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Summary: Background: Timing drug administration to endogenous circadian rhythms may enhance treatment efficacy. In the Chronotype sub-study of the Treatment in Morning versus Evening (TIME) clinical trial we examined whether timing of usual antihypertensive medications according to patient chronotype (a behavioural marker of personal circadian rhythm) may influence clinical cardiovascular outcomes. Methods: This was a cohort sub-study of TIME, a prospective, randomised, open-label, blinded-endpoint, UK clinical trial of morning versus evening dosing of usual antihypertensive medications and cardiovascular outcomes. On August 3rd, 2020, all active TIME participants were invited to complete a validated chronotype questionnaire. Chronotype was quantitatively assessed as the mid sleep time on free days corrected for sleep debt on workdays (MSFsc). We analysed associations between chronotype and antihypertensive dosing time and explored their combined effect on cardiovascular outcomes (a composite endpoint of hospitalisation for non-fatal myocardial infarction (MI) or non-fatal stroke, and single components) using proportional hazard time-to-event models adjusted for baseline covariates. These were used to specifically test for interactions between dosing time and chronotype. Findings: Between August 3, 2020, and March 31, 2021, 5358 TIME participants completed the online questionnaire. 2778 were previously randomised to morning dosing and 2580 to evening dosing of their usual antihypertensives. Chronotype was symmetrically distributed around a median MSFsc of 3:07 am. The composite endpoint increased for later MSFsc (later chronotype) dosed in the morning but not in those dosed in the evening (hazard ratios 1.46 [95% CI 1.14–1.86] and 0.96 [95% CI 0.70–1.30] per hour of MSFsc, respectively; interaction p = 0.036). Later chronotype was associated with increased risk of hospitalisation for non-fatal MI in the morning dosing group, and reduced risk in the evening dosing group (hazard ratios 1.62 [95% CI 1.18–2.22] and 0.66 [95% CI 0.44–1.00] per hour of MSFsc, respectively; interaction p

Background: Peripheral artery disease (PAD) is recognized as a significant contributor to the public health burden in the cardiovascular field and has a significant rate of morbidity and mortality. In the intermediate stages, exercise therapy is recommended by the guidelines, although supervised programs are scarcely available. This single-center observational study aimed to evaluate the long-term outcomes of patients with PAD and claudication receiving optimal medical care and follow-up or revascularization procedures or structured home-based exercise. Methods: The records of 1590 PAD patients with claudication were assessed at the Vascular Surgery Unit between 2008 and 2017. Based on the findings of the recruitment visit, patients were assigned to one of the three following groups according to the available guidelines: Revascularization (Rev), structured exercise therapy (Ex), or control (Co). The exercise program was prescribed at the hospital and executed at home with two daily 10-minute interval walking sessions at a pain-free speed. The number and date of deaths, all-cause hospitalizations, and peripheral revascularizations for 5 years were collected from the Emilia-Romagna regional database. Results: At entry, 137 patients underwent revascularization; 1087 patients were included in the Ex group, and 366 were included in the Co group. At baseline, patients in the Rev group were significantly younger and had fewer comorbidities (p < 0.001). A propensity score matching analysis was performed, and three balanced subgroups of 119 patients were each created. The mortality rate was significantly (p < 0.001) greater in the Co (45%) group than in the Rev (11%) and Ex (11%) groups, as was the incidence of all-cause hospitalizations (Co: 95%; Rev 56%; Ex 60%; p < 0.001). There were no differences in peripheral revascularizations (Co: 19%; Rev: 17%; Ex 11%). Conclusions: In PAD patients with claudication, both revascularization procedures and structured home-based exercise sessions are associated with better long-term clinical outcomes than walking advice and follow-up only.

Abstract Background Falls are among the most common and serious adverse events for hospitalised patients. In-hospital falls pose a major medical and economic challenge for public health worldwide. Nevertheless, the issue is often addressed without regard to certain relevant variables such as the time of the fall. The aim of this study was to determine the effect of the implementation of a nurse-led intervention based on the temporal patterns of falls and their aetiology on the occurrence of falls. Methods A mixed-method research design was carried out in three phases: a) a longitudinal prospective study (audits, chronobiological analyses and implementation of a multicentre nurse-led intervention based on temporal patterns of falls); b) a retrospective study of fall records; and c) a qualitative study based on focus groups. The protocol was published in 2021. Results A difference was observed in the number of fall records before and after the chronopreventive intervention (retrospective: 64.4% vs. 35.6%; p

Background: Psoriasis is an inflammatory disease for which the implications and repercussions go far beyond the skin. Psoriasis patients suffer not only due to its skin manifestations and related symptoms but also because of comorbidities and a huge emotional impact. Objective: The objective of this study was to investigate chronotype and sleep quality in a group of Italian psoriatic patients. Materials and Methods: An observational, cross-sectional, web-based study was set up by the Dermatology and Clinical Medicine Sections of the Department of Medical Sciences, University of Ferrara, Italy. The web questionnaire was sent to an email list of an Italian association of psoriatic patients with the aim of recording their main demographic, social, historical, and clinical data. The survey included two questionnaires: the Morningness–Eveningness Questionnaire (MEQ) and the Pittsburg Sleep Quality Index (PSQI). Results: Two hundred and forty-three psoriatic patients (mean age 52.9 ± 12.8 yrs., 32.5% males and 67.5% females) filled out the questionnaire. A good 63.8% of them were affected with psoriasis for more than 10 years, 25.9% reported having a diffuse psoriasis, and 66.7% were on treatment at the time they completed the questionnaire. With reference to chronotype, the mean MEQ score was 55.2 ± 10.7; furthermore, 44% of the patients were “morning-oriented types”, M-types, or “larks”, 44.5% were “intermediate-types” or I-types, and 11.5% were “evening-oriented types”, E-types, or “owls”. No correlations were found between chronotype and psoriasis extension. Based on the PSQI results, 72.8% of the study population was judged to have a low sleep quality. Sleep disturbance was significantly related to female sex, living alone, and the presence of comorbidities. Conclusions: Sleep disturbance is very common in psoriatic patients, especially in those with comorbidities, in females, and in patients who live alone. The chronotype in psoriatic patients does not appear different when compared to the general population, nor does it seem to have any link with psoriasis severity.

Decreased arterial perfusion is a typical condition of patients with peripheral artery disease (PAD), with the microvascular picture particularly present among women. This observational study aimed to detect foot perfusion changes by infrared thermography (IRT) after a home-based exercise program in both sexes. A total of 76 PAD patients with claudication (72 ± 4 years; 52 males) were enrolled in a structured in-home exercise program composed of two daily 8 min interval walking sessions (1:1 walk:rest ratio) with progressively increasing speed. Outcome measures collected at baseline (T0) and at each hospital visit after 5 weeks, 12 weeks and 20 weeks included foot temperature measured by IRT (anterior tibial, posterior tibial, dorsalis pedis and arcuate artery regions), ankle brachial index and the 6 min walking test. After 20 weeks, foot temperature in both limbs showed a significant increasing trend, with a mean variation of 1.3 °C for the more impaired limb and 0.9 °C for the contralateral limb (t = 8.88, p < 0.001 and t = 5.36; p < 0.001, respectively), with significant changes occurring after 5 weeks of training. The sex-oriented analysis did not highlight any significant difference, with an improvement of mean foot temperature of 1.5 ± 0.6 °C in females versus 1.2 ± 0.5 °C in males (p = 0.42). Ankle brachial index and performance also significantly improved over time (p < 0.001) without gender differences. In patients with PAD, a structured low-intensity exercise program significantly improved foot temperature and exercise capacity without any sex-related difference.

Sex and gender have been gaining ever greater attention due to their associated risks, dynamics, patterns and protective factors underlying substance abuse and addiction. Such differentiations and the clarification of complexities thereof take on even greater relevance in light of drug abuse scope worldwide. According to the 2022 World Drug Report released by the United Nations Office on Drugs and Crime (UNODC), in 2020 an estimated 284 million people worldwide aged 15–64 had used a drug within the last 12 months. The authors have set out to shed a light on determinants and contributing factors of drug abuse based on sex and gender and outline policy and medicolegal remarks aimed at delineating sex- and gender-based approaches towards drug abuse therapeutic interventions that are both therapeutically and ethically/legally viable and grounded in an evidence-based set of standards. Neurobiological data suggest that estrogen may facilitate drug taking by interacting with reward- and stress-related systems. In animal research, the administration of estrogen increases drug taking and facilitates the acquisition, escalation, and reinstatement of cocaine-seeking behavior. From a medicolegal perspective, it is of utmost importance to take into account the whole picture constituting each patient profile, which certainly includes gender factors and contributors, when outlining a therapeutic approach. Failure to do so could lead to negligence-based malpractice allegations, in light of the scientific findings representing best practices with which clinicians need to comply when caring for SUD patients.

There is no evidence of seasonal variation in visits to clinics dedicated to sexually transmitted infections (STIs) in Italy, nor of changes after the advent of the COVID-19 pandemic. An observational, retrospective, multicentric study was conducted to record and analyze all the visits to the STI clinics of the Dermatology Units of the University Hospitals of Ferrara and Bologna and of the Infectious Disease Unit of Ferrara, Italy, between January 2016 and November 2021. Overall, 11.733 visits were registered over a 70-month study period (63.7% males, mean age 34.5 ± 12.8 yrs). The mean number of monthly visits significantly decreased from the advent of the pandemic (136) compared to before (177). In the pre-pandemic period, visits to STI clinics increased in the autumn/winter months when compared to spring/summer, while the trend was the opposite in the pandemic period. Thus, during the pandemic, both an overall significant reduction in visits to STI clinics and a reversal in their seasonality were observed. These trends affected males and females equally. The marked decrease, mostly found in the pandemic winter months, can be linked to the “lockdown”/self-isolation ordinances and social distancing measures during the colder months, coinciding with the spread of the COVID-19 infection, which limited the opportunities for meeting and socializing.

We evaluated the sex-specific difference in response upon participation in an exercise program with respect to the risk of adverse clinical outcomes among patients with peripheral artery disease (PAD) and claudication. The records of 400 PAD patients were assessed between 2012 and 2015. Two hundred of them were addressed to a walking program prescribed at the hospital and executed at home at symptom-free walking speed (Ex), while the remaining 200 acted as a control group (Co). The number and date of deaths, all-cause hospitalizations, and amputations for a 7-year period were collected from the regional registry. At baseline, no differences were observed (MEXn = 138; FEXn = 62; MCOn = 149; FCOn = 51). The 7-year survival rate was significantly higher in FEX (90%) than in MEX (82% hazard ratio, HR: 0.542 95% CI 0.331–0.885), FCO (45%, HR: 0.164 95% CI 0.088–0.305), and MCO (44%; HR: 0.157 95% CI 0.096–0.256). A significantly lower rate of hospitalization (p < 0.001) and amputations (p = 0.016) was observed for the Ex group compared to the Co group, without differences by sex. In conclusion, in PAD patients, active participation in a home-based pain-free exercise program was associated with a lower rate of death and better long-term clinical outcomes, particularly among women.

Abstract Background Accidental falls in hospitals are serious events concerning the safety of the patients. Recent studies demonstrated that the time of falls is a key factor to be considered in prevention. It has been shown that the time of day, the day of the week and the month of the year impact on the occurrence of falls. The aim of the study is to determine the effect of the application of a programme of preventive measures based on the temporal patterns of the risk factors on the hospital fall occurrence. Methods A mixed-method research design. The following three phases will be carried out: 1) Longitudinal prospective study in two parts: (a) audits and seminars of healthcare professionals focused on an effective and efficient hospital falls register. Multi-Component and Single Cosinor analyses will be performed to obtain the temporal patterns of hospital falls and their related variables and (b) implementation of a based-temporal patterns, multidimensional prevention programme. 2) Retrospective study of falls registered in institutional databases. 3) Qualitative study based on focus groups (physicians, nurses and nursing assistants). The study protocol was approved in 2018. Discussion With regard to the safety of patients, hospital falls are serious events. Recent studies have demonstrated that the time of falls is a key factor to be considered in prevention. It has been shown that the time of day, the day of the week and the month of the year impact on the occurrence of falls. It is imperative to study temporal patterns of hospital falls to effectively and comprehensively define the aetiology of falls and, therefore, design preventive strategies. A reduction of the number of in-hospital falls and related injuries is expected, as well as an improvement in the quality of life of patients. Considering temporal patterns and levels of mood and sleep of healthcare professionals will achieve an improvement in patient safety. Trial registration Retrospectively registered in ClinicalTrials.gov ID: NCT04367298.

Despite progress made in recent decades, gender bias is still present in scientific publication authorship. The underrepresentation of women and overrepresentation of men has already been reported in the medical fields but little is known in the fields of exercise sciences and rehabilitation. This study examines trends in authorship by gender in this field in the last 5 years. All randomized controlled trials published in indexed journals from April 2017 to March 2022 through the widely inclusive Medline dataset using the MeSH term “exercise therapy” were collected, and the gender of the first and last authors was identified through names, pronouns and photographs. Year of publication, country of affiliation of the first author, and ranking of the journal were also collected. A chi-squared test for trends and logistic regression models were performed to analyze the odds of a woman being a first or last author. The analysis was performed on a total of 5259 articles. Overall, 47% had a woman as the first author and 33% had a woman as the last author, with a similar trend over five years. The trend in women’s authorship varied by geographical area, with the higher representation of women authors in Oceania (first: 53.1%; last: 38.8%), North-Central America (first: 45.3%; last: 37.2%), and Europe (first: 47.2%; last: 33.3%). The logistic regression models (p < 0.001) indicated that women have lower odds of being authors in prominent authorship positions in higher-ranked journals. In conclusion, over the last five years, in the field of exercise and rehabilitation research, women and men are almost equally represented as first authors, in contrast with other medical areas. However, gender bias, unfavoring women, still exists, especially in the last authorship position, regardless of geographical area and journal ranking.

No abstract present.

This observational study aimed to monitor the 5-year trends of kidney function in patients with peripheral artery disease (PAD) and concomitant chronic kidney disease (CKD) enrolled or not enrolled into a rehabilitative exercise program. Sixty-six patients (aged 72 ± 10, males n = 52) at KDOQI stages III-IV and PAD at Rutherford’s stage I-III were included in the study, with a group (Exercise, EX; n = 32) receiving a 6-month structured pain-free home-based walking program and a group (Control, CO; n = 34) receiving walking advice and optimal nephrological care. Outcomes included kidney function measured through serum creatinine (sCr) and clinical outcomes, including the rate of advance of CKD stages and admission to dialysis, revascularizations, and hospitalizations. At baseline, the two groups were comparable for age, nephropathy, medications, comorbidities, and PAD severity. Patients in the EX group safely completed the exercise program. SCr values were slightly increased in EX (baseline: 2.35 ± 0.32; 5-year: 2.71 ± 0.39 mg/dL) and progressively worsened in CO (baseline: 2.30 ± 0.31; 5-year 4.22 ± 0.42 mg/dL), with a significant between-group difference (p = 0.002). The control group also showed a higher number of dialysis admissions (5 vs. 0, p = 0.025) and advancing CKD stage as well a higher risks for lower limb revascularization (hazard ratio: 2.59; 95%CI: 1.11–6.02; p = 0.027) and for all-cause hospitalization (hazard ratio: 1.77; 95%CI: 1.05–2.97; p = 0.031). PAD-CKD patients enrolled in a low-moderate intensity home-exercise program showed more favorable long-term trends in kidney function and clinical outcomes than patients with usual care. These preliminary observations need to be confirmed in randomized trials.

The human oral microbiome (HOM) is the second largest microbial community after the gut and can impact the onset and progression of several localized and systemic diseases, including those of viral origin, especially for viruses entering the body via the oropharynx. However, this important aspect has not been clarified for the new pandemic human coronavirus SARS-CoV-2, causing COVID-19 disease, despite it being one of the many respiratory viruses having the oropharynx as the primary site of replication. In particular, no data are available about the non-bacterial components of the HOM (fungi, viruses), which instead has been shown to be crucial for other diseases. Consistent with this, this study aimed to define the HOM in COVID-19 patients, to evidence any association between its profile and the clinical disease. Seventy-five oral rinse samples were analyzed by Whole Genome Sequencing (WGS) to simultaneously identify oral bacteria, fungi, and viruses. To correlate the HOM profile with local virus replication, the SARS-CoV-2 amount in the oral cavity was quantified by digital droplet PCR. Moreover, local inflammation and secretory immune response were also assessed, respectively by measuring the local release of pro-inflammatory cytokines (L-6, IL-17, TNFα, and GM-CSF) and the production of secretory immunoglobulins A (sIgA). The results showed the presence of oral dysbiosis in COVID-19 patients compared to matched controls, with significantly decreased alpha-diversity value and lower species richness in COVID-19 subjects. Notably, oral dysbiosis correlated with symptom severity (p = 0.006), and increased local inflammation (p < 0.01). In parallel, a decreased mucosal sIgA response was observed in more severely symptomatic patients (p = 0.02), suggesting that local immune response is important in the early control of virus infection and that its correct development is influenced by the HOM profile. In conclusion, the data presented here suggest that the HOM profile may be important in defining the individual susceptibility to SARS-CoV-2 infection, facilitating inflammation and virus replication, or rather, inducing a protective IgA response. Although it is not possible to determine whether the alteration in the microbial community is the cause or effect of the SARS-CoV-2 replication, these parameters may be considered as markers for personalized therapy and vaccine development.

Abstract Background Small bowel adenocarcinoma (SBA) is a rare neoplasm, which can occur in a sporadic form or can be associated with a number of predisposing conditions such as hereditary syndromes and immune-mediated intestinal disorders, e.g. celiac disease (CD). However, the features of SBA in the context of CD remain only partly understood. This study was aimed to show the main clinical features, diagnostic procedures and management options of SBA cases detected in a large cohort of celiac patients diagnosed in a single tertiary care center. Methods We retrospectively reviewed all the SBA cases detected in a cohort of 770 CD patients (599 females; F / M ratio: 3.5:1; median age at diagnosis 36 years, range 18–80 years), diagnosed at the Celiac Disease Referral Center of our University Hospital (Bologna, Italy) from January 1995 to December 2014. Results Five (0.65%) out of our 770 CD patients developed SBA. All of them were female with a mean age of 53 years (range 38–72 years). SBA, diagnosed at the same time of the CD diagnosis in three cases, was localized in the jejunum in four cases and in the duodenum in one case. The clinical presentation of SBA was characterized by intestinal sub-occlusion in two cases, while the predominant manifestation of the remaining three cases was iron deficiency anaemia, abdominal pain and acute intestinal obstruction, respectively. All the patients were referred to surgery, and three cases with advanced stage neoplasia were also treated with chemotherapy. The overall survival rate at 5 years was 80%. Conclusions Although in a limited series, herein presented CD-related SBA cases were characterized by a younger age of onset, a higher prevalence in female gender and a better overall survival compared to sporadic, Crohn- and hereditary syndrome-related SBA.

Background: Obesity and other eating disorders are an actual public health problem, especially in childhood and adolescents, and could be also related with chronotype. The aim of this systematic review was to determine the relationship between eating disorders, obesity and the different chronotypes in children and adolescents. Methods: A systematic review of observational studies evaluating young populations dealing with and evaluating chronotype was conducted. Electronic searches were performed in six international databases. A qualitative thematic-categorical analysis was carried out and a random-effects model was used for the quantitative analysis (meta-analysis). Results: Fifteen studies were included, but quantitative analysis was only carried out in three of them. Children and adolescents with an evening chronotype had higher body mass index, consumed more junk food or were more predisposed to suffer from food addiction and night eating syndrome. Conclusions: Children and adolescents with evening chronotype had higher tendency to incorrect eating behaviors and were suffering from overweight/obesity. Environment but also lifestyle factors should be considered in the association between chronotype and eating disorders and obesity.

The most common drugs that are consumed by young people are alcohol and tobacco, which are especially prevalent in universities. These risk behaviours can be determined by a series of intrinsic and extrinsic factors. The aim of this study was to evaluate the consumption of alcohol and tobacco by Spanish university students and the relationship between the Mediterranean diet, sexual attitudes and opinions, and chronotype. A multicentre observational study enrolled 457 students from two public universities in Spain. The study period was from December 2017 to January 2018. The majority of the participants consumed alcohol (90.2%), tobacco consumption was low (27.2%), with a high percentage of students (78.6%) having a low dependence on nicotine. The surveyed students demonstrated a high adherence to the Mediterranean diet, which was shown to be associated with less risky alcohol consumption. The Mediterranean diet is a part of healthy lifestyle, and avoiding heavy drinking results in the intention to maintain such a lifestyle. In addition, unhealthy eating habits (skipping breakfast, eating sweets and pastries daily, and fast-food consumption) had a tendency to induce risky alcohol consumption. Therefore, to promote healthy lifestyle habits, it is considered important to establish programs that promote healthy diets in university settings and to evaluate them periodically.

Circadian rhythm perturbations can impact the evolution of different conditions, including autoimmune diseases. This narrative review summarizes the current understanding of circadian biology in inflammatory joint diseases and discusses the potential application of chronotherapy. Proinflammatory cytokines are key players in the development and progression of rheumatoid arthritis (RA), regulating cell survival/apoptosis, differentiation, and proliferation. The production and secretion of inflammatory cytokines show a dependence on the human day–night cycle, resulting in changing cytokine plasma levels over 24 h. Moreover, beyond the circadian rhythm of cytokine secretion, disturbances in timekeeping mechanisms have been proposed in RA. Taking into consideration chronotherapy concepts, modified-release (MR) prednisone tablets have been introduced to counteract the negative effects of night-time peaks of proinflammatory cytokines. Low-dose MR prednisone seems to be able to improve the course of RA, reduce morning stiffness and morning serum levels of IL-6, and induce significant clinical benefits. Additionally, methotrexate (MTX) chronotherapy has been reported to be associated with a significant improvement in RA activity score. Similar effects have been described for polymyalgia rheumatica and gout, although the available literature is still limited. Growing knowledge of chronobiology applied to inflammatory joint diseases could stimulate the development of new drug strategies to treat patients in accordance with biological rhythms and minimize side effects.

Exercise therapy in the intermediate stages of peripheral artery disease (PAD) represents an effective solution to improve mobility and quality of life (QoL). Home-based programs, although less effective than supervised programs, have been found to be successful when conducted at high intensity by walking near maximal pain. In this randomized trial, we aim to compare a low-intensity, pain-free structured home-based exercise (SHB) program to an active control group that will be advised to walk according to guidelines. Sixty PAD patients aged > 60 years with claudication will be randomized with a 1:1 ratio to SHB or Control. Patients in the training group will be prescribed an interval walking program at controlled speed to be performed at home; the speed will be increased weekly. At baseline and after 6 months, the following outcomes will be collected: pain-free walking distance and 6-min walking distance (primary outcome), ankle-brachial index, QoL by the VascuQoL-6 questionnaire, foot temperature by thermal camera, 5-time sit-to-stand test, and long-term clinical outcomes including revascularization rate and mortality. The home-based pain-free exercise program may represent a sustainable and cost effective option for patients and health services. The trial has been approved by the CE-AVEC Ethics Committee (898/20). Registration details: Clinicaltrials.gov NCT04751890 [Registered: 12 February 2021].

Takotsubo syndrome (TTS) is a clinical syndrome characterized by transient left ventricular dysfunction, ischemic electrocardiographic changes, and minimal release of myocardial enzymes without obstructive coronary artery disease. This syndrome that mimics an acute myocardial infarction is prevalent among female patients and is regarded as a benign medical condition. The precise pathophysiological mechanism of TTS is complex and not completely understood, but specific emotional or physical events precipitate this syndrome that represents a typical condition characterized by interactions between cardiovascular and neuropsychological diseases. In addition, many different neurological disorders, such as stroke, subarachnoid bleeding, head injury, epilepsy, and bacterial meningitis, have directly or indirectly related to TTS; unfortunately, these acute neurological diseases represented the cause of death in patients nominated for organ donation and in particular for the heart donor. This article reviews the relationship between TTS and solid organ transplantation; in particular, this article highlights the possible mechanisms underlying the induction of TTS in pre- and post-transplantation phases and in heart-transplant patients.

This review was performed to investigate the association between treatment with dialysis and Takotsubo syndrome in patients with end-stage renal disease. We systematically explored the PubMed database using the search terms “Takotsubo cardiomyopathy” and/or “stress-induced cardiomyopathy” and/or “Takotsubo syndrome” in combination with “dialysis” and “uremia.” Of 3630 articles found, 8 articles reporting 10 cases were selected for analysis. Most patients were women, and their age ranged from 51 to 84 years. Diabetes mellitus and hypertension were diagnosed in 40% of patients, and glomerular disease was diagnosed in 30%. One only patient was treated with peritoneal dialysis; all others were treated with hemodialysis. The outcome was unfavorable in only one patient. An association between Takotsubo syndrome and dialysis is uncommon, but not negligible, and comorbidities play a major role in determining the clinical outcome.

Cancer represents important comorbidity, and data on outcomes are usually derived from selected oncologic units. Our aim was to evaluate possible sex-related differences and factors associated with in-hospital mortality (IHM) in a consecutive cohort of elderly patients with cancer admitted to internal medicine. We included all patients admitted to our department with a diagnosis of cancer during 2018. Based on the International Classification of Diseases, 9th Revision, Clinical Modification, demography, comorbidity burden, and diagnostic procedures were evaluated, with IHM as our outcome. We evaluated 955 subjects with cancer (23.9% of total hospital admissions), 42.9% were males, and the mean age was 76.4 ± 11.4 years. Metastatic cancer was diagnosed in 18.2%. The deceased group had a higher modified Elixhauser Index (17.6 ± 7.7 vs. 14 ± 7.3, p < 0.001), prevalence of cachexia (17.9% vs. 7.2%, p < 0.001), and presence of metastasis (27.8% vs. 16.3%, p = 0.001) than survivors. Females had a higher age (77.4 ± 11.4 vs. 75.5 ± 11.4, p = 0.013), and lower comorbidity (10.2 ± 5.9 vs. 12.0 ± 5.6, p < 0.001) than males. IHM was not significantly different among sex groups, but it was independently associated with cachexia and metastasis only in women. Comorbidities are highly prevalent in patients with cancer admitted to the internal medicine setting and are associated with an increased risk of all-cause mortality, especially in female elderly patients with advanced disease.

Sedentariness of patients affected by end-stage kidney disease (ESKD) expose them to high risk of unfavorable clinical outcomes. Exercise training is effective in improving physical function, quality of life (QoL) and long-term outcomes. However, the existing barriers related to patients, programs and dialysis staff limit patient participation and call for new strategies. This pragmatic nonrandomized trial will test the impact on ESKD population of an intervention proposed by an exercise facilitator regularly present in a dialysis center. The patient will be free to choose among three-month walking and/or resistance low-intensity training programs: (a) guided physical activity increase; (b) home-based exercise; (c) in-hospital (pre/post dialysis) supervised exercise; (d) performance assessment only. The first phase will define feasibility and the characteristics and preference of responders. The second phase will evaluate safety and patients’ adherence. Outcome measures will be collected at baseline, after three-month and at six-month follow-up. They will include: aerobic capacity, QoL, gait speed, strength, depression and long-term clinical outcomes (hospitalization and mortality). The trial was approved by the Area-Vasta Emilia-Romagna Centro Ethics Committee with approval number 48/2019. Written informed consent will be obtained from all participants. The results of the study will be presented in international congresses, published in peer-reviewed journals and communicated to the patient community. Registration details: Clinicaltrials.gov NCT04282616 [Registered:24/02/2020].

A person’s chronotype determines different habits, among which are eating and physical activity. Furthermore, at the university stage, social and organisational factors have a direct effect on students’ daily attitudes and habits. Adherence to the Mediterranean diet is linked to better sleep quality and less social jet lag, but association with chronotype or sexual opinion remains unclear. The aim of this study was to assess the associations between chronotype, adherence to the Mediterranean Diet, and sexual opinion. A multicentre observational study enrolled 457 students, from the University of Castilla-La Mancha and the University of Cordoba. Sociodemographic data and adherence to the Mediterranean diet, chronotype, physical activity, and sexual opinion were collected with validated questionnaires. The study period was from December 2017 to January 2018. Our results reported that students with an evening chronotype (E-type), with evening preferences, had a lower adherence to the Mediterranean diet and showed a higher tendency towards erotophilia. E-type students reported a significantly lower intake of fruits, vegetables, pulses, cereals, and olive oil, and higher breakfast skipping. Therefore, among the measures to promote healthy habits (obesity prevention, sexual education, socialisation, etc.), chronotype and an analysis of the impact of the schedules established by the universities must be considered.

Background: The aim of this study was to relate the weekend (WE) effect and acute kidney injury (AKI) in elderly patients by using the Italian National Hospital Database (NHD). Methods: Hospitalizations with AKI of subjects aged ≥ 65 years from 2000–2015 who were identified by the ICD-9-CM were included. Admissions from Friday to Sunday were considered as WE, while all the other days were weekdays (WD). In-hospital mortality (IHM) was our outcome, and the comorbidity burden was calculated by the modified Elixhauser Index (mEI), based on ICD-9-CM codes. Results: 760,664 hospitalizations were analyzed. Mean age was 80.5 ± 7.8 years and 52.2% were males. Of the studied patients, 9% underwent dialysis treatment, 24.3% were admitted during WE, and IHM was 27.7%. Deceased patients were more frequently comorbid males, with higher age, treated with dialysis more frequently, and had higher admission during WE. WE hospitalizations were more frequent in males, and in older patients with higher mEI. IHM was independently associated with dialysis-dependent AKI (OR 2.711; 95%CI 2.667–2.755, p < 0.001), WE admission (OR 1.113; 95%CI 1.100–1.126, p < 0.001), and mEI (OR 1.056; 95% CI 1.055–1.057, p < 0.001). Discussion: Italian elderly patients admitted during WE with AKI are exposed to a higher risk of IHM, especially if they need dialysis treatment and have high comorbidity burden.

Metformin (dimethyl biguanide) is a synthetic derivative of guanidine, isolated from the extracts of Galega officinalis, a plant with a prominent antidiabetic effect. Since its discovery more than 50 years ago, metformin represents a worldwide milestone in treatment of patients with type 2 diabetes (T2D). Recent evidence in humans indicates novel pleiotropic actions of metformin which span from its consolidated role in T2D management up to various regulatory properties, including cardio- and nephro-protection, as well as antiproliferative, antifibrotic, and antioxidant effects. These findings, together with ground-breaking studies demonstrating its ability to prolong healthspan and lifespan in mice, provided the basis for defining metformin as a potential antiaging molecule. Moreover, emerging in vivo and in vitro evidence support the novel hypothesis that metformin can exhibit immune-modulatory features. Studies suggest that metformin interferes with key immunopathological mechanisms involved in systemic autoimmune diseases, such as the T helper 17/regulatory T cell balance, germinal centers formation, autoantibodies production, macrophage polarization, cytokine synthesis, neutrophil extracellular traps release, and bone or extracellular matrix remodeling. These effects may represent a powerful contributor to antiaging and anticancer properties exerted by metformin and, from another standpoint, may open the way to assess whether metformin can be a candidate molecule for clinical trials involving patients with immune-mediated diseases. In this article, we will review the available preclinical and clinical evidence regarding the effect of metformin on individual cells of the immune system, with emphasis on immunological mechanisms related to the development and maintenance of autoimmunity and its potential relevance in treatment of autoimmune diseases.

We report a case of a 53-year old man admitted because of fever (38.5°C) and atypical chest pain. He also complained of epigastric pain spread to left hypochondrium and exacerbated by breathing. In his past medical history, Hodgkin’s lymphoma, gastric MALToma (oncologic follow-up only), hypothyroidism, and hypertension are recorded. Fifteen days prior actual hospital admission, the patient underwent angioplasty with stenting due to a ST elevation myocardial infarction. Moreover, he was enrolled in the experimental clinical double-blind trial GEMINI-ACS [1], designed to compare the safety of rivaroxaban vs aspirin in addition to either clopidogrel or ticagrelor. Thus, his complete therapy included also ticagrelor, bisoprolol, perindopril, levothyroxine, pantoprazole, and atorvastatin. At the time of admission chest X-ray showed bilateral pleural effusion. Blood chemistry panel showed moderate anemia, increase of inflammatory indexes, in particular fibrinogen 1057 mg/dl (normal range 150-400 mg/dl), C-reactive-protein 17.6 mg/dl (normal range

Background: The aim of this study was to investigate the association between acute kidney injury (AKI) and in-hospital mortality (IHM) in a large nationwide cohort of elderly subjects in Italy. Methods: We analyzed the hospitalization data of all patients aged ≥65 years, who were discharged with a diagnosis of AKI, which was identified by the presence of the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), and extracted from the Italian Health Ministry database (January 2000 to December 2015). Data regarding age, gender, dialysis treatment, and comorbidity, including the development of sepsis, were also collected. Results: We evaluated 760,664 hospitalizations, the mean age was 80.5 ± 7.8 years, males represented 52.2% of the population, and 9% underwent dialysis treatment. IHM was 27.7% (210,661 admissions): Deceased patients were more likely to be older, undergoing dialysis treatment, and to be sicker than the survivors. The population was classified on the basis of tertiles of comorbidity score (the first group 7.48 ± 1.99, the second 13.67 ± 2,04, and third 22.12 ± 4.13). IHM was higher in the third tertile, whilst dialysis-dependent AKI was highest in the first. Dialysis-dependent AKI was associated with an odds ratios (OR) of 2.721; 95% confidence interval (CI) 2.676−2.766; p < 0.001, development of sepsis was associated with an OR of 1.990; 95% CI 1.948−2.033; p < 0.001, the second tertile of comorbidity was associated with an OR of 1.750; 95% CI 1.726−1.774; p < 0.001, and the third tertile of comorbidity was associated with an OR of 2.522; 95% CI 2.486−2.559; p < 0.001. Conclusions: In elderly subjects with AKI discharge codes, IHM is a frequent complication affecting more than a quarter of the investigated population. The increasing burden of comorbidity, dialysis-dependent AKI, and sepsis are the major risk factors.

Restless leg syndrome (RLS) disrupts sleep, affecting the quality of life of patients with various chronic diseases. We assessed the prevalence of RLS in peripheral artery disease (PAD) patients and the effects of a pain-free exercise program. A total of 286 patients with claudication were enrolled in a home-based low-intensity exercise program prescribed at the hospital. RLS was determined through standardized questions. Hemodynamics, degree of calf deoxygenation, and mobility were assessed using the ankle-brachial-index, a treadmill test assisted by near-infrared spectroscopy and the 6-min walk test, respectively. During hospital visits, persistence of RLS, adherence to exercise, hemodynamics, and mobility were assessed. At the enrollment, 101 patients (35%) presented RLS, with higher prevalence among females (p = 0.032). Compared to RLS-free patients, they showed similar hemodynamics but more severe calf deoxygenation (p < 0.001) and lower mobility (p = 0.040). Eighty-seven RLS patients (83%) reported the disappearance of symptoms after 39 (36−70) days of exercise. This subgroup, compared to nonresponders, showed higher adherence (p < 0.001), hemodynamic (p = 0.041), and mobility improvements (p = 0.003). RLS symptoms were frequent in PAD but were reduced by a pain-free walking exercise aimed at inducing peripheral aerobic adaptations. The concomitant recovery of sleep and mobility may represent a synergistic action against the cardiovascular risk in PAD.

Background: The available evidence on the effects of daylight saving time (DST) transitions on major cardiovascular diseases is limited and conflicting. We carried out the first meta-analysis aimed at evaluating the risk of acute myocardial infarction (AMI) following DST transitions. Methods: We searched cohort or case-control studies evaluating the incidence of AMI, among adults (≥18 y), during the weeks following spring and/or autumn DST shifts, versus control periods. The search was made in MedLine and Scopus, up to 31 December 2018, with no language restriction. A summary odds ratio of AMI was computed after: (1) spring, (2) autumn or (3) both transitions considered together. Meta-analyses were also stratified by gender and age. Data were combined using a generic inverse-variance approach. Results: Seven studies (>115,000 subjects) were included in the analyses. A significantly higher risk of AMI (Odds Ratio: 1.03; 95% CI: 1.01–1.06) was observed during the two weeks following spring or autumn DST transitions. However, although AMI risk increased significantly after the spring shift (OR: 1.05; 1.02–1.07), the incidence of AMI during the week after winter DST transition was comparable with control periods (OR 1.01; 0.98–1.04). No substantial differences were observed when the analyses were stratified by age or gender. Conclusion: The risk of AMI increases modestly but significantly after DST transitions, supporting the proposal of DST shifts discontinuation. Additional studies that fully adjust for potential confounders are required to confirm the present findings.

The study retrospectively evaluated the association between rehabilitative outcomes and risk of peripheral revascularizations in elderly peripheral artery disease (PAD) patients with claudication. Eight-hundred thirty-five patients were enrolled. Ankle-brachial index (ABI) and maximal walking speed (Smax) were measured at baseline and at discharge from a structured home-based rehabilitation program. For the analysis, patients were divided according to a baseline ABI value (severe: ≤0.5; moderate: ≥0.5) and according to hemodynamic or functional rehabilitative response (responder: ABI ≥ 0.10 and/or Smax > 0.5 km/h). Three-year outcomes were collected from the regional registry. According to the inclusion criteria (age 60⁻80, ABI < 0.80; program completion) 457 patients, 146 severe and 311 moderate, were studied. The whole population showed significant functional and hemodynamic improvements at discharge, with 56 revascularizations and 69 deaths at follow-up. Compared to the moderate group, the severe group showed a higher rate of revascularizations (17% vs. 10%, p < 0.001) and deaths (29% and 8%, respectively; p < 0.001). However, patients with severe PAD who were ABI responders after rehabilitation showed less revascularizations than non-responders (13% vs. 21%; hazard ratio (HR): 0.52) and were not different from patients with moderate disease (9%). Superimposable rates were observed for Smax responders (13% vs. 21%; HR: 0.55; moderate 10%). In conclusion, elderly patients with severe PAD empowered by better rehabilitation outcomes showed lower rates of peripheral revascularizations and deaths that were comparable to patients with moderate PAD.

The expression of proinflammatory cytokines/chemokines has been reported in in vitro/ex vivo settings of chronic venous insufficiency (CVI), but the identification of circulating mediators that might be associated with altered hemodynamic forces or might represent innovative biomarkers is still missing. In this study, the circulating levels of 31 cytokines/chemokines involved in inflammatory/angiogenic processes were analysed in (i) CVI patients at baseline before surgical hemody namic correction, (ii) healthy subjects, and (iii) CVI patients after surgery. In a subgroup of CVI patients, in whom the baseline levels of cytokines/chemokines were analyzed in paired blood samples obtained from varicose vein and forearm vein, EGF, PDGF, and RANTES were increased at the varicose vein site as compared to the general circulation. Moreover, while at baseline, CVI patients showed increased levels of 14 cytokines/chemokines as compared to healthy subjects, 6 months after surgery, 11 cytokines/chemokines levels were significantly reduced in the treated CVI patients as compared to the CVI patients before surgery. Of note, a patient who exhibited recurrence of the disease 6 months after surgery, showed higher levels of EGF, PDGF, and RANTES compared to nonrecurrent patients, highlighting the potential role of the EGF/PDGF/RANTES triad as sensitive biomarkers in the context of CVI.

The aim of this study is to establish changes in leg volumes in healthy subjects (HS) after prolonged standing and prolonged lying. The study was carried out on two HS groups: the group A (20 subjects) included physicians and nurses who underwent a water plethysmography test, before and after eight hours of standing still in the operating room. The group B (20 subjects) included volunteers who were assessed before and after 10 h of supine resting. Group A: baseline leg volume was 1857.5 mL±196.9 on the right and 1850 mL±194.7 on the left limb. After eight hours of hydrostatic pressure action the two lower limbs volume was significantly increased to 1945 mL±209.6, and to 1940 mL±216.2, respectively (P2=0.95, P2=−0.98, P