Explore the vast range of titles available.

Purpose of Review Randomized controlled trials (RCTs) in heart failure (HF) are becoming increasingly complex and expensive to conduct and if positive deliver expensive therapy tested only in selected populations. Recent Findings Electronic health records and clinical cardiovascular quality registries are providing opportunities for pragmatic and registry-based prospective randomized clinical trials (RRCTs). Simplified regulatory, ethics, and consent procedures; recruitment integrated into real-world care; and simplified or automated baseline and outcome collection allow assessment of study power and feasibility, fast and efficient recruitment, delivery of generalizable findings at low cost, and potentially evidence-based and novel use of generic drugs with low costs to society. Summary There have been no RRCTs in HF to date. Major challenges include generating funding, international collaboration, and the monitoring of safety and adherence for chronic HF treatments. Here, we use the Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction (SPIRRIT-HFpEF), to be conducted in the Swedish Heart Failure Registry, to exemplify the advantages and challenges of HF RRCTs.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) support revascularization, inhibition of inflammation, regulation of apoptosis, and promotion of the release of beneficial factors. Thus, they are regarded as a promising candidate for the treatment of intractable spinal cord injury (SCI). Clinical studies on patients with early chronic SCI (from 2 months to 1 year post-injury), which is clinically common, are rare; therefore, we will conduct a prospective, multicenter, randomized, placebo-controlled, single-blinded clinical trial at the Third Affiliated Hospital of Sun Yat-sen University, West China Hospital of Sichuan University, and Shanghai East Hospital, Tongji University School of Medicine, China. The trial plans to recruit 66 early chronic SCI patients. Eligible patients will undergo randomization at a 2:1 ratio to two arms: the observation group and the control group. Subjects in the observation group will receive four intrathecal transplantations of stem cells, with a dosage of 1 × 106/kg, at one calendar month intervals. Subjects in the control group will receive intrathecal administrations of 10 mL sterile normal saline in place of the stem cell transplantations. Clinical safety will be assessed by the analysis of adverse events and laboratory tests. The American Spinal Injury Association (ASIA) total score will be the primary efficacy endpoint, and the secondary efficacy outcomes will be the following: ASIA impairment scale, International Association of Neural Restoration-Spinal Cord Injury Functional Rating Scale, muscle tension, electromyogram, cortical motor and cortical sensory evoked potentials, residual urine volume, magnetic resonance imaging-diffusion tensor imaging, T cell subtypes in serum, neurotrophic factors and inflammatory factors in both serum and cerebrospinal fluid. All evaluations will be performed at 1, 3, 6, and 12 months following the final intrathecal administration. During the entire study procedure, all adverse events will be reported as soon as they are noted. This trial is designed to evaluate the clinical safety and efficacy of subarachnoid transplantation of hUC-MSCs to treat early chronic SCI. Moreover, it will establish whether cytotherapy can ameliorate local hostile microenvironments, promote tracking fiber regeneration, and strengthen spinal conduction ability, thus improving overall motor, sensory, and micturition/defecation function in patients with early chronic SCI. This study was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University, China (approval No. [2018]-02) on March 30, 2018, and was registered with ClinicalTrials.gov (registration No. NCT03521323) on April 12, 2018. The revised trial protocol (protocol version 4.0) was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University, China (approval No. [2019]-10) on February 25, 2019, and released on ClinicalTrials.gov on April 29, 2019.

AimThis systematic review and meta-analysis sought to identify return to play (RTP) rates following Achilles tendon rupture and evaluate what measures are used to determine RTP.DesignA systematic review and meta-analysis were performed. Studies were assessed for risk of bias and grouped based on repeatability of their measure of RTP determination.Data sourcesPubMed, CINAHL, Web of Science and Scopus databases were searched to identify potentially relevant articles.Eligibility criteria for selecting studiesStudies reporting RTP/sport/sport activity in acute, closed Achilles tendon rupture were included.Results108 studies encompassing 6506 patients were included for review. 85 studies included a measure for determining RTP. The rate of RTP in all studies was 80% (95% CI 75% to 85%). Studies with measures describing determination of RTP reported lower rates than studies without metrics described, with rates being significantly different between groups (p<0.001).Conclusions80 per cent of patients returned to play following Achilles tendon rupture; however, the RTP rates are dependent on the quality of the method used to measure RTP. To further understand RTP after Achilles tendon rupture, a standardised, reliable and valid method is required.

Abstract Aims Although conventional interventions for people at high risk of developing type 2 diabetes are usually conducted face-to-face, such interventions are burdensome for health care providers. We developed a lifestyle intervention program combining lifestyle coaching via a smartphone application augmented by intermittently scanned continuous glucose monitoring without burdening health care providers. Its effectiveness for glycemic control and body weight reduction in people at risk of type 2 diabetes was investigated. Materials and Methods For this 12-week randomized unblinded trial with offline recruitment, participants with a hemoglobin A1c level of 5.6% to 6.4% or a fasting blood glucose of 110 to 125 mg/dL and body mass index (BMI) >23 kg/m2 but <40 kg/m2 were randomly assigned to the intervention group (App) and control group (C). The primary endpoint was the difference in time in range of blood glucose between 70 and 140 mg/dL (3.9-7.8 mmol/L) before and after the study period between the 2 groups. Results Among 168 patients (mean age, 48.1 years; mean BMI, 26.6 kg/m2; and male, 80.4%), 82 and 86 were assigned to the App group and C group, respectively. After 12 weeks, time in range of blood glucose at 70 to 140 mg/dL significantly improved in the App group compared with the C group (−2.6 minutes/day vs +31.5 minutes/day, P = .03). Changes in time above range did not differ, whereas time below range (blood glucose <70 mg/dL; +23.5 minutes/day vs −8.9 minutes/day, P = .02) improved in the App group. BMI (−0.26 vs −0.59, P = .017) was reduced in the App group compared with the C group. Conclusion Intervention with a smartphone app and intermittently scanned continuous glucose monitoring increased glycemic control accompanied by decreased carbohydrate intake and weight loss. Further trials are needed to confirm whether these interventions can reduce incident type 2 diabetes.

Objective The primary objective of this study is to review the evidence for aspirin use to prevent the growth of vestibular schwannomas (VS) and to propose a prospective trial to determine the progression‐free survival of VS patients after up to 42 months of treatment with aspirin. Secondary study objectives are to determine the effect of aspirin on VS growth, hearing function, serum biomarker levels, and the quality of life, as well as to determine the tolerability of aspirin treatment and whether serum biomarker and salicylate levels predict the response to aspirin. Study Design Literature review. Setting Six academic and private medical centers. Methods Review of recent English literature regarding prophylactic aspirin use for VS. Results The retrospective reviews on the utility of aspirin to prevent VS growth are inconclusive. Eighty‐four patients have been enrolled in a prospective double‐blinded, placebo‐controlled trial thus far to determine the effect of aspirin on VS. Conclusions Completion of a robust study design is necessary. The current aspirin dose has been well tolerated, with minimal adverse events to date. Level of Evidence Review of retrospective studies: Level 4; Proposed randomized, placebo‐controlled, double‐blinded clinical trial: Level 2. This article reviews the data for and against the use of aspirin to prevent the growth of vestibular schwannomas. It then proposes a randomized placebo‐controlled double‐blinded study to clarify contradictory retrospective findings.

Purpose The need of patellar resurfacing in total knee arthroplasty (TKA) is a subject of debate. This systematic review of overlapping meta-analyses aimed to assess and analyze current evidence regarding patellar resurfacing and non-resurfacing in TKA. Methods A systematic literature search was performed in March 2017 in PubMed, CINAHL and Cochrane Library. Inclusion criteria were meta-analysis of randomized controlled trials that compared TKA with and without patellar resurfacing considering as outcomes re-operations rate, complications, anterior knee pain, functional scores. The quality of meta-analyses was evaluated with AMSTAR score and the most relevant meta-analysis was determined by applying the Jadad algorithm. Results Ten meta-analyses, published between 2005 and 2015, were included in the systematic review. Two studies found a significantly increased Knee Society Score in the resurfacing group. According to four meta-analyses, anterior knee pain incidence was lower in resurfacing group. Six of the included studies described a greater risk of re-intervention in the non-resurfacing groups. The overall quality of included studies was moderate. The most relevant meta-analysis reported no differences in functional scores and incidence of anterior knee pain between the groups. Conclusions Comparable outcomes were found when comparing patellar resurfacing and non-resurfacing in TKA. The higher risk of re-operations after non-resurfacing should be interpreted with caution due to the methodological limitations of the meta-analyses regarding search criteria, heterogeneity and the inherent bias of easier indication to reoperation when the patella is not resurfaced. There is no clear superiority of patellar resurfacing compared to patellar retention. Level of evidence Level II, systematic review of meta-analyses.

Background A serious complication after pancreatoduodenectomy (PD) is postoperative pancreatic fistula (POPF). The aim of this study was to analyse the incidence and predictive factors for POPF by using a large nationwide cohort. Methods Data from the Swedish National Registry for Pancreatic and Periampullary Cancer for all patients undergoing a PD from 2010 until 30th June 2018 were collected. The material was analysed in two groups, no POPF and clinically relevant (grade B and C) POPF. Results A total of 2503 patients underwent PD, of which 245 (10%) developed POPF. Patients with POPF had significantly more overall complications (Clavien Dindo ≥3a, 75% vs. 21%, p  < 0.001) and longer hospital stay (median 23 [16–35] vs. 11 [8–15], p  < 0.001) than patients without POPF. The risk of POPF was higher with increased BMI (OR 1.08, p  < 0.001). Preoperative presence of diabetes (OR 0.52, p  = 0.012) and preoperative biliary drainage (OR 0.34, p  < 0.001) reduced the risk of POPF. Reconstruction with pancreaticojejunostomy caused a more than two folded increase in POPF compared with pancreaticogastrostomy (OR 2.41, p  < 0.001). Weight gain ≥2 kg on postoperative day 1 was also a risk factor (OR 1.76, p  < 0.001). Conclusion A high BMI, a pancreaticojejunostomy and postoperative weight gain were risk factors for developing POPF. Diabetes or preoperative biliary drainage was protective.

Purpose The hypothesis of this meta-analysis was to assess whether laparoscopic approach shows real benefits over Lichtenstein technique in recurrent inguinal hernia repair. Methods A literature search for prospective randomized trials comparing laparoscopic and Lichtenstein procedure in recurrent inguinal hernia repair was performed. Trials were reviewed for primary outcome measures: re-recurrence, chronic inguinal pain and ischemic orchitis; and for secondary outcome measures. Standardized mean difference (SMD) was calculated for continuous variables and odds ratio for dichotomous variables. Results Seven studies comparing laparoscopic and Lichtenstein technique were considered suitable for the pooled analysis. Overall 647 patients with recurrent inguinal hernia were randomized to either laparoscopic repair (333, 51.5 %, transabdominal preperitoneal approach, TAPP and totally extraperitoneal approach, TEP) or anterior open repair (314, 48.5 %, Lichtenstein operation). Patients who underwent laparoscopic repair experienced significantly less chronic pain (9.2 % vs. 21.5 %, p  = 0.003). Patients of the laparoscopic group had a significantly earlier return to normal daily activities (13.9 vs. 18.4 days, SMD = −0.68, 95 % CI = −0.94 to –0.43, p  < 0.000001). Operative time was significantly longer in laparoscopic operations (62.9 vs. 54.2 min, SMD 0.46, 95 % CI 0.03, 0.89; p  = 0.04). No other differences were found. Conclusions Laparoscopy showed reduced chronic inguinal pain and an earlier return to normal daily activities but significantly longer operative time. Despite the expected advantages, the choice between laparoscopy and other techniques still depends on local expertise availability. Only dedicated centers are able to routinely offer laparoscopy for recurrent inguinal hernia repair.

Background: Matrix-associated autologous chondrocyte implantation (ACI) is a well-established treatment for cartilage defects. High-level evidence at midterm follow-up is limited, especially for ACI using spheroids (spherical aggregates of ex vivo expanded human autologous chondrocytes and self-synthesized extracellular matrix). Purpose: To assess the safety and efficacy of 3-dimensional matrix-associated ACI using spheroids to treat medium to large cartilage defects on different locations in the knee joint (patella, trochlea, and femoral condyle) at 5-year follow-up. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 75 patients aged 18 to 50 years with medium to large (4-10 cm2), isolated, single cartilage defects, International Cartilage Repair Society grade 3 or 4, were randomized on a single-blind basis to treatment with ACI at 1 of 3 dose levels: 3 to 7, 10 to 30, or 40 to 70 spheroids/cm2 of defect size. Outcomes were assessed via changes from baseline Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee score, and modified Lysholm assessments at 1- and 5-year follow-up. Structural repair was evaluated using MOCART (magnetic resonance observation of cartilage repair tissue) score. Treatment-related adverse events were assessed up to 5 years for all patients. The overall KOOS at 12 months was assessed for superiority versus baseline in a 1-sample, 2-sided t test. Results: A total of 73 patients were treated: 24 in the low-dose group, 25 in the medium-dose group, and 24 in the high-dose group. The overall KOOS improved from 57.0 ± 15.2 at baseline to 73.4 ± 17.3 at 1-year follow-up (P < .0001) and 76.9 ± 19.3 at 5-year follow-up (P < .0001), independent of the applied dose. The different defect locations (patella, trochlea, and weightbearing part of the femoral condyles; P = .2216) and defect sizes (P = .8706) showed comparable clinical improvement. No differences between the various doses were observed. The overall treatment failure rate until 5 years was 4%. Most treatment-related adverse events occurred within the first 12 months after implantation, with the most frequent adverse reactions being joint effusion (n = 71), arthralgia (n = 14), and joint swelling (n = 9). Conclusion: ACI using spheroids was safe and effective for defect sizes up to 10 cm2 and showed maintenance of efficacy up to 5 years for all 3 doses that were investigated. Registration: NCT01225575 (ClinicalTrials.gov identifier); 2009-016816-20 (EudraCT number).

BackgroundRoux-en-Y gastric bypass (LRYGB) has weight-independent effects on glycemia in obese type 2 diabetic patients, whereas sleeve gastrectomy (LSG) is less well characterized. This study aims to compare early weight-independent and later weight-dependent glycemic effects of LRYGB and LSG.MethodsEighteen LRYGB and 15 LSG patients were included in the study. Glucose, insulin, GLP-1, and GIP levels were monitored during a modified 30 g oral glucose tolerance test before surgery and 2 days, 3 weeks, and 12 months after surgery. Patients self-monitored glucose levels 2 weeks before and after surgery.ResultsPostoperative fasting blood glucose decreased similarly in both groups (LRYGB vs. SG; baseline—8.1 ± 0.6 vs. 8.2 ± 0.4 mmol/l, 2 days—7.8 ± 0.5 vs. 7.4 ± 0.3 mmol/l, 3 weeks—6.6 ± 0.4 vs. 6.6 ± 0.3 mmol/l, respectively, P < 0.01 vs. baseline for both groups; 12 months—6.6 ± 0.4 vs. 5.9 ± 0.4, respectively, P < 0.05 for LRYGB and P < 0.001 for LSG vs. baseline, P = ns between the groups at all times). LSG, but not LRYGB, showed increased peak insulin levels 2 days postoperatively (mean ± SEM; LSG + 58 ± 14%, P < 0.01; LRYGB − 8 ± 17%, P = ns). GLP-1 levels increased similarly at 2 days, but were higher in LRYGB at 3 weeks (AUC; 7525 ± 1258 vs. 4779 ± 712 pmol × min, respectively, P < 0.05). GIP levels did not differ. Body mass index (BMI) decreased more after LRYGB than LSG (− 10.1 ± 0.9 vs. − 7.9 ± 0.5 kg/m2, respectively, P < 0.05).ConclusionLRYGB and LSG show very similar effects on glycemic control, despite lower GLP-1 levels and inferior BMI decrease after LSG.