Objective To investigate the clinical manifestations at diagnosis and during follow-up in patients with 22q11.2 deletion syndrome to better define the natural history of the disease. Study design A ...retrospective and prospective multicenter study was conducted with 228 patients in the context of the Italian Network for Primary Immunodeficiencies. Clinical diagnosis was confirmed by cytogenetic or molecular analysis. Results The cohort consisted of 112 males and 116 females; median age at diagnosis was 4 months (range 0 to 36 years 10 months). The diagnosis was made before 2 years of age in 71% of patients, predominantly related to the presence of heart anomalies and neonatal hypocalcemia. In patients diagnosed after 2 years of age, clinical features such as speech and language impairment, developmental delay, minor cardiac defects, recurrent infections, and facial features were the main elements leading to diagnosis. During follow-up (available for 172 patients), the frequency of autoimmune manifestations ( P = .015) and speech disorders ( P = .002) increased. After a median follow-up of 43 months, the survival probability was 0.92 at 15 years from diagnosis. Conclusions Our data show a delay in the diagnosis of 22q11.2 deletion syndrome with noncardiac symptoms. This study provides guidelines for pediatricians and specialists for early identification of cases that can be confirmed by genetic testing, which would permit the provision of appropriate clinical management.
Atrial fibrillation (AF) is the most common cardiac arrhythmia in adults and has been independently related to increased morbidity and mortality. AF is a frequent arrhythmia in infective endocarditis ...(IE). Nevertheless, there are no data on how AF affects the clinical outcome of patients with endocarditis. Our purpose was to investigate patient characteristics, microbiology, echocardiographic findings, in-hospital course, and prognosis of patients with IE who develop new-onset AF (NAF) and compare them with those who remained in sinus rhythm (SR) or had previous AF (PAF). From 1997 to 2014, 507 consecutive patients with native left-sided IE were prospectively recruited at 3 tertiary care centers. We distinguished 3 groups according to the type of baseline heart rhythm during hospitalization and previous history of AF: NAF group (n = 52), patients with no previous history of AF and who were diagnosed as having NAF during hospitalization; SR group (n = 380), patients who remained in SR; and PAF group (n = 75), patients with PAF. Patients with NAF were older than those who remained in SR (68.3 vs 59.6 years, p <0.001). At admission, heart failure was more common in NAF group (53% vs 34.3%, p <0.001), whereas stroke (p = 0.427) was equally frequent in all groups. During hospitalization, embolic events occurred similarly (p = 0.411). In the multivariate analysis, NAF was independently associated with heart failure (odds ratio 3.56, p <0.01) and mortality (odds ratio 1.91, p = 0.04). In conclusion, the occurrence of NAF in patients with IE was strongly associated with heart failure and higher in-hospital mortality independently from other relevant clinical variables.
In-hospital mortality of patients with infective endocarditis (IE) remains exceedingly high. Quick recognition of parameters accurately identifying high-risk patients is of paramount importance. The ...objective of this study was to analyze the incidence and severity of thrombocytopenia at presentation and its prognostic impact in patients with native valve left-sided IE. We studied a cohort of 533 consecutive episodes of native valve left-sided IE prospectively recruited. We distinguished 2 groups: group I (n = 175), episodes who had thrombocytopenia at admission, and group II (n = 358) gathered all the episodes who did not. Thrombocytopenia at admission was defined as a platelet count of <150,000/μl. No differences were found in the need for surgery, but in-hospital mortality was significantly higher in patients with thrombocytopenia (p <0.001). Mortality rate was associated with the degree of thrombocytopenia (p <0.001). In the multivariable analysis, thrombocytopenia at admission was an independent predictor of higher mortality (p = 0.002). A synergistic interaction between thrombocytopenia and Staphylococcus aureus on mortality risk was also observed (p = 0.04). In conclusion, thrombocytopenia at admission is an early risk marker of increased mortality in patients with native valve left-sided IE. Mortality rates increased with increasing severity of thrombocytopenia. Thrombocytopenia at admission should be used as an early marker for risk stratification in patients with native valve IE to identify those at risk of complicated in-hospital evolution and increased mortality.
Abstract Objective The objective was to assess whether fluid balance had a determinant impact on mortality rate in a cohort of critically ill patients with severe sepsis or septic shock. Design A ...prospective and observational study was carried out on an inception cohort. Setting The setting was an intensive care unit of a university hospital. Patients Patients admitted consecutively in the intensive care unit who were diagnosed with severe sepsis or septic shock were included. Interventions Demographic, laboratory, and clinical data were registered, as well as time of septic shock onset, illness severity (Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment), and comorbidities. Daily and accumulated fluid balance was registered at 24, 48, 72, and 96 hours. Survival curves representing 28-day mortality were built according to the Kaplan-Meier method. Results A total of 42 patients were included in the analysis: men, 64.3%; mean age, 61.8 ± 15.9 years. Septic shock was predominant in 69% of the cases. Positive blood cultures were obtained in 17 patients (40.5%). No age, sex, Sepsis-related Organ Failure Assessment, creatinine, lactate, venous saturation of O2, and troponin differences were observed upon admission between survivors and nonsurvivors. However, higher Simplified Acute Physiology Score II was observed in nonsurvivors, P = .016. Nonsurvivors also showed higher accumulated positive fluid balance at 48, 72, and 96 hours with statistically significant differences. Besides, significant differences ( P = .02) were observed in the survival curve with the risk of mortality at 72 hours between patients with greater than 2.5 L and less than 2.5 L of accumulated fluid balance. Conclusions Fluid administration at the onset of severe sepsis or septic shock is the first line of hemodynamic treatment. However, the accumulated positive fluid balance in the first 48, 72, and 96 hours is associated with higher mortality in these critically ill patients.
Native valve infective endocarditis (IE) in patients with normal valves has increased in the last decades. Whether patients with normal valves present a similar prognosis to those with pathologic ...valves is unresolved. Our aim is to describe epidemiologic and clinical differences between patients with left-sided IE and normal valves and those with native pathologic valves. We analyzed 945 consecutive episodes of IE, 435 of which involved left-sided nonprosthetic IE. They were classified into 2 groups: episodes in normal valves (normal group, n = 173) and episodes in pathologic valves (abnormal group, n = 262). Patients in the normal group were younger, Staphylococcus aureus and Streptococcus bovis were more frequently isolated, and vegetations were more frequently found. Heart failure, septic shock, and the need for surgery or death were more common. Multivariate analysis identified the following as factors independently associated with normal valve IE: age <65 years, S bovis , S aureus , heart failure, and vegetation detection. Factors independently associated with in-hospital events included S aureus , periannular complications, heart failure, and septic shock development. In conclusion, compared with patients with abnormal valve IE, patients with IE on normal valves were younger, had a more virulent microbiological profile, developed heart failure and septic shock more frequently, needed more surgical procedures, and had worse prognosis.
Background Infective endocarditis (IE) due to Streptococcus bovis has been classically associated with elderly patients, frequently involving >1 valve, with large vegetations and high embolic risk, ...which make it a high-risk group. Our aim is to analyze the current clinical profile and prognosis of S bovis IE episodes, in comparison to those episodes caused by viridans group streptococci and enterococci. Methods We analyzed 1242 consecutive episodes of IE prospectively recruited on an ongoing multipurpose database, of which 294 were streptococcal left-sided IE and comprised our study group. They were classified into 3 groups: group I (n = 47), episodes of IE due to S bovis ; group II (n = 134), episodes due to viridans group streptococci; and group III (n = 113), those episodes due to enterococci. Results The incidence of enterococci IE has significantly increased in the last 2 decades (6.4% 1996-2004 vs 11.1% 2005-2013; P = .005), whereas the incidence of IE due to S bovis and viridans streptococci have remained stable (4% and 10%, respectively). Gender distribution was similar in the 3 groups. Patients with S bovis and enterococci IE were older than those from group II. Nosocomial acquisition was more frequent in group III. Concerning comorbidity, diabetes mellitus (36.7% vs 9.2% vs 26.8%; P < .001) was more common in groups I and III. Chronic renal failure was more prevalent in patients from group III (4.2% vs 1.5% vs 19%; P < .001). Prosthetic valve IE was more frequent in enterococcal IE. Infection upon normal native valves was more frequent in S bovis IE. Colorectal tumors were found in 69% of patients from this group. Vegetation detection was similar in the 3 groups. However, vegetation size was smaller in S bovis IE. During hospitalization, in-hospital complications and in-hospital mortality were higher in enterococci episodes. Conclusions S bovis IE accounts for 3.8% of all IE episodes in our cohort; it is associated with a high prevalence of colonic tumors, with predominance of benign lesions, and affects patients without preexisting valve disease. It is related to small vegetations and a low rate of in-hospital complications, including systemic embolisms. In-hospital mortality is similar to that of viridans group streptococci.
Objective To estimate the contribution of 9 obesity-related polymorphisms and a genetic predisposition score (GPS) on anthropometric and biochemical variables before and after a weight loss ...intervention program in overweight/obese Spanish adolescents. Study design Overweight/obese adolescents (n = 168; 12-16 years) participating in the EVASYON program were genotyped for 9 obesity-related single nucleotide polymorphisms in the FTO, MC4R, TMEM18, IL6, PPARG, and ADIPQ genes. Results At baseline, the GPS showed a significant association with body mass index-standard deviation score (BMI-SDS) and fat mass. After 3 months of intervention, this GPS also showed a relationship with the variation of both anthropometric measurements. After adjusting for baseline BMI-SDS, subjects with a lower GPS had a greater improvement on metabolic profile, as well as a better response to physical activity, compared with those subjects with a higher GPS. Conclusions The GPS seems to have an important relationship with BMI-SDS and fat mass both at baseline and after a 3-month weight loss lifestyle intervention. Obese and overweight adolescents with a lower GPS have a greater benefit of weight loss after 3 months of a multidisciplinary lifestyle intervention.
The objective of the study is to investigate the impact of anemia (defined as hemoglobin concentration of <12 g/dl in women and 13 g/dl in men) on prognosis and to study the effect of recovery from ...anemia on echocardiographic and clinical parameters in patients with aortic stenosis (AS). This was a prospective study in 315 patients with moderate or severe AS. Patients with anemia received oral iron (ferrous sulfate with mucoproteose, 160 mg iron/day) and erythropoietin, if needed, or intravenous iron, if necessary. The following tests were performed before and after normalization of hemoglobin values: echocardiogram, 6-minute walk test, N-terminal B-type natriuretic peptide, and measures of depression, cognitive impairment, and dependence. Patient mean age was 74 years (SD 9). Mean follow-up was 25 months (SD 8). Anemia prevalence in the overall group was 22% (n = 70). Patients who are anemic had a higher rate of complications at follow-up (mortality, hospital admission, or need for valve procedure; 80% vs 62%, p = 0.009). In total, 89% of patients recovered from anemia, with a mean time to recovery of 4.6 weeks (SD 1.4). Improvements were observed on echocardiographic parameters of peak velocity (4.1 to 3.7 m/s, p = 0.02) and mean gradient (44 to 35 mm Hg, p = 0.02). Performance on the 6-minute walk test improved from 235 to 303 m (p <0.001). Median N-terminal B-type natriuretic peptide value decreased from 612 to 189 pg/dl (p <0.001). In conclusion, patients with AS and anemia have a worse prognosis than those without anemia. Resolution of anemia is associated with improvements in echocardiographic parameters and functional status, suggesting that treatment of iron deficiency is a relevant option in the management of patients with AS, particularly in nonoperable cases.
Background Several new targeted genes and clinical subtypes have been identified since publication in 2008 of the report of the last international consensus meeting on diagnosis and classification of ...epidermolysis bullosa (EB). As a correlate, new clinical manifestations have been seen in several subtypes previously described. Objective We sought to arrive at an updated consensus on the classification of EB subtypes, based on newer data, both clinical and molecular. Results In this latest consensus report, we introduce a new approach to classification (“onion skinning”) that takes into account sequentially the major EB type present (based on identification of the level of skin cleavage), phenotypic characteristics (distribution and severity of disease activity; specific extracutaneous features; other), mode of inheritance, targeted protein and its relative expression in skin, gene involved and type(s) of mutation present, and–when possible–specific mutation(s) and their location(s). Limitations This classification scheme critically takes into account all published data through June 2013. Further modifications are likely in the future, as more is learned about this group of diseases. Conclusion The proposed classification scheme should be of value both to clinicians and researchers, emphasizing both clinical and molecular features of each EB subtype, and has sufficient flexibility incorporated in its structure to permit further modifications in the future.
Summary Background In the TRIBE study, FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab significantly improved progression-free survival of patients with metastatic ...colorectal cancer compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. In this updated analysis, we aimed to provide mature results for overall survival—a secondary endpoint—and report treatment efficacy in RAS and BRAF molecular subgroups. Methods TRIBE was an open-label, multicentre, phase 3 randomised study of patients (aged 18–70 years with Eastern Cooperative Oncology Group ECOG performance status of 2 or less and aged 71–75 years with an ECOG performance status of 0) with unresectable metastatic colorectal cancer who were recruited from 34 Italian oncology units. Patients were randomly assigned (1:1) via a web-based procedure to receive FOLFIRI plus bevacizumab or FOLFOXIRI plus bevacizumab. Bevacizumab was given as a 5 mg/kg intravenous dose. FOLFIRI consisted of a 180 mg/m2 intravenous infusion of irinotecan for 60 min followed by a 200 mg/m2 intravenous infusion of leucovorin for 120 min, a 400 mg/m2 intravenous bolus of fluorouracil, and a 2400 mg/m2 continuous infusion of fluorouracil for 46 h. FOLFOXIRI consisted of a 165 mg/m2 intravenous infusion of irinotecan for 60 min, followed by an 85 mg/m2 intravenous infusion of oxaliplatin given concurrently with 200 mg/m2 leucovorin for 120 min, followed by a 3200 mg/m2 continuous infusion of fluorouracil for 48 h. Tissue samples for RAS and BRAF mutational status analyses were centrally collected. In this updated analysis, we assessed the secondary endpoint of overall survival in the main cohort and treatment efficacy in RAS and BRAF molecular subgroups. All analyses were by intention to treat. TRIBE was concluded on Nov 30, 2014. The trial is registered with ClinicalTrials.gov , number NCT00719797. Findings Between July 17, 2008, and May 31, 2011, 508 patients were randomly assigned. At a median follow-up of 48·1 months (IQR 41·7–55·6), median overall survival was 29·8 months (95% CI 26·0–34·3) in the FOLFOXIRI plus bevacizumab group compared with 25·8 months (22·5–29·1) in the FOLFIRI plus bevacizumab group (hazard ratio HR 0·80, 95% CI 0·65–0·98; p=0·03). Median overall survival was 37·1 months (95% CI 29·7–42·7) in the RAS and BRAF wild-type subgroup compared with 25·6 months (22·4–28·6) in the RAS -mutation-positive subgroup (HR 1·49, 95% CI 1·11–1·99) and 13·4 months (8·2–24·1) in the BRAF -mutation-positive subgroup (HR 2·79, 95% CI 1·75–4·46; likelihood-ratio test p<0·0001). Treatment effect was not significantly different across molecular subgroups (pinteraction =0·52). Interpretation FOLFOXIRI plus bevacizumab is a feasible treatment option for those patients who meet the inclusion criteria of the present study, irrespective of baseline clinical characteristics and RAS or BRAF mutational status. Funding GONO (Gruppo Oncologico del Nord Ovest) Cooperative Group and ARCO Foundation.
