Sex-related differences and chronobiology of ST-elevation myocardial infarction: findings from a single hub center in Italy.

OBJECTIVE: Type I acute myocardial infarction (AMI) is a life-threatening condition. Time of event and rescue procedures, and sex-specific differences may play a crucial role. We aimed to investigate chronobiological patterns and sex-specific differences in a cohort of AMI patients referred to a single hub center in Italy. PATIENTS AND METHODS: We considered all patients consecutively admitted for AMI (STEMI) to the Hospital of the Heart, in Massa, Tuscany (a region of Italy), between 2006 to 2018, who underwent interventional procedures. Sex, age, time of hospital admission, outcome (discharged alive/deceased), main comorbidities, and time between symptom onset and emergency medical service (EMS) activation, were analyzed. Chronobiologic analysis was applied according to hour of day, month, and season of the year. RESULTS: Overall 2,522 patients (mean age 64.6±13.1 years, 73% males) were considered. In-hospital death (IHM) occurred in 96 subjects (3.8%). At univariate analysis, deceased subjects were more likely to be female, older, with longer wait for EMS activation and with interventional procedures during night-time. The multivariate analysis identified female sex, age, history of ischemic heart disease, and night-time interventional procedure as independently associated factors to IHM. Chronobiologic analysis showed a pattern with a main morning peak for total sample, males, and females (p=0.00027; p=0.0006); p=0.0121, respectively). Events showed a higher peak in summer, with no differences by sex, but IHM was higher in winter. Females showed a higher delay for EMS activation, compared to males (p<0.001), but with no effects on prognosis. On the contrary, males with a delay showed higher mortality. CONCLUSIONS: Great effort should be spent to reduce patient-related delays in interventional procedures, being this issue crucial in both sexes.

Nurses, sleep disturbances, desynchronization of circadian rhythms, and performance: a dangerous liaison? A narrative mini-review.

OBJECTIVE: Nursing is a high-stress occupation, and recent research of circadian rhythm desynchronization has focused on its consequences for nurses' health. Moreover, shiftwork, sleep disturbances, nightmares, and health issues are closely related to individual circadian preferences ('chronotype'). The aim of this narrative mini-review was to check the available literature to collect findings on the interrelationships among these aspects, as well as to determine the possible consequences for performance. MATERIALS AND METHODS: We explored the PubMed, EMBASE and Google Scholar electronic databases using the search terms 'Nursing', 'Stress', 'Sleep disturbances', 'Nightmares', 'Circadian rhythm', 'Desynchronization', 'Chronotype', 'Performance', and 'Sex/Gender'. Due to the wide heterogeneity of studies, with most including only some of these terms, we proceeded to single data extractions after analyzing the studies case by case and decided to conduct a narrative mini-review. RESULTS: Shift work, due to the regular alterations of the daily light profile, disrupts the normal circadian sleep-wake cycle and is associated with impaired health among rotational shift workers, with nurses on the frontline. Circadian desynchronization may be associated with adverse effects on nurses' health and may be a risk factor for stress, metabolic disorders, and sleep disturbances, including nightmares, and stress operates in a bidirectional fashion. Chronotype plays a crucial role as well, since the asynchrony between one's chronotype and social working hours (social jetlag) may generate problems, since the time-of-day and optimal performance are strongly connected. CONCLUSIONS: Circadian rhythms, chronotype, sleep, health, and working performance are strongly connected. The assessment of chronotype could represent a tool to identify health care personnel at higher risk of circadian disruption, allowing for mitigation of work-related stress and sleep disturbances, and reducing the risk of making working errors.

Hospital readmissions to internal medicine departments: a higher risk for females?

OBJECTIVE: Readmissions to hospital after discharge are considered adverse, serious and costly outcomes. In the last years, two new scores have been proposed to identify patients at high risk of hospital readmission, the HOSPITAL and the Elders Risk Assessment (ERA) indexes. The aim of this study was to evaluate these two scores and the risk of death among internal medicine readmitted patients. PATIENTS AND METHODS: During a 30-month period, we identified 613 readmitted patients out of 13,237 admissions. Age, sex, length-of-hospital stay (LOS), and deaths were retrospectively analyzed. Readmissions with diagnosis coincident with the index hospitalization were classified as avoidable, whilst those with a different diagnosis were defined as non-avoidable. HOSPITAL score for 30-day potentially avoidable readmission and ERA indexes were calculated. RESULTS: Readmitted patients (56.6% women), were aged 79±10.4 years. The incidence of 30-day readmission was 20.4 patients/month. Re-hospitalization could be classified as avoidable in 286 cases (46.7%), and death at the end of follow-up was recorded in 366 (59.7%). HOSPITAL score ≥ 7 and ERA score ≥ 16, both able to identify high risk patients for readmission, were present in 108 (17.6%) and 385 (64.4%) of cases, respectively. Patients with non-avoidable readmissions were older, more frequently female, diabetic, and had higher ERA score than subjects with avoidable readmission. Multivariate logistic regression analysis showed that non-avoidable readmissions were independently associated with female gender (OR 1.410 [95% CI 1.012-1.964], p=0.042), and age (OR 1.025 [95% CI 1.006-1.043], p=0.01), while only age (OR 1.034 [95% CI 1.015-1.054], p<0.001) and ERA score (OR 1.047 [95% CI 1.001-1.095], p=0.047) were independently associated with death at the end of follow-up. CONCLUSIONS: Although re-hospitalization represents frequent phenomenon related to age, non-avoidable readmissions mainly involve female patients. ERA score appears to be an useful practical tool, able to identify high risk patients.

Seasonal and weekly patterns of hospital admissions for acute diverticulitis.

OBJECTIVE: Onset and hospitalization of acute diseases do not occur randomly, but exhibit preferred high-risk temporal periods. The aim of this study, based on the database of hospital admissions of the Emilia-Romagna region of Italy, was to evaluate the possible existence of a seasonal or weekly pattern of hospitalization for acute diverticulitis (AD), and different rates of complications between weekend (WE) vs. weekday (WD) admissions. PATIENTS AND METHODS: The study included all emergency hospital admissions in Emilia Romagna Region for AD between 1999 and 2011 (ICD-9-CM codes: 562.11-562.13). Day of admission was categorized, respectively, into four 3-month intervals, twelve 1-month intervals, seven 1-day intervals for statistical analysis, performed by c2 test goodness of fit and partial Fourier series on total number of cases, males and females, nonfatal or fatal cases, without and with hemorrhage. RESULTS: The database contained records of 29,428 events of AD, relative to 24,843 different patients (mean age: 71.2 ± 13.8 years; 40.5% males). Chronobiological analysis yielded a biphasic rhythmic pattern in AD admissions, characterized by two peaks in Autumn and Spring. As for day of admission, a progressive decrease of frequency during the week was observed. In turn, a slight increase of admissions on WE was observed for hemorrhagic events. CONCLUSIONS: An excess burden of hospitalization for AD is observed in the region Emilia-Romagna of Italy, with demonstration of a biphasic cyclical pattern with peaks in Autumn and Spring. Again, a decreasing number of Monday to Friday admissions was observed. Further studies are needed to identify possible underlying causes.

Exercise training and endothelial progenitor cells in haemodialysis patients.

Haemodialysis patients have few endothelial progenitor cells (EPCs) and an unfavourable cardiovascular outcome. The effects on peripheral blood CD34(+) cells and EPCs of a 6-month walking exercise programme were studied. Thirty dialysis patients (20 males, age 67 +/- 12 years) were prescribed exercise (two daily 10-min home walking sessions at moderate intensity, group E, n = 16) or not prescribed exercise (control, group C, n = 14). On entry and after 6 months peripheral blood CD34(+) cells, EPCs (assessed as CD34(+) cells co-expressing AC133 and vascular endothelial growth factor receptor 2 [VEGFR2], and as endothelial colony-forming units [e-CFU]) and exercise capacity (6-min walking distance, 6MWD) were evaluated. In group E, 6MWD and e-CFU increased significantly during the study period, with no significant changes in CD34(+) or CD34(+) AC133(+) VEGFR2(+) cell numbers. The change in e-CFU was directly and significantly correlated to patient-reported training load. Group C showed no significant change in any variable. In haemodialysis patients, moderate-intensity exercise selectively increased the number of e-CFU.

Influence of lifestyle measures on hypertriglyceridaemia.

Hypertriglyceridaemia is a common dyslipidaemia encountered in clinical practice. People with hypertriglyceridaemia are frequently obese, insulin-resistant, hypertensive or diabetic, all of which are risk factors for cardiovascular diseases. Hypertriglyceridaemia also contributes to metabolic syndrome, in which an atherogenic diet, sedentary lifestyle, overweight/obesity and genetic factors interact. A multi-factorial intervention for all risk factors is necessary, including weight reduction, dietary modification and increased physical exercise. This review focuses on the influence of diet, sedentary lifestyle and negative habits (such as excessive alcohol intake, smoking and drug addiction) on hypertriglyceridaemia as well as the effects of lifestyle change.

High output heart failure due to an iatrogenic arterio-venous fistula after lumbar disc surgery.

Vascular injury is a rare but not uncommon complication of spinal surgery and associated with dramatic consequences. Congestive heart failure secondary to a hyperkinetic circulation can occur in systemic diseases and in arterio-venous fistulae. A 57-year-old man was admitted to hospital complaining of dyspnoea and oedema of the left leg. Eight days previously he had undergone a discectomy at L4-L5. On auscultation a systolic-diastolic murmur was noted over the entire abdomen. An echocardiogram demonstrated an enlarged right atrium, severe mitral and tricuspid regurgitation and increased pulmonary artery pressure. An abdominal CT demonstrated irregular dilatation of the left common iliac vein and through a fistula and simultaneous opacification of the right common iliac artery; subsequently, this was also confirmed by angiography. The patient underwent an emergency endovascular stent-graft of the right common iliac artery with normalization of the venous return pressure and quick resolution of the heart failure. It is important for the physician involved in clinical work to keep in mind all the possible post-surgical complications that can occur in symptomatic patients who have recently undergone an intervention.

Exercise capacity and circulating endothelial progenitor cells in hemodialysis patients.

Mobilization of circulating endothelial progenitor cells (EPCs) is increased after acute exercise and training. This study aims to evaluate whether, in a low performance population, EPC levels may be related to exercise capacity in steady state conditions. Study population consisted of sixteen hemodialysis patients. The distance walked in the 6-minute walking test (6 MWD) and the maximal speed attained in an incremental treadmill test were used to assess the exercise capacity. Physical functioning was measured by the scale on the SF36 questionnaire. Quantification of peripheral blood CD34(+) cells and enumeration of EPCs, assessed as CD34(+) cells coexpressing AC 133 and vascular endothelial growth factor receptor-2, were performed. Hemoglobin concentration, white blood cells, high-sensitivity C-reactive protein, total cholesterol, and triglycerides were measured. Statistical analysis examined the relationship between blood progenitors cells versus performance parameters, laboratory parameters, age, body mass index, hemodialysis duration, and erythropoietin therapy. Univariate analysis revealed a significant association between percentage values of EPC and performance parameters only: 6 MWD (r=0.720; p=0.0017), maximal treadmill speed (r=0.721; p=0.0016), and physical functioning score (r=0.506; p=0.0453). A similar statistical association between EPC absolute values and performance parameters was found. No correlation between CD34 (+) and any parameter under study was observed. Multivariate analysis indicated 6 MWD as the most significant independent factor associated with EPC level. EPC percentage value was significantly lower (p=0.0087) in the worse (6 MWD < 300 m, n=8) than in the better performing group (6 MWD > 300 m, n=8). In a group of renal patients, mobilization of EPCs was related to the degree of exercise capacity, suggesting a possible connection with the cardiovascular risk in low performance populations limited by chronic diseases.

Seasonal variation in onset of acute appendicitis.

PURPOSE: Several acute diseases exhibit a circannual pattern. The present study was aimed to verify the possible existence of a seasonal variability in the onset of acute appendicitis (AA). PATIENTS AND METHODS: All cases of AA diagnosed at the St Anna Hospital of Ferrara, Italy, from 1998 to 2004, were considered. The total sample was divided into subgroups by gender, age (< or = 19 and > or = 20 years), and ICD9-CM code. For statistical analysis, the distribution of symptom onset was tested for uniformity by the chi2 test for goodness of fit, and chronobiological analysis was performed by applying partial Fourier series. RESULTS: In the 7-year period analysis, 1331 consecutive cases of AA (673 males) were observed. The analysis showed, for total population, a seasonal variation with a peak in summer and a nadir in spring. Subjects < or = 19 years (n = 654) showed a higher frequency of events in winter (winter = 191 cases, 29.2%; spring = 154 cases, 23.5%, summer = 142 cases, 21.7%, autumn = 167 cases, 25.5%, chi2 = 8.07 p = 0.046), whereas subjects > or = 20 years (n = 677) showed a higher frequency in summer (winter = 150, 22.2%, spring = 151, 22.3%, summer = 214, 31.6%, autumn = 162, 23.9%, chi2 = 16.33 p = 0.001; difference between the two groups: chi2: 19.2, p < 0.001). Cases of AA with peritonitis (ICD-9 540.0, n = 90), were more frequent in summer (winter = 18, 20%, spring = 19, 21.17%, summer = 38, 42.2%, autumn = 15, 16.7%, chi2 = 14.22, p = 0.002), and chronobiological analysis found a statistically significant peak of higher incidence in July (PR 68.2, 95%CL: May-September, p = 0.006). CONCLUSIONS: The existence of a seasonal pattern in the onset of AA is confirmed, with differences in relation to age.

Chronobiology of rupture and dissection of aortic aneurysms.

A growing body of evidence suggests that the occurrence of cardiovascular events is not evenly distributed over time, but shows peculiar temporal patterns that vary with time of day, day of the week, and month (season) of the year. These patterns coincide with the temporal variation in the pathophysiologic mechanisms that trigger cardiovascular events and the physiologic changes in body rhythms. These two factors in combination contribute to the periodicity in susceptibility to acute cardiovascular events. The classic assumption of epidemiologic studies that there is a constancy in risk for disease during the various time domains has now been challenged by the emerging new concept of chronorisk. In the last two decades temporal patterns (circadian, weekly, seasonal) have been identified for several acute cardiovascular diseases, such as acute myocardial infarction, sudden death, pulmonary embolism, and stroke, with peak incidence for most in the morning and during winter. One of the most life-threatening cardiovascular emergencies, aortic aneurysm rupture or dissection, also demonstrates periodicity, characterized by a similar temporal distribution, which suggests a common pathophysiologic mechanism or triggers similar to other cardiovascular acute emergencies. We review the data on chronobiology of acute aortic rupture or dissection, and discuss various pathophysiologic mechanisms that account for this variability. It is likely that identification of consistent recurring patterns in the underlying risk mechanisms could provide potential new insights for more precise diagnosis and efficacious therapeutic intervention.

Oxidative stress in essential hypertension.

A major cause for endothelial dysfunction in essential hypertension is decreased availability of nitric oxide (NO). Impairment in NO bioavailability is likely to be the consequence of multiple mechanisms affecting NO synthesis as well as NO breakdown. An alteration in the redox balance in endothelial cells leads to increased superoxide anion production and oxidative stress. This in turn not only exerts negative effects on vascular tone, but is also able to activate important mechanisms (such as platelet activity, leukocyte adhesion, vascular smooth muscle cell proliferation and expression of adhesion molecules) with an established central role in the pathogenesis of hypertensive target organ damage. As a consequence, a drug therapy able to restore NO availability in essential hypertensive patients would probably exert additional benefits, as compared to blood pressure lowering per se, in terms of prevention of target organ damage and improved prognosis of these patients. Unfortunately, as of today only the antagonists of the renin-angiotensin system and the calcium-channel blockers have shown some ability in this respect, whereas no longitudinal intervention study has been undertaken, so far, to prove that the restoration of NO bioavailability through an antihypertensive treatment may confer additional prognostic advantage to essential hypertensive patients.

Seasonal variation in onset of pulmonary embolism is independent of patients' underlying risk comorbid conditions.

As for many cardiovascular events, pulmonary embolism (PE) is not randomly distributed over time, but shows rhythmic patterns. The purpose of this study was to investigate whether such temporal pattern of occurrence varied in subgroups of patients according to different risk comorbid conditions. All cases of PE observed at the Hospital of Ferrara, Italy, from 1998 to 2001, were considered. After determination of the day of onset, the population was grouped by gender and the most common underlying risk comorbid conditions, e.g., deep vein thrombosis (DVT), neoplasms, cardiomyopathies, traumas/surgical operations, diabetes mellitus, pulmonary diseases, hypertension, cerebrovascular diseases, heart failure, hematologic diseases. For statistical analysis, chi-square test for goodness of fit and partial Fourier series were used. A total of 784 cases (mean age 71 +/- 14 years) were included. Frequency of onset was higher in winter for total population (p = 0.002), men (p = 0.004), DVT (p = 0.001), pulmonary disease (p = 0.008), cardiomyopathies (p = 0.011), and major traumas/surgical operations (p = 0.049). Chronobiologic analysis identified a winter peak for total population (p = 0.008), men (p < 0.001), DVT (p = 0.006), pulmonary diseases (p = 0.017), and hypertension (p = 0.026). This study confirms the winter peak of PE and provides evidence that it is not influenced by the underlying clinical conditions, but probably by endogenous variations.

[Epistaxis and circadian rhythm]. / Epistassi e ritmi circadiani.

It is known that many physiological variables show a rhythmic variability along a time span, e.g.: day, week, month or year. It is possible that the temporal overlapping of a constellation of factors may act as favouring and/or triggering factors for the onset of several acute diseases. Among these, epistaxis shows a circadian variability too. Such pattern, characterised by a prevalent peak in the morning and a secondary one in the evening, strictly resembles that of arterial blood pressure. The lack of differences between the temporal pattern of hypertensive and normotensive subjects suggests that the physiological pattern of blood pressure, and not strictly a condition of hypertension, may play a favouring role in certain hours of the day, probably together other local factors.