recreation and quality of life, and International Knee Documentation Committee (IKDC) Subjective Knee Form. Results Thirteen (24%) patients were “moderate-to-high FAM risk.” Moderate-to-high FAM risk patients had lower odds of return to sport at 12 months (OR = 0.3, p = .05) and lower KOOS sports/recreation at 6 months (st. beta = −0.27, p = .05), KOOS quality of life at 12 months (st. beta = −0.42, p = .007), and IKDC at 6 (st. beta = −0.29, p = .04) and 12 months (st. beta = −0.47, p = .001). Higher expectation was associated with lower 6-month IKDC (st. beta = −0.36, p = .008) and 12-month KOOS quality of life (st. beta = −0.29, p = .05). Conclusions Preoperative FAM risk influences patient-reported outcomes and return to sport at 6 and 12 months.

Purpose Identifying hospitalizations for serious infections among patients dispensed biologic therapies within healthcare databases is important for post-marketing surveillance of these drugs. We determined the positive predictive value (PPV) of an ICD-10-CM-based diagnostic coding algorithm to identify hospitalization for serious infection among patients dispensed biologic therapy within the FDA's Sentinel Distributed Database. Methods We identified health plan members who met the following algorithm criteria: (1) hospital ICD-10-CM discharge diagnosis of serious infection between July 1, 2016 and August 31, 2018; (2) either outpatient/emergency department infection diagnosis or outpatient antimicrobial treatment within 7 days prior to hospitalization; (3) inflammatory bowel disease, psoriasis, or rheumatological diagnosis within 1 year prior to hospitalization, and (4) were dispensed outpatient biologic therapy within 90 days prior to admission. Medical records were reviewed by infectious disease clinicians to adjudicate hospitalizations for serious infection. The PPV (95% confidence interval [CI]) for confirmed events was determined after further weighting by the prevalence of the type of serious infection in the database. Results Among 223 selected health plan members who met the algorithm, 209 (93.7% [95% CI, 90.1%-96.9%]) were confirmed to have a hospitalization for serious infection. After weighting by the prevalence of the type of serious infection, the PPV of the ICD-10-CM algorithm identifying a hospitalization for serious infection was 80.2% (95% CI, 75.3%-84.7%). Conclusions The ICD-10-CM-based algorithm for hospitalization for serious infection among patients dispensed biologic therapies within the Sentinel Distributed Database had 80% PPV for confirmed events and could be considered for use within pharmacoepidemiologic studies.

BACKGROUND: Patients with COVID-19 seem to be prone to the development of arrhythmias. The objective of this trial was to determine the characteristics, clinical significance and therapeutic consequences of these arrhythmias in COVID-19 patients requiring intensive care unit (ICU) treatment. METHODS AND RESULTS: A total of 113 consecutive patients (mean age 64.1 ± 14.3 years, 30 (26.5%) female) with positive PCR testing for SARS-CoV2 as well as radiographically confirmed pulmonary involvement admitted to the ICU from March to May 2020 were included and observed for a cumulative time of 2321 days. Fifty episodes of sustained atrial tachycardias, five episodes of sustained ventricular arrhythmias and thirty bradycardic events were documented. Sustained new onset atrial arrhythmias were associated with hemodynamic deterioration in 13 cases (35.1%). Patients with new onset atrial arrhythmias were older, showed higher levels of Hs-Troponin and NT-proBNP, and a more severe course of disease. The 5 ventricular arrhythmias (two ventricular tachycardias, two episodes of ventricular fibrillation, and one torsade de pointes tachycardia) were observed in 4 patients. All episodes could be terminated by immediate defibrillation/cardioversion. Five bradycardic events were associated with hemodynamic deterioration. Precipitating factors could be identified in 19 of 30 episodes (63.3%), no patient required cardiac pacing. Baseline characteristics were not significantly different between patients with or without bradycardic events. CONCLUSION: Relevant arrhythmias are common in severely ill ICU patients with COVID-19. They are associated with worse courses of disease and require specific treatment. This makes daily close monitoring of telemetric data mandatory in this patient group.

Objectives: To determine the effectiveness of a family-centred intervention for patients with traumatic brain injury and family members. Design: Open-labelled, two-armed randomised controlled trial. Settings: Outpatient clinic and family residences. Participants: Sixty-one patients (33 women) with traumatic brain injury, with mean (SD) age 43.8 (12.2), and 63 family members (33 women), with mean (SD) age 42.6 (11.3), were assign to intervention ( n = 30 families) and control group ( n = 31 families). Intervention: An eight-session single-family intervention to improve individual and family functioning. Outcome measures: Self-reported questionnaires at start-of-treatment, median (IQR) 11.4 (8.4, 15.9) months post-injury, and at two follow-ups, 2.7 (2.3, 3.8) and 9.2 (8.2, 9.9) months after start-of-treatment. Primary outcome measures were the SF-36 Mental Component Summary (MCS) and Caregiver Burden Scale (CGB). Secondary outcome measures were the Family Adaptability and Cohesion Evaluation Scale (FACES) and Quality of Life after Brain Injury Questionnaire (QOLIBRI). Group differences were analysed with linear mixed-model analysis for repeated measurements. Results: No significant between-group differences were found. The intervention group significantly improved on the MCS, the CGB and FACES in the treatment period, whereas the controls did not. The mean (SD) MCS change in the treatment period was 2.4 (1.1) points P = 0.028 in the intervention group. Mean (SE) MCS scores were 47.9 (1.26) and 47.3 (1.27) in the intervention and control group at last follow-up. Conclusions: Receiving an eight-session family intervention, in addition to specialised rehabilitation for the patients, was not superior to rehabilitation at a specialised traumatic brain injury outpatient clinic.

BACKGROUND Myocutaneous pedicled flaps are the method of choice for sternal reconstruction after deep sternal wound infection (DSWI) following cardiac surgery. We set out to investigate whether free flaps provide a superior alternative for particularly extended sternal defects. METHODS Between October 2008 and February 2020, 86 patients with DSWI underwent sternal reconstruction with myocutaneous flaps at our institution. Patients were retrospectively grouped into pedicled (A; n = 42) and free flaps (B, n = 44). The objective was to compare operative details, outcome variables, surgical as well as medical complication rates between both groups, retrospectively. Binary logistic regression analysis was applied to determine the effect of increasing defect size on flap necrosis. RESULTS Rates of partial flap necrosis (>5% of the skin island) were significant higher in pedicled flaps (n = 14), when compared to free flaps (n = 4) (OR: 5.0; 33 vs. 9%; p = .008). Increasing defect size was a significant risk factor for the incidence of partial flap necrosis of pedicled flaps (p = .012), resulting in a significant higher rate of additional surgeries (p = .036). Binary regression model revealed that the relative likelihood of pedicled flap necrosis increased by 2.7% with every extra square-centimeter of defect size. CONCLUSION To avoid an increased risk of partial flap necrosis, free flaps expand the limits of extensive sternal defect reconstruction with encouragingly low complication rates and proved to be a superior alternative to pedicled flaps in selected patients.

Background Fear of recurrence (FoR) is a distressing consequence of cancer. Little is known about the prevalence of FoR in different treatment groups and factors associated with FoR among prostate cancer (PCa) survivors. Objective To investigate the prevalence of high FoR among PCa survivors after radical prostatectomy (RP) or under active surveillance (AS) and to explore clinical and psychological factors potentially associated with FoR. Design, setting, and participants This is a retrospective cross-sectional study of 606 patients with PCa, treated with either RP (n = 442) or AS (n = 164) at two Norwegian regional hospitals. The 440 patients (73%) who gave consent to participate were invited in 2017 to complete a questionnaire measuring FoR, self-rated health, adverse effects, and psychological factors at a mean of 4.1 yr (standard deviation 1.7) after their treatment decision. Clinical data were retrieved from medical records. Outcome measurements and statistical analysis FoR was measured using the Concerns About Recurrence Questionnaire, with high FoR defined as a sum score of =12 points (range 0–40). Using multivariable logistic regression analyses, factors associated with high FoR were identified. Results and limitations One-third of the participants had high FoR; scores were higher in the AS group and in the RP group with treatment failure. Younger age was significantly associated with high FoR in the AS group, while high prostate-specific antigen at diagnosis, biochemical recurrence, positive surgical margin, higher fatigue, and a type D personality were significantly associated with high FoR in the RP group. Conclusions At 4 yr after a diagnosis of PCa, high FoR was common, especially among AS patients and among RP patients with treatment failure. Patient summary In this study, we examined fear that their disease will return or progress among prostate cancer survivors. We found that such fear was common, especially among young patients under active surveillance and among radical prostatectomy patients with treatment failure or with certain psychological features., Take Home Message Among prostate cancer survivors, fear of recurrence is common when on active surveillance and after radical prostatectomy with treatment failure. Lower age, high prostate-specific antigen at diagnosis, a positive surgical margin, biochemical recurrence, and certain psychological characteristics were associated with high fear of recurrence.

The CYP4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at individual patients' level to capture the possible effect of ethnicity, gene-gene interaction or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data. The final collection consists 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95%CI 7-10%), with a higher effect in females, in patients taking acenocoumarol and in Whites. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived. This article is protected by copyright. All rights reserved.

SUMMARY Skin is one of the target tissues of rejection in face transplants and, because of its easy accessibility, has become the gold standard in the diagnosis of rejection. The allograft contains deeper tissues where rejection can occur, but samples cannot be obtained because of difficult access. Deep tissue changes were monitored on computed tomographic scans of the midface in six face transplant recipients with the help of image segmentation. The maxillary sinus was identified as a dynamic anatomical compartment. Observed changes in volume of the aeration relative to the opacification (aeration coefficient) of the maxillary sinus were quantified with the help of image segmentation. Changes in the aeration coefficient as a surrogate of mucosal swelling were quantified and related to time, treatment, and skin rejection grade. Lower aeration coefficients were found only in patients with transplanted maxillary sinus mucosa. Pathologic changes were not observed in face transplant recipients with a native maxillary sinus. The data show that the aeration coefficient was significantly lower at the time of biopsy-proven allograft rejection. Neither mechanical, nor infectious, nor medication side effects sufficiently explain the findings presented herein. The authors' findings are important to consider for clinical management of face transplant patients who receive parts of the sinonasal tract. The authors identify a potential radiologic biomarker of deep tissue allograft rejection. In the future, the proposed methodology might prove useful in monitoring deeper dynamic tissue changes in vascularized composite allografts and might help in designing patient-specific, individualized treatment strategies.

OBJECTIVES Fetal aortic valvuloplasty (FAV) for severe aortic stenosis (AS) has shown promise in averting progression to hypoplastic left heart syndrome. After FAV, predicting which fetuses will achieve a biventricular (BiV) circulation after birth remains challenging. Identifying predictors of postnatal circulation on late gestation echocardiography will improve parental counseling. METHODS Liveborn patients who underwent FAV and had late gestation echocardiography available were included (2000-2017, n = 96). Multivariable logistic regression and classification and regression tree analysis were utilized to identify independent predictors of BiV circulation. RESULTS Among 96 fetuses, 50 (52.1%) had BiV circulation at the time of neonatal discharge. In multivariable analysis, independent predictors of biventricular circulation included left ventricular (LV) long axis z-score (OR 3.2, 95% CI 1.8-5.7, p

Purpose Some studies have indicated age-specific differences in quality of life (QoL) among breast cancer (BC) patients. The aim of this study was to compare patient-reported outcomes after conventional and oncoplastic breast surgery in two distinct age groups. Methods Patients who underwent oncoplastic and conventional breast surgery for stage I-III BC, between 6/2011–3/2019, were identified from a prospectively maintained database. QoL was prospectively evaluated using the Breast-Q questionnaire. Comparisons were made between women Results One hundred thirty-three patients were included. Seventy-three of them were ≥ 60 years old. 15 (20.5%) of them received a round-block technique (RB) / oncoplastic breast-conserving surgeries (OBCS), 10 (13.7%) underwent nipple-sparing mastectomies (NSM) with deep inferior epigastric perforator flap (DIEP) reconstruction, 23 (31.5%) underwent conventional breast-conserving surgeries (CBCS), and 25 (34.2%) received total mastectomy (TM). Sixty patients were younger than 60 years, 15 (25%) thereof received RB/OBCS, 22 (36.7%) NSM/DIEP, 17 (28.3%) CBCS, and 6 (10%) TM. Physical well-being chest and psychosocial well-being scores were significantly higher in older women compared to younger patients (88.05 vs 75.10; p p = 0.002, respectively). In multivariate linear regression, longer time intervals had a significantly positive effect on the scales Physical Well-being Chest (p = 0.014) and Satisfaction with Breasts (p = 0.004). No significant results were found concerning different types of surgery. Conclusion Our findings indicate that age does have a relevant impact on postoperative QoL. Patient counseling should include age-related considerations, however, age itself cannot be regarded as a contraindication for oncoplastic surgery.

We present a case of Kluyveromyces marxianus keratitis nine months after Descement's membrane endothelial keratoplasty (DMEK) in a patient with Fuchs endothelial disease. Endothelial scraping revealed this rare yeast infection at the interface between graft and host cornea. Immediate antifungal treatment with intracameral and corneal intrastromal injections of voriconazole and amphotericin B remained unsuccessful, requiring penetrating keratoplasty. This case highlights the challenging management of keratomycosis in patients with endothelial grafts.

Purpose Arthroscopic lateral retinacular release (LRR) has long been considered the gold standard for the treatment for anterior knee pain caused by lateral retinacular tightness (LRT). However, one-third of patients experience continuous pain postoperatively, which is thought to be related to persistent maltracking of the patella and altered femoro-tibial kinematics. Therefore, the aim of the present study was to simultaneously assess femoro-tibial and patello-femoral kinematics and identify the influence of arthroscopic LRR. Methods Sixteen healthy volunteers and 12 patients with unilateral, isolated LRT were prospectively included. Open MRI scans with and without isometric quadriceps contraction were performed in 0°, 30° and 90° of knee flexion preoperatively and at 12 months after surgery. Patellar shift, tilt angle, patello-femoral contact area and magnitude of femoro-tibial rotation were calculated by digital image processing. Results Postoperatively, patellar shift was significantly reduced at 90° of knee flexion compared to preoperative values. The postoperative patellar tilt angle was found to be significantly smaller at 30° of knee flexion compared to that preoperatively. Isometric muscle contractions did not considerably influence patellar shift or tilt in either group. The patello-femoral contact area increased after LRR over the full range of motion (ROM), with significant changes at 0° and 90°. Regarding femoro-tibial kinematics, significantly increased femoral internal rotation at 0° was observed in the patient group preoperatively, whereas the magnitude of rotation at 90° of knee flexion was comparable to that of healthy individuals. The pathologically increased femoral internal rotation at 30° without muscular activity could be significantly decreased by LRR. With isometric quadriceps contraction no considerable improvement of femoral internal rotation could be achieved by LRR at 30° of knee flexion. Conclusions Patello-femoral and femoro-tibial joint kinematics could be improved, making LRR a viable surgical option in carefully selected patients with isolated LRT. However, pathologically increased femoral internal rotation during early knee flexion remained unaffected by LRR and thus potentially accounts for persistent pain. Level of evidence II.

BACKGROUND: Prolonged critically ill patients frequently develop debilitating muscle weakness that can affect both peripheral nerves and skeletal muscle. In-depth knowledge on the temporal contribution of neural and muscular components to muscle weakness is currently incomplete. METHODS: We used a fluid-resuscitated, antibiotic-treated, parenterally fed murine model of prolonged (5 days) sepsis-induced muscle weakness (caecal ligation and puncture; n = 148). Electromyography (EMG) measurements were performed in two nerve-muscle complexes, combined with histological analysis of neuromuscular junction denervation, axonal degeneration, and demyelination. In situ muscle force measurements distinguished neural from muscular contribution to reduced muscle force generation. In myofibres, imaging and biomechanics were combined to evaluate myofibrillar contractile calcium sensitivity, sarcomere organization, and fibre structural properties. Myosin and actin protein content and titin gene expression were measured on the whole muscle. RESULTS: Five days of sepsis resulted in increased EMG latency (P = 0.006) and decreased EMG amplitude (P

BACKGROUND CONTEXT Positive psychosocial factors early after surgery, such as resilience and self-efficacy, may be important characteristics for informing individualized postoperative care. PURPOSE To examine the association of early postoperative resilience and self-efficacy on 12-month physical function, pain interference, social participation, disability, pain intensity, and physical activity after lumbar spine surgery. STUDY DESIGN/SETTING Pooled secondary analysis of prospectively collected trial data from two academic medical centers. PATIENT SAMPLE Two hundred and forty-eight patients who underwent laminectomy with or without fusion for a degenerative lumbar condition. OUTCOME MEASURES Physical function, pain inference, and social participation (ability to participate in social roles and activities) were measured using the Patient Reported Outcomes Measurement Information System. The Oswestry Disability Index, Numeric Rating Scale, and accelerometer activity counts were used to measure disability, pain intensity, and physical activity, respectively. METHODS Participants completed validated outcome questionnaires at 6 weeks (baseline) and 12 months after surgery. Baseline positive psychosocial factors included resilience (Brief Resilience Scale) and self-efficacy (Pain Self-Efficacy Questionnaire). Multivariable linear regression analyses were used to assess the associations between early postoperative psychosocial factors and 12-month outcomes adjusting for age, sex, study site, randomized group, fusion status, fear of movement (Tampa Scale for Kinesiophobia), and outcome score at baseline. This study was funded by Patient-Centered Outcomes Research Institute and Foundation for Physical Therapy Research. There are no conflicts of interest. RESULTS Resilience at 6 weeks after surgery was associated with 12-month physical function (unstandardized beta=1.85 [95% confidence interval [CI]: 0.29; 3.40]), pain interference (unstandardized beta=−1.80 [95% CI: −3.48; −0.12]), social participation (unstandardized beta=2.69 [95% CI: 0.97; 4.41]), and disability (unstandardized beta=−3.03 [95% CI: −6.04; −0.02]). Self-efficacy was associated with 12-month disability (unstandardized beta=−0.21 [95% CI: −0.37; −0.04]. CONCLUSIONS Postoperative resilience and pain self-efficacy were associated with improved 12-month patient-reported outcomes after spine surgery. Future work should consider how early postoperative screening for positive psychosocial characteristics can enhance risk stratification and targeted rehabilitation management in patients undergoing spine surgery.

Background: Synovial cysts of the hip are commonly found in patients with intra- or extraarticular pathologies of the joint. Symptoms are mostly unspecific. To date there are no guidelines for a gold standard of treatment. Aim of this article is to show up how lesions of the ligamentum teres (LT) might possibly lead to a specific formation of synovial cysts of the hip joint and how this can be treated arthroscopically. Methods: This case series included 3 patients with ganglia of the hip. All patients had impingement symptoms, combined with untypical location of pain. All patients qualified for joint preserving surgery and underwent hip arthroscopy with pre- and postoperative MRI imaging. The mean follow-up time was 22 months. Results: MRI imaging showed extensive ganglia, presumably originating from the pelvic root of LT, extending to the obturator lodge. In 2 of 3 cases MRI showed lesions of the LT. Hip arthroscopy revealed damage of the LT in all cases, caused by chronic instability of the joint. The postoperative MRI showed a complete regression of the ganglia in all patients after offset correction. After follow-up, 2 of 3 patients were mostly symptom free. One patient was still suffering from a chronic weakness of the gluteus medius muscle. Conclusion: Whenever unspecific radiating pain of surrounding areas of the hip is encountered and cannot be explained by common pathologies of the hip, possible compression of nerves by ganglion cysts should be excluded. This should be done by MRI arthrography. A partial rupture of the LT can occur during FAI with consecutive formation of ganglia in the obturator canal, compressing the obturator nerve. Primarily the articular pathology needs to be repaired. In our cases, this was feasible by hip arthroscopy, as a minimally invasive and safe technique.

AIM To analyse responses from dental practitioners (DPs) on how secure they felt as a newly graduated dentist, level of confidence or self-efficacy when performing root canal treatment (RCT), and if undergraduate (UG) education in Endodontics adequately met their needs in a dental practice. METHODOLOGY An electronic questionnaire was sent to 459 dentists who graduated from the University of Bergen, Bergen, Norway, between 2008 and 2018. The survey consisted of questions with closed-end options and Likert scale (1-5). An open-ended free text option was always provided. RESULTS A total of 314 (68.4%) DPs answered the questionnaire. Of these, 87 (27.8%) were men and 224 (71.3%) were women. Three respondents did not disclose their gender. As a newly graduated dentist, 37.3% of the respondents felt secure when performing RCT, 30.7% felt indifferent, and 32.0% felt insecure. The majority (72.4%) of respondents were either confident or very confident when performing RCT, 21.3% were indifferent, and 6.3% had little or no confidence. A majority of DPs (84.4%) self-evaluated the quality of their root fillings as good or very good, and 15.2% were indifferent. Only one DP selected 'not good' and none selected 'bad'. There were significant gender differences where male DPs felt more secure than female DPs when performing RCT (P

Purpose of Review We investigated the risk profiles of patients using direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA) in European cohort studies to estimate the importance of potential (measured or unmeasured) confounding factors in analyses comparing these drugs. We searched MEDLINE and EMBASE (2008–2018) for relevant studies and extracted information on age, sex, comorbidity, Charlson comorbidity index, HAS-BLED score (assessing risk of bleeding) and CHA2DS2-VASc score (assessing risk of stroke). Recent Findings Overall, 66 studies with 2,808,757 patients were included. Most patients were from France (37%), Denmark (24%) and Germany (23%). In 56 studies (85%), the focus was on patients with atrial fibrillation. Of the 43 studies comparing DOAC with VKA users, 33% reported a higher and 16% a lower age of DOAC compared with VKA users. The mean age varied by about 1 year in most of these studies. Rivaroxaban was used in the widest age range. Patients with DOAC more often had a history of stroke or bleedings, and patients with VKA more often had a history of diabetes, renal failure, cancer, heart failure or other heart diseases. Most studies did not observe differences regarding the HAS-BLED score or the CHA2DS2-VASc score between groups. Summary Our review suggests that there are relevant differences in the risk profiles of DOAC versus VKA users and between users of individual DOACs. Reported HAS-BLED or CHA2DS2-VASc scores did not reflect these differences. These patterns require careful consideration in the interpretation of observational studies comparing the effectiveness and the risks of these drugs, also when comparing the results of studies conducted in different countries.

Background The validated Stockholm3 test is used to improve PC detection. Stockholm3, however, was developed using systematic biopsies. We aimed to assess Stockholm3 operating performance when using MRI-targeted biopsies for PC detection. Methods A prospective cohort of 532 men was considered for prostate biopsy during 2016-2017. All men underwent Stockholm3 testing and MRI before biopsy. All PIRADs ≥3 lesion underwent targeted biopsy; all men underwent systematic biopsy. The primary outcome was ISUP Grade Group ≥2 (GG ≥ 2) PC. Detection strategies included: (1) systematic biopsies alone, (2) targeted biopsies alone, (3) targeted with associated systematic biopsies for MRI+, and (4) all biopsies in all men. For each strategy, the Stockholm3 operating characteristics were assessed with discrimination, calibration, and decision curve analysis (DCA). Results Median age was 65 years, median PSA was 6.2 ng/mL, median Stockholm3 score was 16.5%, and overall detection of GG ≥ 2 PC was 36% (193/532). Stockholm3 showed accurate discrimination for separating GG ≥ 2 cancer from benign and GG1, with an area under the curve of 0.84-0.86 depending on the biopsy strategy. Calibration analysis showed that Stockholm3 underestimated risks for GG ≥ 2 PC risk using MRI-targeted biopsies: there was a net benefit over biopsies in all men for Stockholm3 at risk thresholds varying from >3% in systematic biopsies to >15% in targeted with systematic biopsies in MRI+ men. When using a Stockholm3 score of >10% cutoff, a range of 32-38% of biopsies could be avoided while missing 5-11% of GG ≥ 2 PC and 0-3% of GG ≥ 3 PC. Conclusions Stockholm3 shows high discriminatory performance in an MRI-targeted biopsy setting, however risks are underpredicted due to MRI-targeted biopsies being more sensitive than the systematic biopsies for which Stockholm3 was developed. Stockholm3, along with any risk prediction model developed for systematic prostate biopsy decisions, will need recalibration for optimal use in an MRI-driven biopsy setting.

INTRODUCTION Preterm delivery (

AIM:To estimate the extent of off-label prescribing of antidepressants in older adults and to characterize patients with off-label vs on-label prescriptions of antidepressants using a large German health claims database. METHODS:Using data from the German Pharmacoepidemiological Research Database (GePaRD), we conducted a cross-sectional study in adults aged 65 years or older with a dispensation of an antidepressant between 1 January 2009 and 31 December 2015 after a period of 365 days without such a dispensation. We assessed the overall and annual proportion of off-label prescriptions of antidepressants by class and individual substance. RESULTS: Among 263 276 incident users of antidepressants, the proportion of off-label prescribing was 43.6% (95% CI 43.4-43.8%) with little variation between 2009 and 2015 (42.2-44.4%). The proportion of off-label use was higher in men (49%) than women (41%). While the proportion of off-label prescriptions was highest for tri- and tetracyclic antidepressants with 56.2% (amitriptyline 54.6%, maximum 65.9% for trimipramine), it amounted to 41.8% for selective serotonin reuptake inhibitors (citalopram 41.6%, maximum 46.0% for escitalopram) and was 51.2% for mirtazapine. Indicators of overall morbidity were similar in both groups, eg, pain was coded in 72% of off-label users vs 77% of on-label users (insomnia 20% vs 24%). CONCLUSION: Our study suggests a high prevalence of off-label antidepressant use among older adults in Germany, which was not restricted to certain classes of antidepressants or individual antidepressants. Given the unclear risk-benefit ratio, studies investigating the safety of off-label use among older adults for individual antidepressants are urgently needed.

Purpose To assess the prevalence and potential indications of PDE5 inhibitor use among pregnant and reproductive-age women in the United States. Methods We identified women 15 to 50 years with a livebirth from January 2001 through March 2018 in Sentinel Database. We assessed the prevalence of PDE5 inhibitor use prior to and during pregnancy by trimester, identified potential on- and off-label indications using predefined diagnosis codes recorded within 90 days before the estimated last menstrual period through delivery. Separately, we used data from IQVIA's National Prescription Audit and Total Patient Tracker to estimate the dispensed prescriptions for PDE5 inhibitors and the number of patients with PDE5 inhibitor prescriptions. Results We identified approximately 3.3 million pregnancies during 2001 to 2018, 96 of which had PDE5 inhibitor use during pregnancy. Prevalence of PDE5 inhibitor use was 2.61, 0.62, and 0.62 per 100, 000 live-born pregnancies during the first, second, or third trimesters, respectively. Among women exposed to a PDE5 inhibitor from 90 days before conception to the end of pregnancy, 25.0%, 31.1%, and 15.5% had a diagnosis code for fetal growth restriction, preeclampsia, and pulmonary arterial hypertension. In IQVIA data, an estimated 223, 000 prescriptions from July 2015 through June 2018 and 58, 000 women received prescriptions for PDE5 inhibitors in 2017, of whom approximately 15, 000 (26%) were aged 15 to 50 years. Conclusion We found a low prevalence of PDE5 inhibitor use in pregnant and reproductive-age women. Given the very low prevalence of use and the inconsistency of neonatal mortality data across STRIDER centers, the risk to public health is low at present.

Identifying risk factors for unplanned hospital readmission is beneficial in terms of costs and utilization of resources. This systematic review aimed to identify and compare the rates and common reasons for readmission following reconstructive and esthetic surgery. Adhering to PRISMA guidelines, we searched PubMed, Web of Science, and CENTRAL database. No publication date or language restrictions were applied. Outcomes included 30-day readmission rate, reasons for readmission, and complications after reconstructive or esthetic surgery. Weighted individual study estimates were used to calculate pooled 30-day readmission rates using a random-effects approach. Risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe pooled estimates for risk factors. A total of 29 studies were included in the meta-analysis. Overall readmission rates were 10.3% (95%CI 6.3–14.3) after head and neck reconstruction, 4.6% (95%CI 3.7–5.5) after breast reconstruction, 2.4% (95%CI 1.57–3.17) after other breast surgeries, 3.0% (95%CI 0.2–5.8) after esthetic surgery, and 14.1% (95%CI 2.0–26.2) after free tissue transfer of any type. Statistically significant risk factors after head and neck reconstructions included pre-existing diabetes (RR 1.20; 95%CI 1.09–1.33), congestive heart failure (RR 1.67; 95%CI 1.43–1.94), prior radiation (OR1.17; 95%CI 1.06–1.30), and perioperative blood transfusion (OR 1.44; 95%CI:1.22–1.70). There is a large difference for readmission rates depending on the complexity of the procedure. Few studies report unplanned readmission rates in esthetic surgery and general free tissue transfer. Whereas readmissions after head and neck reconstruction are well-evaluated, risk factors for other reconstructive surgeries are poorly reported. Closer follow-up visits and outpatient resources could decrease readmission rates. Level of Evidence: Not ratable.

Background and aims [177Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) is a new therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). However, identification of reliable prognostic factors is hampered by heterogeneous treatment regimens applied in previous studies. Hence, we sought clinical factors able to predict response and survival to PSMA-RLT in a homogenous group of patients, all receiving 7400 MBq every 4 weeks. Patients and methods Data of 61 patients (mean age 71.6 ± 6.9 years, median basal PSA 70.7 [range 1.0–4890 μg/L]), pretreated with abiraterone/enzalutamide (75.4%) and docetaxel/cabazitaxel (68.9%), received three cycles of PSMA-RLT (mean 7321 ± 592 MBq) at four weekly intervals and were analyzed retrospectively. General medical conditions and laboratory parameters of every patients were regularly assessed. Response to therapy was based on PSA levels 1 month after the 3rd cycle. Binary logistic regression test and Kaplan-Meier estimates were used to evaluate predictors and overall survival (OS). Results Forty-nine (80.3%) patients demonstrated a therapy response in terms of any PSA decline, while 21 (19.7%) patients showed increase or no changes in their PSA levels. Baseline hemoglobin (Hb) significantly predicted PSA reductions of ≥ 50% 4 weeks after receiving the 3rd PSMA-RLT (P = 0.01, 95% CI: 1.09–2.09) with an AUC of 0.68 (95% CI: 0.54–0.81). The levels of basal Hb and basal PSA were able to predict survival of patients, both P P = 0.016). Also, patients with basal PSA levels ≤ 650 μg/L had a significantly longer survival than patients with basal PSA levels > 650 μg/L (median survival not reached vs. 97 weeks, P = 0.031). Neither pretreatments with abiraterone/enzalutamide or docetaxel/cabazitaxel nor distribution of metastasis affected survival and rate of response to PSMA-RLT. Conclusion Basal Hb level is an independent predictor for therapy response and survival in patients receiving PSMA-RLT every 4 weeks. Both baseline PSA ≤ 650 μg/L and normal Hb levels were associated with longer survival.

COVID-19 is a recent emerging pandemic whose prognosis is still unclear. Diagnostic tools are the main players that not only indicate a possible infection but can further restrict the transmission and can determine the extent to which disease progression would occur.In this paper, we have performed a narrative and critical review on different technology-based diagnostic strategies such as molecular approaches including real-time reverse transcriptase PCR, serological testing through enzyme-linked immunosorbent assay, laboratory and point of care devices, radiology-based detection through computed tomography and chest X-ray, and viral cell cultures on Vero E6 cell lines are discussed in detail to address COVID-19. This review further provides an overview of emergency use authorized immunodiagnostic and molecular diagnostic kits and POC devices by FDA for timely and efficient conduction of diagnostic tests. The majority of the literature cited in this paper is collected from guidelines on protocols and other considerations on diagnostic strategies of COVID-19 issued by WHO, CDC, and FDA under emergency authorization.Such information holds importance to the health professionals in conducting error-free diagnostic tests and researches in producing better clinical strategies by addressing the limitations associated with the available methods.

Irradiation therapy limits the utilization of silicone implants for breast reconstruction due to a significant risk for capsular contracture. The injection of the collagenase of the bacterium Clostridium histolyticum (CCH) might trivialize this risk by providing a minimal-invasive treatment option by capsular contracture degradation. However, efficacy in degrading breast implant capsules induced by fractionated irradiation remains unclear. Twenty-four rats in three groups received miniature silicone implants in a submuscular pocket. After 3D dose calculation and treatment field definition, rats of two groups underwent fractionated radiotherapy (6 × 8 Gy) using a linear accelerator. A third group served as control. On day 120, one irradiated group received injections of 0.3 mg/ml collagenase. Administration of plain solvent solution served as control in the two other groups. Outcome parameters included CT-imaging, histology, vessel wall analysis, immunohistochemistry, chemical collagen quantification and gene expression analysis. Fractioned irradiation leads to a significant increase in collagen deposition around silicone implants with higher capsule thickness and collagen density when comparing all groups. Additionally, significant alterations of collagen fiber deposition were evident. Vessel wall thickness was significantly increased after radiotherapy. The injection of collagenase led to a significant reduction of capsule thickness, collagen density and content. However, the collagenase application induced a significant overexpression of TGFβ1. No side effects were monitored. The CCH proved to be a safe and effective approach to degrade capsule tissue induced by fractionated irradiation in an animal model. This may pave its way for clinical application in implant-based breast reconstruction patients. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

STUDY DESIGN Secondary analysis of randomized controlled trial data. OBJECTIVE The aim of this study was to examine whether preoperative physical performance is an independent predictor of patient-reported disability and pain at 12 months after lumbar spine surgery. SUMMARY OF BACKGROUND DATA Patient-reported outcome measures (PROMs) are commonly used to assess clinical improvement after lumbar spine surgery. However, there is evidence in the orthopedic literature to suggest that PROMs should be supplemented with physical performance tests to accurately evaluate long-term outcomes. METHODS A total of 248 patients undergoing surgery for degenerative lumbar spine conditions were recruited from two institutions. Physical performance tests (5-Chair Stand and Timed Up and Go) and PROMs of disability (Oswestry Disability Index: ODI) and back and leg pain (Brief Pain Inventory) were assessed preoperatively and at 12 months after surgery. RESULTS Physical performance tests and PROMs significantly improved over 12 months following lumbar spine surgery (P

Background Elevated lactate levels may be caused by increased production suggestive of tissue ischemia; however, they may also occur without evidence of ischemia, by catecholamine activation of beta receptors. The purpose of this study was to determine the factors associated with increased lactate levels during and after lung transplantation and to evaluate whether lactate levels were associated with increased time to extubation and postoperative complications. Methods This was a retrospective study of patients who underwent lung transplantation between January 2015 and May 2017 at the University of Michigan, Ann Arbor, MI. Multivariable linear regression was used to determine the factors associated with peak lactate levels and to find the associations between lactate levels and outcomes of nitric oxide time, intubation time, length of stay, and creatinine level. Logistic regression was used to determine the associations between lactate levels and acute kidney injury and atrial fibrillation. Results A total of 86 patients underwent single-lung transplantation (n = 17; 20%) or double-lung transplantation (n = 69; 80%). All patients initially had normal lactate levels. On univariate analysis, lactate levels at several time points were correlated with subsequent acute kidney injury, increased time to extubation, and increased nitric oxide time. After adjustment, the study found that higher peak intensive care unit lactate levels (regression coefficient B = 0.046; interquartile range, 0.006, 0.086; P = .025) were associated with longer length of stay. Conclusions Cardiopulmonary bypass time, total ischemic time, and catecholamine use were associated with higher lactate levels, whereas nitric oxide and higher pulmonary artery pressures were associated with lower levels. Increased lactate levels were independently associated with longer intubation times, postoperative acute kidney injury, and longer length of stay.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible fibrotic disease associated with respiratory failure. The disease remains idiopathic, but repeated alveolar epithelium injury, disruption of alveolar-capillary integrity, abnormal vascular repair, and pulmonary vascular remodeling are considered possible pathogenic mechanisms. Also, the development of comorbidities such as pulmonary hypertension (PH) could further impact disease outcome, quality of life and survival rates in IPF.The current review provides a comprehensive literature survey of the mechanisms involved in the development and manifestations of IPF and their links to PH pathology. This review also provides the current understanding of molecular mechanisms that link the two pathologies and will specifically decipher the role of endothelial to mesenchymal transition (EndMT) along with the possible triggers of EndMT. The possibility of targeting EndMT as a therapeutic option in IPF is discussed.With a steady increase in prevalence and mortality, IPF is no longer considered a rare disease. Thus, it is of utmost importance and urgency that the underlying profibrotic pathways and mechanisms are fully understood, to enable the development of novel therapeutic strategies.

The thumb’s radial collateral ligament (RCL) plays an important role in stabilizing the first metacarpophalangeal joint (MCP-1). RCL injuries are rare and treatment recommendations are inconsistent in the current literature. The aim of this study was to report on long-term outcomes following surgical repair of thumb RCL tear and to identify prognostic risk factors for treatment failure. Patients with RCL tear from 10/1998 to 10/2019 were included in the present retrospective single center cohort study. In follow-up visits, participants were assessed regarding pain, range of motion and strength as well as with disability of shoulder, arm and hands (DASH), and the Short-Form 36 (SF36) questionnaires. Finally, predictive factors of postoperative deficits were identified. 43 patients fulfilled inclusion criteria. Median age was 43.5 years (range 18–80 years). The most frequent mechanism of injury was a fall or impact. Bony avulsions were identified in 46.5% (20/43). Time from injury to surgery was 12 days (0–276 days). One Stener-like lesion was observed intraoperatively among our patients. After surgical repair, the MCP-1 joint was stable in every patient. Mean time to follow-up was 5.3 years (1 month to 17 years). Persistency of pain in the MCP-1 joint was reported by 11 patients. Postoperative averaged score was 3.75 on DASH and 44.96 on SF36, respectively. The average grip and pinch strength was 32.7 kg and 8.37 kg, respectively. Predictive factors of postoperative deficits were delay of surgery of > 3 weeks (OR 10.72, p 0.017) and palmar subluxation prior to surgery (OR 8.86, p 0.019). Long-term follow-up has proven that surgical repair of RCL enables the patient to regain adequate stability and strength of the MCP-1 joint and minimizes disability. Predictive risk factors of pain persistency after surgery are surgical delay and palmar subluxation of the MCP-1 joint.

Hemodialysis (HD) dependence is known to impact the integrity of bone and has long been associated with metabolic bone disease and other adverse events postoperatively. The aim of this study is to analyze postoperative outcomes following revision hip and knee arthroplasty in hemodialysis-dependent (HDD) patients and to characterize the common indications for revision procedures among this patient population.A total of 1779 HDD patients who underwent a revision joint arthroplasty (930 revision total knee arthroplasty [TKA] and 849 revision total hip arthroplasty [THA]) between 2005 and 2014 were identified from a retrospective database review. Our resulting study groups of revision TKA and THA HDD patients were compared to their respective matched control groups for hospital length of stay (LOS), 90-day mean total cost, hospital readmission, and other major medical and surgical complications.HD was significantly associated with increased LOS (7.7 ± 8.3 vs 4.8 ± 4.5; P.001), mean 90-day total cost ($47,478 ± $33,413 vs $24,286 ± $21,472; P.001), hospital readmission (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.96-2.58; P.001), septicemia (OR, 3.18; 95% CI, 2.70-3.74; P.001), postoperative infection (OR, 1.72; 95% CI, 1.50-1.98; P.001), and mortality (OR, 3.99; 95% CI, 3.12-5.06; P.001) following revision TKA. Among revision THA patients, HD was associated with increased LOS (9.4 ± 9.5 vs 5.7 ± 5.7; P.001), mean 90-day total cost ($40,182 ± $27,082 vs $26,519 ± $22,856; P.001), hospital readmission (OR, 2.33; 95% CI, 2.02-2.68; P.001), septicemia (OR, 3.61; 95% CI, 3.05-4.27; P.001), and mortality (OR, 3.55; 95% CI, 2.86-4.37; P.001).HD remains a significant risk factor for increased LOS, mean total cost, hospital readmission, septicemia, and mortality following revision joint arthroplasty.