Semaglutide and Diuretic Use in Obesity-Related Heart Failure with Preserved Ejection Fraction: A Pooled Analysis of the STEP-HFpEF and STEP-HFpEF-DM trials.

BACKGROUND AND AIMS: In the STEP-HFpEF trial program, treatment with semaglutide resulted in multiple beneficial effects in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Efficacy may vary according to baseline diuretic use, and semaglutide treatment could modify diuretic dose. METHODS: In this pre-specified analysis of pooled data from the STEP-HFpEF and STEP-HFpEF-DM trials (n=1145), which randomized participants with HFpEF and body mass index ≥30 kg/m2 to once weekly semaglutide 2.4 mg or placebo for 52 weeks, we examined whether efficacy and safety endpoints differed by baseline diuretic use, as well as the effect of semaglutide on loop diuretic use and dose changes over the 52-week treatment period. RESULTS: At baseline, across no diuretic (n=220), non-loop diuretic only (n=223), and loop diuretic (<40 [n=219], 40 [n=309], and >40 [n=174] mg/day furosemide-equivalents) groups, there was progressively higher prevalence of hypertension and atrial fibrillation; and severity of obesity and heart failure. Over 52 weeks of treatment, semaglutide had a consistent beneficial effect on change in body weight across diuretic use categories (adjusted mean difference vs. placebo ranged from -8.8% [95% CI -10.3, -6.3] to -6.9% [95% CI -9.1, -4.7] from no diuretics to the highest loop diuretic dose category; interaction P=0.39). Kansas City Cardiomyopathy Questionnaire clinical summary score improvement was greater in patients on loop diuretics compared to those not on loop diuretics (adjusted mean difference vs. placebo: +9.3 [6.5; 12.1] vs. +4.7 points [1.3, 8.2]; P=0.042). Semaglutide had consistent beneficial effects on all secondary efficacy endpoints (including 6-min walk distance) across diuretic subgroups (interaction P=0.24-0.92). Safety also favored semaglutide versus placebo across the diuretic subgroups. From baseline to 52 weeks, loop diuretic dose decreased by 17% in the semaglutide group vs. a 2.4% increase in the placebo group (P<0.0001). Semaglutide (vs. placebo) was more likely to result in loop diuretic dose reduction (odds ratio [OR] 2.67 [95% CI 1.70, 4.18]) and less likely dose increase (OR 0.35 [95% CI 0.23, 0.53]; P<0.001 for both) from baseline to 52 weeks. CONCLUSIONS: In patients with obesity-related HFpEF, semaglutide improved heart failure-related symptoms and physical limitations across diuretic use subgroups, with more pronounced benefits among patients receiving loop diuretics at baseline. Reductions in weight and improvements in exercise function with semaglutide versus placebo were consistent in all diuretic use categories. Semaglutide also led to a reduction in loop diuretic use and dose between baseline and 52 weeks. CLINICALTRIALS.GOV REGISTRATION: NCT04788511 and NCT04916470.

Maxillary sinus floor augmentation with autogenous bone graft compared with composite grafts: A one-year single-blinded randomized controlled trial.

OBJECTIVE: The objective was to assess the one year implant treatment outcome and patient-related outcome measures (PROMs) following maxillary sinus floor augmentation (MSFA) with autogenous bone graft (ABG) from the zygomatic buttress (control) compared with 1:1 mixture of ABG and anorganic porcine bone mineral (APBM) (Test I) or biphasic bone graft material (BBGM) (Test II). MATERIALS AND METHODS: Sixty healthy patients (34 females, 26 males) were randomly allocated to either control or test groups. Outcome measures included survival of suprastructures and implants, implant stability quotient, health status of peri-implant tissue, peri-implant marginal bone loss, frequency of complications, and PROMs using Oral Health Impact Profile-14 combined with questionnaire assessing patient perception of peri-implant soft tissue, prosthetic solution, implant function, and implant treatment outcome using visual analogue scale. Mean differences were expressed with standard deviation and 95% confidence interval. Level of significance was .05. RESULTS: All suprastructures and implants were well-functioning after one year of functional implant loading. There was no significant difference between control and test groups in any of the applied outcome measures. The implant stability significantly increased from implant placement to abutment connection within all groups (p < .001). High patient satisfaction and significant improvement in oral health-related quality of life was also reported within all groups. CONCLUSION: This study demonstrates that MSFA with composite grafts containing minimal amounts of ABG reveals comparable implant treatment outcomes as compared with ABG alone, after one year of functional implant loading. Extensive ABG harvesting in conjunction with MSFA therefore seems not to be needed.

Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes.

BACKGROUND: Obesity and type 2 diabetes are prevalent in patients with heart failure with preserved ejection fraction and are characterized by a high symptom burden. No approved therapies specifically target obesity-related heart failure with preserved ejection fraction in persons with type 2 diabetes. METHODS: We randomly assigned patients who had heart failure with preserved ejection fraction, a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more, and type 2 diabetes to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS: A total of 616 participants underwent randomization. The mean change in the KCCQ-CSS was 13.7 points with semaglutide and 6.4 points with placebo (estimated difference, 7.3 points; 95% confidence interval [CI], 4.1 to 10.4; P<0.001), and the mean percentage change in body weight was -9.8% with semaglutide and -3.4% with placebo (estimated difference, -6.4 percentage points; 95% CI, -7.6 to -5.2; P<0.001). The results for the confirmatory secondary end points favored semaglutide over placebo (estimated between-group difference in change in 6-minute walk distance, 14.3 m [95% CI, 3.7 to 24.9; P = 0.008]; win ratio for hierarchical composite end point, 1.58 [95% CI, 1.29 to 1.94; P<0.001]; and estimated treatment ratio for change in CRP level, 0.67 [95% CI, 0.55 to 0.80; P<0.001]). Serious adverse events were reported in 55 participants (17.7%) in the semaglutide group and 88 (28.8%) in the placebo group. CONCLUSIONS: Among patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes, semaglutide led to larger reductions in heart failure-related symptoms and physical limitations and greater weight loss than placebo at 1 year. (Funded by Novo Nordisk; STEP-HFpEF DM ClinicalTrials.gov number, NCT04916470.).

Proteomics couples electrical remodelling to inflammation in a murine model of heart failure with sinus node dysfunction.

AIMS: In patients with heart failure (HF), concomitant sinus node dysfunction (SND) is an important predictor of mortality, yet its molecular underpinnings are poorly understood. Using proteomics, this study aimed to dissect the protein and phosphorylation remodelling within the sinus node in an animal model of HF with concurrent SND. METHODS AND RESULTS: We acquired deep sinus node proteomes and phosphoproteomes in mice with heart failure and SND and report extensive remodelling. Intersecting the measured (phospho)proteome changes with human genomics pharmacovigilance data, highlighted downregulated proteins involved in electrical activity such as the pacemaker ion channel, Hcn4. We confirmed the importance of ion channel downregulation for sinus node physiology using computer modelling. Guided by the proteomics data, we hypothesized that an inflammatory response may drive the electrophysiological remodeling underlying SND in heart failure. In support of this, experimentally induced inflammation downregulated Hcn4 and slowed pacemaking in the isolated sinus node. From the proteomics data we identified proinflammatory cytokine-like protein galectin-3 as a potential target to mitigate the effect. Indeed, in vivo suppression of galectin-3 in the animal model of heart failure prevented SND. CONCLUSION: Collectively, we outline the protein and phosphorylation remodeling of SND in heart failure, we highlight a role for inflammation in electrophysiological remodelling of the sinus node, and we present galectin-3 signalling as a target to ameliorate SND in heart failure.

High-throughput DNA extraction and cost-effective miniaturized metagenome and amplicon library preparation of soil samples for DNA sequencing.

Reductions in sequencing costs have enabled widespread use of shotgun metagenomics and amplicon sequencing, which have drastically improved our understanding of the microbial world. However, large sequencing projects are now hampered by the cost of library preparation and low sample throughput, comparatively to the actual sequencing costs. Here, we benchmarked three high-throughput DNA extraction methods: ZymoBIOMICS™ 96 MagBead DNA Kit, MP BiomedicalsTM FastDNATM-96 Soil Microbe DNA Kit, and DNeasy® 96 PowerSoil® Pro QIAcube® HT Kit. The DNA extractions were evaluated based on length, quality, quantity, and the observed microbial community across five diverse soil types. DNA extraction of all soil types was successful for all kits, however DNeasy® 96 PowerSoil® Pro QIAcube® HT Kit excelled across all performance parameters. We further used the nanoliter dispensing system I.DOT One to miniaturize Illumina amplicon and metagenomic library preparation volumes by a factor of 5 and 10, respectively, with no significant impact on the observed microbial communities. With these protocols, DNA extraction, metagenomic, or amplicon library preparation for one 96-well plate are approx. 3, 5, and 6 hours, respectively. Furthermore, the miniaturization of amplicon and metagenome library preparation reduces the chemical and plastic costs from 5.0 to 3.6 and 59 to 7.3 USD pr. sample. This enhanced efficiency and cost-effectiveness will enable researchers to undertake studies with greater sample sizes and diversity, thereby providing a richer, more detailed view of microbial communities and their dynamics.

Small bowel anastomosis in emergency surgery.

BACKGROUND: Emergency laparotomy is associated with a high morbidity and mortality rate. The decision on whether to perform an anastomosis or an enterostomy in emergency small bowel resection is guided by surgeon preference alone, and not evidence based. We examined the risks involved in small bowel resection and anastomosis in emergency surgery. METHODS: A retrospective study from 2016 to 2019 in a university hospital in Denmark, including all emergency laparotomies, where small-bowel resections, ileocecal resections, right hemicolectomies and extended right hemicolectomies where performed. Demographics, operative data, anastomosis or enterostomy, as well as postoperative complications were recorded. Primary outcome was the rate of bowel anastomosis. Secondary outcomes were the anastomotic leak rate, mortality and complication rates. RESULTS: During the 3.5-year period, 370 patients underwent emergency bowel resection. Of these 313 (84.6%) received an anastomosis and 57 (15.4%) an enterostomy. The 30-day mortality rate was 12.7% (10.2% in patients with anastomosis and 26.3% in patients with enterostomy). The overall anastomotic leak rate was 1.6%, for small-bowel to colon 3.0% and for small-bowel to small-bowel 0.6%. CONCLUSION: A primary anastomosis is performed in more than eight out of 10 patients in emergency small bowel resections and is associated with a very low rate of anastomotic leak.

Profiling native pulmonary basement membrane stiffness using atomic force microscopy.

Mammalian cells sense and react to the mechanics of their immediate microenvironment. Therefore, the characterization of the biomechanical properties of tissues with high spatial resolution provides valuable insights into a broad variety of developmental, homeostatic and pathological processes within living organisms. The biomechanical properties of the basement membrane (BM), an extracellular matrix (ECM) substructure measuring only ∼100-400 nm across, are, among other things, pivotal to tumor progression and metastasis formation. Although the precise assignment of the Young's modulus E of such a thin ECM substructure especially in between two cell layers is still challenging, biomechanical data of the BM can provide information of eminent diagnostic potential. Here we present a detailed protocol to quantify the elastic modulus of the BM in murine and human lung tissue, which is one of the major organs prone to metastasis. This protocol describes a streamlined workflow to determine the Young's modulus E of the BM between the endothelial and epithelial cell layers shaping the alveolar wall in lung tissues using atomic force microscopy (AFM). Our step-by-step protocol provides instructions for murine and human lung tissue extraction, inflation of these tissues with cryogenic cutting medium, freezing and cryosectioning of the tissue samples, and AFM force-map recording. In addition, it guides the reader through a semi-automatic data analysis procedure to identify the pulmonary BM and extract its Young's modulus E using an in-house tailored user-friendly AFM data analysis software, the Center for Applied Tissue Engineering and Regenerative Medicine processing toolbox, which enables automatic loading of the recorded force maps, conversion of the force versus piezo-extension curves to force versus indentation curves, calculation of Young's moduli and generation of Young's modulus maps, where the pulmonary BM can be identified using a semi-automatic spatial filtering tool. The entire protocol takes 1-2 d.

The Body weight Reducing Effects of Tirzepatide in People with and without Type 2 Diabetes: A Review on Efficacy and Adverse Effects.

Obesity is becoming more frequent and has several negative health impacts. Recent advances in weight management strategies have primarily resided in pharmaceutical treatments, and the glucagon-like peptide-1 (GLP-1) receptor agonists have shown great potential in terms of body weight reduction in addition to improving glycemic control in patients with type 2 diabetes (T2D). Recently, the dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide has been developed. Tirzepatide has shown strong effects on glycated hemoglobin (HbA1C) levels in several clinical trials including participants with T2D (SURPASS program). In addition to its lowering effect on HbA1C, tirzepatide leads to substantial reductions in body weight, and a series of clinical trials (SURMOUNT program) have investigated the effects on body weight as the primary outcome. In these two trial programs, tirzepatide in doses of 5 mg to 15 mg administered subcutaneously once weekly resulted in body weight reduction of up to 15% in participants with T2D and up to 21% in participants without T2D, despite comparable baseline bodyweight. Across the two trial programs, adverse effects were mainly gastrointestinal (nausea, diarrhea, and vomiting) occurring with similar incidences of vomiting and lower incidences of diarrhea and nausea in trial participants with T2D compared to trials participants without T2D. Overall, discontinuation due to adverse events occurred in 3-7% of participants with no major differences between individuals with and without T2D. The higher weight-reducing efficacy of tirzepatide in trial participants without T2D is currently unexplained and may be partly reflected in dissimilarities in frequencies of gastrointestinal adverse events. The weight reducing effects of tirzepatide hold great promise for weight management in obese patients regardless of the presence of T2D.

Incidence of dislocation and associated risk factors in patients with a femoral neck fracture operated with an uncemented hemiarthroplasty.

BACKGROUND: Several factors might be associated with risk of dislocating following uncemented hemiarthroplasty (HA) due to femoral neck fracture (FNF). Current evidence is limited with great variance in reported incidence of dislocation (1-15%). Aim of this study was to identify the cumulative incidence of first-time dislocation following HA and to identify the associated risk factors. METHOD: We performed a retrospective cohort study of patients receiving an HA (BFX Biomet stem, posterior approach) at Copenhagen University Hospital, Bispebjerg, in 2010-2016. Patients were followed until death or end of study (dec 2018). Dislocation was identified by code extraction from the Danish National Patient Registry. Variables included in the multivariate model were defined pre-analysis to include: age, sex and variables with a p-value < 0.1 in univariate analysis. A regression model was fitted for 90 days dislocation as the assumption of proportional hazard rate (HR) was not met here after. RESULTS: We identified 772 stems (some patients occurred with both right and left hip) and 58 stems suffered 90 dislocations during the observation period, resulting in a 7% (CI 5-9) incidence of dislocation 90 days after index surgery. 55 of the 58 stems (95%) experienced the first dislocation within 90 days after surgery. Only absence of dementia was identified as an independent protective factor in the cause-specific model (HR 0.46 (CI 0.23-0.89)) resulting in a 2.4-fold cumulative risk of experiencing a dislocation in case of dementia. Several other variables such as age, sex, various medical conditions, surgery delay and surgical experience were eliminated as statistical risk factors. We found a decrease in survival probability for patients who experienced a dislocation during follow-up. CONCLUSIONS: The incidence of first-time dislocation of HA (BFX Biomet stem, posterior approach) in patients with a hip fracture is found to be 7% 90 days after surgery. Due to the non-existing attribution bias, we claim it to be the true incidence. Dementia was among several variables identified as the only risk factor for dislocation. In perspective, we may consider treating patients with dementia by other methods than HA e.g., HA with cement or with a more constrained solution. Also, a surgical approach that reduce the risk of dislocation should be considered.

Amyloid-ß aggregates activate peripheral monocytes in mild cognitive impairment.

The peripheral immune system is important in neurodegenerative diseases, both in protecting and inflaming the brain, but the underlying mechanisms remain elusive. Alzheimer's Disease is commonly preceded by a prodromal period. Here, we report the presence of large Aß aggregates in plasma from patients with mild cognitive impairment (n = 38). The aggregates are associated with low level Alzheimer's Disease-like brain pathology as observed by 11C-PiB PET and 18F-FTP PET and lowered CD18-rich monocytes. We characterize complement receptor 4 as a strong binder of amyloids and show Aß aggregates are preferentially phagocytosed and stimulate lysosomal activity through this receptor in stem cell-derived microglia. KIM127 integrin activation in monocytes promotes size selective phagocytosis of Aß. Hydrodynamic calculations suggest Aß aggregates associate with vessel walls of the cortical capillaries. In turn, we hypothesize aggregates may provide an adhesion substrate for recruiting CD18-rich monocytes into the cortex. Our results support a role for complement receptor 4 in regulating amyloid homeostasis.

Histological and radiological outcome after horizontal guided bone regeneration with bovine bone mineral alone or in combination with bone in edentulous atrophic maxilla: A randomized controlled trial.

OBJECTIVE: To assess the radiological and histological outcome after horizontal guided bone regeneration (GBR) with deproteinized bovine bone mineral (DBBM) alone or in combination with particulate autogenous bone (PAB). MATERIALS AND METHODS: Eighteen edentulous patients with an alveolar ridge of ≤4 mm were included in this split-mouth randomized controlled trial. Horizontal GBR with a graft composition of 100% DBBM (100:0) on one side and 90% DBBM and 10% PAB (90:10) on the other side were conducted in all patients. Cone beam computed tomography (CBCT) was obtained preoperatively, immediately postoperative, and after 10 months of healing. Width and volumetric changes in the alveolar process were measured on CBCT. Implants were placed after 10 months of graft healing where biopsies were obtained for histomorphometrical evaluation. RESULTS: The gained widths were 4.9 (±2.4) mm (100:0) and 4.5 (±2.0) mm (90:10) at 3 mm from the top of the crest, and 5.6 (±1.3) mm (100:0) and 4.6 (±2.1) mm (90:10) at 6 mm from the top of the crest. The mean volumetric reductions were 32.8% (±23.8) (100:0) and 38.2% (±23.2) (90:10). Histomorphometry revealed that mean percentages of bone were 50.8% (±10.7) (100:0) and 46.4% (±11.3) (90:10), DBBM were 31.6% (±12.6) (100:0) and 35.4% (±14.8) (90:10), and non-mineralized tissue were 17.6% (±11.7; 100:0) and 18.2% (±18.2) (90:10). No significant differences were evident between in any evaluated parameters. CONCLUSIONS: There were no additional effects of adding PAB to DBBM regarding bone formation, width changes, or volumetric changes after 10 months of graft healing.

Effects of Semaglutide on Symptoms, Function, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction and Obesity: A Prespecified Analysis of the STEP-HFpEF Trial.

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity experience a high burden of symptoms and functional impairment, and a poor quality of life. In the STEP-HFpEF trial (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity), once-weekly semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight. This prespecified analysis investigated the effects of semaglutide on the primary and confirmatory secondary end points across the range of the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores at baseline and on all key summary and individual KCCQ domains. METHODS: STEP-HFpEF randomly assigned 529 participants with symptomatic HF, an ejection fraction of ≥45%, and a body mass index of ≥30 kg/m2 to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. Dual primary end points change in KCCQ-Clinical Summary Score (CSS) and body weight. Confirmatory secondary end points included change in 6-minute walk distance, a hierarchical composite end point (death, HF events, and change in KCCQ-CSS and 6-minute walk distance) and change in C-reactive protein. Patients were stratified by KCCQ-CSS tertiles at baseline. Semaglutide effects on the primary, confirmatory secondary, and select exploratory end points (N-terminal pro-brain natriuretic peptide) were examined across these subgroups. Semaglutide effects on additional KCCQ domains (Total Symptom Score [including symptom burden and frequency], Physical Limitations Score, Social Limitations Score, Quality of Life Score, and Overall Summary Score) were also evaluated. RESULTS: Baseline median KCCQ-CSS across tertiles was 37, 59, and 77 points, respectively. Semaglutide consistently improved primary end points across KCCQ tertiles 1 to 3 (estimated treatment differences [95% CI]: for KCCQ-CSS, 10.7 [5.4 to 16.1], 8.1 [2.7 to 13.4], and 4.6 [-0.6 to 9.9] points; for body weight, -11 [-13.2 to -8.8], -9.4 [-11.5 to -7.2], and -11.8 [-14.0 to -9.6], respectively; Pinteraction=0.28 and 0.29, respectively); the same was observed for confirmatory secondary and exploratory end points (Pinteraction>0.1 for all). Semaglutide-treated patients experienced improvements in all key KCCQ domains (estimated treatment differences, 6.7-9.6 points across domains; P≤0.001 for all). Greater proportion of semaglutide-treated versus placebo-treated patients experienced at least 5-, 10-, 15-, and 20-point improvements in all KCCQ domains (odds ratios, 1.6-2.9 across domains; P<0.05 for all). CONCLUSIONS: In patients with HFpEF and obesity, semaglutide produced large improvements in HF-related symptoms, physical limitations, exercise function, inflammation, body weight, and N-terminal pro-brain natriuretic peptide, regardless of baseline health status. The benefits of semaglutide extended to all key KCCQ domains. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04788511.

Bilateral sagittal split osteotomy with or without concomitant removal of third molars: a retrospective cohort study of related complications and bone healing.

PURPOSE: To carry out a comparative evaluation of the intra- and postoperative complications, and bone healing, following bilateral sagittal split osteotomy (BSSO) with or without concomitant removal of third molars. MATERIAL AND METHODS: A retrospective analysis was performed of two cohorts subjected to BSSO with the intraoperative removal of third molars (test group) versus the removal of third molars at least 6 months prior to BSSO (control group), comprising at least 1 year of clinical and radiographic follow-up. Partially or completely erupted third molars were extracted immediately before completing the osteotomy, whereas impacted third molars were removed after the osteotomy had been performed. Hardware reinforcement was performed in bimaxillary cases where concomitant molar extraction impeded placement of the retromolar bicortical screw of the hybrid technique. RESULTS: A total of 80 surgical sites were included (40 in each group). Concomitant extraction of the molar represented a mean increase in surgery time of 3.7 min (p < 0.001). No additional complications occurred in the test group (p = 0.476). The gain in bone density was preserved in both groups (p = 0.002), and the increase was of the same magnitude in both (p = 0.342), despite the fact that the immediate and final postoperative bone densities were significantly higher in the control group (p = 0.020). CONCLUSION: The results obtained support concomitant molar extraction with BSSO as a feasible option.

Effect of four eggshell repair materials on weight loss during incubation of white leghorn chicken eggs.

Egg weight loss during incubation is a key indicator used to monitor successful egg development and is closely related to hatchability and chick survival. Artificial incubation is one of the most important captive breeding techniques used in conservation efforts to bolster avian populations. To repair damage to the eggshell and ensure embryonic viability during incubation, a variety of repair coverings can be applied. This study tested the impact of four repair materials (nail polish, synthetic glue, medical dressing, and molten wax film) on egg weight loss during incubation. We found no impact on weight loss for coverings smaller than 35% of the eggshell surface, nor did we find any differences between covering types. The average egg weight loss decreased as the coverage area increased, and the weight loss did not differ when blunt versus sharp-end coverings were compared. Given the relative insensitivity of egg weight loss and survival to the type of patch material used, we concluded that the selection of material for the purpose of weight loss management could be based on practical considerations, such as ease of application and availability.

Intensified acute in-hospital physiotherapy for patients after hip fracture surgery: a pragmatic, randomized, controlled feasibility trial.

PURPOSE: Intensified acute in-hospital physiotherapy (IP) after hip fracture (HF) may enhance patient's ability to regain basic mobility at discharge. The primary objective was to assess the feasibility of IP. Secondary to estimate the effect of IP on regained basic mobility at discharge. MATERIALS AND METHODS: In a pragmatic, randomized, unblinded feasibility trial, 60 patients (mean age 79 years, 41 women) with HF and an independent pre-fracture basic mobility level were randomized (2:1) to IP with two daily sessions on weekdays focusing on functional training and weight-bearing activities (n = 40) versus usual care (UC) physiotherapy once daily (n = 20). Feasibility outcomes included physiotherapy completion rates, reasons for non-successful completion, and adverse events. The primary effect outcome was recovery of basic mobility (Cumulated Ambulation Score (CAS)). RESULTS: Eighty-two percent of the sessions in the IP group were successfully- or partially completed versus 94% of the sessions in the UC group. No adverse events occurred. The main reason for not completing physiotherapy was fatigue. At discharge (median 7 days), 50% in the IP group had regained their pre-fracture basic mobility level (CAS = 6) versus 16% in the UC group; odds ratio = 5.33, 95%CI [1.3;21.5]. CONCLUSIONS: IP seems feasible for patients after HF surgery, and it may enhance recovery. Fatigue was the primary obstacle to completing IP.

Two daily physiotherapy sessions focusing on functional training and weight-bearing activities are feasible for patients after isolated hip fracture surgery, including subtrochanteric fracture, and may enhance recovery of basic mobility at discharge.During hospitalization, patient participation in intensified physiotherapy is mainly restricted by fatigue.Systematic assessment and management of fatigue may improve the completion of physiotherapy and recovery of basic mobility.

Opportunity to Perform - Should Simulation-Based Surgical Training be Provided on Demand or on Supply?

Introduction: The aim of the study was to assess the surgical case volume of residents before and after simulation-based training in hip fracture surgery provided on demand versus knee and shoulder arthroscopy provided on supply. Materials and Methods: A retrospective analysis of surgical case volume in hip fracture surgery and arthroscopic shoulder and knee procedures 90 days before and after simulation-based training of either procedure. Sixty-nine orthopedic residents voluntarily participating in either simulation-based training. Hip fracture surgery simulation was provided on supply, ie, whenever 1-2 residents applied for the course, while the arthroscopic simulation course was supplied twice yearly. Results: Thirty-four residents participated in hip fracture simulation on demand and 35 residents participated in arthroscopic simulation on supply. The surgical case volume of hip fracture osteosynthesis increased from median 2.5 (range: 0-21) to median 11.5 (1-17) from 90 days before to the 90 days after the simulation-based training on demand. The median difference was 6.5 procedures (p < 0.0003). On the contrary, the surgical case volume in shoulder and knee arthroscopy was low both before and after the simulation on supply, ie, median 2 (0-22) before and median 1 (0-31) after. The median difference was 0 (p = 0.21). Conclusions: Simulation on demand was associated with increased opportunities to perform in the clinical environment after the simulation-based training compared with simulation on supply. Simulation-based training should be aligned with the clinical rotation of the residents. Simulation on demand instead of supply on fixed dates may overcome this organizational issue of aligning training with the opportunity to perform.

Preprosthetic Surgery-Narrative Review and Current Debate.

This review describes the role of modern preprosthetic surgery. The atrophic edentulous jaw can cause severe functional impairment for patients, leading to inadequate denture retention, reduced quality of life, and significant health problems. The aim of preprosthetic surgery is to restore function and form due to tooth loss arising from congenital deformity, trauma, or ablative surgery. Alveolar bone loss is due to disuse atrophy following tooth loss. The advent of dental implants and their ability to preserve bone heralded the modern version of preprosthetic surgery. Their ability to mimic natural teeth has overcome the age-old problem of edentulism and consequent jaw atrophy. Controversies with preprosthetic surgery are discussed: soft tissue versus hard tissue augmentation in the aesthetic zone, bone regeneration versus prosthetic tissue replacement in the anterior maxilla, sinus floor augmentation versus short implants in the posterior maxilla-interpositional bone grafting versus onlay grafts for vertical bone augmentation. Best results for rehabilitation are achieved by the team approach of surgeons, maxillofacial prosthodontists/general dentists, and importantly, informing patients about the available preprosthetic surgical options.

Taxonomic and environmental distribution of bacterial amino acid auxotrophies.

Many microorganisms are auxotrophic-unable to synthesize the compounds they require for growth. With this work, we quantify the prevalence of amino acid auxotrophies across a broad diversity of bacteria and habitats. We predicted the amino acid biosynthetic capabilities of 26,277 unique bacterial genomes spanning 12 phyla using a metabolic pathway model validated with empirical data. Amino acid auxotrophy is widespread across bacterial phyla, but we conservatively estimate that the majority of taxa (78.4%) are able to synthesize all amino acids. Our estimates indicate that amino acid auxotrophies are more prevalent among obligate intracellular parasites and in free-living taxa with genomic attributes characteristic of 'streamlined' life history strategies. We predicted the amino acid biosynthetic capabilities of bacterial communities found in 12 unique habitats to investigate environmental associations with auxotrophy, using data compiled from 3813 samples spanning major aquatic, terrestrial, and engineered environments. Auxotrophic taxa were more abundant in host-associated environments (including the human oral cavity and gut) and in fermented food products, with auxotrophic taxa being relatively rare in soil and aquatic systems. Overall, this work contributes to a more complete understanding of amino acid auxotrophy across the bacterial tree of life and the ecological contexts in which auxotrophy can be a successful strategy.