Predicting spontaneous early neurological recovery after acute ischemic stroke

We assessed predictors of spontaneous early neurological recovery after acute ischemic stroke by means of multivariate analysis in a cohort of 1,473 consecutive patients treated at one academic center. At hospital discharge, spontaneous neurological improvement or good outcome was defined as grades 0-2 of the Rankin scale, and poor outcome (no improvement or in-hospital death) as grades 3-5. Spontaneous recovery of neurological deficit at the time of discharge from the hospital was observed in 16% of patients with cerebral infarction (n = 238). Dysarthria-clumsy hand syndrome improved in 44% of patients and was the only variable significantly associated with in-hospital functional recovery in three logistic regression models that in addition to lacunar syndromes, included demographic variables, cardiovascular risk factors, and clinical variables [odds ratio (OR) 2.56], neuroimaging findings (OR 2.48), and outcome data (OR 2.39), respectively. Clinical factors related to severity of infarction available at stroke onset have a predominant influence upon in-hospital outcome and may help clinicians to assess prognosis more accurately. Our work gives a contribution into prognostic factors after acute ischemic stroke. With regard to patterns of stroke, dysarthria-clumsy hand syndrome was a significant predictor of spontaneous in-hospital recovery in ischemic stroke patients.     

Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia.

PURPOSE: To investigate whether allogeneic stem-cell transplantation (allo-SCT) may overcome the negative impact of unmutated VH genes in the outcome of patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: We analyzed the outcome of patients who underwent SCT according to their VH mutational status. RESULTS: Thirty-four patients (14 allo-SCT and 20 autologous SCT [auto-SCT]) presented unmutated VH genes and 16 patients presented mutated VH genes (nine allo-SCT and seven auto-SCT). Tumoral burden pre-SCT was significantly higher in the allo-SCT patients independent of the VH mutational status. The risk of relapse was significantly higher after auto-SCT (5-year risk, 61%; 95% CI, 44% to 84%) than after allo-SCT (5-year risk 12%, 95% CI, 3% to 44%; P < .05). In the unmutated group, 13 of 20 auto-SCT and two of 14 allo-SCT patients experienced disease progression, with a risk of relapse at 5 years of 66% (95% CI, 48% to 93%) v 17% (95% CI, 5% to 60%), respectively (P = .01). CONCLUSION: These results show that allo-SCT may overcome the unfavorable effect of unmutated VH genes in patients with CLL.     

Follicular lymphoma international prognostic index

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs 120 g/L), number of nodal areas (> 4 vs 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk ( 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.      

Identification of somatic gene mutations in penile squamous cell carcinoma

There is a lack of studies on somatic gene mutations and cell signaling driving penile carcinogenesis. Our objective was to analyze somatic mutations in genes downstream of EGFR in penile squamous cell carcinomas, especially the mTOR and RAS/MAPK pathways. We retrospectively analyzed somatic mutations in 10 in situ and 65 invasive penile squamous cell carcinomas by using Sequenom's Mass Spectrometry iPlex Technology and Oncocarta v1.0 Panel. The DNA was extracted from FFPE blocks and we identified somatic missense mutations in three in situ tumors and in 19 invasive tumors, mostly in PIK3CA, KRAS, HRAS, NRAS, and PDGFA genes. Somatic mutations in the PIK3CA gene or RAS family genes were neither associated with tumor grade, stage or outcome, and were equally often identified in hrHPV positive and in hrHPV negative tumors that showed no p53 expression. Mutations in PIK3CA, KRAS, and HRAS are frequent in penile squamous cell carcinoma and likely play a role in the development of p53‐negative tumors. Although the presence of these mutations does not seem to correlate with tumoral behavior or outcome, they could be biomarkers of treatment failure with anti‐EGFR mAb in patients with penile squamous cell carcinoma. © 2015 Wiley Periodicals, Inc.     

Risk factors for pneumonia in the intubated patient

The information gathered here helps to explain why risk factors in the development of VAP vary from series to series. It also explains why different investigators have found opposite effects when evaluating the antibiotics. Antibiotic therapy has a bimodal effect in the development of VAP. Antibiotics protect against pneumonia development within the first days of MV, especially against types caused by endogenous flora, but they are responsible for selection of a set of resistant pathogens that are associated with significant attributable mortality, such as P aeruginosa and MRSA. These observations suggest that risk factors vary depending on the exposure to risk (ie, length of stay or MV). This variable should be considered when stratifying patients for risk factor analysis and also in the design of clinical trials for VAP prophylaxis.     

White blood cell count is associated with carotid and femoral atherosclerosis

ObjectiveRelationship of high sensitivity C-reactive protein (hsCRP) with Metabolic Syndrome (MetS) is well documented in many populations, but comprehensive data is lacking in Indian population. Thus, we set out to investigate the association of hsCRP levels with MetS and its features and the effect of obesity and insulin resistance on this association in urban Indians.MethodsThis is a cross-sectional study that included 9517 subjects comprising 4066 subjects with MetS. MetS was defined according to the modified National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP III) criteria for Asians.ResultsMedian levels of hsCRP were considerably higher in individuals with MetS with higher levels in women compared to men. Among the features of MetS, waist circumference was most strongly correlated with hsCRP levels (r = 0.28) and contributed maximally (β = 0.025 mg/l ln hsCRP, P = 7.4 × 10^?147). Subjects with high risk hsCRP levels (>3 mg/l) were at high risk of MetS (OR (95% CI) = 1.65(1.41–1.92), P = 1.7 × 10^?10). Risk of MetS increased in a dose dependent manner from low risk to high risk hsCRP category with increase in BMI and HOMA-IR.ConclusionsOur findings suggest that hsCRP predicts the risk of MetS, independent of obesity and insulin resistance, and therefore, can be a valuable tool to aid the identification of individuals at risk of MetS. The study provides a lead for future investigation for effects of hsCRP, obesity, and insulin resistance on MetS in this population.     

A new genetic abnormality leading to TP53 gene deletion in chronic lymphocytic leukaemia

The analysis of chromosomal abnormalities provides significant prognostic information in patients with chronic lymphocytic leukaemia (CLL), a disease with a highly heterogeneous clinical course. Chromosomal abnormalities commonly found are trisomy 12, del(13)(q14), del(11)(q22-23), del(17)(p13) and del(6)(q21). Translocations are present in some patients and affect regions recurrently involved in CLL. This report describes the clinical and pathological characteristics of four CLL patients showing a new recurrent chromosomal abnormality dic(8;17)(p11;p11), that implied loss of the TP53 gene in all cases. In addition, TP53 gene was mutated in three out of four patients. Mechanically, Low Copy Repeats (LCR) in 17p12 and 8p11 may explain the origin of the translocation by non-allelic homologous recombination (NAHR). Isolated dic(8;17)(p11;p11) in patients with mutated IGHV genes status may not have the same prognostic impact as other mutations or deletions affecting the TP53 gene. Larger series are needed to better evaluate the clinical impact of this chromosomal aberration during the course of the disease.     

Preliminary prospective explanatory observation on the impact of 3-month steroid therapy on the objective measures of sleep-disordered breathing

Background  

Excess endogenous steroids are a risk factor for obstructive sleep apnea (OSA). The role of exogenous steroids in this setup is not known. In this study, we prospectively looked at the consequences of a 3-month steroid treatment on the objective measures of sleep-disordered breathing.