The Effect of a 2-Year Intervention Consisting of Diet,Physical Exercise,Cognitive Training,and Monitoring of Vascular Risk on Chronic Morbidity—the FINGER Randomized Controlled Trial

Objective

To verify whether a multidomain intervention lowers the risk of developing new chronic diseases in older adults.

From clinician to researcher--a first-hand account

While teaching and clinical care may be somewhat intuitive, research is much less so, and a lack of research experience or opportunity to do research can be frustrating to the faculty member who is trying to become well-rounded. In an effort to ease the transition from clinical teacher to clinical researcher, the faculty of dentistry at Dalhousie University has developed a research mentorship program. The purpose of this paper is to report on the opportunities and challenges that 2 dental clinicians experienced when they participated in the pilot phase of an epidemiologic survey of the oral health status of seniors. In their academic role, these 2 clinical examiners, who were full-time faculty members, concentrated on classroom and clinical teaching. Although neither had previous clinical research experience, both were interested in broadening their horizons by engaging in research in the hope of attaining a variety of positive outcomes.     

Shiga Toxin Promotes Podocyte Injury in Experimental Hemolytic Uremic Syndrome via Activation of the Alternative Pathway of Complement

Shiga toxin (Stx)–producing Escherichia coli is the offending agent of postdiarrhea-associated hemolytic uremic syndrome (HUS), a disorder of glomerular ischemic damage and widespread microvascular thrombosis. We previously documented that Stx induces glomerular complement activation, generating C3a responsible for microvascular thrombosis in experimental HUS. Here, we show that the presence of C3 deposits on podocytes is associated with podocyte damage and loss in HUS mice generated by the coinjection of Stx2 and LPS. Because podocyte adhesion to the glomerular basement membrane is mediated by integrins, the relevance of integrin-linked kinase (ILK) signals in podocyte dysfunction was evaluated. Podocyte expression of ILK increased after the injection of Stx2/LPS and preceded the upregulation of Snail and downregulation of nephrin and α-actinin-4. Factor B deficiency or pretreatment with an inhibitory antibody to factor B protected mice against Stx2/LPS-induced podocyte dysregulation. Similarly, pretreatment with a C3a receptor antagonist limited podocyte loss and changes in ILK, Snail, and α-actinin-4 expression. In cultured podocytes, treatment with C3a reduced α-actinin-4 expression and promoted ILK-dependent nuclear expression of Snail and cell motility. These results suggest that Stx-induced activation of the alternative pathway of complement and generation of C3a promotes ILK signaling, leading to podocyte dysfunction and loss in Stx-HUS.     

Is posterior percutaneous screw-rod instrumentation a safe and effective alternative approach to TLSO rigid bracing for single-level pyogenic spondylodiscitis? Results of a retrospective cohort analysis

Background contextCurrently, treatment for patients diagnosed with noncomplicated (ie, known infectious agent, no neurologic compromise, and preserved spinal stability) pyogenic spondylodiscitis (PS) is based on intravenous antibiotics and rigid brace immobilization. Since January 2010, we started offering our patients percutaneous posterior screw-rod instrumentation as an alternative approach to rigid bracing. Supposed benefits of posterior percutaneous instrumentation over rigid bracing are earlier free mobilization, increased comfort, and faster recovery.PurposeTo evaluate safety and effectiveness of posterior percutaneous spinal instrumentation for single-level PS and compare clinical and quality-of-life outcomes with standard thoracolumbosacral orthosis (TLSO) rigid bracing.Study design/SettingRetrospective observational cohort study.Patient sampleTwenty-seven patients consecutively diagnosed with single-level noncomplicated lower thoracic or lumbar PS from January 2010 to December 2011.Outcome measuresHealing rate, healing time, and changes in segmental kyphosis Cobb angle were compared in the two treatment groups. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complete blood count at regular time points until complete healing were also obtained. Self-report measures included Visual Analog Scale (VAS), Short-Form 12 (SF-12), and EuroQol five-dimension (EQ-5D) questionnaires.MethodsAt enrollment, patients were offered to choose between 24/7 TLSO rigid bracing for 3 to 4 months and bridging posterior percutaneous screw-rod instrumentation followed by soft bracing for 4 weeks after surgery. All patients underwent antibiotic therapy accordingly to isolated infectious agents. Patients were seen in the clinic at 1, 3, 6, and 9 months, and ESR, CRP, complete blood count, VAS, SF-12, and EQ-5D questionnaires were obtained. Segmental kyphosis was measured at diagnosis and at 9 months follow-up. Two-way repeated-measures analysis of variance was used to assess group and time differences across time points.ResultsFifteen patients chose conservative treatment, whereas 12 patients chose surgical treatment. Complete infection healing was achieved in all patients with no significant differences in healing time (p<.366). C-reactive protein and ESR levels decreased in both groups accordingly with positive response to therapy with no significant differences. Surgically treated patients had significantly lower VAS scores at 1 month (2.76±0.80 vs. 5.20±1.21, p<.001) and 3 months (2.31±0.54 vs. 2.85±0.54, p<.016) post-diagnosis over TLSO patients. Moreover, surgery patients also showed steeper and statistically significant improvements in SF-12 scores over TLSO patients at 1, 3, and 6 months post-diagnosis (p<.012); no significant differences were detected at the other time points. EuroQol five-dimension index was significantly higher in surgery patients at 1 month (0.764±0.043 vs. 0.458±0.197, p<.001) and 3 months (0.890±0.116 vs. 0.688±0.142, p<.001); no significant changes were observed in segmental pre- and posttreatment kyphosis between the two groups. No instrumentation-related complications were observed in any patient.ConclusionsPosterior percutaneous spinal instrumentation is a safe, feasible, and effective procedure in relieving pain, preventing deformity, and neurologic compromise in patients affected by noncomplicated lower thoracic (T9–T12) or lumbar PS. Posterior instrumentation did not offer any advantage in healing time over TLSO rigid bracing because infection clearance is strongly dependent on proper antibiotic therapy. Nevertheless, surgical stabilization was associated with faster recovery, lower pain scores, and improved quality of life compared with TLSO conservative treatment at 1, 3, and 6 months after treatment.     

Pancreatic surgery is a safe teaching model for tutoring residents in the setting of a high-volume academic hospital: a retrospective analysis of surgical and pathological outcomes

BackgroundAcademic hospitals must train future surgeons, but whether residents could negatively affect the outcomes of major procedures is a matter of concern. The aim of this study is to assess if pancreatic surgery is a safe teaching model.MethodsOutcomes of 1230 major pancreatic resections performed at a high-volume pancreatic teaching hospital between 2015 and 2018 were compared according to the first surgeon type, attending vs resident.ResultsResidents performed a selection of 132 (16%) pancreaticoduodenectomies (PD) and 46 (11%) distal pancreatectomies (DP). For PD, pancreatic fistula (25% vs 0, p < 0.001), biliary fistula (7.1% vs 3.5%, p = 0.04) and operative time (400 vs 390 min, p < 0.001) were lower for residents but post-pancreatectomy hemorrhage was higher (20.5% vs 13% p = 0.024). For DP, pancreatic fistula rate was lower for residents (31.7% vs 17.5% p = 0.046). There was no difference in terms of lymph nodes retrieval both for PDs and DPs, while the R1 resections were more frequent among PDs performed by attending surgeons (31.5% vs 15.7%, p = 0.023).ConclusionThe active participation of residents does not negatively affect outcomes of major pancreatic resections in a high-volume center. By means of case selection and continuous tutoring, pancreatic surgery represents a safe and valid teaching model.     

Liver transplant recipients infected with SARS‐CoV‐2 in the early postoperative period: Lessons from a single center in the epicenter of the pandemic

The impact of coronavirus disease‐19 (COVID‐19) in liver recipients remains largely unknown. Most data derive from small retrospective series of patients transplanted years ago. We aimed to report a single‐center case series of five consecutive patients in the early postoperative period of deceased‐donor liver transplantation who developed nosocomial COVID‐19. Two patients presented important respiratory discomfort and eventually died. One was 69 years old and had severe coronary disease. She rapidly worsened after COVID‐19 diagnosis on 9th postoperative day. The other was 67 years old with non‐alcoholic steatohepatitis, who experienced prolonged postoperative course, complicated with cytomegalovirus infection and kidney failure. He was diagnosed on 36th postoperative day and remained on mechanical ventilation for 20 days, ultimately succumbing of secondary bacterial infection. The third, fourth, and fifth patients were diagnosed on 10th, 11th, and 18th postoperative day, respectively, and presented satisfactory clinical evolution. These last two patients were severely immunosuppressed, since one underwent steroid bolus for acute cellular rejection and another also used anti‐thymocyte globulin for treating steroid‐resistant rejection. Our novel experience highlights that COVID‐19 may negatively impact the postoperative course, especially in elder and obese patients with comorbidities, and draws attention to COVID‐19 nosocomial spread in the early postoperative period.     

Thermal and mechanical pain sensitization in patients with osteoarthritis of the knee

Objective: The aim was to assess sensitization using quantitative sensory testing in mechanical and thermal modes in individuals with and without osteoarthritis (OA) of the knee. Pain thresholds were correlated with functionality, symptoms of depression and intensity of pain. Methods: Thirty control volunteers and 30 patients with OA of the knee were assessed. Punctate pain thresholds using Von Frey filaments and thermal pain thresholds using a Thermal Sensory Analyzer were evaluated in the periarticular region of the knee and forearm. Using a digital pressure algometer, pressure pain thresholds were assessed in the periarticular region of the knee and on the root exit zone on the lumbar and sacral spine. Results: Punctate, pressure, and thermal pain thresholds differed significantly between participants with and without OA (p < 0.05). Values in those with OA were consistent with pain sensitization. Pressure pain thresholds also showed moderate and negative correlations with data on functionality, symptoms of depression and intensity of pain (?0.36 < r > ?0.56), contributing up to 30% of their variability. Conclusions: Allodynia and hyperalgesia were demonstrated in the OA group, suggesting central sensitization in patients with mild to moderate severity of joint damage. Correlation between mechanical hypersensitivity and psychosocial factors seems to be small, despite of its significance.     

Mutation in sodium-calcium exchanger 1 (NCX1) causes cardiac fibrillation in zebrafish

Cardiac fibrillation, a form of cardiac arrhythmia, is the most common cause of embolic stroke and death associated with heart failure. The molecular mechanisms underlying cardiac fibrillation are largely unknown. Here we report a zebrafish model for cardiac fibrillation. The hearts of zebrafish tremblor (tre) mutants exhibit chaotic movements and fail to develop synchronized contractions. Calcium imaging showed that normal calcium transients are absent in tre cardiomyocytes, and molecular cloning of the tre mutation revealed that the tre locus encodes the zebrafish cardiac-specific sodium-calcium exchanger (NCX) 1, NCX1h. Forced expression of NCX1h or other calcium-handling molecules restored synchronized heartbeats in tre mutant embryos in a dosage-dependent manner, demonstrating the critical role of calcium homeostasis in maintaining embryonic cardiac function. By creating mosaic zebrafish embryos, we showed that sporadic NCX1h-null cells were not sufficient to disrupt normal cardiac function, but clustered wild-type cardiomyocytes contract in unison in tre mutant hearts. These data signify the essential role of calcium homeostasis and NCX1h in establishing rhythmic contraction in the embryonic zebrafish heart.