Effectiveness of balance exercise and brisk walking on alleviating non-motor and motor symptoms in people with mild-to-moderate Parkinson's Disease: A randomized clinical trial with 6-month follow-up.

OBJECTIVE: Investigate the effects of balance exercise and brisk walking on non-motor and motor symptoms, balance and gait functions, walking capacity, and balance confidence in Parkinson's disease (PD) at post-training and 6-month follow-up. DESIGN: Two-arm, assessor-blinded randomized controlled trial SETTING: University research laboratory and the community PARTICIPANTS: Ninety-nine eligible individuals with mild to moderate PD INTERVENTIONS: Participants were randomized to balance and brisk walking group (B&B, n=49) or active control group (CON, n=50). B&B received ten 90-minute sessions of balance exercises and brisk walking supervised by physical therapists for 6 months (week 1-6: weekly, week 7-26: monthly), whilst CON practiced whole-body flexibility and upper limb strength exercise at same dosage (180 minutes/week). Both groups performed unsupervised home exercises 2-3 times/week during intervention and continued at follow-up. MAIN OUTCOMES AND MEASURES: Primary outcomes were Movement Disorder Society Unified Parkinson Disease Rating Scale non-motor (MDS-UPDRS-I) and motor (MDS-UPRDS-III) scores. Secondary outcomes were Mini-Balance Evaluation Systems Test (Mini-BEST) score, comfortable gait speed (CGS), six-minute walk distance (6MWD), dual-task timed-up-and-go (DTUG) time, and Activities-Specific Balance Confidence Scale (ABC) score. RESULTS: Eighty-three individuals completed the 6-month intervention with no severe adverse effects. The mean between-group (95% CI) difference for the MDS-UPDRS non-motor score was 1.50 (0.19-2.81) at 6 months and 1.09 (-0.66-2.85) at 12 months. The mean between-group (95% CI) difference for the MDS-UPDRS motor score was 3.75 (0.69-6.80) at 6 months and 4.57 (1.05-8.01) at 12 months. At 6 months and 12 months, there were significant between-group improvements of the B&B group in Mini-BEST score, CGS, 6MWD and DTUG time. CONCLUSIONS: This combined balance and brisk walking exercise program alleviates non-motor and motor symptoms and improves walking capacity, balance, and gait functions post-training, with positive carry-over effects for all except non-motor outcomes, at 6-month follow-up in mild to moderate PD.

Exploration of Germline Correlates and Risk of Immune-Related Adverse Events in Advanced Cancer Patients Treated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of many tumor types, and durable responses can be observed in select populations. However, patients may exhibit significant immune-related adverse events (irAEs) that may lead to morbidity. There is limited information on whether the presence of specific germline mutations may highlight those at elevated risk of irAEs. We evaluated 117 patients with metastatic solid tumors or hematologic malignancies who underwent genomic analysis through the ongoing Personalized OncoGenomics (POG) program at BC Cancer and received an ICI during their treatment history. Charts were reviewed for irAEs. Whole genome sequencing of a fresh biopsy and matched normal specimens (blood) was performed at the time of POG enrollment. Notably, we found that MHC class I alleles in the HLA-B27 family, which have been previously associated with autoimmune conditions, were associated with grade 3 hepatitis and pneumonitis (q = 0.007) in patients treated with combination PD-1/PD-L1 and CTLA-4 inhibitors, and PD-1 inhibitors in combination with IDO-1 inhibitors. These data highlight that some patients may have a genetic predisposition to developing irAEs.

Upfront Versus Delayed Systemic Therapy in Patients With Oligometastatic Cancer Treated With SABR in the Phase 2 SABR-5 Trial.

PURPOSE: The optimal sequencing of local and systemic therapy for oligometastatic cancer has not been established. This study retrospectively compared progression-free survival (PFS), overall survival (OS), and SABR-related toxicity between upfront versus delay of systemic treatment until progression in patients in the SABR-5 trial. METHODS AND MATERIALS: The single-arm phase 2 SABR-5 trial accrued patients with up to 5 oligometastases across SABR-5 between November 2016 and July 2020. Patients received SABR to all lesions. Two cohorts were retrospectively identified: those receiving upfront systemic treatment along with SABR and those for whom systemic treatment was delayed until disease progression. Patients treated for oligoprogression were excluded. Propensity score analysis with overlap weighting balanced baseline characteristics of cohorts. Bootstrap sampling and Cox regression models estimated the association of delayed systemic treatment with PFS, OS, and grade ≥2 toxicity. RESULTS: A total of 319 patients with oligometastases underwent treatment on SABR-5, including 121 (38%) and 198 (62%) who received upfront and delayed systemic treatment, respectively. In the weighted sample, prostate cancer was the most common primary tumor histology (48%) followed by colorectal (18%), breast (13%), and lung (4%). Most patients (93%) were treated for 1 to 2 metastases. The median follow-up time was 34 months (IQR, 24-45). Delayed systemic treatment was associated with shorter PFS (hazard ratio [HR], 1.56; 95% CI, 1.15-2.13; P = .005) but similar OS (HR, 0.90; 95% CI, 0.51-1.59; P = .65) compared with upfront systemic treatment. Risk of grade 2 or higher SABR-related toxicity was reduced with delayed systemic treatment (odds ratio, 0.35; 95% CI, 0.15-0.70; P < .001). CONCLUSIONS: Delayed systemic treatment is associated with shorter PFS without reduction in OS and with reduced SABR-related toxicity and may be a favorable option for select patients seeking to avoid initial systemic treatment. Efforts should continue to accrue patients to histology-specific trials examining a delayed systemic treatment approach.

Dedicated esophageal imaging may be unnecessary in marijuana-associated spontaneous pneumomediastinum: Findings from a retrospective cohort study.

Background: Marijuana use has become more common since its legalization, as have reports of marijuana-associated spontaneous pneumomediastinum. Non-spontaneous causes such as esophageal perforation are often ruled out on presentation due to the severe consequences of untreated disease. Here we seek to characterize the presentation of marijuana-associated spontaneous pneumomediastinum and explore whether esophageal imaging is necessary in the setting of an often benign course and rising healthcare costs. Materials and Methods: Retrospective review was performed for all 18-55 year old patients evaluated at a tertiary care hospital between 1/1/2008 and 12/31/2018 for pneumomediastinum. Iatrogenic and traumatic causes were excluded. Patients were divided into marijuana and control groups. Results: 30 patients met criteria, with 13 patients in the marijuana group. The most common presenting symptoms were chest pain/discomfort and shortness of breath. Other symptoms included neck/throat pain, wheezing, and back pain. Emesis was more common in the control group but cough was equally prevalent. Leukocytosis was present in most patients. Four out of eight of computed tomography esophagarams in the control group showed a leak requiring intervention, while only one out of five in the marijuana group showed even a possible subtle extravasation of contrast but this patient ultimately was managed conservatively given the clinical picture. All standard esophagrams were negative. All marijuana patients were managed without intervention. Discussion: Marijuana-associated spontaneous pneumomediastinum appears to have a more benign clinical course compared to non-spontaneous pneumomediastinum. Esophageal imaging did not change management for any marijuana cases. Perhaps such imaging could be deferred if clinical presentation of pneumomediastinum in the setting of marijuana use is not suggestive of esophageal perforation. Further research into this area is certainly worth pursuing.

Analysis of the determinants of sleep quality in a Spanish population: a study protocol for a cross-sectional study.

INTRODUCTION: Sleep problems are a growing public health concern being related, among others, to an increased risk of cardiovascular diseases or worse cognitive functioning. In addition, they can affect aspects related to personal motivation and quality of life. However, very few studies have analysed the possible determinants of sleep quality in the adult population as a whole, establishing patterns based on these determinants.The objectives are to evaluate the determinants of sleep quality in a representative sample of the general adult population between 25 and 65 years old, and to establish patterns of sleep quality based on lifestyles, psychological factors, morbidities, sociodemographic variables, biological markers and other possible determinants. METHODS AND ANALYSIS: Descriptive observational cross-sectional study. The study population will include a representative sample of 500 people between 25 and 65 years old from the cities of Salamanca and Ávila (Spain) selected by random sampling stratified by age groups and sex. A 90-minute visit will be performed, during which sleep quality will be assessed. The variables collected will be: morbidity, lifestyles (physical activity, diet, toxic habits), psychological factors (depression, stress, occupational stress and anxiety), socioeconomic and work-related variables, habitability conditions of the habitual residence and rest area, screen time, relaxation techniques and melatonin as a biological marker related to sleep quality. DISCUSSION: With the results of this work, improved interventions for behaviour modification could be designed, as well as intervention and education programmes or other research aimed at improving sleep quality. ETHICS AND DISSEMINATION: This study has a favourable opinion from the Ethics Committee for Drug Research of the Health Areas of Salamanca and Ávila (CEim Code: PI 2021 07 815). The results of this study will be published in international impact journals of different specialties. TRIAL REGISTRATION NUMBER: NCT05324267.

Immunotherapy: Recent Advances and Its Future as a Neoadjuvant, Adjuvant, and Primary Treatment in Colorectal Cancer.

Immunotherapy in colorectal cancer (CRC) has made great strides within the past decade. Immune checkpoint inhibitors are a class of immunotherapy and have been shown to greatly improve patient outcomes in mismatch repair-deficient (dMMR) CRC. Now, they are part of the standard of care for this subset of CRC. Because of this, there has been a growing interest in the efficacy and timing of immunotherapy for other subsets of CRC, including locally advanced, metastatic, and microsatellite stable (MSS). In this review, we aim to examine the three main classes of immunotherapy for CRC-immune checkpoint inhibitors (ICIs), adoptive cell transfer therapy (ACT), and tumor vaccines-and discuss the most recent advances and future directions for each.

Elevated bile acid metabolism and microbiome are associated with suppressed cell proliferation and better survival in breast cancer.

Bile acids are metabolized by the gut microbiome and are involved in fat absorption. Contrary to their carcinogenic role in gastrointestinal cancers, bile acids have been reported to inhibit cancer cell proliferation in breast cancer. The microbiome of breast cancer tissues may also influence cancer proliferation. We hypothesized that bile acid metabolism reflects its accumulation and is associated with certain microbiomes, breast cancer biology, and patient survival. Transcriptomic and clinicopathological information of a total of 6050 patients in three large open primary breast cancer cohorts (GSE96058, METABRIC, TCGA) and 16S rRNA gene sequence microbiome data of breast cancer tissues in TCGA were analyzed by high and low bile acid metabolism scores calculated by gene set variation analysis (GSVA). Breast cancers with high bile acid metabolism had a significantly improved survival across all three cohorts. Metabolic pathways related to the production and regulation of bile acids were consistently enriched in high bile acid metabolism groups across all cohorts. On the other hand, the low bile acid metabolism group was associated with higher Ki67 expression and Nottingham histological grade, as well as enrichment of cell proliferation-related gene sets. Intratumoral heterogeneity, homologous recombination deficiency, mutational load, activation of cancer immunity, and infiltration of anticancer immune cells were also higher in this group. Gammaretrovirus, Hymenobacter, Anaerococcus, and Collimonas were significantly more abundant in the high bile acid metabolism group compared to Lactobacillus, Ruegeria, and Marichromatium in the low metabolism group. Surprisingly, almost all Hallmark cell proliferation-associated gene sets were highly enriched in all three microorganisms that were abundant in the low bile acid metabolism group. In conclusion, microorganisms abundant in the breast tumor microenvironment with low bile acid metabolism are associated with aggressive cancer biology, including increased cell proliferation and poor survival.

The clinical impact of COVID-19 on patients with cancer in British Columbia: An observational study.

Objective: We evaluated survival outcomes for patients with cancer and COVID-19 in this population-based study. Methods: A total of 631 patients who tested positive for severe acute respiratory syndrome coronavirus 2 and were seen at BC Cancer between 03/03/2020 and 01/21/2021 were included, of whom 506 had a diagnosis of cancer and PCR-confirmed positive test for coronavirus disease 2019. Patient clinical characteristics were retrospectively reviewed and the influence of demographic data, cancer diagnosis, comorbidities, and anticancer treatment(s) on survival following severe acute respiratory syndrome coronavirus 2 infection were analyzed. Results: Age ≥65 years (Hazard Ratio [HR] 4.77, 95% Confidence Interval [CI] 2.72-8.35, P < 0.0001), those with Eastern Cooperative Oncology Group Performance Status ≥2 (HR 8.36, 95% CI 2.89-24.16, P < 0.0001), hypertension (HR 3.17, 95% CI 1.77-5.66, P < 0.0001), and metastatic/advanced stage (HR 3.70, 95% CI 1.77-7.73, P < 0.0001) were associated with worse coronavirus disease 2019 specific survival outcomes following severe acute respiratory syndrome coronavirus 2 infection. Patients with lung cancer had the highest 30-day COVID-19 specific mortality (25.0%), followed by genitourinary (18.1%), gastrointestinal (16.0%), and other cancer types (<10.0%). Patients with the highest 30-day coronavirus disease 2019 specific mortality according to treatment type were those on chemotherapy (23.0%), rituximab (22.2%), and immunotherapy (16.7%) while patients on hormonal treatments (2.2%) had better survival outcomes (P = 0.041) compared to those on other anticancer treatments. Conclusion: This study provides further evidence that patients with cancer are at increased risk of mortality from coronavirus disease 2019 and emphasizes the need for vaccination.

Effectiveness of a multiple health-behaviour-change intervention in increasing adherence to the Mediterranean Diet in adults (EIRA study): a randomized controlled hybrid trial.

BACKGROUND: The present study describes the effectiveness of a complex intervention that addresses multiple lifestyles to promote healthy behaviours in increasing adherence to the Mediterranean diet (MD).  METHODS: Cluster-randomised, hybrid clinical trial controlled with two parallel groups. The study was carried out in 26 primary Spanish healthcare centres. People aged 45-75 years who presented at least two of the following criteria were included: smoker, low adherence to the MD or insufficient level of physical activity. The intervention group (IG) had three different levels of action: individual, group, and community, with the aim of acting on the behaviours related to smoking, diet and physical activity at the same time. The individual intervention included personalised recommendations and agreements on the objectives to attain. Group sessions were adapted to the context of each healthcare centre. The community intervention was focused on the social prescription of resources and activities performed in the environment of the community of each healthcare centre. Control group (CG) received brief advice given in the usual visits to the doctor's office. The primary outcome was the change, after 12 months, in the number of participants in each group with good adherence to the MD pattern. Secondary outcomes included the change in the total score of the MD adherence score (MEDAS) and the change in some cardiovascular risk factors. RESULTS: Three thousand sixty-two participants were included (IG = 1,481, CG = 1,581). Low adherence to the MD was present in 1,384 (93.5%) participants, of whom 1,233 initiated the intervention and conducted at least one individual visit with a healthcare professional. A greater increase (13.7%; 95% CI, 9.9-17.5; p < 0.001) was obtained by IG in the number of participants who reached 9 points or more (good adherence) in the MEDAS at the final visit. Moreover, the effect attributable to the intervention obtained a greater increase (0.50 points; 95% CI, 0.35 to 0.66; p < 0.001) in IG. CONCLUSIONS: A complex intervention modelled and carried out by primary healthcare professionals, within a real clinical healthcare context, achieved a global increase in the adherence to the MD compared to the brief advice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03136211. Retrospectively registered on 02/05/2017 https://clinicaltrials.gov/ct2/show/NCT03136211.

The Role of the Microbiome on the Pathogenesis and Treatment of Colorectal Cancer.

The gut microbiome has long been known to play a role in various aspects of health modulation, including the pathogenesis of colorectal cancer (CRC). With immunotherapy recently emerging as a successful treatment in microsatellite instability high (MSI-high) CRC, and with a newly demonstrated involvement of the gut microbiome in the modulation of therapeutic responses, there has been an explosion of research into the mechanisms of microbial effects on CRC. Harnessing and reprogramming the microbiome may allow for the expansion of these successes to broader categories of CRC, the prevention of CRC in high-risk patients, and the enhancement of standard treatments. In this review, we pull together both well-documented phenomena and recent discoveries that pertain to the microbiome and CRC. We explore the microbial mechanisms associated with CRC pathogenesis and progression, recent advancements in CRC systemic therapy, potential options for diagnosis and prevention, as well as directions for future research.

Impaired Hand Function and Its Association With Self-Perceived Hand Functional Ability and Quality of Life in Parkinson Disease.

OBJECTIVE: Comprehensive hand function in people with Parkinson disease (PD) has been underevaluated. The objectives were to compare self-perceived and objective hand functions of PD and controls, compare outcomes between more and less affected hand subgroups, and evaluate relationship between self-perceived and objective outcomes in subgroups. DESIGN: A total of 165 PD and 82 healthy participants completed the Jebsen-Taylor Hand Function Test, Purdue Pegboard Test, grip strength test, and Manual Ability Measure-16 in a cross-sectional study. PD participants completed the Parkinson Disease Questionnaire-39. Associations between objective and self-perceived/quality of life outcomes in PD groups were analyzed, and nondominant and dominant more affected subgroups performance was compared. RESULTS: PD participants had significantly worse performance in most Jebsen-Taylor Hand Function Test and all Purdue Pegboard Test items, lower Manual Ability Measure-16 scores, and poorer handgrip strength. Weak associations were found between dexterity, but not grip strength, and self-perceived functional hand ability and Parkinson Disease Questionnaire-39 scores in PD subgroups. For nondominant more affected subgroup, poorer dexterity was associated with better Parkinson Disease Questionnaire-39 Activity of Daily Living domain scores. CONCLUSION: People with mild to moderate PD were shown to have poorer manual dexterity, reduced grip strength, and lower self-perceived functional hand ability than controls. Associations between dexterity and self-perceived outcomes highlight the importance of unimanual and bimanual training.

Tumor Biomarker Testing for Metastatic Colorectal Cancer: a Canadian Consensus Practice Guideline.

The systemic therapy management of metastatic colorectal cancer (mCRC) has evolved from primarily cytotoxic chemotherapies to now include targeted agents given alone or in combination with chemotherapy, and immune checkpoint inhibitors. A better understanding of the pathogenesis and molecular drivers of colorectal cancer not only aided the development of novel targeted therapies but led to the discovery of tumor mutations which act as predictive biomarkers for therapeutic response. Mutational status of the KRAS gene became the first genomic biomarker to be established as part of standard of care molecular testing, where KRAS mutations within exons 2, 3, and 4 predict a lack of response to anti- epidermal growth factor receptor therapies. Since then, several other biomarkers have become relevant to inform mCRC treatment; however, there are no published Canadian guidelines which reflect the current standards for biomarker testing. This guideline was developed by a pan-Canadian advisory group to provide contemporary, evidence-based recommendations on the minimum acceptable standards for biomarker testing in mCRC, and to describe additional biomarkers for consideration.

Exceptional response to combination ipilimumab and nivolumab in metastatic uveal melanoma: Insights from genomic analysis.

Uveal melanoma is the most common intraocular malignancy and has a poor prognosis compared to other melanoma subtypes with a median overall survival of 6-10 months. With immune checkpoint inhibitor therapy, either PD-1 inhibitor alone or combination ipilimumab/nivolumab (anti-CTLA-4/anti-PD-1), responses are rare and often not durable. We present a case report of a now 66-year-old woman with diffuse metastatic uveal melanoma previously treated with a combination of ipilimumab/nivolumab, followed by maintenance nivolumab. Almost complete resolution of all sites of metastatic disease was observed except for one liver metastasis which regressed partially on immunotherapy. Notably, the patient had a significantly elevated BMI and developed widespread vitiligo on treatment. Whole-genome and transcriptome analysis was performed on the residual liver biopsy and molecular markers that may have contributed to the exceptional response were investigated. Several alterations were observed in genes involved in T-cell responses. Estimates of tumour infiltrating immune cells indicated a high level of plasma cells compared to other uveal melanoma cases, a finding previously associated with indolent disease. The patient also carried several germline SNPs that may have contributed to her treatment response as well as widespread vitiligo. Whole-genome and transcriptome sequencing have provided insight into potential molecular underpinnings of an exceptional treatment response in a tumour type typically associated with poor prognosis. Immunological findings suggest a role for plasma cells in the tumour microenvironment. Elevated BMI and the development of vitiligo may be clinically relevant factors for predicting response to immune checkpoint inhibitor therapy, warranting further studies in patients with uveal melanoma.

[Impact of covid-19 vaccination on hospitalization in a third-level hospital.] / Impacto de la vacunación frente a la covid-19 sobre la hospitalización en un hospital de tercer nivel.

OBJECTIVE: This study presents information on the evolution of severe cases of SARS-CoV-2 infection that required hospitalization since the beginning of vaccination in Spain. The objective was to know the impact of vaccination against COVID-19 on the hospitalization of patients with SARS-CoV-2 infection, hospital mortality and readmissions for this cause, and to describe the characteristics of vaccinated patients who required admission. METHODS: A retrospective, observational epidemiological study was conducted of all patients admitted with SARS-CoV-2 infection confirmed by a diagnostic test for active infection (PDIA) in a tertiary hospital, from January 2021 to June 2021. The incidence of admissions was calculated based on the vaccination status of the patients and age groups at different times according to the progress of the strategy of vaccination COVID-19. RESULTS: Between December 27, 2020 and June 30, 2021, 1,308 patients with positive PDIA were admitted to the University Hospital of Salamanca, of which 1,167 (89.2%) were not vaccinated, 129 (9.9%) had received one dose of vaccine and 12 (0.9%) were fully vaccinated. Of the latter, none were admitted to the ICU and 2 died. CONCLUSIONS: Vaccination against COVID-19 has contributed to the decrease in hospitalizations, since February 2021, of older and institutionalized people. Fully vaccinated people have a lower risk of admission to the ICU and death. These data, together with the information available on recent cases of new SARS-CoV-2 infections in unvaccinated young people, are in favor of achieving high vaccination coverage of the entire population in the shortest possible time.

OBJETIVO: Este estudio presenta información sobre la evolución de los casos graves de infección SARS-CoV-2 que requirieron hospitalización desde el inicio de la vacunación en España. El objetivo fue conocer el impacto de la vacunación frente a COVID-19 sobre la hospitalización de pacientes con infección SARS-CoV-2, la mortalidad intrahospitalaria y los reingresos por esta causa, y describir las características de los pacientes vacunados que precisaron ingreso. METODOS: Se realizó un estudio epidemiológico observacional retrospectivo, de todos los pacientes ingresados con infección por SARS-CoV-2 confirmada mediante una prueba de diagnóstico de infección activa (PDIA) en un hospital de tercer nivel, de enero de 2021 a junio de 2021. Se calculó la incidencia de ingresos en función del estado vacunal de los pacientes y grupos de edad en diferentes momentos según el avance de la campaña de vacunación. RESULTADOS: Entre el 27 de diciembre de 2020 y el 30 de junio de 2021 ingresaron en el Hospital Universitario de Salamanca 1.308 pacientes con PDIA positiva, de los cuales 1.167 (89,2%) no estaban vacunados, 129 (9,9%) habían recibido una dosis de vacuna y 12 (0,9%) estaban completamente vacunados. De estos últimos, ninguno ingresó en UCI y 2 fallecieron. CONCLUSIONES: La vacunación frente a COVID-19 ha contribuido al descenso de las hospitalizaciones desde el mes de febrero de 2021, sobre todo en personas mayores e institucionalizadas. Las personas completamente vacunadas parecen tener menor riesgo de ingreso en UCI y fallecimiento. Estos datos, junto con la información disponible de los casos recientes de nuevas infecciones por SARS-CoV-2 en personas jóvenes no vacunadas, están a favor de conseguir una cobertura vacunal elevada de toda la población en el menor tiempo posible.

Impacto de la vacunación frente a la COVID-19 sobre la hospitalización en un hospital de tercer nivel / Impact of COVID-19 vaccination on hospitalization in a third-level hospital

Fundamentos: Este estudio presenta información sobre la evolución de los casos graves de infección SARS-CoV-2 que requirieron hospitalización desde el inicio de la vacunación en España. El objetivo fue conocer el impacto de la vacunación frente a COVID-19 sobre la hospitalización de pacientes con infección SARS-CoV-2, la mortalidad intrahospitalaria y los reingresos por esta causa, y describir las características de los pacientes vacunados que precisaron ingreso. Métodos: Se realizó un estudio epidemiológico observacional retrospectivo, de todos los pacientes ingresados con infección por SARS-CoV-2 confirmada mediante una prueba de diagnóstico de infección activa (PDIA) en un hospital de tercer nivel, de enero de 2021 a junio de 2021. Se calculó la incidencia de ingresos en función del estado vacunal de los pacientes y grupos de edad en diferentes momentos según el avance de la campaña de vacunación. Resultados: Entre el 27 de diciembre de 2020 y el 30 de junio de 2021 ingresaron en el Hospital Universitario de Salamanca 1.308 pacientes con PDIA positiva, de los cuales 1.167 (89,2%) no estaban vacunados, 129 (9,9%) habían recibido una dosis de vacuna y 12 (0,9%) estaban completamente vacunados. De estos últimos, ninguno ingresó en UCI y 2 fallecieron. Conclusiones: La vacunación frente a COVID-19 ha contribuido al descenso de las hospitalizaciones desde el mes de febrero de 2021, sobre todo en personas mayores e institucionalizadas. Las personas completamente vacunadas parecen tener menor riesgo de ingreso en UCI y fallecimiento. Estos datos, junto con la información disponible de los casos recientes de nuevas infecciones por SARS-CoV-2 en personas jóvenes no vacunadas, están a favor de conseguir una cobertura vacunal elevada de toda la población en el menor tiempo posible.(AU)

Background: This study presents information on the evolution of severe cases of SARS-CoV-2 infection that required hospitalization since the beginning of vaccination in Spain. The objective was to know the impact of vaccination against COVID-19 on the hospitalization of patients with SARS-CoV-2 infection, hospital mortality and readmissions for this cause, and to describe the characteristics of vaccinated patients who required admission. Methods: A retrospective, observational epidemiological study was conducted of all patients admitted with SARS-CoV-2 infection confirmed by a diagnostic test for active infection (PDIA) in a tertiary hospital, from January 2021 to June 2021. The incidence of admissions was calculated based on the vaccination status of the patients and age groups at different times according to the progress of the strategy of vaccination COVID-19. Results: Between December 27, 2020 and June 30, 2021, 1,308 patients with positive PDIA were admitted to the University Hospital of Salamanca, of which 1,167 (89.2%) were not vaccinated, 129 (9.9%) had received one dose of vaccine and 12 (0.9%) were fully vaccinated. Of the latter, none were admitted to the ICU and 2 died. Conclusions: Vaccination against COVID-19 has contributed to the decrease in hospitalizations, since February 2021, of older and institutionalized people. Fully vaccinated people have a lower risk of admission to the ICU and death. These data, together with the information available on recent cases of new SARS-CoV-2 infections in unvaccinated young people, are in favor of achieving high vaccination coverage of the entire population in the shortest possible time.(AU)

Impact of Tumor Location on Patient Outcomes in Small Bowel Cancers.

BACKGROUND: Small bowel cancers are rare gastrointestinal malignancies and tumor location impact on outcomes is unclear. MATERIAL AND METHODS: A retrospective review was performed on stage I to IV small bowel cancer cases from 2000 to 2017 in British Columbia, Canada. Baseline patient characteristics, disease-free survival (DFS) and overall survival (OS) were evaluated by tumor location and systemic therapy use patterns were summarized. RESULTS: Of 340 patients included, primary tumor distribution was: duodenum (51.2%), ileum (19.1%), jejunum (18.5%), and unspecified (11.2%). Median DFS for stage I to III disease was 37.7, 49.1, and 26.7 months for duodenal, jejunal, and ileal tumors (P = .018). Median OS was 9.6, 35.2, and 20.1 months for duodenal, jejunal, and ileal tumors (P < .0001). Compared to duodenal primaries, both jejunal and ileal tumors were associated with significantly improved OS (HR 0.43, P < .001 for jejunal; HR 0.71, P = .035 for ileal). Adjuvant therapy was given to 21.6% of stage II and 50.6% of stage III cancers. Among patients with metastatic disease, median OS was 4.2, 11.4, and 6.9 months for duodenal, jejunal, and ileal tumors (P = .0019). Jejunal tumors had the best prognosis (HR 0.48, P = .001 vs. duodenum). CONCLUSION: Survival differences exist when small bowel cancers were assessed by tumor location, and jejunal tumors portended better prognosis overall.

Effects of cocoa-rich chocolate on cognitive performance in postmenopausal women. A randomised clinical trial.

OBJECTIVES: The aim of this research was to evaluate the effects of adding 10 g of cocoa-rich chocolate (99%) to the habitual diet on cognitive performance in postmenopausal women. METHODS: Following a randomised controlled parallel clinical trial, a total of 140 postmenopausal women aged 50-64 were recruited. The intervention group (n = 73) consumed daily 10 g of chocolate (99% cocoa) in addition to their usual food intake for 6 months, whereas the control group (n = 67) did not receive any intervention. Attention and executive functions, verbal memory, working memory, phonological fluency, category fluency and clinical variables were assessed at baseline and 6 months. RESULTS: Trail Making Test B execution time showed a decreased of -12.08 s (95% CI: -23.99, -0.18; p = 0.047) in the intervention group compared to the control group, after adjusting for age, educational level, time elapsed from the beginning of menopause and daily energy consumption (Cohen's d = -0.343). Attention, immediate or delayed verbal memory, phonological or category fluency, and working memory remained unchanged. CONCLUSIONS: The consumption of cocoa-rich (99%) chocolate in addition to the habitual diet could be related to a slight improvement in cognitive performance regarding cognitive flexibility and processing speed in postmenopausal women, with no changes in the rest of the cognitive performance variables evaluated.Trial registration: This clinical trial has been registered at clinicaltrials.gov as NCT03492983.

The emergence of targetable pathways in colorectal cancer.

Colorectal cancer continues to be one of the leading causes of cancer-related morbidity and mortality globally. Despite an overall decreasing incidence of the disease, early-onset colorectal cancer is a growing concern. Fluoropyrimidine-based doublet chemotherapy has remained the backbone of treatment in the metastatic setting during the past 2 decades. The increasing accessibility and decreasing cost of molecular profiling have made it possible to acquire further insight into prognostic and predictive biomarkers that ultimately help physicians to provide precision medicine in the clinic. In this review, we describe a contemporary biomarker-driven approach to first-line and subsequent-line therapies and highlight the important molecular alterations that affect the treatment of advanced colorectal cancer, along with the supporting clinical trial data.

Six-Month Community-Based Brisk Walking and Balance Exercise Alleviates Motor Symptoms and Promotes Functions in People with Parkinson's Disease: A Randomized Controlled Trial.

BACKGROUND: In Parkinson's disease (PD), sustained aerobic exercise is a promising therapy in delaying motor disability. Brisk walking is a moderate intensity aerobic training, which could be translated to community practice at low cost, but its effects on motor symptoms remains unclear. OBJECTIVE: To determine the effectiveness of a six-month brisk walking and balance program in alleviating motor symptoms, and promoting functional, gait, and balance performance in people with PD. METHODS: Seventy individuals with mild to moderate PD were randomly assigned to a brisk walking (BW) group or an active control (CON) group. BW group received ten 90-minute supervised brisk walking and balance exercise for six months (weeks 1-6: once/week, weeks 7-26: once/month). CON group received upper limb training. Both groups performed 2-3 self-practice sessions weekly. Primary outcome was Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score. Secondary outcomes were fast gait speed (FGS), timed-up-and-go (TUG) time, six-minute walk distance (6MWD), and Mini-Balance Evaluation Systems Test (Mini-BEST) score. RESULTS: Sixty-four participants (33 BW/31 CON) completed training. BW group showed greater significant decreases from baseline than CON group in MDS-UPDRS motor score after six weeks (-5.5 vs -1.6, p < 0.001) and 6 months (-6.0 vs -1.4, p < 0.001) of training. BW group also showed greater significant improvement from the baseline than CON group for TUG time, FGS, 6MWD, and mini-BEST score (all p < 0.05). CONCLUSION: The six-month brisk walking and balance program alleviates motor symptoms, promotes functional and gait performance, walking capacity, and dynamic balance in people with mild to moderate PD.