Physical deconditioning is involved in the impaired exercise tolerance of patients with multiple sclerosis (MS), but data on the effects of aerobic training (AT) in this population are scanty. The ...purpose of this study was to compare the effects of an 8-week AT program on exercise capacity-in terms of walking capacity and maximum exercise tolerance, as well as its effects on fatigue and health-related quality of life-as compared with neurological rehabilitation (NR) in subjects with MS.
Nineteen subjects (14 female, 5 male; mean age X+/-SD=41+/-8 years) with mild to moderate disability secondary to MS participated in a randomized crossover controlled study. Eleven subjects (8 female, 3 male; mean age X+/-SD=44+/-6 years) completed the study.
After AT, but not NR, the subjects' walking distances and speeds during a self-paced walk were significantly improved, as were their maximum work rate, peak oxygen uptake, and oxygen pulse during cardiopulmonary exercise tests. The increases in peak oxygen uptake and maximum work rate, but not in walking capacity, were significantly higher after AT, as compared with after NR. Additionally, the subjects who were most disabled tended to benefit more from AT. There were no differences between AT and NR in effects on fatigue, and the results showed that AT may have partially affected health-related quality of life.
The results suggest that AT is more effective than NR in improving maximum exercise tolerance and walking capacity in people with mild to moderate disability secondary to MS.
The cytokine release syndrome or cytokine storm, which is the hyper-induction of inflammatory responses has a central role in the mortality rate of COVID-19 and some other viral infections. ...Interleukin-6 (IL-6) is a key player in the development of cytokine storms. Shedding of interleukin-6 receptor (IL-6Rα) results in the accumulation of soluble interleukin-6 receptors (sIL-6R). Only relatively few cells express membrane-bound IL-6Rα. However, sIL-6R can act on potentially all cells and organs through the ubiquitously expressed gp130, the coreceptor of IL-6Rα. Through this, so-called trans-signaling, IL-6-sIL-6R is a powerful factor in the development of cytokine storms and multiorgan involvement. Some bacteria (e.g., Serratia marcescens, Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes), commonly considered to cause co-infections during viral pneumonia, can directly induce the shedding of membrane receptors, including IL-6Rα, or enhance endogenous shedding mechanisms causing the increase of sIL-6R level. Here we hypothesise that bacteria promoting shedding and increase the sIL-6R level can be an important contributing factor for the development of cytokine storms. Therefore, inhibition of IL-6Rα shedding by drastically reducing the number of relevant bacteria may be a critical element in reducing the chance of a cytokine storm. Validation of this hypothesis can support the consideration of the prophylactic use of antibiotics more widely and at an earlier stage of infection to decrease the mortality rate of COVID-19. Video abstract.
Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway ...blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn's disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1
immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1
cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1
microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.
Background
Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant ...chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer.
Patients and Methods
In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margins and a low number of lymph nodes harvested), as well as tumor histologic subtype, were associated with cancer-specific survival in 66 stage II non-ampullary small bowel adenocarcinoma patients, collected through the Small Bowel Cancer Italian Consortium. A central histopathology review was performed. Mismatch repair deficiency was tested by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2, and confirmed by polymerase chain reaction for microsatellite instability.
Results
We identified mismatch repair deficiency, glandular/medullary histologic subtype, and celiac disease as significant predictors of favorable cancer-specific survival using univariable analysis with retained significance in bivariable models adjusted for pT stage. Among the high-risk features, only T4 showed a significant association with an increased risk of death; however, its prognostic value was not independent of mismatch repair status.
Conclusions
Mismatch repair protein expression, histologic subtype, association with celiac disease, and, in the mismatch repair proficient subset only, T stage, may help identify patients who may benefit from adjuvant chemotherapy.
Graphic Abstract
Most Crohn’s disease-associated small bowel carcinomas (CrD-SBCs) are diagnosed in advanced stage and have poor prognosis. To improve diagnosis and therapy, a better knowledge of tumour precancerous ...lesions, histotypes and prognostic factors is needed. We investigated histologically and immunohistochemically 52 CrD-SBCs and 51 small bowel carcinomas unrelated to inflammatory disease, together with their tumour-associated mucosa, looking for Crohn-selective changes. Histologic patterns and phenotypic markers potentially predictive of CrD-SBC histogenesis and prognosis were analysed. Cytokeratin 7 or MUC5AC-positive metaplastic changes were found in about half of investigated CrD-SBCs, significantly more frequently than in CrD-unrelated SBCs. They correlated with metaplastic changes of their associated mucosa, while being absent in normal ileal mucosa. Histologic patterns suggestive for progression of some cytokeratin 7 and/or MUC5AC-positive metaplastic lesions into cancer of the same phenotype were also observed. Patient survival analyses showed that tumour cytokeratin 7 or MUC5AC expression and non-cohesive histotype were adverse prognostic factors at univariable analysis, while cytokeratin 7 and non-cohesive histotype were also found to predict worse survival in stage- and age-inclusive multivariable analyses. Besides conventional dysplasia, hyperplasia-like non-conventional lesions were observed in CrD-SBC-associated mucosa, with patterns suggestive for a histogenetic link with adjacent cancer. In conclusion the cytokeratin 7 and/or MUC5AC-positive metaplastic foci and the non-conventional growths may have a role in cancer histogenesis, while tumour cytokeratin 7 and non-cohesive histotype may also predict poor patient survival. Present findings are worth being considered in future prospective histogenetic and clinical studies.
Background
While in the last 5 years several studies have been conducted in Italy on the prevalence of mental disorders in adults, to date no epidemiological study has been targeted on mental ...disorders in adolescents.
Method
A two-phase study was conducted on 3,418 participants using the child behavior checklist/6–18 (CBCL) and the development and well-being assessment (DAWBA), a structured interview with verbatim reports reviewed by clinicians.
Results
The prevalence of CBCL caseness and DSM-IV disorders was 9.8% (CI 8.8–10.8%) and 8.2% (CI 4.2–12.3%), respectively. DSM-IV Emotional disorders were more frequently observed (6.5% CI 2.2–10.8%) than externalizing disorders (1.2% CI 0.2–2.3%). In girls, prevalence estimates increased significantly with age; furthermore, living with a single parent, low level of maternal education, and low family income were associated with a higher likelihood of suffering from emotional or behavioral problems.
Conclusions
Approximately one in ten adolescents has psychological problems. Teachers and clinicians should focus on boys and girls living with a single parent and/or in disadvantaged socioeconomic conditions.
Abstract
Background and Aims
Crohn’s disease-associated small bowel carcinoma is a rare event, usually reported to have a severe prognosis. However, in previous investigations we have found a ...minority of cases displaying a relatively favourable behaviour, thus outlining the need to improve the histopathological prediction of Crohn’s disease-associated small bowel carcinoma prognosis.
Methods
As in recent studies on colorectal cancer, a substantial improvement in prognostic evaluations has been provided by the histological analysis of the tumour invasive front; we therefore systematically analysed the tumour budding and poorly differentiated clusters in the invasive front of 47 Crohn’s disease-associated small bowel carcinomas collected through the Small Bowel Cancer Italian Consortium.
Results
Both tumour budding and poorly differentiated cluster analyses proved highly effective in prognostic evaluation of Crohn’s disease-associated small bowel carcinomas. In addition, they retained prognostic value when combined with two other parameters, i.e. glandular histology and stage I/II, both known to predict a relatively favourable small bowel carcinoma behaviour. In particular, association of tumour budding and poorly differentiated clusters in a combined invasive front score allowed identification of a minor subset of cancers 12/47, 25% characterised by combined invasive front low grade coupled with a glandular histology and a low stage I or II and showing no cancer-related death during a median follow-up of 73.5 months.
Conclusions
The improved distinction of lower- from higher-grade Crohn’s disease-associated small bowel carcinomas provided by invasive front analysis should be of potential help in choosing appropriate therapy for these rare and frequently ominous neoplasms.
We aimed to analyze the prevalence and impact of COPD in older patients hospitalized in internal medicine or geriatric wards, and to investigate adherence to the Global Initiative for Chronic ...Obstructive Lung Disease (GOLD) guidelines, associated clinical factors, and outcomes.
Data were obtained from REgistro POliterapie SIMI (REPOSI), a prospective multicenter observational registry that enrolls inpatients aged ≥65 years.
Older hospitalized patients enrolled from 2008 to 2016 with a diagnosis of COPD.
We evaluated adherence to the 2018 GOLD guidelines at admission and discharge, by examining the prescription of inhaled bronchodilators and corticosteroids in COPD patients. We also evaluated the occurrence of outcomes and its association with COPD and guideline adherence.
At hospital admission, COPD was diagnosed in 1302 (21.5%) of 6046 registered patients. COPD patients were older, with more impaired clinical and functional status and multiple comorbidities. Overall, 34.3% of COPD patients at admission and 35.6% at discharge were adherent to the GOLD guidelines. Polypharmacy (≥5 drugs) at admission odds ratio (OR): 3.28, 95% confidence interval (CI): 2.24-4.81, a history of acute COPD exacerbation (OR: 2.65, 95% CI: 1.44-4.88) at admission, smoking habit (OR: 1.45, 95% CI: 1.08-1.94), and polypharmacy at discharge (OR: 6.76, 95% CI: 4.15-11.0) were associated with adherence to guidelines. COPD was independently associated with the risk of cardiovascular and respiratory death and rehospitalization occurrence compared to patients without COPD during follow-up. Adherence to guidelines was inversely associated with the occurrence of death from all causes (OR: 0.12, 95% CI: 0.02-0.90).
COPD was common in older patients acutely hospitalized, showing an impaired functional and clinical status. Prescriptions for older COPD patients were often not adherent to GOLD guidelines. Poor adherence to guidelines was associated with a worse clinical status. There is a need to improve adherence to guidelines in treating COPD patients, with the ultimate goal of reducing clinical events.
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