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Background: Sarcopenia is a comorbidity associated with heart failure, which aggravates its prognosis. Objectives: To analyze the differential characteristics of polypathological patients with acute heart failure (AHF) based on the presence of low muscle strength, as well as to study whether this condition is associated with a worse prognosis. Methods: An observational study of 377 patients with a diagnosis of acute heart failure from the prospective multicentric PROFUND-IC registry was carried out. The main variable is low muscle strength, which is assessed with dynamometry or prehensile strength. Epidemiological and anthropometric characteristics, as well as associated comorbidities, were analyzed. Likewise, the etiology of the AHF episode, the number of admissions in the previous year, and the NYHA scale were also included. Finally, scores on functionality, treatment established, and mortality and readmission rates were studied. Quantitative variables are described as mean, and standard deviation, and qualitative variables are expressed as absolute numbers and percentages. A descriptive and bivariate analysis was performed according to the presence of low muscle strength (handgrip <27 kg in men and <16 kg in women), using the Welch test for quantitative measures and Chi-square for qualitative variables. In addition, Kaplan-Meier curves of readmission and mortality and a logistic regression analysis were also performed. Results: 377 patients were included (56% female, mean age 83 years). 310 (82.23%) had low muscle strength. Those with low muscle strength were older (84 vs. 78 years, p < 0.001), with more cognitive impairment (11.9% vs. 0%, p = 0.021), worse functional class ( p = 0.016), lower scores in the Barthel index and Rockwood scale ( p < 0.001), and higher in the PROFUND index ( p < 0.001). They had higher rates of readmission and mortality without statistically significant differences. The PROFUND index is significantly associated with low muscle strength (OR 1.19, CI (1.09-1.31), p < 0.001). Conclusions: Elderly polypathological patients with acute heart failure and low muscle strength have a higher PROFUND index and a lower probability of survival per year.

Fat-soluble vitamins, including vitamins A, D, E, and K, are energy-free molecules that are essential to the body's functioning and life. Their intake is almost exclusively exogenous, i.e., dietary. As a result, fat-soluble vitamin deficiencies are rarer in industrialized countries than in countries with limited resources. Certain groups of people are particularly affected, such as newborns or growing children, pregnant or breastfeeding women, and elderly or isolated individuals. Deficiencies in vitamins A, D, E, and K are also relatively frequent in subjects with digestive tract disorders, liver diseases, chronic pathologies, or in intensive care patients. Deficiencies or excesses of fat-soluble vitamins are responsible for a variety of more or less specific clinical pictures. Certain syndromes are typical of fat-soluble vitamin deficiency, such as the combination of ophthalmological and immunity impairments in the case of vitamin A deficiency or hemorrhagic syndrome and osteopenia in the case of vitamin E deficiency. This is also the case for osteomalacia, muscular weakness, even falls, and rickets in the case of vitamin D deficiency. Diagnosis of a deficiency in one of the fat-soluble vitamins relies on blood tests, which are not always essential for routine use. In this context, a therapeutic test may be proposed. Treatment of deficiencies requires vitamin supplementation, a well-balanced diet, and treatment of the cause.

Background/Objectives: Heart failure (HF) is a highly prevalent clinical syndrome with serious morbidity and mortality. Furthermore, acute heart failure (AHF) is the main cause of hospital admission in people aged 65 years or more. Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) have been shown to improve the survival and quality of life in patients with HF regardless of left ventricular ejection fraction (LVEF). Our aims were to describe the characteristics of adults with multiple pathologies admitted with acute heart failure as the main diagnosis and of the population treated with SGLT2is, as well as to evaluate if their use was associated with lower readmission and mortality rates. Methods : A prospective study of patients from the PROFUND-IC registry who were admitted with AHF as the main diagnosis was conducted. Clinical and analytical characteristics were analyzed, as well as readmissions and mortality. Descriptive and bivariate analyses of the sample between those taking SGLT2is and those who were not were performed, using the chi-square test for qualitative variables and Welch's test for quantitative measures, as well as the Fisher and Wilcoxon tests as indicated for nonparametric tests. Kaplan-Meier curves were constructed to analyze the readmission and mortality of patients at 12 months based on SGLT2i treatment. Finally, a propensity score matching was performed, guaranteeing that the observed effect of the drug was not influenced by the differences in the characteristics between the groups. Results: There were 750 patients included: 58% were women, and the mean age was 84 years. Functional class II according to the NYHA scale predominated (54%), and the mean LVEF was 51%. SGLT2 inhibitors were prescribed to only 28% of patients. Most of the patients were men (48.6% vs. 39.8%, p = 0.029), they were younger (82 vs. 84 years, p = 0.002), and their LVEF was lower (48% vs. 52%, p < 0.001). Lower mortality was observed in the group treated with SGLT2is, both during baseline admission (2.4% vs. 6.9%, p = 0.017) and at the 12-month follow-up (6.2% vs. 13%, p = 0.023); as well as a lower readmission rate (23.8% vs. 38.9%, p < 0.001). After the propensity score matching, a decrease in the 12-month readmission rate continued to be observed in the group treated with SGLT2is ( p = 0.03). Conclusions: SGLT2is use was associated with lower readmission rates at the 12-month follow-up in older adults with multiple pathologies admitted with acute heart failure.

Background/Objectives : Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods : We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results : The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions : There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Background: Individuals suffering from heart failure (HF) and cardiorenal syndrome (CRS) represent a special group of patients considering their age, multiple health issues, and treatment challenges. These factors make them more susceptible to frequent hospital stays and a higher mortality rate. UMIPIC is a multidisciplinary care model program for patients with heart failure follow up provided by internists and nurses who are experts in this entity. Our study delved into the effectiveness of this specialized care program (UMIPIC) in mitigating these risks for HF and CRS patients., Methods: We analyzed the medical records of 3255 patients diagnosed with HF and CRS types 2 and 4, sourced from the RICA registry. These patients were divided into two distinct groups: those enrolled in the UMIPIC program (1205 patients) and those under standard care (2050 patients). Using propensity score matching, we ensured that both groups were comparable. The study focused on tracking hospital admissions and mortality rates for one year after an HF-related hospital stay., Results: Patients in the UMIPIC group experienced fewer hospital readmissions due to HF compared to their counterparts (20% vs. 32%; Hazard Ratio [HR] = 0.48; 95% Confidence Interval [95% CI]: 0.40-0.57; p < 0.001). They also showed a lower mortality rate (24% vs. 36%; HR = 0.64; 95% CI: 0.54-0.75; p < 0.001). Furthermore, the UMIPIC group had fewer total hospital admissions (36% vs. 47%; HR = 0.58; 95% CI: 0.51-0.66; p < 0.001)., Conclusions: The UMIPIC program, centered on holistic and ongoing care, effectively reduces both hospital admissions and mortality rates for HF and CRS patients after a one-year follow-up period.

Background: Most patients diagnosed with heart failure (HF) are older adults with multiple comorbidities. Multipathological patients constitute a population with common characteristics: greater clinical complexity and vulnerability, frailty, mortality, functional deterioration, polypharmacy, and poorer health-related quality of life with more dependency., Objectives: To evaluate the clinical characteristics of hospitalized patients with acute heart failure and to determine the prognosis of patients with acute heart failure according to the Short Physical Performance Battery (SPPB) scale., Methods: Observational, prospective, and multicenter cohort study conducted from September 2020 to May 2022 in patients with acute heart failure as the main diagnosis and NT-ProBNP > 300 pg. The cohort included patients admitted to internal medicine departments in 18 hospitals in Spain. Epidemiological variables, comorbidities, cardiovascular risk factors, cardiovascular history, analytical parameters, and treatment during admission and discharge of the patients were collected. Level of frailty was assessed by the SPPB scale, and dependence, through the Barthel index. A descriptive analysis of all the variables was carried out, expressed as frequencies and percentages. A bivariate analysis of the SPPB was performed based on the score obtained (SPPB ≤ 5 and SPPB > 5). For the overall analysis of mortality, HF mortality, and readmission of patients at 30 days, 6 months, and 1 year, Kaplan-Meier survival curves were used, in which the survival experience among patients with an SPPB > 5 and SPPB ≤ 5 was compared., Results: A total of 482 patients were divided into two groups according to the SPPB with a cut-off point of an SPPB < 5. In the sample, 349 patients (77.7%) had an SPPB ≤ 5 and 100 patients (22.30%) had an SPPB > 5. Females (61%) predominated in the group with an SPPB ≤ 5 and males (61%) in those with an SPPB > 5. The mean age was higher in patients with an SPPB ≤ 5 (85.63 years). Anemia was more frequent in patients with an SPPB ≤ 5 (39.5%) than in patients with an SPPB ≥ 5 (29%). This was also seen with osteoarthritis (32.7%, p = 0.000), diabetes (49.6%, p = 0.001), and dyslipidemia (69.6%, p = 0.011). Patients with an SPPB score > 5 had a Barthel index < 60 in only 4% ( n = 4) of cases; the remainder of the patients (96%, n = 96) had a Barthel index > 60. Patients with an SPPB > 5 showed a higher probability of survival at 30 days ( p = 0.029), 6 months ( p = 0.031), and 1 year ( p = 0.007) with (OR = 7.07; 95%CI (1.60-29.80); OR: 3.9; 95%CI (1.30-11.60); OR: 6.01; 95%CI (1.90-18.30)), respectively. No statistically significant differences were obtained in the probability of readmission at 30 days, 6 months, and 1 year ( p > 0.05)., Conclusions: Patients admitted with acute heart failure showed a high frequency of frailty as assessed by the SPPB. Patients with an SPPB ≤ 5 had greater comorbidities and greater functional limitations than patients with an SPPB > 5. Patients with heart failure and a Barthel index > 60 frequently presented an SPPB < 5. In daily clinical practice, priority should be given to performing the SPPB in patients with a Barthel index > 60 to assess frailty. Patients with an SPPB ≤ 5 had a higher risk of mortality at 30 days, 6 months, and 1 year than patients with an SPPB ≤ 5. The SPPB is a valid tool for identifying frailty in acute heart failure patients and predicting 30-day, 6-month, and 1-year mortality.

Aim: Since beds are unavailable, we prospectively investigated whether early hospital discharge will be safe and useful in patients hospitalized for COVID-19, regardless of their need for home oxygen therapy., Population and Methods: Extending the initial inclusion criteria, 62 patients were included and 51 benefited from home telemonitoring, mainly assessing clinical parameters (blood pressure, heart rate, respiratory rate, dyspnea, temperature) and peripheral saturation (SpO 2 ) at follow-up., Results: 47% of the patients were older than 65 years; 63% needed home oxygen therapy and/or presented with more than one comorbidity. At home, the mean time to dyspnea and tachypnea resolutions ranged from 21 to 24 days. The mean oxygen-weaning duration was 13.3 ± 10.4 days, and the mean SpO 2 was 95.7 ± 1.6%. The nurses and/or doctors managed 1238 alerts. Two re-hospitalizations were required, related to transient chest pain or pulmonary embolism, but no death occurred. Patient satisfaction was good, and 743 potential days of hospitalization were saved for other patients., Conclusion: The remote monitoring of vital parameters and symptoms is safe, allowing for early hospital discharge in patients hospitalized for COVID-19, whether or not home oxygen therapy was required. Oxygen tapering outside the hospital allowed for a greater reduction in hospital stay. Randomized controlled trials are necessary to confirm this beneficial effect.

Introduction: Heart failure is an extremely prevalent disease in the elderly population of the world. Most patients present signs and symptoms of decompensation of the disease due to worsening congestion. This congestion has been clinically assessed through clinical signs and symptoms and complementary imaging tests, such as chest radiography. Recently, pulmonary and inferior vena cava ultrasound has been shown to be useful in assessing congestion but its prognostic significance in elderly patients has been less well evaluated. Objectives: This study aims to compare the clinical and radiological characteristics and predictive values for mortality in patients admitted for heart failure through the determination of B lines by lung ultrasound and the degree of collapsibility of the inferior vena cava (IVC). Secondarily, the study aims to assess the prediction of 30-day mortality based on the diameter of the IVC by means of the ROC curve. Methods: This is an observational cohort study based on data collected in the PROFUND-IC study, a nationwide multicentric registry of patients admitted with decompensated heart failure. Data were collected from these patients between October 2020 and April 2022. Results: A total of 482 patients were entered into the PROFUND-IC registry between October 2020 and April 2022. Bedside clinical ultrasound was performed during admission in 301 patients (64.3%). The number of patients with more than 6 B-lines on lung ultrasound amounted to 194 (66%). Statistically significant differences in 30-day mortality (22.1% vs. 9.2%; p = 0.01) were found in these patients. The sum of patients with IVC collapsibility of less than 50% amounted to 195 (67%). Regarding prognostic value, collapsibility data were significant for the number of admissions in the last year (12.5% vs. 5.5%; p = 0.04), in-hospital mortality (10.1% vs. 3.3%, p = 0.04) and 30-day mortality (22.6% vs. 8.1%; p < 0.01), but not for readmissions. Regarding the prognostic value of IVC diameter for 30-day mortality, the area under the ROC curve (AUC) was 0.73, with a p < 0.01. The curve cut-off point with the highest sensitivity (70%) and specificity (70.3%) was for an IVC value of 22.5 mm. In the logistic regression analysis, we observed that the variable most associated with patient survival at 30 days was the presence of a collapsible inferior vena cava, with more than 50% OR 0.359 (CI 0.139−0.926; p = 0.034). Conclusions: The subgroups of patients analyzed with more than six B lines per field and IVC collapsibility less than or equal to 50%, as measured by clinical ultrasound, had higher 30-day mortality rates than patients who did not fall into these subgroups. IVC diameter may be a good independent predictor of 30-day mortality in patients with decompensated heart failure. Comparing both ultrasound variables, it seems that in our population, the assessment of the inferior vena cava may be more associated with short-term prognosis than the pulmonary congestion variables assessed by B lines.

Introduction: There are studies that evaluate the association between chronic obstructive pulmonary disease (COPD) and heart failure (HF) but there is little evidence regarding the prognosis of this comorbidity in older patients admitted for acute HF. In addition, little attention has been given to the extracardiac and extrapulmonary symptoms presented by patients with HF and COPD in more advanced stages. The aim of this study was to evaluate the prognostic impact of COPD on mortality in elderly patients with acute and advanced HF and the clinical manifestations and management from a palliative point of view. Methods: The EPICTER study (“Epidemiological survey of advanced heart failure”) is a cross-sectional, multicenter project that consecutively collected patients admitted for HF in 74 Spanish hospitals. Demographic, clinical, treatment, organ-dependent terminal criteria (NYHA III-IV, LVEF <20%, intractable angina, HF despite optimal treatment), and general terminal criteria (estimated survival <6 months, patient/family acceptance of palliative approach, and one of the following: evidence of HF progression, multiple Emergency Room visits or admissions in the last six months, 10% weight loss in the last six months, and functional impairment) were collected. Terminal HF was considered if the patient met at least one organ-dependent criterion and all the general criteria. Both groups (HF with COPD and without COPD) were compared. A Kaplan−Meier survival analysis was performed to evaluate the presence of COPD on the vital prognosis of patients with HF. Results: A total of 3100 patients were included of which 812 had COPD. In the COPD group, dyspnea and anxiety were more frequently observed (86.2% vs. 75.3%, p = 0.001 and 35.4% vs. 31.2%, p = 0.043, respectively). In patients with a history of COPD, presentation of HF was in the form of acute pulmonary edema (21% vs. 14.4% in patients without COPD, p = 0.0001). Patients with COPD more frequently suffered from advanced HF (28.9% vs. 19.4%; p < 0.001). Consultation with the hospital palliative care service during admission was more frequent when patients with HF presented with associated COPD (94% vs. 6.8%; p = 0.036). In-hospital and six-month follow-up mortality was 36.5% in patients with COPD vs. 30.7% in patients without COPD, p = 0.005. The mean number of hospital admissions during follow-up was higher in patients with HF and COPD than in those with isolated HF (0.63 ± 0.98 vs. 0.51 ± 0.84; p < 0.002). Survival analysis showed that patients with a history of COPD had fewer survival days during follow-up than those without COPD (log Rank chi-squared 4.895 and p = 0.027). Conclusions: patients with HF and COPD had more severe symptoms (dyspnea and anxiety) and also a worse prognosis than patients without COPD. However, the prognosis of patients admitted to our setting is poor and many patients with HF and COPD may not receive the assessment and palliative care support they need. Palliative care is necessary in chronic non-oncologic diseases, especially in multipathologic and symptom-intensive patients. This is a clinical care aspect to be improved and evaluated in future research studies.

Background: Patients with heart failure encompass a heterogeneous group, but they are mostly elderly patients with a large burden of comorbid conditions. Objective: The aim of this study was to compare the clinical characteristics and the prognostic impact on hospital admissions and mortality in a population of patients with HF with different types of caregivers (family members, professionals, and the patient himself). Methods: We conducted an observational study from a prospective registry. Patients from the National Registry of Heart Failure (RICA), which belongs to the Working Group on Heart Failure and Atrial Fibrillation of the Spanish Society of Internal Medicine (SEMI), were included. Patients with heart failure were classified, according to the type of main caregiver, into four groups: the patient himself/herself, a partner, children, or a professional caregiver. A bivariable analysis was performed between the clinical, analytical, therapeutic, and prognostic characteristics of the different groups. The endpoints of the study were all-cause mortality at 1 year; mortality at 120 days; and the readmission rate for HF at 30 days, 120 days, and 1 year of follow-up. In all cases, the level of statistical significance was set at p < 0.05. Results: A total of 2147 patients were enrolled in this study; women represented 52.4%, and the mean age was 81 years. The partner was the caregiver for 703 patients, children were caregivers for 1097 patients, 199 patients had a professional caregiver, and only 148 patients were their own caregivers. Women were more frequently cared for by their children (65.8%) or a professional caregiver (61.8%); men were more frequently cared for by their spouses (68.7%) and more frequently served as their own caregivers (59.5%) (p < 0.001). No statistically significant differences were observed in relation to readmissions or mortality at one year of follow-up between the different groups. A lower probability of readmission and death was observed for patients who received care from a partner or children/relative, with log-rank scores of 11.2 with p= 0.010 and 10.8 with p = 0.013. Conclusions: Our study showed that the presence of a family caregiver for elderly patients with heart failure was associated with a lower readmission rate and a lower mortality rate at 120 days of follow-up. Our study also demonstrated that elderly patients with good cognitive and functional status can be their own caregivers, as they obtained good health outcomes in terms of readmission and mortality. More prospective studies and clinical trials are needed to evaluate the impact of different types of caregivers on the outcomes of patients with heart failure.

Background: Heart failure (HF) is a syndrome with high prevalence, mainly affecting elderly patients, where the presence of associated comorbidities is of great importance. Methods: An observational study from a prospective registry was conducted. Patients identified from the National Registry of Heart Failure (RICA), which belongs to the Working Group on Heart Failure and Atrial Fibrillation of the Spanish Society of Internal Medicine (SEMI), were included. The latter is a prospective, multicenter registry that has been active since 2008. It includes individual consecutive patients over 50 years of age with a diagnosis of HF at hospital discharge (acute decompensated or new-onset HF). Results: In total, 5424 patients were identified from the registry. Forty-seven percent were men and mean left ventricular ejection fraction (LVEF) was 51.4%; 1132 had a score of 0 to 2 according to the PROFUND index, 3087 had a score of 3 to 6, and 952 patients had a score of 7 to 10 points. In the sample, 252 patients had a score above 11 points. At the end of the year of follow-up, 61% of the patients died. This mortality increased proportionally as the PROFUND index increased, specifically 75% for patients with PROFUND greater than 11. The Kaplan-Meier survival curve shows that survival at one year progressively decreases as the PROFUND index value increases. Thus, subjects with scores greater than seven (intermediate-high and high-risk) presented the worst survival with a log rank of 0.96 and a p < 0.05. In the regression analysis, we found a higher risk of death from any cause at one year in the group with the highest risk according to the PROFUND index (score greater than 11 points (HR 1.838 (1.410−2.396)). Conclusions: The PROFUND index is a good index for predicting mortality in patients admitted for acute HF, especially in those subjects at intermediate to high risk with scores above seven. Future studies should seek to determine whether the PROFUND index score is simply a prognostic marker or whether it can also be used to make therapeutic decisions for those subjects with very high short-term mortality.

Background: Type 2 diabetes mellitus (T2DM) is a risk factor for the development of heart failure with reduced ejection fraction (HFrEF)., Aims: (1) To describe and compare the clinical characteristics and the use of diagnostic and therapeutic procedures among subjects hospitalized with HFrEF according to the presence of type 2 diabetes mellitus (T2DM) and sex; (2) to assess the effect of T2DM and sex on hospital outcomes among the patients hospitalized with HFrEF using propensity score matching (PSM); and (3) to identify which clinical variables were associated to in-hospital mortality (IHM) among the patients hospitalized with HFrEF and T2DM according to their sex., Methods: A retrospective cohort study from 2016 to 2019 using the Spanish National Hospital Discharge Database was conducted. The diagnosis and procedures were codified with the International Classification of Disease 10th version (ICD10). Subjects aged ≥ 40 with a primary diagnosis of HFrEF were included. We included those patients with a diagnosis of T2DM in any diagnosis position. The descriptive statistics used were total and relative frequencies (percentages), means with standard deviations, and medians with an interquartile range. To control the effect of confounding variables when T2DM patients and non-T2DM patients were compared, we matched the cohorts using PSM. Multivariable logistic regression models were used to identify which study variables independently affected the IHM among men and women with HF and T2DM. Also, this multivariable method was applied for sensitivity analyses to confirm the results of the PSM., Results: A total of 28,894 patients were included. T2DM was present in 39.59%. Women with T2DM more frequently had atrial fibrillation, valvular heart disease, anemia, dementia, depression, and hyponatremia than men with T2DM. However, men had more coronary heart disease, chronic renal disease, COPD, and obstructive sleep apnea. All the procedures were significantly more commonly used among men than women. Blood transfusion was the only procedure more frequently identified among women with T2DM. For the sensitivity analysis in patients with T2DM hospitalized with HFrEF, we confirmed the results of the PSM, finding that women had a 14% higher risk of dying in the hospital than men (OR 1.14; 95% CI 1.01-1.35). Obesity seemed to have a protective effect (OR 0.85; 95% CI 0.73-0.98) on the in-hospital morality., Conclusions: Subjects with diabetes are admitted for HFrEF and have a greater number of comorbidities than non-diabetics. Diabetic women have a higher mortality rate than men with diabetes and all the procedures evaluated were significantly more often used among men than women.

Introduction: Heart failure (HF) and cancer are currently the leading causes of death worldwide, with an increasing incidence with age. Little is known about the treatment received and the prognosis of patients with acute HF and a prior cancer diagnosis., Objective: to determine the clinical characteristics, palliative treatment received, and prognostic impact of patients with acute HF and a history of solid tumor., Methods: The EPICTER study ("Epidemiological survey of advanced heart failure") is a cross-sectional, multicenter project that consecutively collected patients admitted for acute HF in 74 Spanish hospitals. Patients were classified into two groups according to whether they met criteria for acute HF with and without solid cancer, and the groups were subsequently compared. A multivariable logistic regression analysis was conducted, using the forward stepwise method. A Kaplan-Meier survival analysis was performed to evaluate the impact of solid tumor on prognosis in patients with acute HF., Results: A total of 3127 patients were included, of which 394 patients (13%) had a prior diagnosis of some type of solid cancer. Patients with a history of cancer presented a greater frequency of weight loss at admission: 18% vs. 12% ( p = 0.030). In the cancer group, functional impairment was noted more frequently: 43% vs. 35%, p = 0.039). Patients with a history of solid cancer more frequently presented with acute HF with preserved ejection fraction (65% vs. 58%, p = 0.048) than reduced or mildly reduced. In-hospital and 6-month follow-up mortality was 31% (110/357) in patients with solid cancer vs. 26% (637/2466), p = 0.046., Conclusion: Our investigation demonstrates that in-hospital mortality and mortality during 6-month follow-up in patients with acute HF were higher in those subjects with a history of concomitant solid tumor cancer diagnosis.

Pandemics and lockdowns may be associated with unpremeditated consequences, such as bodyweight changes, isolation, as well as sedentarity. Reports have been published on malnutrition among patients suffering from COVID-19. This study aimed to highlight the short-term effects of the lockdown on the nutritional health of elderly people living at home and benefiting from home care services, yet without any COVID-19 pathology. In 50 subjects displaying weight, body mass index, and MNA score stability two months earlier, we observed significant alterations in these parameters following the lockdown. Thus, malnutrition rose from 28-34% to 58%. Furthermore, trigger factors for malnutrition changed, with social isolation accounting for 64% of the confinement's deleterious effects among the elderly. In conclusion, despite the elderly being not directly affected by SARS-CoV2, the nutritional status of elderly subjects living at home with no or only mild autonomy loss was greatly and rapidly affected by the lockdown. Moreover, the main trigger factors for malnutrition were essentially related to social isolation and depressive syndromes. Knowing the impact of confinement on the elderly's health, these results may help further modulate ongoing public health interventions in case of future lockdowns.

Multidisciplinary management of worsening heart failure (HF) in the elderly improves survival. To ensure patients have access to adequate care, the current HF and French health authority guidelines advise establishing a clearly defined HF patient pathway. This pathway involves coordinating multiple disciplines to manage decompensating HF. Yet, recent registry data indicate that insufficient numbers of patients receive specialised cardiology care, which increases the risk of rehospitalisation and mortality. The patient pathway in France involves three key stages: presentation with decompensated HF, stabilisation within a hospital setting and transitional care back out into the community. In each of these three phases, HF diagnosis, severity and precipitating factors need to be promptly identified and managed. This is particularly pertinent in older, frail patients who may present with atypical symptoms or coexisting comorbidities and for whom geriatric evaluation may be needed or specific geriatric syndrome management implemented. In the transition phase, multi-professional post-discharge management must be coordinated with community health care professionals. When the patient is discharged, HF medication must be optimised, and patients educated about self-care and monitoring symptoms. This review provides practical guidance to clinicians managing worsening HF in the elderly.

Background: The incidence of cholecystectomy is increasing as the result of the aging worldwide. Our aim was to determine the influence of heart failure on in-hospital outcomes in patients undergoing cholecystectomy in the Spanish National Health System (SNHS)., Methods: We conducted a retrospective study using the Spanish National Hospital Discharge Database. Patients older than 17 years undergoing cholecystectomy in the period 2007-2015 were included. Demographic and administrative variables related to patients' diseases as well as procedures were collected., Results: 478,111 episodes of cholecystectomy were identified according to the data from SNHS hospitals in the period evaluated. From all the episodes, 3357 (0.7%) were excluded, as the result the sample was represented by 474,754 episodes. Mean age was 58.3 (+16.5) years, and 287,734 (60.5%) were women ( p < 0.001). A primary or secondary diagnosis of HF was identified in 4244 (0.89%) ( p < 0.001) and mean age was 76.5 (+9.6) years. A higher incidence of all main complications studied was observed in the HF group ( p < 0.001), except stroke ( p = 0.753). Unadjusted in-hospital mortality was 1.1%, 12.9% in the group with HF versus 1% in the non HF group ( p < 0.001). Average length of hospital stay was 5.4 (+8.9) days, and was higher in patients with HF (16.2 + 17.7 vs. 5.3 + 8.8; p < 0.001). Risk-adjusted in-hospital mortality models' discrimination was high in both cases, with AUROC values = 0.963 (0.960-0.965) in the APRG-DRG model and AUROC = 0.965 (0.962-0.968) in the CMS adapted model. Median odds ratio (MOR) was high (1.538 and 1.533, respectively), stating an important variability of risk-adjusted outcomes among hospitals., Conclusions: The presence of HF during admission increases in hospital mortality and lengthens the hospital stay in patients undergoing cholecystectomy. However, mortality and hospital stay have significantly decreased during the study period in both groups (HF and non HF patients).

The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide, with more than two million deaths. Evidence indicates the critical role of the vascular endothelium in its pathophysiology but, like potential changes in functional vasodilation, the vascular effect of SARS-CoV-2 at a given distance from the acute infection is largely unknown. We assessed brachial artery flow-mediated dilatation (FMD) in 27 COVID-19 patients needing conventional or intensive care unit hospitalization, three months after SARS-CoV-2 infection diagnosis and in nine age- and sex- matched control subjects. Interestingly, the FMD was lower in COVID-19 patients as compared to controls (8.2 (7.2-8.9) vs. 10.3 (9.1-11.7)); p = 0.002, and half of the hospitalized COVID-19 survivors presented with a reduced FMD < 8% at three months of COVID-19 onset. Impaired FMD was not associated with severe or critical SARS-CoV-2 infection, reflected by ICU hospitalization, total hospitalization duration, or severity of lung damage. In conclusion, reduced FMD is often observed even three months after hospitalization for SARS-CoV-2 infection, but such alteration predominantly appears to not be related to COVID-19 severity. Longer and larger follow-up studies will help to clarify the potential prognosis value of FMD among COVID-19 patients, as well as to further determine the mechanisms involved.

Background: Femoral neck fracture (FNF) is a common condition with a rising incidence, partly due to aging of the population. It is recommended that FNF should be treated at the earliest opportunity, during daytime hours, including weekends. However, early surgery shortens the available time for preoperative medical examination. Cardiac evaluation is critical for good surgical outcomes as most of these patients are older and frail with other comorbid conditions, such as heart failure. The aim of this study was to determine the impact of heart failure on in-hospital outcomes after surgical femoral neck fracture treatment., Methods: We performed a retrospective study using the Spanish National Hospital Discharge Database, 2007-2015. We included patients older than 64 years treated for reduction and internal fixation of FNF. Demographic characteristics of patients, as well as administrative variables, related to patient's diseases and procedures performed during the episode were evaluated., Results: A total of 234,159 episodes with FNF reduction and internal fixation were identified from Spanish National Health System hospitals during the study period; 986 (0.42%) episodes were excluded, resulting in a final study population of 233,173 episodes. Mean age was 83.7 (±7) years and 179,949 (77.2%) were women ( p < 0.001). In the sample, 13,417 (5.8%) episodes had a main or secondary diagnosis of heart failure (HF) ( p < 0.001). HF patients had a mean age of 86.1 (±6.3) years, significantly older than the rest ( p < 0.001). All the major complications studied showed a higher incidence in patients with HF ( p < 0.001). Unadjusted in-hospital mortality was 4.1%, which was significantly higher in patients with HF (18.2%) compared to those without HF (3.3%) ( p < 0.001). The average length of stay (LOS) was 11.9 (±9.1) and was also significantly higher in the group with HF (16.5 ± 13.1 vs. 11.6 ± 8.7; p < 0.001)., Conclusions: Patients with HF undergoing FNF surgery have longer length of stay and higher rates of both major complications and mortality than those without HF. Although their average length of stay has decreased in the last few years, their mortality rate has remained unchanged.

Introduction: The worldwide pandemic, coronavirus disease 2019 (COVID-19) is a novel infection with serious clinical manifestations, including death. Our aim is to describe the first non-ICU Spanish deceased series with COVID-19, comparing specifically between unexpected and expected deaths. Methods: In this single-centre study, all deceased inpatients with laboratory-confirmed COVID-19 who had died from March 4 to April 16, 2020 were consecutively included. Demographic, clinical, treatment, and laboratory data, were analyzed and compared between groups. Factors associated with unexpected death were identified by multivariable logistic regression methods. Results: In total, 324 deceased patients were included. Median age was 82 years (IQR 76-87); 55.9% males. The most common cardiovascular risk factors were hypertension (78.4%), hyperlipidemia (57.7%), and diabetes (34.3%). Other common comorbidities were chronic kidney disease (40.1%), chronic pulmonary disease (30.3%), active cancer (13%), and immunosuppression (13%). The Confusion, BUN, Respiratory Rate, Systolic BP and age ≥65 (CURB-65) score at admission was >2 in 40.7% of patients. During hospitalization, 77.8% of patients received antivirals, 43.3% systemic corticosteroids, and 22.2% full anticoagulation. The rate of bacterial co-infection was 5.5%, and 105 (32.4%) patients had an increased level of troponin I. The median time from initiation of therapy to death was 5 days (IQR 3.0-8.0). In 45 patients (13.9%), the death was exclusively attributed to COVID-19, and in 254 patients (78.4%), both COVID-19 and the clinical status before admission contributed to death. Progressive respiratory failure was the most frequent cause of death (92.0%). Twenty-five patients (7.7%) had an unexpected death. Factors independently associated with unexpected death were male sex, chronic kidney disease, insulin-treated diabetes, and functional independence. Conclusions: This case series provides in-depth characterization of hospitalized non-ICU COVID-19 patients who died in Madrid. Male sex, insulin-treated diabetes, chronic kidney disease, and independency for activities of daily living are predictors of unexpected death.

Introduction: Heart failure decompensation can be triggered by many factors, including anemia. In cases of iron deficiency anemia or iron deficiency without anemia, endoscopic studies are recommended to rule out the presence of gastrointestinal neoplasms or other associated bleeding lesions., Objectives: The aims of this study were to (i) examine trends in the incidence, clinical characteristics, and in-hospital outcomes of patients hospitalized with heart failure from 2002 to 2017 who underwent esophagogastroduodenoscopy (EGD) and/or colonoscopy, and to (ii) identify factors associated with in-hospital mortality (IHM) among patients with heart failure who underwent an EGD and/or a colonoscopy., Methods: We conducted an observational retrospective epidemiological study using the Spanish National Hospital Discharge Database (SNHDD) between 2002 and 2017. We included hospitalizations of patients with a primary discharge diagnosis of heart failure. Cases were reviewed if there was an ICD-9-CM or ICD-10 procedure code for EGD or colonoscopy in any procedure field. Multivariable logistic regression models were constructed to identify predictors of IHM among HF patients who underwent an EGD or colonoscopy., Results: A total of 51,187 (1.32%) non-surgical patients hospitalized with heart failure underwent an EGD and another 72,076 (1.85%) patients had a colonoscopy during their admission. IHM was significantly higher in those who underwent an EGD than in those who underwent a red blood cell transfusion (OR 1.10; 95%CI 1.04-1.12). However, the use of colonoscopy seems to decrease the probability of IHM (OR 0.45; 95%CI 0.41-0.49). In patients who underwent a colonoscopy, older age seems to increase the probability of IHM. However, EGD was associated with a lower mortality (OR 0.60; 95% CI 0.55-0.64)., Conclusion: In our study, a decrease in the number of gastroscopies was observed in relation to colonoscopy in patients with heart failure. The significant ageing of the hospitalized HF population seen over the course of the study could have contributed to this. Both procedures seemed to be associated with lower in-hospital mortality, but in the case of colonoscopy, the risk of in-hospital mortality was higher in elderly patients with heart failure and associated neoplasms. Colonoscopy and EGD seemed not to increase IHM in patients with heart failure.

Introduction: Inflammation is a fundamental phenomenon in heart failure, but the prognostic or therapeutic role of markers such as interleukin-6 (IL-6) has not yet been clarified. The objective of this study is to describe the clinical profile of patients with elevated IL-6 and determine if they have worse clinical outcomes., Methods: A retrospective c.ohort observational study including 78 patients with heart failure followed up at the Heart Failure Outpatient Clinic of the Internal Medicine Department. IL-6 was determined in all patients, who were then assigned into two groups according to IL-6 level (normal or high). Clinical and prognostic data were collected to determine the differences in both groups., Results: The average age was 79 years, 60% female. A total of 53.8% of the patients had elevated IL-6 (group 2). Patients with elevated IL-6 presented more frequently with anemia mellitus (64.3% vs. 41.7%; p = 0.046), atrial fibrillation (83.3% vs. 61.9% p = 0.036), dyslipidemia (76.2% vs. 58.2%; p = 0.03), higher creatinine levels (1.35 mg/dL vs. 1.08 mg/dL; p = 0.024), lower glomerular filtration rate (43.6 mL/min/m 2 vs. 59.9 mL/min/m 2 ; p = 0.007), and anemia 25% vs. 52.4% p = 0.014. The factors independently associated with the increase in IL-6 were anemia 3.513 (1.163-10.607) and renal failure 0.963 (0.936-0.991), p < 0.05. Mortality was higher in the group with elevated IL-6 levels (16% vs. 2%; p = 0.044) with a log-rank p = 0.027 in the Kaplan-Meier curve., Conclusion: Patients with heart failure and elevated IL-6 most often have atrial fibrillation, diabetes mellitus, dyslipidemia, anemia, and renal failure. In addition, mortality was higher and a tendency of higher hospital admission was observed in stable HF patients with elevated IL-6.

(1) Background: Mitral regurgitation (MR) is the second most prevalent valvular heart disease in developed countries. Mitral valve (MV) disease is a common cause of heart failure and a leading cause of morbidity and mortality in the U.S.A. and Europe. (2) Methods: We performed a retrospective study using the Spanish National Hospital Discharge Database, 2001-2015. We included patients that had surgical mitral valve replacement (SMVR) listed as a procedure in their discharge report. We sought to (i) examine trends in incidence of SMVR among women and men in Spain, (ii) compare in-hospital outcomes for mechanical and bioprosthetic SMVR by sex, and (iii) identify factors associated with in-hospital mortality (IHM) after SMVR. (3) Results: We identified 44,340 hospitalizations for SMVR (84% mechanical, 16% bioprosthetic). The incidence of SMVR was higher in women (IRR 1.51; 95% CI 1.48-1.54). The use of mechanical SMVR decreased over time in both sexes and the use of bioprosthetic valves increased over time in both sexes. Men who underwent mechanical and bioprosthetic SMVR had higher comorbidity than women. IHM was significantly lower in women who underwent SMVR than in men (10% vs. 12% p < 0.001 for mechanical and 14% vs. 16% p = 0.025 for bioprosthetic valve, respectively). Major adverse cardiovascular and cerebrovascular events (MACCE) were also significantly lower in women who underwent mechanical and bioprosthetic SMVR. A significant reduction in both in-hospital MACCEs and IHM was observed over the study period regardless of sex. After multivariable logistic regression, male sex was associated with increased IHM only in bioprosthetic SMVR (OR 1.28; 95% CI 1.1-1.5). (4) Conclusions: This nationwide analysis over 15 years of sex-specific outcomes after SMVR showed that incidences are significantly higher in women than men for mechanical and bioprosthetic SMVR. IHM and MACCE have improved over time for SMVR in both sexes. Male sex was independently associated with higher mortality after bioprosthetic SMVR.

Introduction: Telemedicine is believed to be helpful in managing patients suffering from chronic diseases, in particular elderly patients with numerous accompanying conditions. This was the basis for the "GERIATRICS and e-Technology (GER-e-TEC) study", which was an experiment involving the use of the smart MyPredi™ e-platform to automatically detect the exacerbation of geriatric syndromes., Methods: The MyPredi™ platform is connected to a medical analysis system that receives physiological data from medical sensors in real time and analyzes this data to generate (when necessary) alerts. These alerts are issued in the event that the health of a patient deteriorates due to an exacerbation of their chronic diseases. An experiment was conducted between 24 September 2019 and 24 November 2019 to test this alert system. During this time, the platform was used on patients being monitored in an internal medicine unit at the University Hospital of Strasbourg. The alerts were compiled and analyzed in terms of sensitivity, specificity, and positive and negative predictive values with respect to clinical data. The results of the experiment are provided below., Results: A total of 36 patients were monitored remotely, 21 of whom were male. The mean age of the patients was 81.4 years. The patients used the telemedicine solution for an average of 22.1 days. The telemedicine solution took a total of 147,703 measurements while monitoring the geriatric risks of the entire patient group. An average of 226 measurements were taken per patient per day. The telemedicine solution generated a total of 1611 alerts while assessing the geriatric risks of the entire patient group. For each geriatric risk, an average of 45 alerts were emitted per patient, with 16 of these alerts classified as "low", 12 classified as "medium", and 20 classified as "critical". In terms of sensitivity, the results were 100% for all geriatric risks and extremely satisfactory in terms of positive and negative predictive values. In terms of survival analysis, the number of alerts had an impact on the duration of hospitalization due to decompensated heart failure, a deterioration in the general condition, and other reasons., Conclusion: The MyPredi™ telemedicine system allows the generation of automatic, non-intrusive alerts when the health of a patient deteriorates due to risks associated with geriatric syndromes.

This study sought to determine whether the implementation of regular and structured follow-up of patients with chronic heart failure (CHF), combined with therapeutic education and remote monitoring solution, leads to better management. This was a single-center retrospective study conducted in a cohort of patients with proven CHF who were followed up in the Mulhouse region (France) between January 2016 and December 2017 by the Unité de Suivi des Patients Insuffisants Cardiaques (USICAR) unit. These patients received regular protocolized follow-up, a therapeutic education program, and several used a telemedicine platform for a two-year period. The primary endpoint was the number of days hospitalized for heart failure (HF) per patient per year. The main secondary endpoints included the number of days hospitalized for a heart condition other than HF and the number of hospital stays for HF per patient. These endpoints were collected during the year preceding enrollment, at one year of follow-up, and at two years of follow-up. The remote monitoring solution was evaluated on the same criterion. Overall, 159 patients with a mean age of 72.9 years were included in this study. They all had CHF, mainly NYHA Class I-II (88.7%), predominantly of ischemic origin (50.9%), and with altered left ventricular ejection fraction in 69.2% of cases. The mean number of days hospitalized for HF per patient per year was 8.33 (6.84-10.13) in the year preceding enrollment, 2.6 (1.51-4.47) at one year of follow-up, and 2.82 at two years of follow-up (1.30-6.11) ( p < 0.01 for both comparisons). The mean number of days hospitalized for a heart condition other than HF was 1.73 (1.16-2.6), 1.81 (1.04-3.16), and 1.32 (0.57-3.08), respectively ( p = ns). The percentage of hospitalization for HF for each patient was 69.5% (60.2-77.4), 16.2% (10-25.2), and 19.3% (11-31.8), respectively ( p < 0.001 for both comparisons). In the group telemedicine, the mean number of days hospitalized for HF per patient per year was 8.33 during the year preceding enrollment, 2.3 during the first year of follow-up, and 1.7 during the second. This difference was significant ( p < 0.001). The "number of days hospitalized for a heart condition other than HF" was significantly reduced in the group of patient's beneficiating from the remote monitoring solution. This study demonstrates the value of a protocolized follow-up associated with a therapeutic optimization, therapeutic education program, and the use of a remote monitoring solution to improve the management of ambulatory patients with CHF, particularly of moderate severity.

Thyroid pathology is reported internationally in 5-10% of all pregnancies. The overall aim of this research was to determine the prevalence of hypothyroidism and risk factors during the first trimester screening in a Mexican patients sample. We included the records of 306 patients who attended a prenatal control consultation between January 2016 and December 2017 at the Women's Institute in Monterrey, Mexico. The studied sample had homogeneous demographic characteristics in terms of age, weight, height, BMI (body mass index) and number of pregnancies. The presence of at least one of the risk factors for thyroid disease was observed in 39.2% of the sample. Two and three clusters were identified, in which patients varied considerably among risk factors, symptoms and pregnancy complications. Compared to Cluster 0, one or more symptoms or signs of hypothyroidism occurred, while Cluster 1 was characterized by healthier patients. When three clusters were used, Cluster 2 had a higher TSH (thyroid stimulating hormone) value and pregnancy complications. There were no significant differences in perinatal variables. In addition, high TSH levels in first trimester pregnancy are characterized by pregnancy complications and decreased newborn weight. Our findings underline the high degree of disease heterogeneity with existing pregnant hypothyroid patients and the need to improve the phenotyping of the syndrome in the Mexican population.

Agranulocytosis is a rare, but serious and life-threatening hematologic disorder in elderly patients. Idiosyncratic drug-induced agranulocytosis (IDIA) has been classically defined by a neutrophil count below 0.5 × 10 9 /L. The annual incidence of IDIA in Europe is about 1.6-9.2 cases per million inhabitants. Increasing age and female sex have been considered as risk factors for the development of this condition. Besides, it is well known that older people take on average more drugs than younger people. This condition is most often associated with the intake of antibacterial agents, antiplatelets, antithyroids, antipsychotics, antiepileptics and nonsteroidal anti-inflammatory drugs (NSAIDs). Initially, agranulocytosis may present without symptoms, but may quickly progress to a severe infection and sepsis. The causative drug should be immediately stopped. In febrile patients, blood cultures and where indicated, site-specific cultures should be obtained and early treatment with empirical broad-spectrum antibiotics started. Even with adequate treatment, the mortality rate is higher in elderly patients reaching up to 20%. Hematopoietic growth factors have proven to be useful as they shorten the duration of neutropenia. However, data on neutropenia and agranulocytosis in the elderly meeting the criteria of evidence-based medicine are still poor in the literature. This review analyzes the results of our experience as well as other published studies of the universal literature.

Lung diseases such as chronic obstructive pulmonary disease, asthma, pulmonary arterial hypertension, or idiopathic pulmonary fibrosis are major causes of morbidity and mortality. Complex, their physiopathology is multifactorial and includes lung mitochondrial dysfunction and enhanced reactive oxygen species (ROS) release, which deserves increased attention. Further, and importantly, circulating blood cells (peripheral blood mononuclear cells-(PBMCs) and platelets) likely participate in these systemic diseases. This review presents the data published so far and shows that circulating blood cells mitochondrial oxidative capacity are likely to be reduced in chronic obstructive pulmonary disease (COPD), but enhanced in asthma and pulmonary arterial hypertension in a context of increased oxidative stress. Besides such PBMCs or platelets bioenergetics modifications, mitochondrial DNA (mtDNA) changes have also been observed in patients. These new insights open exciting challenges to determine their role as biomarkers or potential guide to a new therapeutic approach in lung diseases.

Objective: The main objective of this study was to evaluate the impact of the French national program on home return of chronic heart failure patients (PRADO-IC) in terms of re-hospitalizations for heart failure (HF) during its deployment in the Bas-Rhin (France)., Patients and Methods: This was a pilot, descriptive, quantitative, retrospective, and bi-centric study (University Hospitals of Strasbourg and Haguenau Hospital Center, France). It included all patients included in the PRADO-IC program from these centers between January 1, 2015 and December 31, 2015. The primary endpoint of our study was the evaluation of the number of 1-year, 6-month, and 30-day re-admissions to the hospital in relation to an acute HF episode, before and after the inclusion of patients in the PRADO-IC program. The secondary endpoints were the number of overall re-hospitalizations (all-cause); the number of days of hospitalization for HF; the time to first re-hospitalization and the average length of hospital stay, before and after inclusion in PRADO-IC; and the overall and cardiovascular mortality rates., Results: 91 patients out of 271 (33,6%) with a mean age of 79.2 years (67-94) were included. They all had chronic HF, essentially class II-III NYHA (90.1%), mostly of ischemic origin (41.9%), with altered left ventricular ejection fraction in 71.4% of cases. A reduction in the mean number of hospitalizations for HF per patient at 30 days, 6 months and 1 year was observed, respectively, from 0.18 ± 0.42 per patient before inclusion to 0.15 ± 0.36 after inclusion (p = 0.56); 0.98 ± 1.04 hospitalizations to 0.53 ± 0.81 at 6 months (p < 0.01); and 1.64 ± 1.14 hospitalizations 1.04 ± 1.05 at 1 year (p < 0.001). Patients were hospitalized less overall after inclusion in the PRADO-IC program. The number of days of hospitalization for HF was reduced after inclusion of patients from 18.02 ± 7.78 days before inclusion to 14.28 ± 11.57 days for the 6 month follow-up (p = 0.006), and from 22.07 ± 10.33 days before inclusion to 16.39 ± 15.94 days for the 1 year follow-up (p < 0.001). In contrast, inclusion in PRADO-IC statistically increased the mean time to first re-hospitalization for HF from mean 99.36 ± 72.39 days before inclusion to 148.11 ± 112.77 days after inclusion (p < 0.001)., Conclusion: This study seems to demonstrate that the PRADO-IC program could improve the management of chronic HF patients in ambulatory care, particularly regarding HF re-hospitalization. However, due to the limitations of the methodology used and the small number of patients, it is advisable to consolidate its initial results with a randomized controlled study on a larger number of patients. In our opinion, its results need to be communicated because, to our knowledge, no equivalent study exists., Competing Interests: The authors declare no conflicts of interest

Besides pumping, the heart participates in hydro-sodium homeostasis and systemic blood pressure regulation through its endocrine function mainly represented by the large family of natriuretic peptides (NPs), including essentially atrial natriuretic (ANP) and brain natriuretic peptides (BNP). Under normal conditions, these peptides are synthesized in response to atrial cardiomyocyte stretch, increase natriuresis, diuresis, and vascular permeability through binding of the second intracellular messenger's guanosine 3',5'-cyclic monophosphate (cGMP) to specific receptors. During heart failure (HF), the beneficial effects of the enhanced cardiac hormones secretion are reduced, in connection with renal resistance to NP. In addition, there is a BNP paradox characterized by a physiological inefficiency of the BNP forms assayed by current methods. In this context, it appears interesting to improve the efficiency of the cardiac natriuretic system by inhibiting cyclic nucleotide phosphodiesterases, responsible for the degradation of cGMP. Recent data support such a therapeutic approach which can improve the quality of life and the prognosis of patients with HF.

Introduction: Idiosyncratic drug-induced neutropenia and agranulocytosis is seldom discussed in the literature, especially for new drugs such as biotherapies outside the context of oncology. In the present paper, we report and discuss the clinical data and management of this relatively rare disorder, with a focus on biotherapies used in autoimmune and auto-inflammatory diseases., Materials and Methods: A review of the literature was carried out using the PubMed database of the US National Library of Medicine. We searched for articles published between January 2010 and May 2019 using the following key words or associations: "drug-induced neutropenia", "drug-induced agranulocytosis", and "idiosyncratic agranulocytosis". We included specific searches on several biotherapies used outside the context of oncology, including: tumor necrosis factor (TNF)-alpha inhibitors, anti-CD20 agents, anti-C52 agents, interleukin (IL) 6 inhibitors, IL 1 inhibitors, and B-cell activating factor inhibitor., Results: Idiosyncratic neutropenia remains a potentially serious adverse event due to the frequency of severe sepsis with severe deep tissue infections (e.g., pneumonia), septicemia, and septic shock in approximately two-thirds of all hospitalized patients with grade 3 or 4 neutropenia (neutrophil count (NC) ≤ 0.5 × 109/L and ≤ 0.1 × 109/L, respectively). Over the last 20 years, several drugs have been strongly associated with the occurrence of idiosyncratic neutropenia, including antithyroid drugs, ticlopidine, clozapine, sulfasalazine, antibiotics such as trimethoprim-sulfamethoxazole, and deferiprone. Transient grade 1-2 neutropenia (absolute blood NC between 1.5 and 0.5 × 109/L) related to biotherapy is relatively common with these drugs. An approximate 10% prevalence of such neutropenia has been reported with several of these biotherapies (e.g., TNF-alpha inhibitors, IL6 inhibitors, and anti-CD52 agents). Grade 3-4 neutropenia or agranulocytosis and clinical manifestations related to sepsis are less common, with only a few case reports to date for most biotherapies. Special mention should be made of late onset and potentially severe neutropenia, especially following anti-CD52 agent therapy. During drug therapy, several prognostic factors have been identified that may be helpful when identifying 'susceptible' patients. Older age (>65 years), septicemia or shock, renal failure, and a neutrophil count ≤0.1 × 109/L have been identified as poor prognostic factors. Idiosyncratic neutropenia should be managed depending on clinical severity, with permanent/transient discontinuation or a lower dose of the drug, switching from one drug to another of the same or another class, broad-spectrum antibiotics in cases of sepsis, and hematopoietic growth factors (particularly G-CSF)., Conclusion: Significant progress has been made in recent years in the field of idiosyncratic drug-induced neutropenia, leading to an improvement in their prognosis (currently, mortality rate between 5 and 10%). Clinicians must continue their efforts to improve their knowledge of these adverse events with new drugs as biotherapies., Competing Interests: The authors have no conflict of interest that are directly relevant of the content of this manuscript. E.A. is the recipient of several grants from different laboratories: Novartis, BMS, Pfizer, Léo Pharma, Boehringer, Ferring, Chugai, Amgen, and Roche, but these sponsors have no part in the research or writing of the present manuscript. Cremmer Consulting Company has edited the text of the present manuscript.

Background: This is a narrative review of both the literature and Internet pertaining to telemedicine projects within the field of heart failure, with special attention placed on remote monitoring of second-generation projects and trials, particularly in France., Results: Since the beginning of the 2000's, several telemedicine projects and trials focused on chronic heart failure have been developed. The first telemedicine projects (e.g., TEN-HMS, BEAT-HF, Tele-HF, and TIM-HF) primarily investigated telemonitoring or for the older ones, telephone follow-up. Numerous second-generation telemedicine projects have emerged in Europe over the last ten years or are still under development for computer science heart failure, especially in Europe, such as SCAD, OSICAT, E-care, PRADO-INCADO, and TIM-HF2. The E-care telemonitoring project fits within the telemedicine 2.0 framework, based on connected objects, new information and communication technologies (ICT) and Web 2.0 technologies. E-care is the first telemedicine project including artificial intelligence (AI). TIM-HF2 is the first positive prospective randomized study with regards to EBM with positive significant clinical benefit, in terms of unplanned cardiovascular hospital admissions and all-cause deaths. The potential contribution of second-generation telemedicine projects in terms of mortality, morbidity, and number of hospitalizations avoided is currently under study. Their impact in terms of health economics is likewise being investigated, taking into account that the economic and social benefits brought up by telemedicine solutions were previously validated by the original telemedicine projects.

The objective of this review is to provide an update on the effectiveness of oral and nasal vitamin B12 (cobalamin) treatment in gastrointestinal (GI) disorders. Relevant articles were identified by PubMed and Google Scholar systematic search, from January 2010 and June 2018, and through hand search of relevant reference articles. Additional studies were obtained from references of identified studies, the Cochrane Library and the ISI Web of Knowledge. Data gleaned from reference textbooks and international meetings were also used, as was information gleaned from commercial sites on the web and data from CARE B12 research group. For oral vitamin B12 treatment, 4 randomized controlled trials (vs. intramuscular), 4 narrative and 4 systematic reviews, and 13 prospective studies fulfilled our inclusion criteria. These studies concerned patients with vitamin B12 deficiency related to: food-cobalamin malabsorption ( n = 6), Biermer's disease ( n = 3), veganism or vegetarianism ( n = 1), total gastrectomy after Roux-en-Y gastric bypass ( n = 2) and Crohn's disease ( n = 1). Four prospective studies include patients with vitamin B12 deficiency related to the aforementioned etiologies, except veganism or vegetarianism. The systematic present review documents that oral vitamin B12 replacement, at a daily dose of 1000 μg (1 mg), was adequate to normalize serum vitamin B12 levels and cure main clinical manifestations related to vitamin B12 deficiency, in GI disorders, and thus, with safety profile. For nasal vitamin B12 treatment, only one preliminary study was available. We conclude that oral vitamin B12 is an effective alternative to intramuscular vitamin B12 (except in patients presenting with severe neurological manifestations). Oral vitamin B12 treatment avoids the discomfort, contraindication (in patients with anticoagulation), and cost of monthly injections.

Background: Despite major advances in its prevention and treatment, febrile neutropenia remains a most concerning complication of cancer chemotherapy. Outside the oncology setting, however, only few data are currently available on febrile neutropenia related to non-chemotherapy drugs. We report here data on 76 patients with febrile neutropenia related to non-chemotherapy drugs, followed up in a referral center within a university hospital., Patients and Methods: Data from 76 patients with idiosyncratic drug-induced febrile neutropenia were retrospectively reviewed. All cases were extracted from a cohort study on agranulocytosis conducted at the Strasbourg University Hospital (Strasbourg, France)., Results: Mean patient age was 52.2 years old (range: 18-93) and gender ratio (F/M) 1.6, with several comorbidities present in 86.8% of patients. The most common causative drugs were: antibiotics (37.4%), antithyroid drugs (17.2%), neuroleptic and anti-epileptic agents (13.1%), non-steroidal anti-inflammatory agents and analgesics (8%), and platelet aggregation inhibitors (8%). Main clinical presentations upon hospitalization included isolated fever (30%), sore throat, acute tonsillitis and sinusitis (18.4%), documented pneumonia (18.4%), septicemia (14.5%), and septic shock (6.6%). Mean neutrophil count at nadir was 0.13 × 10(9)/L (range: 0-0.48). While in hospital, 22 patients (28.9%) worsened clinically and required intensive care unit placement. All patients were promptly treated with broad-spectrum antibiotics, and 45 (59.2%) with hematopoietic growth factors. Mean duration of hematological recovery (neutrophil count ≥1.5 × 10(9)/L) was 7.5 days (range: 2-21), which was reduced to 0.7 days (range: 2-16) ( p = 0.089) with hematopoietic growth factors. Outcome was favorable in 89.5% of patients, whereas eight died., Conclusions: Like in oncology and myelosuppressive chemotherapy settings, idiosyncratic febrile neutropenia is typically serious, about 40% of patients exhibiting severe pneumonia, septicemia, and septic shock, with a mortality rate of 10%. Like in febrile, chemotherapy-related neutropenia, modern and timely management (immediate broad spectrum antibiotherapy, hematopoietic growth factors) may reduce infection-related mortality. All practitioners should be aware of this potential side-effect that may even occur in the event of "daily medication" exposure., Competing Interests: The authors (Rachel Mourot-Cottet, Frédéric Maloisel, Olivier Keller, François Séverac, Thomas Vogel, Martine Tebacher, Jean-Christophe Weber, Georges Kaltenbach, Jacques-Eric Gottenberg, Bernard Goichot, Jean Sibilia, Anne-Sophie Korganow, Raoul Herbrecht, and Emmanuel Andrès) declare that there is no conflict of interest directly relevant to the content of this manuscript. Frédéric Maloisel and Emmanuel Andrès are recipients of several grants from CHUGAI, AMGEN, ROCHE, GSK, PFIZER, and NOVARTIS, yet these sponsors were involved neither in the research nor the writing of the manuscript.