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• Wheezing infants are an important global public health issue in LIMC. • Determining whether wheezing is the correct definition is critical. • A differential diagnosis of the causes of wheezing and other sounds should be made. • Recurrent wheezing [RW] in infants may warrant a therapeutic trial with inhaled steroids. • In LMICS, RW may be prevented by reducing environmental factors such as smoking. • Early exposure to viral infection is a preventable cause of RW. To review the recent evidence in the literature of various aspects of recurrent/severe wheezing in children under 3 in low-middle income countries [LMICS]. A non-systematic review including articles in English. We mainly selected publications from the last 5 years. Studies on epidemiology, aetiology, diagnosis, treatment, and prevention were included in the search. We reviewed differential diagnoses of wheezing that focused on LMICS. We also reviewed aspects of prevention. Many epidemiological studies have shown a variable but significant number of wheezy infants [WI] cases in LMICS when compared to other countries. The differential diagnosis of causes of wheezing in this age group is mandatory, taking into account local facilities. Few treatment options have been well studied for this age group. In LMICS, a pragmatic approach could be considered, as described in the article. It is difficult to study primary prevention for WI and secondary prevention (mainly environmental) may have some impact. A schematic approach for recurrent wheezers is presented, which takes into account settings with limited resources. Severely or recurrently wheezy children under 3 is a common clinical issue in LMICS. Studies on this age group are needed to reduce the significant morbidity. It may be possible to lower the high burden of wheezing in this age group by selecting the phenotype which may respond to inhaled steroids. [ABSTRACT FROM AUTHOR]

Magnesium as a biodegradable material offers promising results in recent studies of different maxillo-facial fracture models. To overcome adverse effects caused by the fast corrosion of pure magnesium in fluid surroundings, various alloys, and surface modifications are tested in animal models. In specified cases, magnesium screws already appeared for clinical use in maxillofacial surgery. The present study aims to compare the bone healing outcome in a non-load-bearing fracture scenario of the forehead in sheep when fixed with standard-sized WE43 magnesium fixation plates and screws with plasma electrolytic oxidation (PEO) surface modification in contrast to titanium osteosynthesis. Surgery was performed on 24 merino mix sheep. The plates and screws were explanted en-bloc with the surrounding tissue after four and twelve weeks. The outcome of bone healing was investigated with micro-computed tomography, histological, immunohistological, and fluorescence analysis. There was no significant difference between groups concerning the bone volume, bone volume/ total volume, and newly formed bone in volumetric and histological analysis at both times of investigation. The fluorescence analysis revealed a significantly lower signal in the magnesium group after one week, although there was no difference in the number of osteoclasts per mm2. The magnesium group had significantly fewer vessels per mm2 in the healing tissue. In conclusion, the non-inferiority of WE43-based magnesium implants with PEO surface modification was verified concerning fracture healing under non-load-bearing conditions in a defect model. Titanium implants, the current gold standard of fracture fixation, can lead to adverse effects linked to the implant material and often require surgical removal. Therefore, degradable metals like the magnesium alloy WE43 with plasma electrolytic oxidation (PEO) surface modification gained interest. Yet, miniplates of this alloy with PEO surface modification have not been examined in a fracture defect model of the facial skeleton in a large animal model. This study shows, for the first time, the non-inferiority of magnesium miniplates compared to titanium miniplates. In radiological and histological analysis, bone healing was undisturbed. Magnesium miniplates can reduce the number of interventions for implant removal, thus reducing the risk for the patient and minimizing the costs. [Display omitted] [ABSTRACT FROM AUTHOR]

• Despite potential benefits, human-nature interactions are understudied in winter. • The frequency of high-engagement nature interaction was low in studied urban parks. • Visitors interacted most often with flora, then fauna and abiotic natural elements. • Behaviors like technology use associated with a lower odds of nature interaction. • Naturalized water features in greenspaces may encourage winter nature interaction. Interaction with urban nature provides many nature-derived benefits for people. However, human-nature interaction studies are conducted primarily during the vegetative season, but remain largely unexplored in winter. We therefore used non-participatory methods (i.e. systematically observing park users on-site) to characterize human-nature interactions in three urban parks in Stuttgart, Germany in the winter of 2020/2021 (N = 13,474 observations). Descriptive statistics were calculated and two multivariate logistic regression models built to serve as the basis for analyses. Results indicated that high-engagement human-nature interaction (i.e. nature photography, active observation, touching, or collecting natural elements) was generally low (2.4 % of observations) and that park visitors most frequently interacted with flora, then fauna, and finally abiotic natural elements. Certain visitation behaviors including technology use and visiting alone were associated with a lower odds of high-engagement nature interaction, whereas walking a dog was associated with a higher odds of high-engagement nature interaction. Additionally, odds of high-engagement nature interaction were higher at sites with a naturalized pond. While these findings are context-specific, they provide insight into the number of people that participate in high-engagement nature interaction, details into how they interact with urban nature in winter, and have potential implications for the design and management of urban greenspaces in future cities that best support both people and nature year round. [Display omitted] [ABSTRACT FROM AUTHOR]

Celiac disease (CeD) is an immune-mediated disorder affecting the small bowel, associated with genetic factors and increasing global prevalence. This study explores the association between CeD, Systemic Lupus Erythematosus (SLE), primary Sjogren syndrome (pSS), and Systemic Sclerosis (SSc). A systematic review and meta-analysis were conducted following PRISMA guidelines. Searches across multiple databases yielded 2728 articles, with 15 studies selected. Data extraction included study characteristics, prevalence of CeD and CeD antibodies in SLE, pSS, and SSc. Quality assessment utilized the Newcastle-Ottawa Scale. The meta-analysis revealed a pooled prevalence of biopsy-proven CeD in SLE, pSS, and SSc of approximately 3%. Seroprevalence of any CeD antibody in SLE, pSS, and SSc ranged from 3% to 10%. Notably, pSS exhibited the highest prevalence at 5.59%. High heterogeneity was observed in seroprevalence across autoimmune conditions. Quality assessment indicated robust methodological quality in the selected studies. This study highlights a significantly higher prevalence of CeD, especially pSS, compared to the general population. The findings underscore the importance of recognizing elevated CeD antibodies in patients with SLE, pSS and SSc emphasizing the need for early detection and comprehensive care for gastrointestinal symptoms in these conditions. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? What are the cognitive profiles of older adults with remitted major depressive disorder (rMDD) with or without mild cognitive impairment (MCI)? How do these profiles differ in terms of clinical, demographic, and brain structure features? • What is the main finding of this study? Using latent profile analysis, we identified three cognitive profiles, with differences in cognition, physical health, education, and brain structure. • What is the meaning of the finding? Older patients with rMDD can be grouped cross-sectionally based on distinct data-driven cognitive profiles that differ from the absence or presence of a diagnosis of MCI. To identify data-driven cognitive profiles in older adults with remitted major depressive disorder (rMDD) with or without mild cognitive impairment (MCI) and examine how the profiles differ regarding demographic, clinical, and neuroimaging measures. Secondary cross-sectional analysis using latent profile analysis. Multisite clinical trial in Toronto, Canada. One hundred seventy-eight participants who met DSM-5 criteria for rMDD without MCI (rMDD-MCI; n = 60) or with MCI (rMDD + MCI; n = 118). Demographic, clinical, neuroimaging measures, and domain scores from a neuropsychological battery assessing verbal memory, visuospatial memory, processing speed, working memory, language, and executive function. We identified three latent profiles: Profile 1 (poor cognition ; n = 75, 42.1%), Profile 2 (intermediate cognition ; n = 75, 42.1%), and Profile 3 (normal cognition ; n = 28, 15.7%). Compared to participants with Profile 3, those with Profile 1 or 2 were older, had lower education, experienced a greater burden of medical comorbidities, and were more likely to have MCI. The profiles did not differ on the severity of residual symptoms, age of onset of rMDD, number of depressive episodes, psychotropic medication, cerebrovascular risk, ApoE4 carrier status, or family history of depression, dementia, or Alzheimer's disease. The profiles differed in cortical thickness of 15 regions, with the most prominent effects for left precentral and pars opercularis, and right inferior parietal and supramarginal. Older patients with rMDD can be grouped cross-sectionally based on data-driven cognitive profiles that differ from the absence or presence of a diagnosis of MCI. Future research should determine the differential risk for dementia of these data-driven subgroups. [ABSTRACT FROM AUTHOR]

Assess the feasibility of a prototype image reconstruction algorithm in correcting motion artifacts in cone-beam computed tomography (CBCT) scans of interventional instruments in the lung. First, phantom experiments were performed to assess the algorithm, using the Xsight lung phantom with custom inserts containing straight or curved catheters. During scanning, the inserts moved in a continuous sinusoidal or breath-hold mimicking pattern, with varying amplitudes and frequencies. Subsequently, the algorithm was applied to CBCT data from navigation bronchoscopy procedures. The algorithm's performance was assessed quantitatively via edge-sharpness measurements and qualitatively by three specialists. In the phantom study, the algorithm improved sharpness in 13 out of 14 continuous sinusoidal motion and five out of seven breath-hold mimicking scans, with more significant effects at larger motion amplitudes. Analysis of 27 clinical scans showed that the motion corrected reconstructions had significantly sharper edges than standard reconstructions (2.81 (2.24–6.46) vs. 2.80 (2.16–4.75), p = 0.003). These results were consistent with the qualitative assessment, which showed higher scores in the sharpness of bronchoscope-tissue interface and catheter-tissue interface in the motion-corrected reconstructions. However, the tumor demarcation ratings were inconsistent between raters, and the overall image quality of the new reconstructions was rated lower. Our findings suggest that applying the new prototype algorithm for motion correction in CBCT images is feasible. The algorithm improved the sharpness of medical instruments in CBCT scans obtained during diagnostic navigation bronchoscopy procedures, which was demonstrated both quantitatively and qualitatively. [ABSTRACT FROM AUTHOR]

Limited comparative data exist on different interventional strategies for endovascular revascularization of complex femoropopliteal interventions. In this study, the authors aimed to compare a stent-avoiding (SA) vs a stent-preferred (SP) strategy, promoting optimal lesion preparation and the use of drug-eluting technologies in both arms. Within a prospective, multicenter, pilot study, 120 patients with symptomatic complex femoropopliteal lesions (Rutherford classification 2-4, mean lesion length 187.7 ± 78.3 mm, 79.2% total occlusions) were randomly assigned in a 1:1 fashion to endovascular treatment with either paclitaxel-coated balloons or polymer-coated, paclitaxel-eluting stents. Lesion preparation including the use of devices for plaque modification and/or removal was at the operators' discretion in both treatment arms. In the SA group, lesion preparation was more frequently performed (71.7% SA [43/60] vs 51.7% [31/60] SP; P = 0.038) with a high provisional stenting rate (48.3% [29/60]). At the 12-month follow-up, primary patency was 78.2% (43/55) in the SA group and 78.6% (44/56) in the SP group (P = 1.0; relative risk: 0.995; 95% CI: 0.818-1.210). Freedom from major adverse events was determined in 93.1% (54/58) in the SA group and in 94.9% (56/59) in the SP group (P = 0.717; relative risk: 0.981; 95% CI: 0.895-1.075), with all adverse events attributable to clinically driven target lesion revascularization. Both endovascular strategies promoting lesion preparation before the use of drug-eluting devices suggest promising efficacy and safety results in complex femoropopliteal procedures with a high proportion of total occlusions through 12 months. Ongoing follow-up will show whether different results emerge over time. (Best Endovascular Strategy for Complex Lesions of the Superficial Femoral Artery [BEST-SFA]; NCT03776799) [Display omitted] [ABSTRACT FROM AUTHOR]

Gait impairment has a major impact on quality of life in patients with Parkinson's disease (PD). It is believed that basal ganglia oscillatory activity at β frequencies (15–30 Hz) may contribute to gait impairment, but the precise dynamics of this oscillatory activity during gait remain unclear. Additionally, auditory cues are known to lead to improvements in gait kinematics in PD. If the neurophysiological mechanisms of this cueing effect were better understood they could be leveraged to treat gait impairments using adaptive Deep Brain Stimulation (aDBS) technologies. We aimed to characterize the dynamics of subthalamic nucleus (STN) oscillatory activity during stepping movements in PD and to establish the neurophysiological mechanisms by which auditory cues modulate gait. We studied STN local field potentials (LFPs) in eight PD patients while they performed stepping movements. Hidden Markov Models (HMMs) were used to discover transient states of spectral activity that occurred during stepping with and without auditory cues. The occurrence of low and high β bursts was suppressed during and after auditory cues. This manifested as a decrease in their fractional occupancy and state lifetimes. Interestingly, α transients showed the opposite effect, with fractional occupancy and state lifetimes increasing during and after auditory cues. We show that STN oscillatory activity in the α and β frequency bands are differentially modulated by gait-promoting oscillatory cues. These findings suggest that the enhancement of α rhythms may be an approach for ameliorating gait impairments in PD. • Integrating MEMD and TDE-HMM to decode deep brain states at short timescales. • Auditory cues induce opposite effects on transient α and low-β activities. • Auditory cues enhance α activity, whilst suppressing synchronisation of β band. [ABSTRACT FROM AUTHOR]

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Many canine cardiac diseases are associated with left atrial (LA) remodeling and decreased function. For accurate assessment of LA indices, large-scale and prospectively determined reference intervals are necessary. To generate reference intervals of LA size and function using two-dimensional and three-dimensional echocardiography. Two hundred and one healthy adult dogs. Left atrial volume was assessed in right parasternal long-axis, left apical four-chamber and two-chamber views using monoplane Simpson's method, two-dimensional and three-dimensional speckle tracking. Additionally, LA diameter was measured in right parasternal short-axis and long-axis views. Furthermore, LA function was determined by measuring strain and calculating LA fractional shortening and ejection fraction. All variables were tested for correlation to heart rate, age, and body weight. For LA diameter and volume, scaling exponents and prediction intervals were generated using allometric scaling. Reference intervals for LA function parameters were calculated using nonparametric methods. Left atrial diameter and volume showed a strong correlation with body weight. The scaling exponent for LA diameter was approximately 1/3 (0.34–0.40) and approximately one for volume measurements (0.97–1.26). Parameters of LA function showed no clinically relevant correlation with body weight, except for two variables, which showed a mild negative correlation. No clinically relevant correlations with age or heart rate were found. Reference intervals for linear, two-dimensional and three-dimensional measurements of LA size and function were established. The wide range of measurement methods offers the opportunity to select the appropriate reference values for LA evaluation depending on the available technical possibilities. [ABSTRACT FROM AUTHOR]

Metastasis suppressor protein 1 (MTSS1) is a prognostic tumour marker in different malignant epithelial tumour entities and previously mainly the MTSS1 expression was analysed. This study evaluated the best analysis method as a prognosis and aggressiveness tumour marker in head and neck squamous cell carcinoma (HNSCC). MTSS1 expression, MTSS1 intensity, interpretation MTSS1 score and MTSS1 edging score were analysed in formalin-fixed paraffin-embedded tissue slices of 60 patients with proven HNSCC and correlated with clinical and pathological outcome parameters. A lack of MTSS1 expression showed tumour aggressiveness, but surprisingly, mainly MTSS1 intensity was correlated with a worse patient outcome. There was a significant correlation between higher MTSS1 intensity and an increased risk for lymph node metastasis (P =.027) and a significant increased risk for extracapsular growth (P =.016). Furthermore, disease-specific survival was worse in cases with higher MTSS1 intensity (P =.001). MTSS1 intensity has a high scientific potential for further studies and could potentially be used as a prognostic marker in diagnostic and therapeutic decision-making. [ABSTRACT FROM AUTHOR]

Immunocompromised patients are at an increased risk of severe legionella infections. We present the results of an outbreak investigation initiated following a fatal case of hospital-acquired legionellosis linked to contaminated water from a toilet-flushing cistern. Additionally, we provide experimental data on the growth of Legionella spp. in flushing cisterns and propose a straightforward protocol for prevention. We monitored the growth of Legionella spp. in the building's hot- and cold-water systems using quantitative bacterial culture on selective agar. Molecular typing of Legionella pneumophila isolates from the infected patient and the water system was conducted through core-genome multi-locus sequence typing (cgMLST). Legionella contamination in the hospital building's cold-water system was significantly higher than in the hot-water system and significantly higher in toilet flushing cistern's water compared with cold water from bathroom sinks and showers. Isolates from the patient and from the flushing cistern of the patient's bathroom were identical by cgMLST. In an experimental setting, daily toilet flushing for a period of 21 days resulted in a 67% reduction in the growth of Legionella spp. in the water of toilet flushing cisterns. Moreover, a one-time disinfection of cisterns with peracetic acid, followed by daily flushing, decreased legionella growth to less than 1% over a period of at least seven weeks in these setting. One-time disinfection of highly contaminated cisterns with peracetic acid and daily toilet flushing as short-term measure can significantly reduce legionella contamination in flushing cisterns. These measures may aid in preventing legionella infection among immunocompromised patients. [ABSTRACT FROM AUTHOR]

It seems puzzling why humans have evolved such a small and rigid birth canal that entails a relatively complex process of labor compared with the birth canal of our closest relatives, the great apes. This study reviewed insights into the evolution of the human birth canal from recent theoretical and empirical studies and discussed connections to obstetrics, gynecology, and orthopedics. Originating from the evolution of bipedality and the large human brain million years ago, the evolution of the human birth canal has been characterized by complex trade-off dynamics among multiple biological, environmental, and sociocultural factors. The long-held notion that a wider pelvis has not evolved because it would be disadvantageous for bipedal locomotion has not yet been empirically verified. However, recent clinical and biomechanical studies suggest that a larger birth canal would compromise pelvic floor stability and increase the risk of incontinence and pelvic organ prolapse. Several mammals have neonates that are equally large or even larger than human neonates compared to the size of the maternal birth canal. In these species, the pubic symphysis opens widely to allow successful delivery. Biomechanical and developmental constraints imposed by bipedality have hindered this evolutionary solution in humans and led to the comparatively rigid pelvic girdle in pregnant women. Mathematical models have shown why the evolutionary compromise to these antagonistic selective factors inevitably involves a certain rate of fetopelvic disproportion. In addition, these models predict that cesarean deliveries have disrupted the evolutionary equilibrium and led to new and ongoing evolutionary changes. Different forms of assisted birth have existed since the stone age and have become an integral part of human reproduction. Paradoxically, by buffering selection, they may also have hindered the evolution of a larger birth canal. Many of the biological, environmental, and sociocultural factors that have influenced the evolution of the human birth canal vary globally and are subject to ongoing transitions. These differences may have contributed to the global variation in the form of the birth canal and the difficulty of labor, and they likely continue to change human reproductive anatomy. [ABSTRACT FROM AUTHOR]

The objectives of this minireview are two-fold. The first is to discuss the evolution of opioid analgesia in perioperative medicine in the context of thoracic non-cardiac surgery. Current standard-of-care, aiming to optimize analgesia and limit undesirable side effects, is discussed in the context of multimodal analgesia, specifically enhanced recovery after thoracic surgery pathways. The second is to review a developing research program that may ultimately add another element to the personalization of analgesic plans for individual cancer patients based on optimizing oncological outcomes. Termed "precision oncoanalgesia," this emerging field aims to elucidate how individual patient-specific tumor omics (genomics, transcriptomics, etc.) may mediate the effects of analgesic drugs on oncological recurrence and survival. [ABSTRACT FROM AUTHOR]

[Display omitted] Knowledge about atrial functional tricuspid regurgitation (afTR) in transcatheter aortic valve replacement (TAVR) patients is scarce. The aim of the study was to analyze the association between the entity and the development of tricuspid regurgitation (TR) in patients undergoing TAVR for aortic stenosis and concomitant TR. We analyzed patients undergoing TAVR for severe aortic stenosis from January 2013 to December 2020 and concomitant at least moderate TR at baseline. afTR was defined as enlargement of the right atrium in relation to the right ventricle. TR development after TAVR and 3-year all-cause mortality were evaluated. Out of 3,474 TAVR patients, we identified 420 patients with concomitant at least moderate TR. A total of 363 patients were included in the study, with 178 patients stratified in the afTR and 185 in the non-afTR group based on a receiver-operating characteristic curve cutoff of 1.132 of the right atrial/right ventricular area ratio. TR improvement after TAVR was observed in significantly less patients with afTR compared with non-afTR (31.1% vs 60.6%; P < 0.001). Multivariate regression analysis confirmed afTR as independent predictor for TR persistence (adjusted OR: 2.80; 95% CI: 1.66-4.76; P < 0.001). Moreover, afTR was associated with aggravation of TR after TAVR (17.0% vs 6.8%; P = 0.013). Three-year all-cause mortality was significantly higher in patients with persistence compared with patients with improvement of TR (P < 0.001). In TAVR patients, afTR is an independent predictor for TR persistence. Moreover, TR persistence is associated with increased 3-year all-cause mortality. [ABSTRACT FROM AUTHOR]

The study aimed to analyze bone regeneration in critical-size defects using hybrid scaffolds biomechanically adapted to the specific defect and adding the growth factor rh BMP-2. For this animal study, ten minipigs underwent bilateral defects in the corpus mandibulae and were subsequently treated with novel cylindrical hybrid scaffolds. These scaffolds were designed digitally to suit the biomechanical requirements of the mandibular defect, utilizing finite element analysis. The scaffolds comprised zirconium dioxide-tricalcium phosphate (ZrO 2 -TCP) support struts and TCP foam ceramics. One scaffold in each animal was loaded with rh BMP-2 (100 μg/cm³), while the other served as an unloaded negative control. Fluorescent dyes were administered every 2 weeks, and computed tomography (CT) scans were conducted every 4 weeks. Euthanasia was performed after 3 months, and samples were collected for examination using micro-CT and histological evaluation of both hard and soft tissue. Intravital CT examinations revealed minor changes in radiographic density from 4 to 12 weeks postoperatively. In the group treated with rh BMP-2, radiographic density shifted from 2513 ± 128 (mean ± SD) to 2606 ± 115 Hounsfield units (HU), while the group without rh BMP-2 showed a change from 2430 ± 131 to 2601 ± 67 HU. Prior to implantation, the radiological density of samples measured 1508 ± 30 mg HA/cm³, whereas post-mortem densities were 1346 ± 71 mg HA/cm³ in the rh BMP-2 group and 1282 ± 91 mg HA/cm³ in the control group (p = 0.045), as indicated by micro-CT measurements. The histological assessment demonstrated successful ossification in all specimens. The newly formed bone area proportion was significantly greater in the rh BMP-2 group (48 ± 10%) compared with the control group without rh BMP-2 (42 ± 9%, p = 0.03). The mean area proportion of remaining TCP foam was 23 ± 8% with rh BMP-2 and 24 ± 10% without rh BMP-2. Successful bone regeneration was accomplished by implanting hybrid scaffolds into critical-size mandibular defects. Loading these scaffolds with rh BMP-2 led to enhanced bone regeneration and a uniform distribution of new bone formation within the hybrid scaffolds. Further studies are required to determine the adaptability of hybrid scaffolds for larger and potentially segmental defects in the maxillofacial region. [ABSTRACT FROM AUTHOR]

Impaired bony healing following bilateral sagittal split osteotomy (BSSO) is a major unmet medical need for affected patients, and rare occurrences can hinder the identification of underlying risk factors. We hypothesised that osseous union following BSSO can be quantified using volumetric analysis, and we aimed to identify the risk factors for impaired bone healing. The percentage change in bony volume was measured in orthognathic patients following BSSO using two consecutive postoperative cone-beam computed tomography scans. Patients' characteristics and treatment parameters were documented, and correlation and regression analyses of these variables performed. Thirty-six patients (23 men and 13 women) with a mean (SD) age of 33.28 (11.86) years were included. The gap site (lingual versus buccal) (p < 0.01) had a significant impact on the change in volume. Age (p = 0.06) showed a trend towards significance. Initial width of the osteotomy gap, sex, and indication for surgery did not influence osseous healing. Increased age at surgery and the side of the buccal osteotomy are independent risk factors for impaired osseous healing following BSSO. [ABSTRACT FROM AUTHOR]

Since the onset of widespread COVID-19 vaccination, increased incidence of COVID-19 vaccine-associated myocarditis (VA-myocarditis) has been noted, particularly in male adolescents. Patients <18 years with suspected myocarditis following COVID-19 vaccination within 21 days were enrolled in the PedMYCVAC cohort, a substudy within the prospective multicenter registry for pediatric myocarditis "MYKKE." Clinical data at initial admission, 3- and 9-months follow-up were monitored and compared to pediatric patients with confirmed non–vaccine-associated myocarditis (NVA-myocarditis) adjusting for various baseline characteristics. From July 2021 to December 2022, 56 patients with VA-myocarditis across 15 centers were enrolled (median age 16.3 years, 91% male). Initially, 11 patients (20%) had mildly reduced left ventricular ejection fraction (LVEF; 45%-54%). No incidents of severe heart failure, transplantation or death were observed. Of 49 patients at 3-months follow-up (median (IQR) 94 (63-118) days), residual symptoms were registered in 14 patients (29%), most commonly atypical intermittent chest pain and fatigue. Diagnostic abnormalities remained in 23 patients (47%). Of 21 patients at 9-months follow-up (259 (218-319) days), all were free of symptoms and diagnostic abnormalities remained in 9 patients (43%). These residuals were mostly residual late gadolinium enhancement in magnetic resonance imaging. Patients with NVA-myocarditis (n=108) more often had symptoms of heart failure (P =.003), arrhythmias (P =.031), left ventricular dilatation (P =.045), lower LVEF (P <.001) and major cardiac adverse events (P =.102). Course of COVID-19 vaccine-associated myocarditis in pediatric patients seems to be mild and differs from non–vaccine-associated myocarditis. Due to a considerable number of residual symptoms and diagnostic abnormalities at follow-up, further studies are needed to define its long-term implications. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Heterogeneity in forests might promote biodiversity not only through an increase in niche volume but also through other processes, such as an increase in resources and their spatial distribution. However, negative relationships between heterogeneity and biodiversity have also been observed, which may indicate that heterogeneity acts as a filter for some species. This study examined the effects of different facets of heterogeneity in forest stands, i.e. deadwood, plant diversity, forest stand structure, and micro-scale topography, on the ecological (functional-phylogenetic) diversity and redundancy of nine animal groups: moths, true bugs, different functional groups of beetles, spiders, birds, and bats. Overall, we found positive effects of heterogeneity on ecological diversity and redundancy. Although the effect of heterogeneity at the local scale was moderate compared with the general effect of region, greater heterogeneity could be beneficial to some species groups and lead to more resilient species communities. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? What are the 10-year trajectories of posttraumatic stress disorder (PTSD) symptoms in older U.S. military Veterans and what defines those at risk for increasing symptoms with aging? • What is the main finding of this study? No/Low PTSD symptoms over time was most common, followed by consistently high, consistently sub-threshold, and increasing symptoms. Those with increasing symptoms were more likely to report cognitive and functional change, negative expectations of aging, and traumatic events over the study period. • What is the meaning of the finding? Most older Veterans are resilient, but some may have continuing or increasing PTSD symptoms with aging indicating a need to consider age-related changes, internalized ageism, and the occurrence and timing of traumatic events. To examine the nature and correlates of 10-year trajectories of posttraumatic stress disorder (PTSD) symptoms in older U.S. military Veterans. A nationally representative web-based survey of older U.S. Veterans who participated in the National Health and Resilience in Veterans Study over 5 waves between 2011 and 2021. A total of 1,843 U.S. Veterans aged 50 and older (mean age = 67). PTSD symptoms were assessed using the PTSD Checklist. Self-report measures at baseline assessed sociodemographic characteristics; trauma exposures; psychiatric and substance use disorders; mental, cognitive, and physical functioning; and psychosocial factors including expectations of aging. Latent growth mixture modeling identified the nature and correlates of 10-year PTSD symptom trajectories. Most of the sample had no/low PTSD symptoms (88.7%), while 6.0% had consistently subthreshold symptoms, 2.7% consistently high symptoms, and 2.6% increasing symptoms. Relative to the no/low symptom group, the subthreshold and high symptom groups reported more medical conditions and cognitive difficulties, with younger age and more lifetime traumatic events additionally linked to the high symptom trajectory. Relative to the no/low symptom group, Veterans with increasing symptoms were more likely to report functional disability and lifetime nicotine use disorder, cognitive difficulties, negative expectations regarding physical and emotional aging, and traumatic events over the study period. Despite high rates of trauma exposure, most older Veterans do not evidence symptomatic PTSD trajectories; however, about 11% do. Results underscore the importance of assessing PTSD symptoms in this population and considering longitudinal trajectories as well as associated risk and protective factors. [ABSTRACT FROM AUTHOR]

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, the roll-out of vaccines and therapeutic agents, as well as the emergence of novel SARS-CoV-2 variants, have shown significant effects on disease severity. Patients hospitalized at our center between January 2020 and April 2022 were attributed to subgroups depending on which SARS-CoV-2 variant was predominantly circulating in Germany: (i) Wild-type: January 1, 2020, to March 7, 2021, (ii) Alpha variant: August 3, 2021, to June 27, 2021, (iii) Delta variant: June 28, 2021, to December 26, 2021, and (iv) Omicron variant: December 27, 2021, to April 30, 2022. Between January 2020 and April 2022, 1500 patients with SARS-CoV-2 infections were admitted to the University Medical Center Hamburg-Eppendorf. The rate of patients who were admitted to the intensive care unit (ICU) decreased from 31.2% (n = 223) in the wild-type group, 28.5% (n = 72) in the Alpha variant group, 18.8% (n = 67) in the Delta variant group, and 13.4% (n = 135) in the Omicron variant group. Also, in-hospital mortality decreased from 20.6% (n = 111) in the wild-type group, 17.5% (n = 30) in the Alpha variant group, 16.8% (n = 33) in the Delta variant group, and 6.6% (n = 39) in the Omicron variant group. The median duration of hospitalization was similar in all subgroups and ranged between 11 and 15 days throughout the pandemic. In-hospital mortality and rate of ICU admission among hospitalized COVID-19 patients steadily decreased throughout the pandemic. However, the practically unchanged duration of hospitalization demonstrates the persistent burden of COVID-19 on the healthcare system. [ABSTRACT FROM AUTHOR]

Surgical care today is no longer evaluated only on clinical outcomes but also on holistic patient wellbeing. Patient-reported outcomes (PROs) are a representation of the patient's perspective on their results and wellbeing. The aim of this review is to establish PROs as the center of healthcare and plastic surgery, to delineate important PROs in plastic surgery practice and research, to discuss the future of PROs within our discipline, and to encourage surgeons to incorporate PROs into their practice. PROs are an important parallel of clinical outcomes in that they can use the patient's perspective to 1) support clinical findings, 2) detect differences in care when there are no clear clinical differences, 3) track progress longitudinally, and 4) support systemic improvements in healthcare. Plastic surgery as a field is naturally aligned with PROs because, as a discipline, we focus on patient form and function. The emerging forefronts of plastic surgery such as lymphedema care, gender-affirming care, peripheral nerve surgery, migraine surgery, and breast implant illness are critically dependent on PROs. In the next decade, we predict that there will be a continued proliferation of robust PRO measures and integration into healthcare delivery. Outcomes research in surgery should continue to evolve as surgeons provide increasingly more benefits to improve patient wellbeing. Plastic surgeons must continue to play a prominent role in the future of PROs. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? To determine whether lipopolysaccharide and inflammatory biomarkers are key drivers of cerebral amyloid-beta (Abeta) deposition in older adults with mild cognitive impairment (MCI) and remitted major depressive disorder (rMDD). • What is the main finding of this study? While many participants demonstrated high Abeta deposition we did not find significant associations between lipopolysaccharide, peripheral inflammatory biomarkers, remitted major depressive disorder, and cerebral deposition of Abeta. • What is the meaning of the finding? While this study did not demonstrate a significant cross sectional association it is possible that inflammatory activation may be associated with Abeta deposition earlier in the disease process and may be more relevant among those with chronic inflammatory activation and more persistent depression. Future longitudinal studies would help clarify whether these potentially modifiable risk factors play a role in the evolution of Alzheimer's neuropathology. Inflammatory activation and increased immune response to lipopolysaccharide occur in both depression and cognitive decline and may link these two conditions. We investigated whether lipopolysaccharide (LPS), LPS binding protein (LBP) and peripheral biomarkers of immune response were associated with increased cerebral deposition of amyloid-beta (Abeta) in older adults with mild cognitive impairment (MCI) and remitted major depressive disorder (rMDD). Cross-sectional analysis. Five academic health centers in Toronto. Older adults with MCI with/without rMDD. We investigated the associations among serum LPS, LBP, biomarkers of inflammatory activation – Interleukin-6 (IL-6), C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and cerebral Abeta deposition quantified by positron emission tomography. Among 133 study participants (82 with MCI and 51 with MCI+rMDD) there was no association between LPS (beta – 0.17, p = 0.8) or LBP (beta - 0.11, p = 0.12) and global deposition of Abeta following adjustment for age, gender, and APOE genotype in multivariable regression analyses. LBP was positively correlated with CRP (r = 0.5, p <0.001) and IL-6 (r = 0.2, p = 0.02) but no inflammatory biomarker was associated with Abeta deposition; rMDD was not associated with deposition of Abeta (beta -0.09, p = 0.22). In this cross-sectional analysis, we did not find an association among LPS/LBP, immune biomarkers or rMDD and global deposition of Abeta. Future analyses should assess the longitudinal relationships between peripheral and central biomarkers of immune activation, depression and cerebral Abeta deposition. [ABSTRACT FROM AUTHOR]

[Display omitted] The actin cytoskeleton has a crucial role in the maintenance of the immune homeostasis by controlling various cellular processes, including cell migration. Mutations in TTC7A have been described as the cause of a primary immunodeficiency associated to different degrees of gut involvement and alterations in the actin cytoskeleton dynamics. This study investigates the impact of TTC7A deficiency in immune homeostasis. In particular, the role of the TTC7A/phosphatidylinositol 4 kinase type III α pathway in the control of leukocyte migration and actin dynamics. Microfabricated devices were leveraged to study cell migration and actin dynamics of murine and patient-derived leukocytes under confinement at the single-cell level. We show that TTC7A-deficient lymphocytes exhibit an altered cell migration and reduced capacity to deform through narrow gaps. Mechanistically, TTC7A-deficient phenotype resulted from impaired phosphoinositide signaling, leading to the downregulation of the phosphoinositide 3-kinase/AKT/RHOA regulatory axis and imbalanced actin cytoskeleton dynamics. TTC7A-associated phenotype resulted in impaired cell motility, accumulation of DNA damage, and increased cell death in dense 3-dimensional gels in the presence of chemokines. These results highlight a novel role of TTC7A as a critical regulator of lymphocyte migration. Impairment of this cellular function is likely to contribute to the pathophysiology underlying progressive immunodeficiency in patients. [ABSTRACT FROM AUTHOR]

The liver is a highly vascularized organ where fluid properties, including vascular pressure, vessel integrity and fluid viscosity, play a critical role in gross mechanical properties. To study the effects of portal pressure, liver confinement, fluid viscosity, and tissue crosslinking on liver stiffness, water diffusion, and vessel size, we applied multiparametric magnetic resonance imaging (mpMRI), including multifrequency magnetic resonance elastography (MRE) and apparent diffusion coefficient (ADC) measurements, to ex vivo livers from healthy male rats (13.6±1.6 weeks) at room temperature. Four scenarios including altered liver confinement, tissue crosslinking, and vascular fluid viscosity were investigated with mpMRI at different portal pressure levels (0-17.5 cmH 2 O). Our experiments demonstrated that, with increasing portal pressure, rat livers showed higher water content, water diffusivity, and increased vessel sizes quantified by the vessel tissue volume fraction (VTVF). These effects were most pronounced in native, unconfined livers (VTVF: 300±120%, p <0.05, ADC: 88±29%, p <0.01), while still significant under confinement (confined: VTVF: 53±32%, p <0.01, ADC: 28±19%, p <0.05; confined-fixed: VTVF: 52±20%, p<0.001, ADC: 11±2%, p <0.01; confined-viscous: VTVF: 210±110%, p <0.01, ADC: 26±9%, p <0.001). Softening with elevated portal pressure (-12±5, p <0.05) occurred regardless of confinement and fixation. However, the liver stiffened when exposed to a more viscous inflow fluid (11±4%, p <0.001). Taken together, our results elucidate the complex relationship between macroscopic-biophysical parameters of liver tissue measured by mpMRI and vascular-fluid properties. Influenced by portal pressure, vascular permeability, and matrix crosslinking, liver stiffness is sensitive to intrinsic poroelastic properties, which, alongside vascular architecture and water diffusivity, may aid in the differential diagnosis of liver disease. Using highly controllable ex vivo rat liver phantoms, hepatic biophysical properties such as tissue-vascular structure, stiffness, and water diffusivity were investigated using multiparametric MRI including multifrequency magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI). Through elaborate tuning of the experimental conditions such as the static portal pressure, flow viscosity, amount and distribution of fluid content in the liver, we identified the contributions of the fluid component to the overall imaging-based biophysical properties of the liver. Our finding demonstrated the sensitivity of liver stiffness to the hepatic poroelastic properties, which may aid in the differential diagnosis of liver diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

The Fascial Distortion Model (FDM) is a relatively new manual therapy approach in the field of musculoskeletal physical therapy, but to date no study has been conducted to compare its' effect in comparison with joint mobilization on patients with shoulder impingement syndrome. The present study aims to compare the efficacy of the FDM versus joint mobilization in pain intensity, pain-free abduction range of motion and function of patients with shoulder impingement syndrome. single-blind, parallel-arm randomized controlled trial. 26 patients diagnosed with shoulder impingement syndrome were equally randomized into 2 groups: manual treatment according to the FDM, and joint mobilization of the shoulder complex. All patients received 3 intervention sessions every other day. Pain intensity (by visual analogue scale), pain-free abduction range of motion (by goniometry) and function (by Persian version of shoulder pain and disability index) were measured before and after every session and at follow-up 2 weeks later. Patients' satisfaction with treatment was also measured (by a 4-point Likert scale) at follow-up. FDM therapy group showed statistically significant greater pain reduction (P = 0.014) and range of motion increment (P = 0.044) than joint mobilization group after intervention, while only range of motion maintained the difference at follow-up (P = 0.034). Function improvement was not statistically different after the intervention (P = 0.582) and at follow-up (P = 0.094). There was no difference in patients' satisfaction with treatment between groups (P > 0.05). The FDM is a safe and effective treatment approach with comparable results to joint mobilization in patients with shoulder impingement syndrome. [ABSTRACT FROM AUTHOR]

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In patients undergoing percutaneous coronary intervention (PCI) in the work-up pre–transcatheter aortic valve replacement (TAVR), the incidence and clinical impact of late bleeding events (LBEs) remain largely unknown. This study sought to determine the incidence, clinical characteristics, associated factors, and outcomes of LBEs in patients undergoing PCI in the work-up pre-TAVR. This was a multicenter study including 1,457 consecutive patients (mean age 81 ± 7 years; 41.5% women) who underwent TAVR and survived beyond 30 days. LBEs (>30 days post-TAVR) were defined according to the Valve Academic Research Consortium-2 criteria. LBEs occurred in 116 (7.9%) patients after a median follow-up of 23 (IQR: 12-40) months. Late bleeding was minor, major, and life-threatening or disabling in 21 (18.1%), 63 (54.3%), and 32 (27.6%) patients, respectively. Periprocedural (<30 days post-TAVR) major bleeding and the combination of antiplatelet and anticoagulation therapy at discharge were independent factors associated with LBEs (P ≤ 0.02 for all). LBEs conveyed an increased mortality risk at 4-year follow-up compared with no bleeding (43.9% vs 36.0; P = 0.034). Also, LBE was identified as an independent predictor of all-cause mortality after TAVR (HR: 1.39; 95% CI: 1.05-1.83; P = 0.020). In TAVR candidates with concomitant significant coronary artery disease requiring percutaneous treatment, LBEs after TAVR were frequent and associated with increased mortality. Combining antiplatelet and anticoagulation regimens and the occurrence of periprocedural bleeding determined an increased risk of LBEs. Preventive strategies should be pursued for preventing late bleeding after TAVR, and further studies are needed to provide more solid evidence on the most safe and effective antithrombotic regimen post-TAVR in this challenging group of patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Characterization of upadacitinib use and switching from dupilumab to upadacitinib among patients with moderate-to-severe atopic dermatitis (AD) is needed. To evaluate the long-term safety and efficacy of continuous upadacitinib 30 mg and switching to upadacitinib after 24 weeks of dupilumab. Adults who completed the phase 3b clinical trial of oral upadacitinib 30 mg vs injectable dupilumab 300 mg (Heads Up) and entered a 52-week open-label extension (OLE) (NCT04195698) were included. All patients received 30-mg upadacitinib during the open-label period. We report results of a prespecified interim OLE 16-week analysis. Patients (n = 239) continuing upadacitinib maintained high levels of skin and itch response. Patients (n = 245) switching from dupilumab experienced additional incremental improvements in clinical responses within 4 weeks of starting upadacitinib. Most patients who did not achieve adequate clinical responses with dupilumab did so with upadacitinib. The safety profile of upadacitinib up to 40 weeks (week 16 of OLE) was consistent with previous phase 3 AD studies, with no new safety risks observed. Open-label study design. Clinical responses are maintained with continuous upadacitinib through 40 weeks and patients regardless of prior dupilumab response experienced improved outcomes when switched to upadacitinib. No new safety risks were observed. [ABSTRACT FROM AUTHOR]

In this paper, we developed a novel data collection and analysis approach that uses manual and automated processing of large datasets and combines them to offset the limitations of past research and practice when it comes to identifying actors in complex environmental governance systems. Our empirical context is wildfire governance in Colorado. Wildfire governance represents a pressing challenge for interested actors in the western United States. We characterize Colorado's wildfire governance system by using big data triangulation techniques to identify key actors and their topical domains to reveal meaningful subgroups. Our results highlight the importance of understanding the pitfalls of each source of data and the potential benefits of combining them to gain a more complete understanding of the system. The true potential of multi-source analysis becomes apparent when one pays special attention to the degree of overlap that exists between sources. Each source reveals a unique makeup of actors (both in terms of individuals and organizational types) and different forms of engagement in the system. In addition to providing different sets of actors, we found evidence of different emergent topics in each data source. • We develop a novel method for processing large quantities of publicly available data for actor identification. • Multi-source data triangulation provides specific insights on the structure of the governance system. • Each source reveals a unique makeup of actors, their roles and topical domains in the system. • Minimal overlap between sources supports the need to critically consider biases and pitfalls associated to data sources. [ABSTRACT FROM AUTHOR]

Focal segmental glomerulosclerosis (FSGS) is a glomerular lesion often associated with nephrotic syndrome. It is also associated with a high risk of progression to end-stage kidney disease. Current treatment of FSGS is limited to systemic corticosteroids or calcineurin inhibition, along with inhibitors of the renin-angiotensin-aldosterone system. FSGS is heterogeneous in etiology, and novel therapies targeting specific, dysregulated molecular pathways represent a major unmet medical need. We have generated a network-based molecular model of FSGS pathophysiology using previously established systems biology workflows to allow computational evaluation of compounds for their predicted interference with molecular processes contributing to FSGS. We identified the anti-platelet drug clopidogrel as a therapeutic option to counterbalance dysregulated FSGS pathways. This prediction of our computational screen was validated by testing clopidogrel in the adriamycin FSGS mouse model. Clopidogrel improved key FSGS outcome parameters and significantly reduced urinary albumin to creatinine ratio (P < 0.01) and weight loss (P < 0.01), and ameliorated histopathological damage (P < 0.05). Clopidogrel is used to treat several cardiovascular diseases linked to chronic kidney disease. Clopidogrel's favorable safety profile and its efficacy in the adriamycin mouse FSGS model thus recommend it as an attractive drug repositioning candidate for clinical trial in FSGS. [ABSTRACT FROM AUTHOR]

Deficits in executive functions (EF) are a common comorbidity among adolescents with epilepsy. EF deficits were previously correlated with altered connectivity of the fronto-parietal and cingulo-opercular neural networks. The current study investigated white matter integrity in adolescents with epilepsy (n = 29) relative to healthy controls (n = 19). Participants completed questionnaires, neuropsychological testing, and brain magnetic resonance imaging (MRI) that included diffusion tensor imaging (DTI) sequences. On BRIEF parent-report questionnaires, adolescents with epilepsy demonstrated lower working memory and planning abilities than healthy controls. Among adolescents with epilepsy, DTI measurements revealed lower fractional anisotropy (FA) within the right superior longitudinal fasciculus, forceps minor, and the superior frontal segment of the corpus callosum, and higher FA in the left uncinate fasciculus, compared to healthy controls. Better working memory ability in the epilepsy group was associated with higher FA in the superior frontal segment of the corpus callosum. Only in healthy controls, working memory and planning were positively associated with FA values in the left UF, forceps minor and the superior frontal segment of the corpus callosum. The current study complements previous functional studies on the same cohort and suggests that EF impairments among adolescents with epilepsy may be related to the altered anatomical organization of white matter tracts. Combining structural and functional data could potentially enrich the neuropsychological assessment of executive functioning in adolescents with epilepsy. • Adolescents with epilepsy exhibited lower fractional anisotropy (FA) than healthy controls in the right superior longitudinal fasciculus, forceps minor, and the superior frontal portion of the corpus callosum. Conversely, adolescents with epilepsy showed comparatively higher FA in the left uncinate fasciculus. • Among adolescents with epilepsy, better working memory scores were associated with higher FA in the superior frontal portion of the corpus callosum. • Among healthy controls, working memory and Planning (on BRIEF parental reports) were positively correlated with FA in the left uncinate fasciculus, forceps minor, and superior frontal portions of the corpus callosum. • Altered structural connectivity may be associated with EF impairments in adolescents with epilepsy. [ABSTRACT FROM AUTHOR]

Radiation oncology (RO) has seen declines in Medicare reimbursement (MCR) in the past decade under the current fee-for-service model. Although studies have explored decline in reimbursement at a per-code level, to our knowledge there are no recent studies analyzing changes in MCR over time for common RO treatment courses. By analyzing changes in MCR for common treatment courses, our study had 3 objectives: (1) to provide practitioners and policymakers with estimates of recent reimbursement changes for common treatment courses; (2) to provide an estimate of how reimbursement will change in the future under the current fee-for-service model if current trends continue; and (3) to provide a baseline for treatment episodes in the event that the episode-based Radiation Oncology Alternative Payment Model is eventually implemented. Specifically, we quantified inflation- and utilization-adjusted changes in reimbursement for 16 common radiation therapy (RT) treatment courses from 2010 to 2020. Centers for Medicare & Medicaid Services Physician/Supplier Procedure Summary databases were used to obtain reimbursement for all RO procedures in 2010, 2015, and 2020 for free-standing facilities. Inflation-adjusted average reimbursement (AR) per billing instance was calculated for each Healthcare Common Procedure Coding System code using 2020 dollars. For each year, the billing frequency of each code was multiplied by the AR per code. Results were summed per RT course per year, and AR for RT courses were compared. Sixteen common RO courses for head and neck, breast, prostate, lung, and palliative RT were analyzed. AR decreased for all 16 courses from 2010 to 2020. From 2015 to 2020, the only course that increased in AR was palliative 2-dimensional 10-fraction 30 Gy, which increased by 0.4%. Courses using intensity modulated RT saw the largest AR decline from 2010 to 2020, ranging from 38% to 39%. We report significant declines in reimbursement from 2010 to 2020 for common RO courses, with the largest declines for intensity modulated RT. Policymakers should consider the significant cuts to reimbursement that have already occurred when considering future reimbursement adjustment under the current fee-for-service model or when considering mandatory adoption of a new payment system with further cuts and the negative effect of such cuts on quality and access to care. [ABSTRACT FROM AUTHOR]

Conventional excision of female genital skin cancers has high rates of local recurrence and morbidity. Few publications describe local recurrence rates (LRRs) and patient-reported outcomes (PROs) after Mohs micrographic surgery (MMS) for female genital skin cancers. To evaluate LRRs, PROs, and interdisciplinary care after MMS for female genital skin cancers. A retrospective case series was conducted of female genital skin cancers treated with MMS between 2006 and 2021 at an academic center. The primary outcome was local recurrence. Secondary outcomes were PROs and details of interdisciplinary care. Sixty skin cancers in 57 patients were treated with MMS. Common diagnoses included squamous cell cancer (n = 26), basal cell cancer (n = 12), and extramammary Paget disease (n = 11). Three local recurrences were detected with a mean follow-up of 61.1 months (median: 48.8 months). Thirty-one patients completed the PROs survey. Most patients were satisfied with MMS (71.0%, 22/31) and reported no urinary incontinence (93.5%, 29/31). Eight patients were sexually active at follow-up and 75.0% (6/8) experienced no sexual dysfunction. Most cases involved interdisciplinary collaboration 71.7% (43/60). Limitations include the retrospective single-center design, heterogeneous cohort, and lack of preoperative function data. Incorporating MMS into interdisciplinary teams may help achieve low LRRs and satisfactory function after genital skin cancer surgery. [ABSTRACT FROM AUTHOR]

The ProCCard study tested whether combining several cardioprotective interventions would reduce the myocardial and other biological and clinical damage in patients undergoing cardiac surgery. Prospective, randomized, controlled trial. Multicenter tertiary care hospitals. 210 patients scheduled to undergo aortic valve surgery. A control group (standard of care) was compared to a treated group combining five perioperative cardioprotective techniques: anesthesia with sevoflurane, remote ischemic preconditioning, close intraoperative blood glucose control, moderate respiratory acidosis (pH 7.30) just before aortic unclamping (concept of the "pH paradox"), and gentle reperfusion just after aortic unclamping. The primary outcome was the postoperative 72-h area under the curve (AUC) for high-sensitivity cardiac troponin I (hsTnI). Secondary endpoints were biological markers and clinical events occurring during the 30 postoperative days and the prespecified subgroup analyses. The linear relationship between the 72-h AUC for hsTnI and aortic clamping time, significant in both groups (p < 0.0001), was not modified by the treatment (p = 0.57). The rate of adverse events at 30 days was identical. A non-significant reduction of the 72-h AUC for hsTnI (−24%, p = 0.15) was observed when sevoflurane was administered during cardiopulmonary bypass (46% of patients in the treated group). The incidence of postoperative renal failure was not reduced (p = 0.104). This multimodal cardioprotection has not demonstrated any biological or clinical benefit during cardiac surgery. The cardio- and reno-protective effects of sevoflurane and remote ischemic preconditioning therefore remain to be demonstrated in this context. [ABSTRACT FROM AUTHOR]

Despite proven benefits of exercise-based cardiac rehabilitation (EBCR), few patients with myocardial infarction (MI) participate in and complete these programs. The Remote Exercise SWEDEHEART study is a large multicenter registry-based cluster randomized crossover clinical trial with a planned enrollment of 1500 patients with a recent MI. Patients at intervention centers will be offered supervised EBCR, either delivered remotely, center-based or as a combination of both modes, as self-preferred choice. At control centers, patients will be offered supervised center-based EBCR, only. The duration of each time period (intervention/control) for each center will be 15 months and then cross-over occurs. The primary aim is to evaluate if remotely delivered EBCR, offered as an alternative to center-based EBCR, can increase participation in EBCR sessions. The proportion completers in each group will be presented in a supportive responder analysis. The key secondary aim is to investigate if remote EBCR is as least as effective as center-based EBCR, in terms of physical fitness and patient-reported outcome measures. Follow-up of major adverse cardiovascular events (cardiovascular- and all-cause mortality, recurrent hospitalization for acute coronary syndrome, heart failure hospitalization, stroke, and coronary revascularization) will be performed at 1 and 3 years. Safety monitoring of serious adverse events will be registered, and a cost-effectiveness analysis will be conducted to estimate the cost per quality-adjusted life-year (QALY) associated with the intervention compared with control. The cluster randomized crossover clinical trial Remote Exercise SWEDEHEART study is evaluating if participation in EBCR sessions can be increased, which may contribute to health benefits both on a group level and for individual patients including a more equal access to health care. The study is registered at ClinicalTrials.gov (Identifier: NCT04260958) [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? This study examined the population-based prevalence and correlates of prolonged grief disorder (PGD) in U.S. veterans. • What is the main finding of this study? In this nationally representative study of 2,441 veterans, 158 (weighted 7.3%) screened positive for PGD. Adverse childhood experiences, female sex, non-natural causes of death, knowing someone who died from coronavirus disease 2019, and number of losses were strongly associated with PGD. Veterans with PGD were significantly more likely to screen positive for posttraumatic stress, major depressive, and generalized anxiety disorders; endorse suicidal thoughts and attempts; and utilize mental health treatment. • What is the meaning of the finding? PGD is prevalent in veterans, and associated with increased psychiatric burden and suicide risk. To examine the point prevalence and correlates of prolonged grief disorder (PGD) in a nationally-representative sample of United States (U.S.) veterans. Data were analyzed from the National Health and Resilience in Veterans Study, a nationally representative study of 2,441 U.S. veterans. A total of 158 (weighted 7.3%) veterans screened positive for PGD. The strongest correlates of PGD were adverse childhood experiences, female sex, non-natural causes of death, knowing someone who died from coronavirus disease 2019, and number of close losses. After adjusting for sociodemographic, military, and trauma variables, veterans with PGD were 5-to-9 times more likely to screen positive for post-traumatic stress disorder, major depressive disorder, and generalized anxiety disorder. After additional adjustment for current psychiatric and substance use disorders, they were 2–3 times more likely to endorse suicidal thoughts and behaviors. Results underscore the importance of targeting PGD as an independent risk factor for psychiatric disorders and suicide risk. [ABSTRACT FROM AUTHOR]

The benefit related to the use of preprocedural computed tomography angiography (CCTA) on top of periprocedural echocardiography to plan percutaneous left atrial appendage closure (LAAC) procedures is still unclear. The authors sought to evaluate the impact of preprocedural CCTA on LAAC procedural success. In the investigator-initiated SWISS-APERO (Comparison of Amplatzer Amulet and Watchman Device in Patients Undergoing Left Atrial Appendage Closure) trial, patients undergoing echocardiography-guided LAAC were randomly assigned to receive the Amulet (Abbott) or Watchman 2.5/FLX (Boston Scientific) device across 8 European centers. According to the study protocol ongoing at the time of the procedure, the first operators had (CCTA unblinded group) or did not have (CCTA blinded group) access to preprocedural CCTA images. In this post hoc analysis, we compared blinded vs unblinded procedures in terms of procedural success defined as complete left atrial appendage occlusion as evaluated at the end of LAAC (short-term) or at the 45-day follow-up (long-term) without procedural-related complications. Among 219 LAACs preceded by CCTA, 92 (42.1%) and 127 (57.9%) were assigned to the CCTA unblinded and blinded group, respectively. After adjusting for confounders, operator unblinding to preprocedural CCTA remained associated with a higher rate of short-term procedural success (93.5% vs 81.1%; P = 0.009; adjusted OR: 2.76; 95% CI: 1.05-7.29; P = 0.040) and long-term procedural success (83.7% vs 72.4%; P = 0.050; adjusted OR: 2.12; 95% CI: 1.03-4.35; P = 0.041). In a prospective multicenter cohort of clinically indicated echocardiography-guided LAACs, unblinding of the first operators to preprocedural CCTA images was independently associated with a higher rate of both short- and long-term procedural success. Further studies are needed to better evaluate the impact of preprocedural CCTA on clinical outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]