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Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

The minimization of nonradiative recombination losses is essential to transcend the efficiency of state-of-the-art organic solar cells (OSCs) and near- infrared (NIR) organic light- emitting diodes (OLEDs). Indeed, reduced nonradiative processes will result in high electroluminescence (EL), external quantum efficiency (EQE(EL)), and low nonradiative voltage losses (Delta V-OC,V- nr) for OSCs. Here, we study the EL properties of a set of polymer-small molecule blends and find a relationship between the EL emission linewidth, EQEEL, and Delta V-OC,V-nr. Based on these findings, we reduce Delta V-OC,V-nr from the typical values around 250 mV down to an unprecedented value of 155 mV using a blend comprising a low- molecular-weight PM6 polymer donor and a highly emissive nonfullerene acceptor (Y16F). Importantly, the PM6:Y16F blend yields an EQE(EL) ( 0.52%) among the best reported fluorescent NIR-OLEDs in the 900-nm range. These findings clearly indicate the existence of organic material blends that combine both excellent photovoltaic and electroluminescent properties. European Union's Horizon 2020 research and innovation program under the Marie-Curie grant [88279]; FWOFWO [G0D0118N, G0B2718N, G0D1521N, I006320N, GOH3816-NAUHL]; European Research Council (ERC)European Commission [864625]; FWO Odysseus program [G0D0115N]

BACKGROUND: Approximately half of all pregnancies in the United States are unintended. However, women who are diagnosed with cancer in their reproductive years may be a unique population. This study examines the prevalence of and identifies factors associated with unplanned pregnancy among cancer survivors. MATERIALS AND METHODS: Female cancer survivors aged 22–45 years, diagnosed between ages 20–35 years and at least 2 years postdiagnosis, and women with no history of cancer were interviewed about their reproductive histories, including pregnancy intention. Using a random matching process, comparison women were assigned an artificial age at cancer diagnosis equal to that of her cancer survivor match. An adjusted Cox model was fit examining time to unintended pregnancy after cancer for each of 1,000 matches. Cox proportional hazards models were also fit to assess associations between participant characteristics and unplanned pregnancy after cancer among survivors. RESULTS: Cancer survivors (n = 1,282) and comparison women (n = 1,073) reported a similar likelihood of having an unplanned pregnancy in models adjusted for race, income, history of sexually-transmitted infection, and history of unplanned pregnancy before diagnosis (adjusted hazard ratio [aHR] 1.06, 95% simulation interval 0.85–1.36). After adjusting for confounders, unplanned pregnancy among survivors was associated with age

It has been demonstrated that acute vagus nerve stimulation (VNS) improves word recognition memory in epilepsy patients. Transcutaneous auricular vagus nerve stimulation (taVNS) has gained interest as a non-invasive alternative to improve cognition. In this prospective randomized cross-over study, we investigated the effect of both invasive VNS and taVNS on verbal memory performance in 15 patients with drug-resistant epilepsy. All patients conducted a word recognition memory paradigm in 3 conditions: VNS ON, VNS OFF and taVNS (3-period 3-treatment cross-over study design). For each condition, patients memorized 21 highlighted words from text paragraphs. Afterwards, the intervention was delivered for 30 s. Immediate recall and delayed recognition scores were obtained for each condition. This memory paradigm was repeated after 6 weeks of VNS therapy in 2 conditions: VNS ON and VNS OFF (2-period 2-treatment cross-over study design). Acute VNS and taVNS did not improve verbal memory performance. Immediate recall and delayed recognition scores were significantly improved after 6 weeks of VNS treatment irrespective of the acute intervention. We can conclude that the previously described positive effects of invasive VNS on verbal memory performance could not be replicated with invasive VNS and taVNS. An improved verbal memory performance was seen after 6 weeks of VNS treatment, suggesting that longer and more repetitive stimulation of the vagal pathway is required to modulate verbal memory performance.Clinical trial registration number: NCT05031208.

Background: Prior studies have identified that survivors of childhood acute lymphoblastic leukemia (ALL) report poor health status. It is unknown how risk-stratified therapy impacts the health status of ALL survivors. Methods: We estimated and compared the prevalence of self-reported poor health status among adult (≥18 years) survivors of childhood ALL diagnosed at age Results: Among 5,119 survivors and 4,693 siblings, survivors were more likely to report poor health status in each domain including poor general health (13.5% vs. 7.4%; PR = 1.92; 95% CI, 1.69–2.19). Compared with 70s, 90sSR and 90sHR were less likely to report poor general health (90sSR: PR = 0.75; 95% CI, 0.57–0.98; 90sHR: PR = 0.58; 95% CI, 0.39–0.87), functional impairment (90sSR: PR = 0.56; 95% CI, 0.42–0.76; 90sHR: PR = 0.63; 95% CI, 0.42–0.95), and activity limitations (90sSR: 0.61; 95% CI, 0.45–0.83; 90sHR: PR = 0.59; 95% CI, 0.38–0.91). An added adjustment for chronic conditions in multivariable models partially attenuated 90sSR risk estimates. Conclusions: Risk-stratified ALL therapy has succeeded in reducing risk for poor general health, functional impairment, and activity limitations among more recent survivors of standard- and high-risk therapy. Impact: Future research into the relationship between risk-stratified therapy, health status, and late health outcomes may provide new opportunities to further improve late morbidity among survivors.

Purpose Little is known about the prevalence of occult lymph node metastases (LNM) in muscle-invasive bladder cancer (MIBC) patients with pathological downstaging of the primary tumor. We aimed to estimate the prevalence of occult LNM in patients without residual MIBC at radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) or neoadjuvant radiotherapy (NAR), and to assess overall survival (OS). Methods Patients with cT2-T4aN0M0 urothelial MIBC who underwent RC plus pelvic lymph node dissection (PLND) with curative intent between January 1995–December 2013 (retrospective Netherlands Cancer Registry (NCR) cohort) and November 2017–October 2019 (prospective NCR-BlaZIB cohort (acronym in Dutch: BlaaskankerZorg In Beeld; in English: Insight into bladder cancer care)) were identified from the nationwide NCR. The prevalence of occult LNM was calculated and OS of patients with y)pT2N0 vs. y)pT2N+ disease was estimated by the Kaplan–Meier method. Results In total, 4657 patients from the NCR cohort and 760 patients from the NCR-BlaZIB cohort were included. Of 1374 patients downstaged to y)pT2, 4.3% (N = 59) had occult LNM 4.1% (N = 49) of patients with cT2-disease and 5.6% (N = 10) with cT3-4a-disease. This was 4.0% (N = 44) in patients without NAC or NAR, 4.5% (N = 10) in patients with NAC, and 13.5% (N = 5) in patients with NAR but number of patients treated with NAR and downstaged disease was small. The prevalence of y)pT2N+ disease was 4.2% (N = 48) in the NCR cohort and 4.6% (N = 11) in the NCR-BlaZIB cohort. For patients with y)pT2N+ and y)pT2N0, median OS was 3.5 years (95% CI 2.5–8.9) versus 12.9 years (95% CI 11.7–14.0), respectively. Conclusion Occult LNM were found in 4.3% of patients with cT2-4aN0M0 MIBC with (near-) complete downstaging of the primary tumor following RC plus PLND. This was regardless of NAC or clinical T-stage. Patients with occult LNM showed considerable worse survival. These results can help in counseling patients for bladder-sparing treatments.

Degradation caused by humidity affects the blocking characteristic of an insulated gate bipolar transistor (IGBT) module, leading to an increased leakage current and/or a reduced voltage blocking capability. The proposed measurement system enables the in situ detection of decreased breakdown voltage and increased leakage current. Thus, it can assess the degradation level of power modules when installed in a converter. This test is intended primarily for wind power converters and can be part of the start-up procedure of the system. The working principle has been validated on predamaged power modules arranged in half-bridge configuration, using a demonstrator implementation of the proposed approach in laboratory experiments. Due to the simplicity of the circuit, this concept is easy to integrate in existing inverter systems at a comparatively low cost.

Background: Maladaptive ER stress signaling in diabetic kidney disease (DKD) is linked to increased glomerular and tubular expression of the cell death-promoting transcription factor C/EBP homologous protein (CHOP). We determined whether therapy with locked nucleic acid (LNA)-modified antisense oligonucleotides (ASOs) targeting CHOP ameliorates experimental DKD. Methods: Following an in vivo dose-escalation study, we determined the efficacy of CHOPASO in the early and later stages of experimental DKD (8- or 16-week-old db/db mice, respectively) alone or in combination with an angiotensin-converting enzyme inhibitor (ACEi). Renal functional parameters and morphological analyses were used to determine the effects. Renal gene expression profiling was conducted to determine differentially regulated genes and pathways. Several human CHOP-ASOs were tested in hyperglycemia-exposed human kidney cells. Results: CHOP-ASOs efficiently reduced renal CHOP expression in diabetic mice and reduced markers of DKD at early and late stages. Early combined intervention (CHOP-ASO and ACEi) efficiently prevented interstitial damage. At the later timepoint, the combined treatment reduced indices of both glomerular and tubular damage more efficiently than either intervention alone. A significantly larger number of genes and disease pathways were affected by CHOP-ASO, including reduced Slc5a2 (sodium-glucose transport protein 2) and PROM1 (CD133). Human CHOP-ASOs efficiently reduced glucose-induced CHOP and prevented cell death of human kidney cells in vitro Conclusions: The ASO-based approach efficiently reduced renal CHOP expression in a diabetic mouse model, providing an additional benefit to an ACEi in particular at later timepoints. These studies demonstrate that ASO-based therapies efficiently reduce maladaptive CHOP expression and ameliorate experimental DKD.

Buried power rail (BPR) is a key scaling booster for CMOS extension beyond the 5-nm node. This work demonstrates, for the first time, the integration of tungsten (W) BPR lines with Si finFETs. BPR technology requires insertion of metal in the front-end-of-line (FEOL) stack. This poses risks of stack deformation and device degradation due to metal-induced stress and contamination. To assess the stack deformation, we demonstrate W-BPR lines which can withstand source/drain activation anneal at 1000 °C, 1.5 s, without adversely impacting the stack morphology. To address the contamination risk, we demonstrate a BPR process module with controlled W recess and void-free dielectric plug formation which keeps the W-line fully encapsulated during downstream FEOL processing. Suitable choice of BPR metal such as W with high melting point which does not diffuse into dielectrics also minimizes the risk of contamination. To assess the device degradation, simulations are carried out showing negligible stress transfer from BPR to the channel. This is experimentally validated when no systematic difference in the dc characteristics of CMOS without BPR versus those in close proximity to floating W-BPR lines is observed. Additionally, the resistance of the recessed W-BPR line is measured $\sim 120~\Omega /\mu \text{m}$ for critical dimension (CD) ~32 nm and height ~122 nm. The recessed W-BPR interface with Ru 3-nm TiN liner via contact can withstand more than 1000 h of electromigration (EM) stress at 6.6 MA/cm2 and 330 °C, making Ru a candidate for via metallization to achieve low resistance contact strategy to BPR.

Introduction: Endoscopic pneumatic pyloric balloon dilation is a treatment option for early postoperative delayed gastric tube emptying following esophageal resection. This study aimed to determine the safety and effectiveness of endoscopic balloon dilation. Methods: Between 2015 and 2018, patients with delayed gastric emptying 8–10 days after esophageal resection with gastric tube reconstruction due to esophageal carcinoma were considered for inclusion. Inclusion criteria were ≥1 of the following: nasogastric tube production ≥500 mL/24 h, ≥300 mL gastric retention, ≥50% gastric tube dilatation on X-ray, or nasogastric tube replacement. Patients were excluded on evidence of anastomotic leakage or reintervention. Success was defined as the ability to expand intake without needing to replace the nasogastric tube. Dilation was performed using a 30-mm Rigiflex balloon. Results: Fifteen patients underwent pyloric dilation, 12 according to the study protocol. Treatment was performed at a median of 12 days (IQR 9–15) postoperatively. Success was achieved in 58%. At 3 months, 8 patients progressed to exclusively oral intake. The remaining 4 patients had supplementary nightly enteral tube feeding. There were no adverse events. Conclusion: Endoscopic balloon dilation of the pylorus is a safe, feasible therapy for early postoperative delayed gastric emptying. With a success rate of 58%, a clinical trial is a necessary next step.

Objectives To investigate the utility of Magnetic Resonance Imaging (MRI) for prostate cancer diagnosis in the Australian setting. Patients and methods All consecutive men who underwent a prostate biopsy (transperineal or transrectal) at Royal Melbourne Hospital between July 2017 to June 2019 were included, totalling 332 patients. Data were retrospectively collected from patient records. For each individual patient, the risk of prostate cancer diagnosis at biopsy based on clinical findings was determined using the European Randomized study of Screening for Prostate Cancer (ERSPC) risk calculator, with and without incorporation of MRI findings. Results MRI has good diagnostic accuracy for clinically significant prostate cancer. A PI‐RADS 2 or lower finding has a negative predictive value of 96% for clinically significant cancer, and a PI‐RADS 3, 4 or 5 MRI scan has a sensitivity of 93%. However, MRI has a false negative rate of 6.5% overall for clinically significant prostate cancers. Pre‐ biopsy MRI may reduce the number of unnecessary biopsies, as up to 50.0% of negative or ISUP1 biopsies have MRI PI‐RADS 2 or lower. Incorporation of MRI findings into the ERSPC calculator improved predictive performance for all prostate cancer diagnoses (AUC 0.77 vs 0.71, P = .04), but not for clinically significant cancer (AUC 0.89 vs 0.87, P = .37). Conclusion MRI has good sensitivity and negative predictive value for clinically significant prostate cancers. It is useful as a pre‐biopsy tool and can be used to significantly reduce the number of unnecessary prostate biopsies. However, MRI does not significantly improve risk predictions for clinically significant cancers when incorporated into the ERSPC risk calculator.

Background In the mid-seventies, biliopancreatic diversion became popular as weight-loss surgery procedure. This bariatric procedure combines distal gastric resection and intestinal malabsorption, leading to greater weight loss and improvement of co-morbidities than other bariatric procedures. Nowadays, biliopancreatic diversion has become obsolete due to the high risk of nutritional complications. However, current patients with biliopancreatic diversions are aging. Consequently, geriatricians and general practitioners will encounter them more often and will be faced with the consequences of late complications. Case presentation A 74-year old female presented with weakness, recurrent falls, confusion, episodes of irresponsiveness, anorexia and weight loss. Her medical history included osteoporosis, herpes encephalitis 8 years prior and a biliopancreatic diversion (Scopinaro surgery) at age 52. Cerebral imaging showed herpes sequelae without major atrophy. Delirium was diagnosed with underlying nutritional deficiencies. Biochemical screening indicated vitamin A deficiency, vitamin E deficiency, zinc deficiency and severe hypoalbuminemia. While thiamin level and fasting blood glucose were normal. However, postprandial hyperinsulinemic hypoglycemia was observed with concomitant signs of confusion and blurred consciousness. After initiating parenteral nutrition with additional micronutrient supplementation, a marked improvement was observed in cognitive and physical functioning. Conclusions Long-term effects of biliopancreatic diversion remain relatively underreported in older patients. However, the anatomical and physiological changes of the gastrointestinal tract can contribute to the development of metabolic and nutritional complications that may culminate in cognitive impairment, functional decline and delirium. Therefore, it is warranted to evaluate the presence of metabolic disturbances and nutritional complications in older patients after biliopancreatic diversion.

Background Z scores are the method of choice to report dimensions in pediatric echocardiography. Z scores based on body surface area (BSA) have been shown to cause systematic biases in overweight and obese children. Using aortic valve (AoV) diameters as a paradigm, the aims of this study were to assess the magnitude of z score underestimation in children with increased body mass index z score (BMI-z) and to determine if a predicting model with height and weight as independent predictors would minimise this bias. Methods In this multicentre, retrospective, cross-sectional study, 15,006 normal echocardiograms in healthy children 1-18 years old were analyzed. Residual associations with body size were assessed for previously published z score. BSA-based and alternate prediction models based on height and weight were developed and validated in separate training and validation samples. Results Existing BSA-based z scores incompletely adjusted for weight, BSA, and BMI-z and led to an underestimation of > 0.8 z score units in subjects with higher BMI-z compared with lean subjects. BSA-based models led to overestimation of predicted AoV diameters with increasing weight or BMI-z. Models using height and weight as independent predictors improved adjustment with body size, including in children with higher BMI-z. Conclusions BSA-based models result in underestimation of z scores in patients with high BMI-z. Prediction models using height and weight as independent predictors minimise residual associations with body size and generate well fitted predicted values that could apply to all children, including those with low or high BMI-z.

Scholars and practitioners in the field of performance management have advocated an increase in the exchange of feedback in the workplace. Practitioners would benefit from guidelines about appropriate feedback frequencies, but the current literature does not offer much guidance. Our study investigates how self-reports of absolute frequencies relate to performance and job satisfaction. In a sample of diverse organizations, employees reported, on average, 3.8 feedback conversations in 3 weeks. Contrary to earlier suggestions that there might be an optimal feedback frequency, we find support for the notion that more feedback is better, without any indication of a downward trend at the highest feedback frequency. Our findings suggest that leader–member exchange may be one underlying mechanism that mediates this relationship.

This scoping review summarizes current evidence with regard to the impact of bariatric surgery on psychological health in adults with obesity. While a large body of evidence reports major metabolic benefit and improved quality of life, there is also ample evidence suggesting an increased incidence of self-harming behavior, a greater likelihood of developing an alcohol problem and higher rates of completed suicide among bariatric patients. Being able to identify the "at risk" patient population requires more longitudinal research into the risk factors for psychological complications after bariatric surgery. Bariatric surgery remains an extremely valuable long-term treatment option for managing obesity; however, there is a need to invest in mitigating psychological complications after the surgery, such as depression, alcohol consumption, and other self-harming behaviors. ispartof: OBESITY SURGERY vol:31 issue:12 pages:5409-5417 ispartof: location:United States status: published

Despite the increasing prevalence and medical burden of obesity, the understanding of gastrointestinal physiology in obesity is scarce, which hampers drug development.To investigate the effect of obesity and food intake on gastrointestinal transit, pressure and pH.An exploratory cross-sectional study using a wireless motility capsule (SmartPill©) was performed in 11 participants with obesity and 11 age- and gender-matched participants with normal weight (group) in fasted and fed state (visit). During the first visit, the capsule was ingested after an overnight fast. During a second visit, the capsule was ingested after a nutritional drink to simulate fed state. Linear mixed models were constructed to compare segmental gastrointestinal transit, pressure and pH between groups (obesity or control) and within every group (fasted or fed).Food intake slowed gastric emptying in both groups (both P 0.0001), though food-induced gastric contractility was higher in participants with obesity compared to controls (P = 0.02). In the small intestine, a higher contractility (P = 0.001), shorter transit (P = 0.04) and lower median pH (P = 0.002) was observed in participants with obesity compared to controls. No differences were observed for colonic measurements.Obesity has a profound impact on gastrointestinal physiology, which should be taken into account for drug development.

ZUSAMMENFASSUNGPatienten mit Diabetes mellitus weisen eine erhöhte Morbidität und Letalität infolge der mikro- und makrovaskulären Komplikationen auf. Zudem kann es bei Erstmanifestation, aber auch während des weiteren Krankheitsverlaufs, zu lebensbedrohlichen Stoffwechselentgleisungen kommen. Treten diabetesbedingte Notfälle auf, ist eine schnelle Diagnose und Therapieeinleitung unerlässlich.

P-type point contact (PPC) germanium detectors are used in rare event and low-background searches, including neutrinoless double beta (0νββ) decay, low-energy nuclear recoils, and coherent elastic neutrino-nucleus scattering. The detectors feature an excellent energy resolution, low detection thresholds down to the sub-keV range, and enhanced background rejection capabilities. However, due to their large passivated surface, separating the signal readout contact from the bias voltage electrode, PPC detectors are susceptible to surface effects such as charge build-up. A profound understanding of their response to surface events is essential. In this work, the response of a PPC detector to alpha and beta particles hitting the passivated surface was investigated in a multi-purpose scanning test stand. It is shown that the passivated surface can accumulate charges resulting in a radial-dependent degradation of the observed event energy. In addition, it is demonstrated that the pulse shapes of surface alpha events show characteristic features which can be used to discriminate against these events.

Dome-shaped supramalleolar osteotomies are a well-established treatment option for correcting ankle deformity. However, the procedure remains technically demanding and is limited by a two-dimensional (2D) radiographic planning of a three-dimensional (3D) deformity. Therefore, we implemented a weight-bearing CT (WBCT) to plan a 3D deformity correction using patient-specific guides.A 3D-guided dome-shaped supramalleolar osteotomy was performed to correct ankle varus deformity in a case series of five patients with a mean age of 53.8 years (range 47-58). WBCT images were obtained to generate 3D models, which enabled a deformity correction using patient-specific guides. These technical steps are outlined and associated with a retrospective analysis of the clinical outcome using the EFAS score, Foot and Ankle Outcome Score (FAOS) and visual analog pain scale (VAS). Radiographic assessment was performed using the tibial anterior surface angle (TAS), tibiotalar angle (TTS), talar tilt angle (TTA), hindfoot angle (HA), tibial lateral surface angle (TLS) and tibial rotation angle (TRA).The mean follow-up was 40.8 months (range 8-65) and all patients showed improvements in the EFAS score, FAOS and VAS (p 0.05). A 3-month postoperative WBCT confirmed healing of the osteotomy site and radiographic improvement of the TAS, TTS and HA (p 0.05), but the TTA and TRA did not change significantly (p 0.05).Dome-shaped supramalleolar osteotomies using 3D-printed guides designed on WBCT are a valuable option in correcting ankle varus deformity and have the potential to mitigate the technical drawbacks of free-hand osteotomies.Level 5 case series.

Introduction Although bacterial co- and superinfections are rarely present in patients with COVID-19, overall antibiotic prescribing in admitted patients is high. In order to counter antibiotic overprescribing, antibiotic stewardship teams need reliable data concerning antibiotic prescribing in admitted patients with COVID-19. Methods In this prospective observational cohort study, we performed a quantitative and qualitative evaluation of antibiotic prescriptions in patients admitted to the COVID-19 ward of a 721-bed Belgian university hospital between 1 May and 2 November 2020. Data on demographics, clinical and microbiological parameters and antibiotic consumption were collected. Defined daily doses (DDD) were calculated for antibiotics prescribed in the context of a (presumed) bacterial respiratory tract infection and converted into two indicators: DDD/admission and DDD/100 hospital bed days. A team of infectious disease specialists performed an appropriateness evaluation for every prescription. A driver analysis was performed to identify factors increasing the odds of an antibiotic prescription in patients with a confirmed COVID-19 diagnosis. Results Of 403 eligible participants with a suspected COVID-19 infection, 281 were included. In 13.8% of the 203 admissions with a COVID-19 confirmed diagnosis, antibiotics were initiated for a (presumed) bacterial respiratory tract co-/superinfection (0.86 DDD/admission; 8.92 DDD/100 bed days; 39.4% were scored as ‘appropriate’). Five drivers of antibiotic prescribing were identified: history of cerebrovascular disease, high neutrophil/lymphocyte ratio in male patients, age, elevated ferritin levels and the collection of respiratory samples for bacteriological analysis. Conclusion In the studied population, the antibiotic consumption for a (presumed) bacterial respiratory tract co-/superinfection was low. In particular, the small total number of DDDs in patients with confirmed COVID-19 diagnosis suggests thoughtful antibiotic use. However, antibiotic stewardship programmes remain crucial to counter unnecessary and inappropriate antibiotic use in hospitalized patients with COVID-19. Trial Registration The study is registered at ClinicalTrials.gov (NCT04544072). Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00535-2.

The ferroelectric properties of hafnium oxide films are strongly influenced by the crystallization process due to the interaction of thermodynamics, kinetics, and mechanical stress. In this work, the influence of annealing temperature on the crystallographic properties and microstructure of Si-doped hafnium oxide thin films as well as their ferroelectric properties are investigated by X-ray diffraction, transmission Kikuchi diffraction, and electrical characterization. The findings reveal the emergence of a [100] and [110] out-of-plane texture for metal-ferroelectric-metal (MFM) and metal-ferroelectric-insulator-semiconductor (MFIS) capacitor structures with increasing annealing temperature, respectively. In combination with observed stress relaxation at higher temperatures and the evolution of the wake-up behavior, insights into the crystallization process and the influence of the interplay of microstructure and stress on the ferroelectric properties of hafnium oxide thin films are given.

Given the environmental challenges facing organizations, there is an increasing interest in how to stimulate the green behavior of employees. This study focuses on how leaders foster green advocacy, a specific category of green behavior that refers to influencing others to demonstrate green behavior by sharing environmental knowledge and discussing environmental issues. Our study, using a sample of 363 employees of a Belgian grocery retail company, provides valuable insights on the complex role of leaders in stimulating green advocacy. The results reveal that environmentally-specific transformational leadership is positively related to employees' green advocacy. Our results further provide insights into the underlying mechanisms explaining this relationship, as we find that environmentally-specific transformational leadership is indirectly related to employees' green advocacy through environmental CSR and organizational environmental support. Finally, leadership integrity is found to positively moderate the direct as well as the indirect relationship between environmentally-specific transformational leadership and green advocacy.

Closed static interlocking nailing with c-arm guidance is the standard procedure for the treatment of closed diaphyseal fractures. In low-income settings, it is still very difficult to carry out such procedures because of few or absent image intensifiers (c-arm) despite the necessity. Authors provide a review of the literature on interlocking intramedullary nailing without fluoroscopy in resource-limited settings, followed by strategies, outcomes, and outlook. A comprehensive search of the PubMed, Web of Science, Embase, and Cochrane Library databases was performed with the help of a biomedical information specialist. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. We identified 15 series of interlocking intramedullary nailing without fluoroscopy in resource-limited settings. All papers focused on the care for long bones (humerus, femur, tibia). All studies discussed the quality of the nailing operative procedure. The entry point was described in five series; the nail insertion in the proximal and distal medullary canal was good in all studies. The distal locking was missed between 0 and 27%. Intraoperative strategies depend on the type of bone affected, the opening of the fracture site, the fracture line, and the availability of a functional orthopaedic table. Three techniques to insert the nail in the proximal and distal fracture fragment with reduction of the fracture site are described. Insertion of distal screws is possible by using ancillary devices. Outcomes are comparable to those of the series using c-arm guidance. In low-income countries, it can been proposed as an alternative to the gold standard in resources constraints settings. In high-income setting this technique can help to reduce exposure of X-ray. There is a need to improve equipment in low-income countries hospitals to make trauma surgery with c-arm a gold standard with a minimal exposure to radiation.

Background The prevalence of a bovine aortic arch configuration is higher in patients treated for thoracic aortic aneurysms and type B dissection; its prevalence in aortic isthmic trauma has not been described. Methods A case control study was performed comparing consecutive patients treated at our institution for acute isthmic aortic transection after blunt trauma between 2002 and 2019 and a control group of consecutive sex-matched individuals undergoing imaging for nonaortic disease. Imaging and clinical findings were reviewed. Subjects were divided into bovine and nonbovine groups and prevalence was compared. The length of the aortic segment between the left subclavian artery (LSA) and the next proximal great vessel was measured in the control population and a comparison was performed between bovine and nonbovine aortic arch subjects. Results Thirty-three consecutive (30 male) patients were reviewed, 66 individuals (60 male) were included in the control group. A higher incidence of bovine arch in trauma patients was found: 57.6% vs. 34.8% (P = 0.007). The median (range, mm) and mean (SD) distance between the bovine trunk and the LSA were 13 mm (2–27) and 12.4 mm (5.9), respectively, compared with 5 mm (1–27) and 7.8 mm (6.1) between the left common carotid and LSA in nonbovine aortic arches (P Conclusion A higher incidence of bovine arch in patients reaching out for surgical treatment for traumatic isthmic aortic transection was found in our population. Clinical interpretation of this finding can lead to several alternatives. Confirmation with larger series and data on prevalence of this anatomic variation in nonsurvivors is needed to provide a better understanding of this finding.

Introduction Antibody-mediated rejection (ABMR) impacts kidney allograft outcome. The diagnosis is made based on findings from invasive kidney transplant biopsy specimens. The aim of this study was to identify a noninvasive urinary protein biomarker for ABMR after kidney transplantation. Methods We performed a multicenter case-control study to identify a urinary biomarker for ABMR (training cohort, n = 249) and an independent, prospective multicenter cohort study for validation (n = 391). We used concomitant biopsies to classify the samples according to the Banff classification. After untargeted protein identification and quantification, we used a support vector machine to train the model in the training cohort. The primary endpoint was the diagnostic accuracy of the urinary biomarker for ABMR in the validation cohort. Results We identified a set of 10 urinary proteins that accurately discriminated patients with (n = 60) and without (n = 189) ABMR in the training cohort with an area under the curve (AUC) of 0.98 (95% confidence interval [CI], 0.96–1.00). The diagnostic accuracy was maintained in the validation cohort (AUC, 0.88; 95% CI, 0.8–0.93) for discriminating the presence (n = 43) from the absence (n = 348) of ABMR. The negative predictive value of the 10-protein marker set for exclusion of ABMR was 0.99, and the positive predictive value was 0.33. The diagnostic accuracy was independent of the reason for performing the biopsy, time after transplantation, and better than the accuracy of gross proteinuria (AUC, 0.76). Conclusions We identified and validated a urinary protein biomarker set that can be used to exclude ABMR., Graphical abstract

Summary Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18–80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6–12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov , NCT02100696 . Findings HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding F Hoffmann-La Roche.

BACKGROUND Demand for male-to-female gender-affirmation surgery is rising. Creation of a vaginal vault and a feminine vulva remains challenging, especially in circumcised patients. The authors present the 15-year results of the technique developed by the senior author (S.M.). METHODS A retrospective case review was performed of all penile inversion vaginoplasties carried out by the senior author between 2003 and 2017. Age, hormonal therapy time, body mass index, smoking, diabetes, circumcision, and the need for full-thickness skin grafts to lengthen the vaginal vault were investigated as potential risk factors for postoperative complications. RESULTS A total of 384 penile inversion vaginoplasties were retained, with 85.7 percent of patients requiring a full-thickness skin graft to lengthen the vaginal vault. Rectum perforation occurred in six patients (1.6 percent). Early revisions were necessary in 8.4 percent of patients and late revision surgery was performed in 37.1 percent of cases. There was no independent risk factor for early complications. Diabetes was an independent risk factor for late revision surgery. After vaginoplasty, 97.2 percent of patients reported being able to engage in penetrative intercourse, and 83.4 percent of patients reported having orgasms. CONCLUSIONS Vaginoplasty is possible in all trans women, with most patients being able to engage in penetrative intercourse and reach an orgasm. To reach the desired depth of 14 cm, the neovaginal vault is usually lined with full-thickness skin grafts from the scrotum and/or abdomen. Diabetes was the only independent risk factor for revision surgery. Rectal tears are a rare complication and can usually be managed conservatively. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, IV.

Purpose: To investigate the safety, clinical efficacy, virus pharmacokinetics, shedding, and immune response after administration of an oncolytic parvovirus (H-1PV, ParvOryx) to patients with metastatic pancreatic ductal adenocarcinoma (PDAC) refractory to first-line therapy. Patients and Methods: This is a noncontrolled, single-arm, open-label, dose-escalating, single-center clinical trial. Seven patients with PDAC and at least one liver metastasis were included. ParvOryx was administered intravenously on 4 consecutive days and as an intralesional injection, 6 to 13 days thereafter. Altogether, three escalating dose levels were investigated. In addition, gemcitabine treatment was initiated on day 28. Results: ParvOryx showed excellent tolerability with no dose-limiting toxicities. One patient had a confirmed partial response and one patient revealed an unconfirmed partial response according to RECIST criteria. Both patients showed remarkably long surivial of 326 and 555 days, respectively. Investigation of pharmacokinetics and virus shedding revealed dose dependency with no excretion of active virus particles in saliva or urine and very limited excretion in feces. H-1PV nucleic acids were detected in tumor samples of four patients. All patients showed T-cell responses to viral proteins. An interesting immunologic pattern developed in tumor tissues and in blood of both patients with partial response suggesting immune activation after administration of ParvOryx. Conclusions: The trial met all primary objectives, revealed no environmental risks, and indicated favorable immune modulation after administration of ParvOryx. It can be considered a good basis for further systematic clinical development alone or in combination with immunomodulatory compounds.

Hip arthroplasty and revision surgery are growing exponentially in OECD countries. In developing countries, it is an infrequent intervention and its practice is limited. It is exposed to a higher rate of infectious and mechanical failures than in developed countries. The aim of the actual study is to provide a review of the literature on total hip arthroplasty series in sub-Saharan Africa followed by an overview of the interest and perspectives of the use of dual mobility (DM) cups. Scopus, EMBASE, Medline, PubMed, and Safoonline databases were searched including papers published at any date. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. All papers from South Africa were excluded. We identified 22 series of total hip arthroplasty in 14 SSA countries. The practice of total hip arthroplasty is not very widespread. The cups used are mostly conventional implants, and complications (mechanical and infectious) are frequent. The interest for the use of dual mobility cups in sub-Saharan Africa can be summarized in two points: mechanical and socio-economical. Dual mobility cups provide more mechanical stability and a reduction in the overall cost of treatment by reducing the rate of complications. These prospects will make it possible to evaluate this medical device in the long term in a hostile environment conductive to complications. The use of dual mobility deserves to be developed in African settings.

BACKGROUND Cancer survivors are at elevated risk for developing mental health (MH) disorders. This study assessed MH service use and unmet service needs among a nationally representative sample of cancer survivors. METHODS Respondents aged 18 to 64 years were identified from the 2015-2018 National Survey of Drug Use and Health data. Outcomes assessed past-year MH service use and self-reported unmet MH needs. Outcomes were compared between respondents who reported a cancer history (survivors) and those who did not (controls), descriptively and in adjusted analyses controlling for sociodemographic factors and health status. Analyses were stratified by age groups (18-34, 35-49, and 50-64 years). RESULTS Comparing 3540 survivors with 149,843 controls, within each age group, a higher proportion of survivors than controls received any MH service (P values

PSMA-PET has become the PET technique of choice to localise the site of biochemically recurrent prostate cancer (PCa). With hybrid PET/MRI, the advantages of MRI are added to molecular characteristic of PET. The aim of this study was to investigate the incremental value of PET/MR versus PET/CT in patients with biochemically recurrent PCa by head-to-head comparison. Thirty-four patients with biochemically recurrent PCa were prospectively included. They underwent [68Ga]Ga-PSMA-11 PET/CT, followed by simultaneous PET/MR. All PET (PETCT, PETMR), CT and MR images were evaluated for number of lesions and location. The number of lesions at specific sites was compared using Wilcoxon-sign-rank test. For PET, the maximum and mean standardised uptake values (SUVs) were calculated for each lesion compared using a two-sided paired t test. PETCT and PETMR scans were positive in 19 and 20 patients, detecting 73 and 79 lesions respectively. All lesions detected on PETCT were also detected on PETMR. CT and MRI only were positive in 14 and 17 patients, detecting 38 and 50 lesions, respectively, which was significantly lower than PETCT and PETMR respectively. Combined interpretation showed more lesions on PET/MR than on PET/CT (88 vs 81). No significant difference in detection of presence of local recurrence nor distant metastases was found. SUVmean and SUVmax values were significantly higher on PETMR than on PETCT in local recurrence and lymph node metastases. [68Ga]Ga-PSMA-11 PET/MR was able to detect biochemically recurrent PCa at least as accurately as PET/CT for local recurrence, lymph node metastasis and distant metastasis. • PSMA PET/MRI detects the location of biochemical recurrence at least as accurately as PET/CT. • Substitution of PET/CT by PET/MRI adds sensitivity in PSMA lesion detection also in the setting of distant recurrence due to both the MR and TOF PET components.

Purpose To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC). Materials and methods We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age. Results pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6–37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p p = 0.002) compared to those with luminal papillary subtype. Conclusions While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.

Venous thromboembolism from a “thrombotic storm”–like syndrome is a major cause of morbidity and mortality in patients with active or “recovered” COVID-19. Patients should be risk-stratified, optimally by a pulmonary embolism (PE) response team (PERT), and considered for escalation of care if found with intermediate or high-risk PE. We present a series of patients with COVID-19-associated PE and thrombotic storm with D-dimer >10 000 ng/mL who underwent successful mechanical thrombectomy for intermediate to high-risk PE. All patients had immediate improvement in hemodynamics and large amounts of thrombi were retrieved.

This analysis deals with the influence of export activities on demand for workers of differing skill levels. Previous literature suggests that productivity of export firms can improve as a result of the lessons learned from experience in international markets and/or that such productivity may be higher from the get-go by virtue of the self-selection effect among firms involved in export activities. Engaging in export activities may potentially lead to changes in employment structure, with a greater tendency to employ more highly skilled workers. To investigate this hypothesis, we applied a conditional difference-in-difference regression model of labor demand for three different skill levels. The data we used for our work was taken from the German IAB Establishment Panel covering the period from 2000 to 2017. Our results show not only the need to control for self-selection into export activity but also that changes in employment patterns appear to be skill-biased among manufacturing firms starting out in export activities. Nevertheless, corresponding findings for firms that have ceased exporting are conspicuous by their absence. Businesses in the service sector that decide to cease exporting appear to shed workers across all skill levels.

[18F]JNJ-64413739 has been evaluated as PET-ligand for in vivo quantification of purinergic receptor subtype 7 receptor (P2X7R) using Logan graphical analysis with a metabolite-corrected arterial plasma input function. In the context of a P2X7R PET dose occupancy study, we evaluated a minimally invasive approach by limiting arterial sampling to baseline conditions. Meanwhile, post dose distribution volumes (VT) under blocking conditions were estimated by combining baseline blood to plasma ratios and metabolite fractions with an MR angiography driven image derived input function (IDIF). Regional postdose VT,IDIF values were compared with corresponding VT,AIF estimates using a arterial input function (AIF), in terms of absolute values, test–retest reliability and receptor occupancy. Compared to an invasive AIF approach, postdose VT,IDIF values and corresponding receptor occupancies showed only limited bias (Bland–Altman analysis: 0.06 ± 0.27 and 3.1% ± 6.4%) while demonstrating a high correlation (Spearman ρ = 0.78 and ρ = 0.98 respectively). In terms of test–retest reliability, regional intraclass correlation coefficients were 0.98 ± 0.02 for VT,IDIF compared to 0.97 ± 0.01 for VT,AIF. These results confirmed that a postdose IDIF, guided by MR angiography and using baseline blood and metabolite data, can be considered for accurate [18F]JNJ-64413739 PET quantification in a repeated PET study design, thus avoiding multiple invasive arterial sampling and increasing dosing flexibility.

Abstract Zirconium-doped hafnium oxide (HZO) crystallizes at low temperatures and is thus ideal to implement ferroelectric (FE) functionalities into the back end of line (BEoL). Therefore, metal-ferroelectric-metal (MFM) capacitors are of great interest. Placed in the BEoL, they can be connected either to the drain- or the gate-contact of a standard logic device to realize different emerging FE-embedded non-volatile memory (eNVM) concepts. However, the low crystallization temperature increases also the risk for a premature crystallization of the HZO films during the growth of the top electrode (TE), in particular, if high-temperature processes like atomic layer deposition (ALD) or chemical vapor deposition (CVD) are used. Herein, the TE is deposited at room temperature via physical vapor deposition (PVD). The impact of different process gas flows on the FE properties of the HZO films is studied by X-ray diffraction and polarization versus electric field measurements. Graphic abstract

Product concept generation and evaluation are critical for the success of new product developments (NPD) because managers need to select the most profitable product concepts. However, current approaches can be restricted to single products and do not cover product families' effects. Similarly, they do not necessarily capture all requirements and usually lack extensive cost analyses. Thus, this paper proposes a framework supporting product concept generation and evaluation by providing an accessible conceptualization to overcome the limitations. Using the so-called Extended Axiomatic Design (EAD) supports designers and managers to configure the requirements across product concepts' various domains while concurrently evaluating their economic consequences. The study applies the framework on a simplified case of a bottle manufacturer to conceptualize four product concepts. The case illustrates how the EAD can be used as a virtual testbed to generate and evaluate new product concepts. Finally, designers and managers can make more informed decisions about product concepts by considering their economic and engineering selection criteria to select the most profitable NPD project configuration.

Product modularisation continuously draws attention of scholars and practitioners since it supports organizations and industries to sustain in high product and service variety at reasonable costs and greater flexibility. This paper aims at revealing current trends and developments in the field of product modularisation by identifying the intellectual structure using a bibliometric review. Our sample accrues 1,366 publications from 2016 up to 2020 across disciplines while using bibliometric coupling composes a network. Analysing the network on similarities, we can not only find clusters of servitisation, closed-loop supply chains, and platform collaboration, because we also identify three trends of digital innovation, sustainability, and platform eco-systems. An analysis of authors currently indicates less integrated communities, which do not entirely refer to each other despite the similarity in their research. Collectively, the study suggests a timely update of current scholar activities and discussions in the field of product modularisation.

Insbesondere nach ausgedehnter Tumorresektion im Kopf-Hals-Bereich stellt der mikrovaskulare Gewebetransfer den Goldstandard in der rekonstruktiven Chirurgie dar. Durch den gestiegenen Anspruch an die postoperative Lebensqualitat kommt es zu einem erhohten Bedarf an funktionell und asthetisch ansprechenden rekonstruktiven Masnahmen. Hierfur steht je nach Ausdehnung und Struktur des Defekts eine Vielzahl unterschiedlicher mikrovaskularer Transplantate zur Verfugung. In der Mund‑, Kiefer- und Gesichtschirurgie spielt v. a. die knocherne Rekonstruktion des Ober- und Unterkiefers eine wichtige Rolle mit dem Ziel, essenzielle Funktionen wie Artikulation, Phonation sowie die Kau- und Schluckfunktion zu erhalten oder wiederherzustellen. Hier hat sich insbesondere durch den Einsatz der virtuellen Planung und deren Ubertragung in den Operationssaal mittels Resektions- oder Osteotomieschablonen und den Einsatz patientenspezifischer Implantate ein hohes Mas an Prazision entwickelt, was die Vorhersagbarkeit des Rekonstruktionsergebnisses entscheidend verbessert hat. Die adaquate kaufunktionelle Rehabilitation nach einer knochernen Rekonstruktion erfordert i. d. R. die Insertion dentaler Implantate zur Verankerung eines Zahnersatzes, was oft mit einem hohen zeitlichen Aufwand bis zur vollstandigen prothetischen Versorgung verbunden ist. Hier bietet der „Jaw-in-a-day-Ansatz“, bei dem die vollstandige dentale Rehabilitation simultan zur Kieferrekonstruktion erfolgt, eine vielversprechende Technik an. Diese setzt jedoch eine sorgfaltige Patientenselektion voraus und muss noch im Langzeitverlauf abschliesend beurteilt werden.