Elevated tricuspid regurgitant jet velocity,reduced forced expiratory volume in 1 second,and mortality in adults with sickle cell disease

Cardiopulmonary disease is the leading cause of mortality in adults with sickle cell disease (SCD). Elevated tricuspid regurgitant jet velocity (TRJV) and reduced forced expiratory volume in 1 second (FEV₁) %predicted are associated with early mortality in SCD; however their relationship and combined effect on survival is unknown. We investigated the relationship between TRJV and FEV₁ %predicted, and their combined effect on mortality, in a retrospective cohort of 189 adults with SCD who underwent both pulmonary function testing and echocardiography. Nineteen (9.9%) of 189 patients died over a median follow‐up of 1.4 years; cardiopulmonary disease was the major cause of death in 52.6%. FEV₁%predicted was negatively associated with TRJV (Spearman rho, ?0.34, P < 0.001). Individuals with FEV₁%predicted ≤70% were more likely to have an elevated TRJV ≥2.5 m/second, compared to those with FEV₁%predicted >70% [45.8% versus 17.1%; odds ratio (OR) 4.1 (95% Confidence interval ([CI] 2.1–8.0); P = 0.001]. In a multivariable cox regression model, the combination of TRJV ≥2.5 m/second and FEV₁%predicted ≤70% predicted earlier mortality [hazard ratio (HR) 4.97 (95% CI 1.30‐18.91; P = 0.019)] after adjusting for age, sex, and nephropathy. Both FEV₁ %predicted ≤70% and TRJV ≥2.5 m/second were independently associated with nephropathy [OR 4.48 (95% CI 1.51–13.31); P = 0.004] and [OR 3.27 (95% CI 1.19–9.00); P = 0.017], respectively. In conclusion, pulmonary and cardiac impairment are associated with, and contribute to mortality in SCD. Therapies aimed at improving reduced FEV₁%predicted and elevated TRJV could improve survival in patients with SCD. Am. J. Hematol. 92:125–130, 2017. © 2016 Wiley Periodicals, Inc.     

Health-related quality of life and persistent symptoms in relation to (R-)CHOP14, (R-)CHOP21, and other therapies among patients with diffuse large B-cell lymphoma: results of the population-based PHAROS-registry

The increasing number of longer-living patients with diffuse large B-cell lymphoma (DLBCL) and serious side effects of treatment urged us to study the health-related quality of life (HRQoL) and persistent (treatment-related) symptoms in unselected patients after different treatment modalities and compare HRQoL of patients with a normative population. The population-based Eindhoven Cancer Registry was used to select all patients diagnosed with DLBCL from 2004 to 2010. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) was completed twice, with a 1-year interval. Detailed data on treatment were extracted from the Population-based HAematological Registry for Observational Studies. Two hundred fifty-six patients responded (84 %, T1). Compared to patients treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days ((R-)CHOP21), those who underwent (R-)CHOP14 more often reported tingling in the hands and feet (27 vs 42 %, p?=?0.02) and fatigue (35 vs 46 %, p?=?0.03) and reported a lower global health status/HRQoL. Mean HRQoL was statistically and clinically relevantly lower among DLBCL patients compared to a normative population (p?DLBCL patients is needed and may help to avoid lasting negative influence on their HRQoL.     

Prediction of liver histological lesions with biochemical markers in patients with chronic hepatitis B

BACKGROUND AIMS: Liver biopsy is the gold standard for assessing hepatitis B virus (HBV)-related histology. The aim was to determine the diagnostic utility of noninvasive serum markers in patients with chronic hepatitis B. METHODS: The aminotransferases and indices including alpha(2)-macroglobulin, apolipoprotein A1, haptoglobin, gamma-glutamyl-transpeptidase (GGT), and total bilirubin (Fibrotest), and ALT (Actitest) were compared with liver histology. The primary outcomes were A2-A3 activity and F2-F4 fibrosis (METAVIR). RESULTS: Two hundred and nine patients were included. Forty-one patients (20%) had A2-A3 activity and 61 (29%) had F2-F4 fibrosis. AST and GGT (P<0.001) were independently associated with A2-A3 activity. AST, ALT, and Actitest accurately predicted activity ((areas under receiver operating characteristic (ROC) curves (AUROC), 0.81-0.82+/-0.04)); an AST or ALT< or =30IU/l excluded significant activity with 96% certainty. Fibrotest accurately predicted F2-F4 fibrosis (AUROC, 0.78+/-0.04). Fibrotest scores (range, 0-1.0) < or =0.20 and >0.80 had negative and positive predictive values of 92%, respectively. Restricting biopsy to patients with intermediate scores (>0.20 and < or =0.80) may prevent liver biopsies in 46% of patients while maintaining 92% accuracy. CONCLUSIONS: The aminotransferases and an index including five biochemical markers are accurate noninvasive markers of HBV-related activity and fibrosis, respectively.     

The Impact of Reconstructive Procedures Following Bariatric Surgery on Patient Well-being and Quality of Life

Background

Massive weight loss following bariatric surgery may lead to an excess of lax, overstretched skin, causing physical discomfort which may affect the patient’s quality of life. Whereas the functional and aesthetic deformity is an expected result of massive weight loss, the role of the plastic surgeon in the multidisciplinary approach of the morbidly obese is still unclear. The purpose of the current study is to evaluate the results of reconstructive surgery following weight loss surgery, focusing on the impact on the physical and psycho-social well-being and quality of life of the patients.

Methods

Out of a group of 465 patients, 61 patients underwent reconstructive surgery following weight loss surgery. In 43 respondents, the quality of life after reconstructive surgery was measured by the Obesity Psychological State Questionnaire. Patient satisfaction was evaluated.

Results

Reconstructive surgery resulted in a significant improvement in quality of life in patients at a mean interval of 42 months between weight loss and reconstructive surgery. The most frequent procedures were abdominoplasty and breast reconstruction. The relative high complication rate of 27.9% was of no influence on quality of life and the majority of the patients (67%) were satisfied with reconstructive surgery.

Conclusions

This study shows that reconstructive surgery following weight loss after bariatric surgery results in a significant improvement in overall quality of life. Reconstructive surgery should be incorporated in the multidisciplinary care programme following weight loss surgery in the morbidly obese patient.     

Timing of cholecystectomy after endoscopic sphincterotomy for common bile duct stones

Background  According to the literature, the conversion rate for laparoscopic cholecystectomy (LC) after endoscopic sphincterotomy (ES) for cholecystodocholithiasis reaches 20%, at least when LC is performed 6 to 8 weeks afterward. It is hypothesized that early planned LC after ES prevents recurrent biliary complications and reduces operative morbidity and hospital stay. Methods  All consecutive patients who underwent LC after ES between 2001 and 2004 were retrospectively evaluated. Recurrent biliary complications during the waiting time for LC, conversion rate, postoperative complications, and hospital stay were documented. Results  This study analyzed 167 consecutive patients (59 men) with a median age of 54 years. The median interval between ES and LC was 7 weeks (range, 1–49 weeks). During the waiting time for LC, 33 patients (20%) had recurrent biliary complications including cholecystitis (n = 18, 11%), recurrent choledocholithiasis (n = 9, 5%), cholangitis (n = 4, 2%), and biliary pancreatitis (n = 2, 1%). Of these 33 patients, 15 underwent a second endoscopic retrograde cholangiography (ERC). The median time between ES and the development of recurrent complications was 22 days (range, 3–225 days). Most of the biliary complications (76%) occurred more than 1 week after ES. Conversion to open cholecystectomy occurred for 7 of 33 patients with recurrent complications during the waiting period, compared with 13 of 134 patients with an uncomplicated waiting period (p = 0.14). This concurred with doubled postoperative morbidity (24% vs 11%; p = 0.09) and a longer hospital stay (median, 4 vs 2 days; p < 0.001). Conclusion  In this retrospective analysis, 20% of all patients had recurrent biliary complications during the waiting period for cholecystectomy after ES. These recurrent complications were associated with a significantly longer hospital stay. Cholecystectomy within 1 week after ES may prevent recurrent biliary complications in the majority of cases and reduce the postoperative hospital stay. The abstract of this work was presented at the Society of American Gastroendoscopic Suregons (SAGES) 2007 annual meeting in Las Vegas, Nevada, USA.     

Effect of a collective educational program for patients with rheumatoid arthritis: a prospective 12-month randomized controlled trial

OBJECTIVE: To evaluate the effect on health and functional status of an 8-week group-education program for rheumatoid arthritis (RA) in addition to usual medical care. METHODS: All consecutive inpatients and outpatients with RA (ACR criteria) were asked to participate in this randomized, prospective, controlled trial. The educational intervention consisted of 8 weekly ambulatory sessions, each lasting 6 hours. Followup was undertaken after 1 year. The primary criterion for judging effectiveness was the Health Assessment Questionnaire (HAQ) score; secondary criteria consisted of coping, medical knowledge, patient global satisfaction, and quality of life scores before the intervention and after 1 year. RESULTS: We asked 1242 inpatients and outpatients to participate in the study: 208 (16.75%) agreed (104 in each group). At baseline, there was no statistically significant difference between the 2 groups. After 1 year, no statistically significant difference was observed between the 2 groups in change in HAQ score: -0.04 +/- 0.46 (education group) vs -0.06 +/- 0.47 (control group) (p = 0.79). Statistically significant differences were found in 3 domains: patient coping (-1.22 +/- 5.55 vs -0.22 +/- 3.81; p = 0.03), knowledge (3.42 +/- 4.73 vs 0.73 +/- 3.78; p < 0.0001), and satisfaction (10.07 +/- 11.70 vs 5.72 +/- 13.77; p = 0.02), all of which were better for the group attending the education sessions. CONCLUSION: Despite improvements in patient coping, knowledge, and satisfaction, the education program was not found to be effective at 1 year. There may have been methodological problems relating to the sensitivity of questionnaires and patient selection, and tailored educational interventions should be considered.     

Which variables best predict change in rheumatoid arthritis therapy in daily clinical practice?

OBJECTIVE:To determine in clinical practice which clinical status variables for rheumatoid arthritis (RA) are most closely associated with a change in disease modifying antirheumatic drug (DMARD) therapy. METHODS: A prospective monocenter study was conducted in 204 consecutive patients with RA. Rheumatologists recorded patient characteristics, treatments, and disease activity data [tender and swollen joint count (28), morning stiffness, visual analog scale (VAS) for pain (0-100 mm), patient global assessment and physician global assessment, Westergren erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)]. The rheumatologists decided whether or not to initiate or change treatment but were not informed that their decisions were part of the investigation. Logistic regression analysis was performed to evaluate which study variables best predict change in therapy. ROC analysis was used to obtain the cutoff value of the different composite indices (DAS28(ESR), DAS28(CRP), SDAI) for treatment change, as well as sensitivity and specificity. RESULTS: The variables that were predictive for a change in treatment were (in descending order): swollen joint count, morning stiffness, CRP, tender joint count, and patient global assessment. Composite index values associated with a decision to modify DMARD therapy were: DAS28(ESR) 4.2 (sensitivity 87%, specificity 70%); DAS28(CRP) 3.6 (sensitivity 86%, specificity 78%); and SDAI 15 (sensitivity 90%, specificity 86%). The discriminative ability of SDAI was better than that of DAS28(CRP) or DAS28(ESR). CONCLUSION: In our study, swollen joint count was the variable with the greatest weight, which explains the observed better performance of SDAI.     

Laparoscopic cholecystectomy for acute cholecystitis should be performed by a laparoscopic surgeon

Background  

The aim of this study was to evaluate the impact of surgical subspecialization on the outcome of laparoscopic cholecystectomy.     

Screening and kinetic studies of catharanthine and ajmalicine accumulation and their correlation with growth biomass in Catharanthus roseus hairy roots

Context Catharanthus roseus (L.) G. Don (Apocynaceae) is still one of the most important sources of terpene indole alkaloids including anticancer and hypertensive drugs as vincristine and vinblastine. These final compounds have complex pathway and many enzymes are involved in their biosynthesis. Indeed, ajmalicine and catharanthine are important precursors their increase can lead to enhance levels of molecules of interest.

Objective This study aims at selecting the highest yield of hairy root line(s) and at identifying best times for further treatments. We study kinetics growth and alkaloids (ajmalicine and catharanthine) accumulation of three selected hairy root lines during the culture cycle in order to determine the relationship between biomass production and alkaloids accumulation.

Materials and methods Comparative analysis has been carried out on three selected lines of Catharanthus roseus hairy roots (LP10, LP21 and L54) for their kinetics of growth and the accumulation of ajamalicine and catharanthine, throughout a 35-day culture cycle. The methanolic extract for each line in different times during culture cycle is analyzed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).

Results Maximum accumulation of the alkaloids is recorded for LP10 line in which the peak of ajmalicine and catharanthine accumulation reached to 3.8 and 4.3?mg/g dry weight (DW), respectively. This increase coincides with an exponential growth phase.

Discussion and conclusion Our results suggest that the evolution of accumulation of ajmalicine and catharanthine are positively correlated with the development of the biomass growth. Significantly, for LP10 line the most promising line to continue optimizing the production of TIAs. Additionally, the end of exponential phase remains the best period for elicitor stimuli.     

Intrasinusoidal cytotoxic CD8+ T cells in nodular regenerative hyperplasia of the liver

Diffuse nodular regenerative hyperplasia (NRH) of the liver is an acquired architectural disturbance that can lead to portal hypertension. Although frequently associated with autoimmune or hematologic malignancies, its exact pathogenesis remains largely unknown. We observed CD8+ cytotoxic T cells in the liver sinusoids of 14 of 44 NRH patients and explored possible relationships between these lymphocytes and vascular damage. The immunophenotype of intrahepatic lymphocytes was determined using immunohistochemical analysis and endothelial injury using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method for apoptosis combined with endothelial cell labeling. Controls for the quantitative analysis of liver-infiltrating lymphocytes consisted of patients with chronic hepatitis C or normal liver (n = 13 and n = 6, respectively). Liver specimens from the 14 patients dislayed intrasinusoidal infiltrate composed of CD3+ and CD8+ lymphocytes, located near atrophic liver cell plates. Significantly more granzyme B+ and CD57+ lymphocytes were observed in NRH than chronic hepatitis C samples with quantitatively similar CD8+ infiltrates. Double-labeling revealed apoptotic endothelial sinusoidal cells in CD8+ T-cell-infiltrated areas in all NRH samples but never in chronic hepatitis C or normal livers. T-cell receptor rearrangement or immunoscope analysis suggested liver-specific polyclonal or oligoclonal T-cell expansions. Clinical and biological characteristics of the 14 patients were similar to those observed in the 30 patients with NRH devoid of lymphocytic infiltration. We report here that CD8+ cytotoxic T cells infiltrated the liver sinusoids of a high percentage (32%) of NRH patients and suggest that some NRH cases might result from chronic, cytotoxic CD8+ T-lymphocyte targeting of sinusoidal endothelial cells.