Changes in muscle morphology in dialysis patients after 6 months of aerobic exercise training.

BACKGROUND: In the present study we investigated the effect of a 6-month aerobic exercise programme on the morphology of the gastrocnemius muscle of end-stage renal disease (ESRD) patients. METHODS: Twenty-four ESRD patients volunteered to participate in the training programme and underwent muscle biopsy before training. Eighteen patients completed the training programme of whom nine agreed to a post-training biopsy (one woman and eight men, mean age 56 +/- 15 years). Data are presented for the nine subjects who were biopsied before (PRE) and after training (POST) and separately for the 15 subjects for whom we only have a biopsy before training (cross-sectional group). RESULTS: There were no significant differences (P > 0.05) in fibre type distribution or myosin heavy chain (MyHC) expression between the cross-sectional and PRE/POST groups. The mean cross-section fibre area after training (POST) increased by 46% compared with the PRE training status (P < 0.01). The proportion of atrophic fibres decreased significantly after training in type I, IIa and IIx fibre populations (from 51 to 15%, 58 to 21% and 62 to 32%, respectively). Significant differences were also found in capillary contact per fibre (CC/F), with the muscle having 24% (P < 0.05) more CC/F compared with the PRE training status. No significant differences in cytochrome c oxidase concentration were found between the groups. CONCLUSIONS: In conclusion, exercise appeared to be beneficial in renal rehabilitation by correcting the fibre atrophy, increasing the cross-section fibre area and improving the capillarization in the skeletal muscle of renal failure patients.     

Sleep apnea-related cognitive deficits and intelligence: an implication of cognitive reserve theory

Cognitive deficits in patients with obstructive sleep apnea syndrome (OSAS) are well demonstrated, but the pathophysiology of these deficits is still controversial, as the relationship between OSA severity and cognitive deficits is usually weak. Our study considers the possible relationship between OSA-related cognitive deficits and the overall intellectual function of OSA patients. Forty-seven OSA patients and 36 normal individuals underwent a neuropsychological battery test assessing attention and alertness. According to the resulting IQ score, patients and controls were divided into a high-intelligence group (IQ > or = 90th percentile) and a normal-intelligence group (50 < or = IQ < 90%ile). Between the two patient groups there were no significant differences noticed, regarding OSA severity or sleepiness. High-intelligence patients showed the same attention/alertness performance compared with the high-intelligence controls. On the contrary, patients with normal-intelligence showed attention/alertness decline compared with the normal-intelligence control group. The two patient groups were re-examined with the same battery test after at least 1 year of CPAP treatment. At re-examination neither patient group showed any differences regarding attention and alertness compared with the control groups. We assume that high-intelligence may have a protective effect against OSA-related cognitive decline, perhaps due to increased cognitive reserve.     

Do microscopic surgical margins matter for primary gastric gastrointestinal stromal tumor?

BackgroundAlthough tumor size and mitotic rate are established prognostic factors for worse survival in patients undergoing surgical resection for gastric gastrointestinal stromal tumors, the impact of microscopic margins, or R1 resection, is not completely established.MethodsPatients who received no neoadjuvant therapy and underwent surgical resection for stage I to III gastric gastrointestinal stromal tumors were identified from the 2010 to 2013 National Cancer Database and divided into 2 cohorts, R0 and R1 resections. Cox proportional hazards ratio and Kaplan Meier survival estimates were utilized to analyze 5-y overall survival.ResultsOf 2,084 patients, those with R1 resection (57, 2.7%) were more likely to have tumors >10 cm (28.1% vs 11.9%, odds ratio 3.51, P = .017) and stage III disease (26.3% vs 11.2%, odds ratio 2.26, P = .047). Although margin status was associated with higher risk tumors, it was not associated with receipt of adjuvant therapy. After multivariate Cox regression, R1 and R0 patients did not have a difference in 5-y overall survival (82.5% vs 88.6%, hazards ratio 1.26, P = .49). When stratified by stage of disease, there remained no difference in survival across all stages when comparing R1 and R0 patients.ConclusionPositive microscopic margins are uncommon but do not appear to impact survival outcomes in patients with resected localized gastric gastrointestinal stromal tumors.     

Moderate Colitis Not Requiring Intravenous Steroids Is Associated with Improved Survival in Stage IV Melanoma after Anti-CTLA4 Monotherapy,But Not Combination Therapy

BackgroundFor patients with melanoma, gastrointestinal immune-related adverse events are common after receipt of anti-CTLA4 therapy. These present difficult decision points regarding whether to discontinue therapy. Detailing the situations in which colitis might predict for improved survival and how this is affected by discontinuation or resumption of therapy can help guide clinical decision-making.Materials and MethodsPatients with stage IV melanoma receiving anti-CTLA4 therapy from 2008 to 2019 were analyzed. Immune-related colitis treated with ≥50 mg prednisone or equivalent daily or secondary immunosuppression was included. Moderate colitis was defined as receipt of oral glucocorticoids only; severe colitis was defined as requiring intravenous glucocorticoids or secondary immunosuppression. The primary outcome was overall survival (OS).ResultsIn total, 171 patients received monotherapy, and 91 received dual checkpoint therapy. In the monotherapy group, 25 patients developed colitis and a nonsignificant trend toward improved OS was observed in this group. Notably, when colitis was categorized as none, moderate or severe, OS was significantly improved for moderate colitis only. This survival difference was not present after dual checkpoint therapy. There were no differences in known prognostic variables between groups, and on multivariable analysis neither completion of all ipilimumab cycles nor resumption of immunotherapy correlated with OS, while the development of moderate colitis did significantly affect OS.ConclusionThis single-institution retrospective series suggests moderate colitis correlates with improved OS for patients with stage IV melanoma treated with single-agent anti-CTLA4, but not dual agent, and that this is true regardless of whether the immune-checkpoint blockade is permanently discontinued.     

The vicious circle between physical,psychological, and physiological characteristics of shift work in nurses: a multidimensional approach

Sleep and Breathing - To compare physical, psychological, and physiological adaptations between rotating and morning shift health workers using objective and subjective approaches. Forty nurses...     

Regenerative Endodontic Procedures for the Treatment of Necrotic Mature Teeth with Apical Periodontitis: A Systematic Review and Meta-analysis of Randomized Controlled Trials

IntroductionRegenerative endodontic procedures (REPs) are intended to repair and regenerate part of the pulp-dentin complex. The aim of this study was to systematically appraise the existing evidence on the effectiveness of REPs on mature teeth with pulp necrosis and apical periodontitis.MethodsElectronic database and hand searches were performed on 8 databases of published and unpublished literature from inception to January 3, 2021, for the identification of randomized controlled trials (RCTs) or prospective clinical trials. The related key words included “regenerative,” “pulp revascularization,” “revitalization procedure,” and “necrotic mature teeth.” A random effects meta-analysis was conducted assessing success as the main outcome treatment. Risk of bias was assessed through the Cochrane Risk of Bias 2.0 tool, and the quality of the evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation approach.ResultsOf the 337 initial hits, 4 RCTs were eligible for inclusion, whereas 3 were included in the quantitative synthesis. Overall, there was no difference in the relative risk for a successful/unsuccessful treatment outcome between REPs or conventional treatment (3 studies, relative risk = 1.03; 95% confidence interval, 0.92–1.15; P = .61; heterogeneity I² = 0.0%, P = .53; prediction interval = 0.51–2.09). Risk of bias ranged from low to raising some concerns, whereas the quality of the evidence was graded as moderate.ConclusionsBased on moderate-quality evidence, REPs appear as a viable treatment alternative for mature necrotic teeth with periapical lesions at present. Furthermore, well-designed RCTs might also provide confirmatory evidence in this respect while also framing a backbone for standardization of the therapeutic protocol of REPs.     

Synchronous cytomegalovirus and Clostridium difficile infection of the pouch: a trigger for chronic pouchitis?

Pouchitis occurs in up to one half of patients after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Cytomegalovirus (CMV) and Clostridium difficile are among the commonest secondary identifiable etiologies. A 17-year-old male with ulcerative colitis underwent IPAA due to refractory disease. Nine months later he experienced bloody diarrhea and fever. Laboratory testing and endoscopy confirmed pouch inflammation. Testing for C. difficile toxins A and B was positive. Histology revealed affluent inclusion bodies and immunohistochemistry detected reactivity against CMV protein. Treatment with metronidazole and vancomycin offered partial improvement, whereas the addition of gancyclovir led to a successful recovery. One month after completion of treatment symptoms recurred. Repeat testing precluded an identifiable infectious cause and the diagnosis of idiopathic chronic pouchitis was established. The patient is currently on maintenance treatment with the probiotic compound VSL#3.     

Differential expression of the TL1A/DcR3 system of TNF/TNFR-like proteins in large vs. small intestinal Crohn's disease

Background

TNF-like cytokine 1A provides co-stimulatory signals to activated lymphocytes through binding to death-domain receptor-3. Decoy receptor-3 inhibits death-domain receptor-3 signalling, rendering immunocytes resistant to apoptosis. These functions may be important for the pathogenesis of Crohn's disease.

Aims

To study the mucosal and systemic expression of Decoy receptor-3 and TNF-like cytokine 1A in Crohn's disease, in relation to disease activity, localization, and response to treatment.

Methods

Soluble Decoy receptor-3 and TNF-like cytokine 1A were measured by ELISA in active or quiescent Crohn's disease. Relative mRNA expression in non-affected and inflamed intestinal mucosa was determined by real-time RT-PCR.

Results

We found significant upregulation of Decoy receptor-3 and its ligands TNF-like cytokine 1A and FasL in inflamed intestinal mucosa of Crohn's disease patients. During active disease, Decoy receptor-3 and TNF-like cytokine 1A were detected in the serum in the majority of patients. Intestinal inflammation was strongly associated with these elevations as they were absent during remission and significantly reduced with anti-inflammatory treatment. Regional diversity was observed as Decoy receptor-3 was upregulated in colonic and ileal sites, whereas TNF-like cytokine 1A was preferentially induced in the large bowel mucosa and systemic circulation of patients with colonic involvement.

Conclusions

TNF-like cytokine 1A and Decoy receptor-3 are upregulated during active Crohn's disease and may participate in disease pathogenesis and offer novel therapeutic opportunities.     

Local Immune Response Predicts Survival in Patients with Thick (T4) Melanomas

Background

Tumor infiltrating lymphocytes (TIL) and histological regression in primary melanoma are generally considered indicators of the local immune response but their roles as prognostic factors have been variably reported. We examined the prognostic role of these variables in patients with high risk (T4) primary melanomas in a large series of patients with long-term follow-up.

Methods

From a prospectively maintained cohort of patients diagnosed between 1971 and 2004, 161 patients were retrospectively identified with primary thick melanomas (>4 mm), no clinical evidence of regional nodal disease (RND) at diagnosis and complete histopathologic data. Univariate and multivariate Cox regression models were performed to identify clinical and histopathologic predictors of disease-specific survival (DSS) and to identify subgroups with differential survival.

Results

Factors significantly associated with decreased DSS by univariate analysis included male gender, age ≥ 60 years, axial anatomic location, presence of ulceration, RND, absence of TIL, and presence of regression. In the final multivariate model, TIL and regression, as interacting variables, and RND status remained significantly associated with DSS. In the presence of TIL, concomitant regression was associated with significantly worse survival (p ≤ 0.0001). In the absence of TIL, there was no effect of regression on survival (p = 0.324).

Conclusions

Primary TIL and regression status and RND status are independently associated with melanoma-specific survival in patients with T4 melanomas; presence of TIL in the primary melanoma with concomitant radial growth phase regression is associated with a poor prognosis and may reflect an ineffective local regional immune response.