Gender Differences in the Interplay between Vitamin D and Microbiota in Allergic and Autoimmune Diseases.

The synergic role of vitamin D and the intestinal microbiota in the regulation of the immune system has been thoroughly described in the literature. Vitamin D deficiency and intestinal dysbiosis have shown a pathogenetic role in the development of numerous immune-mediated and allergic diseases. The physiological processes underlying aging and sex have proven to be capable of having a negative influence both on vitamin D values and the biodiversity of the microbiome. This leads to a global increase in levels of systemic inflammatory markers, with potential implications for all immune-mediated diseases and allergic conditions. Our review aims to collect and analyze the relationship between vitamin D and the intestinal microbiome with the immune system and the diseases associated with it, emphasizing the effect mediated by sexual hormones and aging.

Fasting and Cognitive Impairment.

Fasting is a nutritional practice involving complete food restriction for a varying length of time [...].

Effect of SARS-CoV-2 vaccination in a vulnerable COVID-19 cohort: a real-life experience in an Italian Hospital.

Clinical trials demonstrated that SARS-CoV-2 vaccines reduce COVID-19-related mortality and morbidity. We describe the effect of vaccination on COVID-19-patients admitted at our hospital. Retrospective, single-center study conducted in Genoa, Italy, including patients ≥18years hospitalized for COVID-19 from May to December 2021. Demographical and clinical data were collected, vaccinated (group-A) and not-vaccinated (group-B) patients were compared. Impact of vaccination on mortality, ICU admission, and oxygen need was studied using Cox proportional hazards and logistic regression models after adjusting for propensity scores. Overall, 395 patients SARS-CoV-2 infected were included, of which 150 (38%) were vaccinated and 245 (62%) were not vaccinated. Patients in group-A were older, more disable, and with higher morbidity. Overall, 64 patients (16%) died within 30 days from admission, 34 in Group A (23%), and 30 in group B (12%). However, no statistically significant differences were observed (group-A versus group-B: HR 0.83, 95% CI 0.49-1.40, p = 0.483). On the other hand, vaccination was protective in terms of ICU admission (OR = 0.23, p = 0.046) and oxygen need (OR = 0.33, p = 0.008). Our study confirms that SARS-CoV-2 vaccination reduces morbidity among patients hospitalized for COVID-19. The still high mortality in our cohort of vaccinated individuals could be partially due to vulnerable conditions of our patients.

Ultra-old patients and long-term survival after hip fracture: a real-world assessment.

It's still undetermined whether ultra-old persons, aged >90 years, are able to tolerate hip fracture surgical stress while maintaining their functional reserve, and even fewer studies have investigated the role of frailty on the risk of mortality, disability, or morbidity in the ultra-old. This is a prospective study performed at the Orthogeriatrics Ward of the IRCCS Policlinico San Martino (Genoa, Italy) that consecutively enrolled 205 older adult patients with hip fractures due to low-energy trauma. Namely, 85 patients were categorized as ultra-old, and 120 patients (64-89 years) were the younger control group. Demographic data, perioperative data, and rehabilitation data were collected. Here we estimated the overall survival and related predictive variables in hospitalized ultra-old hip fracture patients based on a methodologically robust frailty stratification (Rockwood 40-item tool). The median OS for the ultra-old was 18.7 months, which also showed a doubled 1-year mortality risk. Our findings assessed that frailty in the presence of malnutrition, delayed verticalization, and post-operative respiratory complications was associated with a two-fold increase in the risk of long-term mortality, irrespective of advanced chronological age in the ultra-old. Although the higher mortality rate in these patients may be related to a priori lower life expectancy, chronological age alone is an insufficient prognostic determinant for unfavorable outcomes. Our multicomponent prognostic score can be used in combination to stratify frailty in the ultra-old for timely screening and to deliver goals of care discussions prior to surgery, potentially targeting new orthogeriatric pathways for the improvement of appropriateness and treatment intensity.

Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer's models.

The effects of fasting-mimicking diet (FMD) cycles in reducing many aging and disease risk factors indicate it could affect Alzheimer's disease (AD). Here, we show that FMD cycles reduce cognitive decline and AD pathology in E4FAD and 3xTg AD mouse models, with effects superior to those caused by protein restriction cycles. In 3xTg mice, long-term FMD cycles reduce hippocampal Aß load and hyperphosphorylated tau, enhance genesis of neural stem cells, decrease microglia number, and reduce expression of neuroinflammatory genes, including superoxide-generating NADPH oxidase (Nox2). 3xTg mice lacking Nox2 or mice treated with the NADPH oxidase inhibitor apocynin also display improved cognition and reduced microglia activation compared with controls. Clinical data indicate that FMD cycles are feasible and generally safe in a small group of AD patients. These results indicate that FMD cycles delay cognitive decline in AD models in part by reducing neuroinflammation and/or superoxide production in the brain.

The Multidisciplinary Approach of Rectal Cancer: The Experience of "COMRE Group" Model.

Background: Total mesorectal excision (TME) is the gold standard to treat locally advanced rectal cancer. This monocentric retrospective study evaluates the results of laparotomic, laparoscopic and robotic surgery in "COMRE GROUP" (REctalCOMmittee). Methods: 327 selected stage I-II-III patients (pts) underwent TME between November 2005 and April 2020 for low or middle rectal cancer; 91 pts underwent open, 200 laparoscopic and 36 robotic TME. Of these, we analyzed the anthropomorphic, intraoperative, anatomopathological parameters and outcome during the follow up. Results: The length of hospital stay was significantly different between robotic TME and the other two groups (8.47 ± 3.54 days robotic vs. 11.93 ± 5.71 laparotomic, p < 0.001; 8.47 ± 3.54 robotic vs. 11.10 ± 7.99 laparoscopic, p < 0.05). The mean number of harvested nodes was higher in the laparotomic group compared to the other two groups (19 ± 9 laparotomic vs. 15 ± 8 laparoscopic, p < 0.001; 19 ± 9 laparotomic vs. 15 ± 7 robotic, p < 0.05). Median follow-up was 52 months (range: 1−169). Overall survival was significantly shorter in the open TME group compared with the laparoscopic one (Chi2 = 13.36, p < 0.001). Conclusions: In the experience of the "COMRE" group, laparoscopic TME for rectal cancer is a better choice than laparotomy in a multidisciplinary context. Robotic TME has a significant difference in terms of hospital stay compared to the other two groups.

Effect of Geriatric Comanagement in Older Patients Undergoing Surgery for Gastrointestinal Cancer: A Retrospective, Before-and-After Study.

OBJECTIVE: To determine the effect of geriatric comanagement on clinical outcomes of older patients undergoing surgery for gastrointestinal cancer. DESIGN: This was a single-center, nonrandomized, before-and-after study, which compared patient outcomes before and after the implementation of geriatric comanagement in an oncological surgery division. SETTING AND PARTICIPANTS: The study included patients aged 70 or older, who were treated for a gastrointestinal cancer at the Oncological Surgery Division of the Policlinico San Martino Hospital (Genoa, Italy). Patients from the control group were treated between January 2015 and October 2018, and the patients who received geriatric comanagement during their stay in the surgical ward were treated between November 2018 and December 2019. METHODS: Patients from both groups received a preoperative comprehensive geriatric assessment in the preoperative phase and were followed according to the Enhanced Recovery After Surgery model in the perioperative period. In the geriatric comanagement group, targeted interventions during daily geriatrician-led ward rounds were performed. Inverse probability weighting was used to adjust estimates for potential baseline confounders. RESULTS: A total of 207 patients were included: 107 in the control group and 90 who received geriatric comanagement. Overall, patients from both groups had similar demographic and clinical characteristics with a median [interquartile range (IQR)] age of 80.0 (77.0, 84.0) years and a pre-frail phenotype [median (IQR) 40-item Frailty Index 0.15 (0.10, 0.26)]. In the geriatric comanagement group, a significant reduction in grade I-V complications (adjusted odds ratio 0.29; 95% CI 0.21-0.40); P < .001) and in 1-year readmissions (adjusted hazard ratio 0.53; 95% CI 0.28-0.98; P < .044) was observed. No difference between the 2 groups in terms of 1-year mortality was detected. CONCLUSIONS AND IMPLICATIONS: Our study supports the implementation of geriatric comanagement in the care of older patients undergoing surgery for gastrointestinal cancer.

Neuropsychiatric Disorders and Frailty in Older Adults over the Spectrum of Cancer: A Narrative Review.

BACKGROUND: The interplay between different neuropsychiatric conditions, beyond dementia, in the presence of a diagnosis of cancer in older adults may mediate patients' fitness and cancer-related outcomes. Here, we aimed to investigate the presence of depression, sleep disturbances, anxiety, attitude, motivation, and support in older adults receiving a diagnosis of cancer and the dimension of frailty in order to understand the magnitude of the problem. METHODS: This review provides an update of the state of the art based on references from searches of PubMed between 2000 and June 2021. RESULTS: The evidence obtained underscored the tight association between frailty and unfavorable clinical outcomes in older adults with cancer. Given the intrinsic correlation of neuropsychiatric disorders with frailty in the realm of cancer survivorship, the evidence showed they might have a correlation with unfavorable clinical outcomes, late-life geriatric syndromes and higher degree of frailty. CONCLUSIONS: The identification of common vulnerabilities among neuropsychiatric disorders, frailty, and cancer may hold promise to unmask similar shared pathways, potentially intercepting targeted new interventions over the spectrum of cancer with the delivery of better pathways of care for older adults with cancer.

Patterns of Comorbidity and In-Hospital Mortality in Older Patients With COVID-19 Infection.

Introduction: Older adults are more susceptible to severe COVID-19, with increased all-cause mortality. This has been attributed to their multimorbidity and disability. However, it remains to be established which clinical features of older adults are associated with severe COVID-19 and mortality. This information would aid in an accurate prognosis and appropriate care planning. Here, we aimed to identify the chronic clinical conditions and the comorbidity clusters associated with in-hospital mortality in a cohort of older COVID-19 patients who were admitted to the IRCCS Policlinico San Martino Hospital, Genoa, Italy, between January and April 2020. Methods: This was a retrospective cohort study including 219 consecutive patients aged 70 years or older and is part of the GECOVID-19 study group. During the study period, upon hospital admission, demographic information (age, sex) and underlying chronic medical conditions (multimorbidity) were recorded from the medical records at the time of COVID-19 diagnosis before any antiviral or antibiotic treatment was administered. The primary outcome measure was in-hospital mortality. Results: The vast majority of the patients (90%) were >80 years; the mean patient age was 83 ± 6.2 years, and 57.5% were men. Hypertension and cardiovascular disease, along with dementia, cerebrovascular diseases, and vascular diseases were the most prevalent clinical conditions. Multimorbidity was assessed with the Cumulative Illness Rating Scale. The risk of in-hospital mortality due to COVID-19 was higher for males, for older patients, and for patients with dementia or cerebral-vascular disease. We clustered patients into three groups based on their comorbidity pattern: the Metabolic-renal-cancer cluster, the Neurocognitive cluster and the Unspecified cluster. The Neurocognitive and Metabolic-renal-cancer clusters had a higher mortality compared with the Unspecified cluster, independent of age and sex. Conclusion: We defined patterns of comorbidity that accurately identified older adults who are at higher risk of death from COVID-19. These associations were independent of chronological age, and we suggest that the identification of comorbidity clusters that have a common pathophysiology may aid in the early assessment of COVID-19 patients with frailty to promote timely interventions that, in turn, may result in a significantly improved prognosis.

Safety and Feasibility of Fasting-Mimicking Diet and Effects on Nutritional Status and Circulating Metabolic and Inflammatory Factors in Cancer Patients Undergoing Active Treatment.

In preclinical studies, fasting was found to potentiate the effects of several anticancer treatments, and early clinical studies indicated that patients may benefit from regimes of modified fasting. However, concerns remain over possible negative impact on the patients' nutritional status. We assessed the feasibility and safety of a 5-day "Fasting-Mimicking Diet" (FMD) as well as its effects on body composition and circulating growth factors, adipokines and cyto/chemokines in cancer patients. In this single-arm, phase I/II clinical trial, patients with solid or hematologic malignancy, low nutritional risk and undergoing active medical treatment received periodic FMD cycles. The body weight, handgrip strength and body composition were monitored throughout the study. Growth factors, adipokines and cyto/chemokines were assessed by ELISA. Ninety patients were enrolled, and FMD was administered every three weeks/once a month with an average of 6.3 FMD cycles/patient. FMD was largely safe with only mild side effects. The patients' weight and handgrip remained stable, the phase angle and fat-free mass increased, while the fat mass decreased. FMD reduced the serum c-peptide, IGF1, IGFBP3 and leptin levels, while increasing IGFBP1, and these modifications persisted for weeks beyond the FMD period. Thus, periodic FMD cycles are feasible and can be safely combined with standard antineoplastic treatments in cancer patients at low nutritional risk. The FMD resulted in reduced fat mass, insulin production and circulating IGF1 and leptin. This trial was registered on Clinicaltrials.gov in July 2018 with the identifier NCT03595540.

SIRT6 enhances oxidative phosphorylation in breast cancer and promotes mammary tumorigenesis in mice.

BACKGROUND: Sirtuin 6 (SIRT6) is a NAD+-dependent deacetylase with key roles in cell metabolism. High SIRT6 expression is associated with adverse prognosis in breast cancer (BC) patients. However, the mechanisms through which SIRT6 exerts its pro-oncogenic effects in BC remain unclear. Here, we sought to define the role of SIRT6 in BC cell metabolism and in mouse polyoma middle T antigen (PyMT)-driven mammary tumors. METHODS: We evaluated the effect of a heterozygous deletion of Sirt6 on tumor latency and survival of mouse mammary tumor virus (MMTV)-PyMT mice. The effect of SIRT6 silencing on human BC cell growth was assessed in MDA-MB-231 xenografts. We also analyzed the effect of Sirt6 heterozygous deletion, of SIRT6 silencing, and of the overexpression of either wild-type (WT) or catalytically inactive (H133Y) SIRT6 on BC cell pyruvate dehydrogenase (PDH) expression and activity and oxidative phosphorylation (OXPHOS), including respiratory complex activity, ATP/AMP ratio, AMPK activation, and intracellular calcium concentration. RESULTS: The heterozygous Sirt6 deletion extended tumor latency and mouse survival in the MMTV-PyMT mouse BC model, while SIRT6 silencing slowed the growth of MDA-MB-231 BC cell xenografts. WT, but not catalytically inactive, SIRT6 enhanced PDH expression and activity, OXPHOS, and ATP/AMP ratio in MDA-MB-231 and MCF7 BC cells. Opposite effects were obtained by SIRT6 silencing, which also blunted the expression of genes encoding for respiratory chain proteins, such as UQCRFS1, COX5B, NDUFB8, and UQCRC2, and increased AMPK activation in BC cells. In addition, SIRT6 overexpression increased, while SIRT6 silencing reduced, intracellular calcium concentration in MDA-MB-231 cells. Consistent with these findings, the heterozygous Sirt6 deletion reduced the expression of OXPHOS-related genes, the activity of respiratory complexes, and the ATP/AMP ratio in tumors isolated from MMTV-PyMT mice. CONCLUSIONS: Via its enzymatic activity, SIRT6 enhances PDH expression and activity, OXPHOS, ATP/AMP ratio, and intracellular calcium concentration, while reducing AMPK activation, in BC cells. Thus, overall, SIRT6 inhibition appears as a viable strategy for preventing or treating BC.

Forecasting Energy Consumption in the EU Residential Sector.

The present paper aims to introduce a top down methodology for the forecasting of residential energy demand in four European countries, namely Germany, Italy, Spain, and Lithuania. The methodology employed to develop the estimation is based on econometric techniques. In particular, a logarithmic dynamic linear constant relationship of the consumption is proposed. Demand is estimated as a function of a set of explaining variables, namely heating degree days and gross domestic product per capita. The results confirm that the methodology can be applied to the case of Germany, Italy, and Spain, whereas it is not suitable for Lithuania. The analysis of elasticities of the demand with respect to the gross domestic product per capita shows a negative value for Germany, -0.629, and positive values for Italy, 0.837, and Spain, 0.249. The forecasting of consumption shows that Germany and Italy are more sensitive to weather conditions with respect to Spain and an increase in the demand of 8% and 9% is expected in case of cold climatic conditions.

New "Smart" Systems for Atmospheric Aerosol and Reactive Gas Sampling in Ambient Air.

Nowadays a recognized need for accurate observations of atmospheric aerosols (AEs) and reactive gases (RGs) exists in the framework of regional, national and global near-surface networks based on permanent or mobile measurement stations. In this context, a paramount and not-trivial issue is related to the correct execution of continuous sampling of ambient air and its subsequent distribution to measurement analyzers hosted inside the stations. Sampling artifacts must be minimized for obtaining reliable pictures of ambient air composition. To respond to this need, a suite of novel "smart" and relatively low-cost systems for the continuous sampling of ambient air was developed in the framework of the 2012⁻2015 I-AMICA Project. These systems were designed to execute AE and RG measurements according with WMO/GAW and ACTRIS recommendations and standard operation procedures. A particular attention was dedicated to the stabilization and control of the sampling flow rates and temperatures. The analysis of one full year of operations at the WMO/GAW regional station of Capo Granitola (GAW ID: CGR, Italy), allowed to conclude that these systems are effective in meeting the technical requirements for correct execution of AE and RG measurements.