Long-term management of chronic heart failure patients in internal medicine.

Chronic heart failure (CHF) is one of the main disabilities in elderly patients requiring frequent hospitalizations with high health care costs. We studied the outcome of CHF outpatient management in reducing hospitalization after discharge from a division of Internal Medicine at a large 3rd referral regional Hospital. 147 CHF inpatients (M:F: 63:84; mean age 76 ± 9.6 years) admitted for acute exacerbation of CHF were followed up as outpatients at 1, 6, 12 and 24 months after discharge. At baseline, patients underwent: laboratory tests, ECG, echocardiogram and a dedicated-intensive health care educational program involving also their families. The rate of hospitalization in the same group of patients was compared with data from the previous 24 months, a period when patients had been seen elsewhere without disease management programs. Patients had high prevalence of comorbidities and the majority was in NYHA class III or IV. Hypertension and valvular heart disease were the most common causes for CHF. Systolic function was preserved (LVEF ≥ 50%) in 61.9% of cases. Functional NYHA class improved significantly after 6 months and remained stable at 24 months. There was a significant increase in the use of the renin-angiotensin system blockers, beta-blockers and diuretics compared to admission to the ward. At 24 months, hospital readmissions were decreased by 42% as compared to the previous 24 months. Risk factors for re-hospitalizations were anemia, NYHA class III or IV and previous hospitalizations. Establishing an intensive outpatient management program for CHF patients leads to long-term beneficial effects with improved clinical parameters and decreased hospitalization in the setting of Internal Medicine.

The grandfather's fever.

An 86-year-old Caucasian man had prior episodes of fever (up to 38 °C), mild abdominal pain, tachycardia, and malaise in the last 3 months, lasting 2-3 days. He never suffered from abdominal or chest pain, rash, or arthralgia. Major causes of fever were excluded (pulmonary, urinary, abdomen, skin infections, neoplasms, and major rheumatologic disorders). The patient was native of Altamura with a family history of familial Mediterranean fever (FMF). The genetic testing confirmed the presence of MEFV gene variants c.442G>C (E148Q) on exon 2 and c.2282G>A (R761H) on exon 10, all in heterozygosity. Mildly elevated serum transaminases suggested an ongoing form of FMF hepatitis on nonalcoholic liver steatosis. The patient started colchicine 1 mg/day that induced symptom control and normalization of inflammatory markers, hyperbilirubinemia, and markers of cholestasis. Symptoms of FMF can appear at any age in life and our patient represents a very late-onset clinical case. The Apulian region has a consistent clustering of MEFV variants and FMF families with affected individuals in multiple consecutive generations. Families show unique clinical features and rare signs of secondary amyloidosis without kidney damage. Genetic and environmental bases of this phenotypic variant are under scrutiny. Colchicine lifetime remains the mainstay of treatment in FMF patients. KEY POINTS: • Familial Mediterranean fever (FMF) is the most frequent hereditary monogenic recurrent fever syndrome, and symptoms can appear at any age in life. • Late-onset FMF approaches 30% in late adulthood, but in general, onset of FMF after the age of 40 (late onset FMF) is rare, usually associated with M694V heterozygosity. • In a local cluster of FMF families (Altamura, Puglia, Southern Italy), we report a very late-onset FMF (variants E148Q, R761H) in an 86-year-old patient with a positive family history of FMF in two generations of descendants. • While lifetime colchicine remains the mainstay of treatment in FMF patients, prospective studies need to identify the characteristics of several phenotypic variants accounting for (very)-late onset FMF.

Familial Mediterranean fever: breaking all the (genetic) rules.

OBJECTIVE: FMF is an inherited autoinflammatory syndrome, characterized by attacks of painful periodic fever caused by diffuse serositis and risk of secondary amyloidosis due to IL-1ß-mediated inflammation. The disease appears to be transmitted through autosomal recessive mutations in the MEFV gene encoding the pyrin protein Although more than 300 variants have been reported worldwide so far, their association with symptom severity, the relative frequencies in different populations and the disease penetrance are far from being completely understood. We investigated genotype-phenotype correlations in two large nuclear families and verified whether commonly used web-based tools can usefully predict variant pathogenicity in FMF. METHODS: Peripheral blood samples were obtained from 15 patients of two families who had been diagnosed with FMF according to international criteria. The entire MEFV coding region was sequenced in all subjects, and 179 MEFV variants were surveyed with five different pathogenicity predictors. RESULTS: The inheritance of FMF could not be explained by traditional autosomal recessivity in both families. In silico tools demonstrated a significant association of variants' pathogenicity with their position along the coding sequence but not with variants' frequency. CONCLUSION: By describing two large families with paradigmatic complexity of FMF genetics, we conclude that established concepts in assessing the causative role of variants identified in mutation screening cannot be easily translated into appropriate genetic counselling in FMF. Furthermore, we demonstrate that variants frequently associated with severe disease are not predicted to significantly impact protein function using in silico algorithms.