Citations

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Background: Prolonged symptoms after COVID-19 are an important concern due to the large numbers affected by the pandemic. Objectives: To ascertain the frequency of gastrointestinal (GI) manifestations as part of long GI COVID. Design: A systematic review and meta-analysis of studies reporting GI manifestations in long COVID was performed. Data Sources and Methods: Electronic databases (Medline, Scopus, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were searched till 21 December 2021 to identify studies reporting frequency of GI symptoms in long COVID. We included studies reporting overall GI manifestations or individual GI symptoms as part of long COVID. We excluded pediatric studies and those not providing relevant information. We calculated the pooled frequency of various symptoms in all patients with COVID-19 and also in those with long COVID using the inverse variance approach. All analysis was done using R version 4.1.1 using packages ‘meta’ and ‘metafor’. Results: A total of 50 studies were included. The frequencies of GI symptoms were 0.12 [95% confidence interval (CI), 0.06–0.22, I 2 = 99%] and 0.22 (95% CI, 0.10–0.41, I 2 = 97%) in patients with COVID-19 and those with long COVID, respectively. The frequencies of abdominal pain, nausea/vomiting, loss of appetite, and loss of taste were 0.14 (95% CI, 0.04–0.38, I 2 = 96%), 0.06 (95% CI, 0.03–0.11, I 2 = 98%), 0.20 (95% CI, 0.08–0.43, I 2 = 98%), and 0.17 (95% CI, 0.10–0.27, I 2 = 95%), respectively, after COVID-19. The frequencies of diarrhea, dyspepsia, and irritable bowel syndrome were 0.10 (95% CI, 0.04–0.23, I 2 = 98%), 0.20 (95% CI, 0.06–0.50, I 2 = 97%), and 0.17 (95% CI, 0.06–0.37, I 2 = 96%), respectively. Conclusion: GI symptoms in patients were seen in 12% after COVID-19 and 22% as part of long COVID. Loss of appetite, dyspepsia, irritable bowel syndrome, loss of taste, and abdominal pain were the five most common GI symptoms of long COVID. Significant heterogeneity and small number of studies for some of the analyses are limitations of the systematic review.

Osteoarthritis (OA) is a common shoulder disorder that impacts shoulder functions. Shoulder arthroplasty is often required to restore function and quality of life. Reverse total shoulder arthroplasty (RSA), which was originally designed mainly for irreparable rotator cuff damage, has gained popularity in recent years for the treatment of advanced shoulder OA instead of the clinically standard total shoulder arthroplasty (TSA). However, this RSA has some nonnegligible flaws such as higher complications rate and economic cost, not mention the following problems caused by irreversible physical structural damage. Therefore, the employment of RSA needs to be carefully considered. This study aimed to compare TSA and RSA in OA patients with or without rotator cuff damage to better guide clinical decision making. We believe the radical use of RSA in patients without rotator cuff deficiency may cause more harm than good. We queried the Nationwide Inpatient Sample (NIS) database from 2011 to 2014 to collect information on OA patients who received TSA and RSA. Patients were divided into 2 groups of comparison according to the presence of rotator cuff deficiency and matched with propensity score analysis. A total of 57,156 shoulder arthroplasties were identified. RSA patients in the rotator cuff deficiency group had significant higher transfusion rates and longer hospital stays. RSA patients without rotator cuff deficiency had a statistically significantly higher number of implant-related mechanical complications, acute upper respiratory infections and postoperative pain. Overall, RSA incurred higher costs in both groups. For OA patients with rotator cuff deficiencies, RSA has its benefits as complication rates were comparable to TSA. For those patients without rotator cuff deficiencies, the use of RSA should be reconsidered as there were more complications with higher severity.

Abstract Activation of innate immunity in the brain is a prominent feature of Alzheimer's disease (AD). The present study investigated the regulation of innate immunity by young serum in a transgenic AD mouse model. We found that young serum significantly reduced the number of neutrophils and microglial reactivity in the brains of APP/PS1 mice. Neutrophil depletion via Ly6G neutralizing antibodies mimicked the benefits of young serum on AD brain functions. Serum proteomic analysis of young serum revealed significant enrichment of the factors VEGF-A and CXCL1, which are crucial for neutrophil migration and chemotaxis, leukocyte migration, and cell chemotaxis. Intravenously injected VEGF-A reversed Aβ-induced decreases in Cdk5 and increases in CXCL1 in vitro and blocked neutrophil infiltration into the AD brain. Endothelial Cdk5 overexpression conferred an inhibitory effect on CXCL1 and neutrophil infiltration and thereby restored memory in APP/PS1 mice. Our data uncover a previously unknown link between blood-derived VEGF signaling and neutrophil infiltration and provide a rationale for targeting endothelial Cdk5 signaling as a potential therapeutic strategy for AD.

AbstractPurposeTo investigate the dependency of dose‐volume histogram (DVH) behavior and precision on underlying discretization using shapes and dose distributions with known analytical DVHs for five commercial DVH calculators.MethodsDVHs and summary metrics were extracted from all five systems using synthetic cone and cylinder objects for which the true volume and DVH curves were known. Trends in the curves and metrics were explored by varying the underlying voxelization of the CT image, structure set, and dose grid as well by varying the geometry of the structure and direction of a linear dose gradient. Using synthetic structures allowed for comparison with ground truth DVH curves to assess their accuracy while an algorithm was additionally developed to assess the precision of each system. The precision was calculated with a novel algorithm that treats any “stair step” behavior in a DVH curve as an uncertainty band and calculates the width, characterized as a percent difference, of the band for various DVH metrics. The underlying voxelization was additionally changed and DVHs were extracted for two clinical examples. The details of how each system calculated DVHs were also investigated and tendencies in the calculated curves, metrics, and precision were related to choices made in the calculation methodology.ResultsCalculation methodology differences that had a noticeable impact on the DVH curves and summary metrics include supersampling beyond the input grids and interpretation of the superior and inferior ends of the structures. Among the systems studied, the median precision ranged from 0.902% to 3.22%, and interquartile ranges varied from 1.09% to 3.91%.ConclusionsCommercial dose‐evaluation solutions can calculate different DVH curves, structure volume measures, and dose statistics for the same input data due to differences in their calculation methodologies. This study highlights the importance of understanding and investigating the DVH calculation when considering a new clinical system and when using more than one system for data transfer.

Abstract Background Much of our understanding about the natural history of pouch-related disorders has been generated from selected populations. We designed a geographically diverse, prospective registry to study the disease course among patients with 1 of 4 inflammatory conditions of the pouch. The primary objectives in this study were to demonstrate the feasibility of a prospective pouch registry and to evaluate the predominant treatment patterns for pouch-related disorders. Methods We used standardized diagnostic criteria to prospectively enroll patients with acute pouchitis, chronic antibiotic-dependent pouchitis (CADP), chronic antibiotic refractory pouchitis (CARP), or Crohn’s disease (CD) of the pouch. We obtained detailed clinical and demographic data at the time of enrollment, along with patient-reported outcome (PRO) measures. Results We enrolled 318 patients (10% acute pouchitis, 27% CADP, 12% CARP, and 51% CD of the pouch). Among all patients, 55% were on a biologic or small molecule therapy. Patients with CD of the pouch were more likely to use several classes of therapy (P < .001). Among patients with active disease at the time of enrollment, 23% with CARP and 40% with CD of the pouch were in clinical remission at 6 months after enrollment. Conclusions In a population where most patients had refractory inflammatory conditions of the pouch, we established a framework to evaluate PROs and clinical effectiveness. This infrastructure will be valuable for long-term studies of real-world effectiveness for pouch-related disorders.

Continuous imaging of internal organs over days could provide crucial information about health and diseases and enable insights into developmental biology. We report a bioadhesive ultrasound (BAUS) device that consists of a thin and rigid ultrasound probe robustly adhered to the skin via a couplant made of a soft, tough, antidehydrating, and bioadhesive hydrogel-elastomer hybrid. The BAUS device provides 48 hours of continuous imaging of diverse internal organs, including blood vessels, muscle, heart, gastrointestinal tract, diaphragm, and lung. The BAUS device could enable diagnostic and monitoring tools for various diseases.

Objectives: Distal biceps tendon tears, although rare, significantly impair patient’s elbow mobility and function. There is a paucity of contemporary literature reporting long term outcomes of distal biceps (DB) injuries. Therefore, the authors sought to identify magnetic resonance imaging (MRI) confirmed distal bicep tears and report on (1) patient demographics and injury characteristics of all patients with distal bicep pathology, (2) outcomes of all patients with non-operatively managed DB pathology, and (3) outcomes of all patients with operatively managed DB pathology. Methods: Patients with an MRI-confirmed distal biceps rupture from 1996 to 2016 were identified through an institutional image database. Patients from the initial search were then cross-referenced with the [REDACTED] 1 to ensure record availability. Patients were included if they had complete medical records and ≥5 years of clinical follow-up. Patients with inflammatory arthritis and enthesitis, polytrauma, or incidental findings without clinical assessment were excluded. Medical records were reviewed to confirm the diagnosis of distal biceps tears and obtain further subject details. Results: A total of 158 patients (22 female, 136 male) with a mean age 51.5 years (44.8-61.2) were identified and included. Baseline patient demographics including BMI, smoking status, dominant-handedness, laborer occupation, and gender were gathered (Table 1). Patients had a mean clinical follow-up of almost 14 years (Table 1, range 8.4 -17.8). Outcomes of the 52 non-operative and 106 operatively managed patients, included severe complications, functional outcomes, and health-related productivity loss are reported in Table 2. There were 7 re-operations (4%), 5 re-ruptures (3%), and overall 35% of the operatively treated cohort experienced a complication. Conclusions: Patients with distal bicep pathology tended to be a male laborer in their 50s without clinically significantly associated risk factors. The majority of patients regained full ROM, and 83% were able to return to work without modifications, irregardless of operative or non-operative management. At long term follow up, patients treated operatively were more likely to report missing time from work and averaged more days missed than their non-operatively treated counterparts. Additionally, operative patients had no statistically significant gains functional outcomes, and were subject to potential post-operative complications. Surgeon bias may play a role in deciding treatment for distal biceps tears. As such, careful patient selection for surgical intervention for distal biceps pathology should be employed; surgeons should consider restricting surgical intervention to patients who have significant clinical symptoms or fail non-operative management. [Table: see text][Table: see text]

Objectives: The medial patellofemoral ligament (MPFL) is the primary soft tissue restraint to lateral patellar translation and is often disrupted with a lateral patellar dislocation. Surgical management for recurrent patellar instability focuses on restoring MPFL function with repair or reconstruction techniques. Recent studies have favored reconstruction over repair, but no long-term, comparative studies are available in the literature. Methods: A total of 55 patients (58 knees) with recurrent lateral instability were treated between 2005 and 2012 with either MPFL repair or MPFL reconstruction. Exclusion criteria included prior or concomitant tibial tubercle osteotomy or trochleoplasty, and follow-up less than 8 years. Pre- and post-operative demographic, surgical, imaging and clinical data were recorded for each patient. Results: MPFL repair was performed on 26 patients (29 knees; 14 females, 15 males) at a mean age of 19.1 years. MPFL reconstruction was performed on 29 patients (29 knees; 18 females, 11 males) at a mean age of 18.2 years. Mean follow-up was 12.0 years (range 8.3-18.9). The reconstruction group had a significantly lower rate of recurrent dislocation compared to the repair group (14% vs 41%, p=0.019) at final follow up. There were no differences in the number of pre-operative dislocations (greater than or less than 3), degree of patellar facet chondromalacia, TT-TG distance, or Tegner scores. The reconstruction group had significantly more time from injury to surgery compared to the repair group (median, 1,460 days vs 627 days, p =0.007). There were no differences in post-operative Tegner, Lysholm or Kujala scores at final follow-up. Additionally, there were no differences in return to play rates (repair 80.8% vs reconstruction 75.0%, p=0.610) or reoperation rates (repair 20.7% vs reconstruction 13.8%, p=0.487). Conclusions: Repair of the MPFL leads to nearly 3-fold higher rate of recurrent patellar dislocation (41% vs. 14%) at long term follow-up compared to MPFL reconstruction. However, MPFL repair and reconstruction provide similar clinical results, return to play rates and reoperation rates. [Table: see text][Table: see text]

AbstractPeripheral nerve injury‐induced spinal microglial proliferation plays a pivotal role in neuropathic pain. So far, key intracellular druggable molecules involved in this process are not identified. The nuclear factor of activated T‐cells (NFAT1) is a master regulator of immune cell proliferation. Whether and how NFAT1 modulates spinal microglial proliferation during neuropathic pain remain unknown. Here it is reported that NFAT1 is persistently upregulated in microglia after spinal nerve ligation (SNL), which is regulated by TET2‐mediated DNA demethylation. Global or microglia‐specific deletion of Nfat1 attenuates SNL‐induced pain and decreases excitatory synaptic transmission of lamina II neurons. Furthermore, deletion of Nfat1 decreases microglial proliferation and the expression of multiple microglia‐related genes, such as cytokines, transmembrane signaling receptors, and transcription factors. Particularly, SNL increases the binding of NFAT1 with the promoter of Itgam, Tnf, Il‐1b, and c‐Myc in the spinal cord. Microglia‐specific overexpression of c‐MYC induces pain hypersensitivity and microglial proliferation. Finally, inhibiting NFAT1 and c‐MYC by intrathecal injection of inhibitor or siRNA alleviates SNL‐induced neuropathic pain. Collectively, NFAT1 is a hub transcription factor that regulates microglial proliferation via c‐MYC and guides the expression of the activated microglia genome. Thus, NFAT1 may be an effective target for treating neuropathic pain.