Photobiomodulation therapy on expression of HSP70 protein and tissue repair in experimental acute Achilles tendinitis

Lasers in Medical Science - The aim of the present study was to investigate the effects of photobiomodulation (PBM) therapy on the expression of heat shock protein 70 (HSP70) and tissue repair in...     

Early cardiotoxicity of the CHOP regimen in aggressive non-Hodgkin's lymphoma.

BACKGROUND: To determine the incidence of early cardiotoxicity induced by the CHOP regimen in patients with aggressive non-Hodgkin's lymphoma (NHL) and to identify associated risk factors. PATIENTS AND METHODS: A retrospective analysis included 135 consecutive patients who had been treated with the CHOP (cyclophosphamide, doxorubicin, vincristin, prednisone) regimen as first-line therapy between 1994 and 2000. The cardiac evaluation was based on a determination of the resting left ventricular ejection function (LVEF) by gated blood-pool imaging. Cardiotoxicity was defined as a significant decrease in LVEF or clinical evidence of congestive heart failure (CHF). RESULTS: Twenty-seven (20%) patients developed a cardiac event within 1 year of treatment. Among these, 14 patients had clinical signs of CHF. Three patients died suddenly from presumed cardiac causes. In multivariate analysis, a cumulative dose of doxorubicin >200 mg/m(2) [odds ratio (OR) = 4.2, P = 0.005)] and age over 50 years (OR = 2.9, P = 0.03) appeared to be significant risk factors. CONCLUSION: Early clinical and subclinical cardiotoxicity was frequent in patients receiving the CHOP regimen. The threshold of the cumulative dose of doxorubicin appeared to be low: at doses >200 mg/m(2), 27% of patients had cardiac events. Elderly patients appeared to be at higher risk. The development of cardioprotective strategies or alternative treatments are mandatory for aggressive NHL patients.     

Atypical antipsychotics: from potassium channels to torsade de pointes and sudden death.

Syncope and sudden death are features of schizophrenia that can be attributed to ischaemic heart disease, the use of antipsychotics (because of proarrhythmia or other reasons such as pharyngeal dyskinesia) or the psychiatric disease itself. Cases have been described with most antipsychotics and have led to the withdrawal, temporary suspension from the market or restricted use of antipsychotics, such as sultopride, droperidol, sertindole or thioridazine. Reviewing the available data shows that all antipsychotics tested affect the cardiac potassium channel, with the concentration that produces 50% inhibition (IC50) ranging from 1 nmol/L (haloperidol) to 6 micromol/L (olanzapine). Experimental in vitro or in vivo electrophysiological studies have shown a dose-dependent increase in the duration of the action potential with various degrees of indicators of serious arrhythmogenicity. However, this does not always translate clinically into an increased duration of the QT interval or increased risk of torsade de pointes or sudden death in clinical trials or pharmacoepidemiological studies. In turn, QT prolongation in clinical trials does not always translate to an increased risk of torsade de pointes or sudden death. The reasons for these apparent discrepancies are unclear and could be related to insufficiently powered field studies, low plasma and tissue drug concentrations with reference to in vitro data or drug effects on other receptors or ion channels that have a protective effect. Alternatively, risks that were not apparent from preclinical or clinical data could be related to the use of the drug in high-risk patients, metabolic interactions or other factors that would only be encountered in large postmarketing populations. The assessment of cardiovascular safety, both preclinical and during premarketing clinical trials, needs to be supported by appropriately powered pharmacoepidemiology studies.     

Impact of G-CSF Prophylaxis on Chemotherapy Dose-Intensity,Link Between Dose-Intensity and Survival in Patients with Metastatic Pancreatic Adenocarcinoma

BackgroundIn metastatic pancreatic adenocarcinoma, few data are available on the use of granulocyte-colony stimulating factor (G-CSF) prophylaxis and its impact on dose-intensity (DI), or the link between DI and progression-free survival (PFS). This study assessed the impact of G-CSF prophylaxis on the DI received by patients and the relationship between full DI and PFS according to chemotherapy regimens.Patients and MethodsPatients from three first-line randomized phase II clinical trials were included in this retrospective cohort. G-CSF prophylaxis groups were identified and balanced according to baseline characteristics using a propensity score. Patients were classified into 2 treatment groups (FOLFIRINOX vs FOLFIRI/nab-paclitaxel (NAB)). DI was a binary variable (full/reduced). Adverse events were defined using NCI-CTCAE v4.0.ResultsOf the 498 patients, 154 (31%) were in “prophylaxis” group; 179 (36%) were treated by FOLFIRINOX and 319 (64%) by FOLFIRI/NAB. In FOLFIRINOX group, G-CSF prophylaxis was significantly associated with a higher rate of full DI (OR, 5.07; 95% CI, 1.52-16.90; P < .01) while in FOLFIRI/NAB group, it was significantly associated with a lower rate of full DI (OR, 0.23; 95% CI, 0.06-0.83; P = .03). Full DI was associated with a non-significant increase in PFS (FOLFIRINOX group: HR 0.83; 95% CI, 0.59-1.16; P = .27; FOLFIRI/NAB group: HR 0.84; 95% CI, 0.63-1.11; P = .22).ConclusionGranulocyte-colony stimulating factor prophylaxis was associated with a higher rate of full DI with FOLFIRINOX. Full DI was associated with a non-significant increase in PFS. These results need to be confirmed prospectively.     

One Health surveillance of West Nile and Usutu viruses: a repeated cross-sectional study exploring seroprevalence and endemicity in Southern France, 2016 to 2020

BackgroundWest Nile virus (WNV) and Usutu virus (USUV), two closely related flaviviruses, mainly follow an enzootic cycle involving mosquitoes and birds, but also infect humans and other mammals. Since 2010, their epidemiological situation may have shifted from irregular epidemics to endemicity in several European regions; this requires confirmation, as it could have implications for risk assessment and surveillance strategies.AimTo explore the seroprevalence in animals and humans and potential endemicity of WNV and USUV in Southern France, given a long history of WNV outbreaks and the only severe human USUV case in France in this region.MethodsWe evaluated the prevalence of WNV and USUV in a repeated cross-sectional study by serological and molecular analyses of human, dog, horse, bird and mosquito samples in the Camargue area, including the city of Montpellier, between 2016 and 2020.ResultsWe observed the active transmission of both viruses and higher USUV prevalence in humans, dogs, birds and mosquitoes, while WNV prevalence was higher in horses. In 500 human samples, 15 were positive for USUV and 6 for WNV. Genetic data showed that the same lineages, WNV lineage 1a and USUV lineage Africa 3, were found in mosquitoes in 2015, 2018 and 2020.ConclusionThese findings support existing literature suggesting endemisation in the study region and contribute to a better understanding of USUV and WNV circulation in Southern France. Our study underlines the importance of a One Health approach for the surveillance of these viruses.     

Cycle of the seminiferous epithelium of the bat Molossus molossus,characterized by tubular morphology and acrosomal development

ObjectiveTo describe the seminiferous epithelium cycle (SEC) by tubular morphology method, and the acrosomal development of individualizing spermatids, and to explore the distinction of the stages between two generations of spermatids.MethodsTesticular fragments were fixed in Karnovsky, embedded in glycol methacrylate and examined under light microscopy and transmission electron microscopy. Sections in 3 μm thickness were stained with toluidine blue for the characterization of the stages of the SEC by the tubular morphology method, or submitted to the PAS reaction for the visualization of the acrosomal formation. Additional details on the acrosomal formation were observed under transmission electron microscopy.ResultsThrough the eight stages described by tubular morphology method, 10 steps of acrosomal formation were observed in the spermatid development, called acrosomal steps. As the spermatids were produced in stage V of the tubular morphology method, it was at this stage from which began the steps of acrosomal development.ConclusionsWe propose association of the acrosomal steps for the first time, with the different stages by tubular morphology method. This method presents an alternative to the existent Methods, allowing interspecific comparisons of the SEC, not only among different species of bats, but also among the other mammals.     

Cholera Vaccination in Urban Haiti

Successful and sustained efforts have been made to curtail the major cholera epidemic that occurred in Haiti in 2010 with the promotion of hygiene and sanitation measures, training of health personnel and establishment of treatment centers nationwide. Oral cholera vaccine (OCV) was introduced by the Haitian Ministry of Health as a pilot project in urban and rural areas. This paper reports the successful OCV pilot project led by GHESKIO Centers in the urban slums of Port-au-Prince where 52,357 persons received dose 1 and 90.8% received dose 2; estimated coverage of the at-risk community was 75%. This pilot study demonstrated the effort, community mobilization, and organizational capacity necessary to achieve these results in a challenging setting. The OCV intervention paved the way for the recent launching of a national cholera vaccination program integrated in a long-term ambitious and comprehensive plan to address Haiti''s critical need in water security and sanitation.     

Hip cortical thickness assessment in postmenopausal women with osteoporosis and strontium ranelate effect on hip geometry

The aims of this study were to assess the relationship between hip geometry and the 5-yr risk of hip fractures in postmenopausal osteoporotic women and the effects of strontium ranelate on these parameters. Using the 5-yr data of a randomized placebo-controlled trial of strontium ranelate (Treatment of Peripheral Osteoporosis Study [TROPOS]), we reanalyzed the hip dual-energy X-ray absorptiometry scans to determine the role of hip geometry in the risk of hip fractures (placebo group, n=636) and to analyze the effects of strontium ranelate (n=483). The outcomes included the hip structure analysis (HSA) parameters: cross-sectional area (CSA), section modulus, cortical thickness, and buckling ratio, measured at femoral neck, intertrochanteric (IT) region, and proximal shaft. The geometric parameters associated with an increased risk of hip fracture over 5yr were IT CSA and femoral shaft cortical thickness independent of age and total-hip bone mineral density (BMD). Using Bonferroni adjustment, IT cortical thickness was associated with the risk of hip fracture. Over 5yr, significant decreases in some femoral dimensions of the placebo group contrast with significant increases in strontium ranelate group after adjustment for age and BMD. Using Bonferroni adjustment, differences between placebo and strontium ranelate groups were no longer significant after adjustment on 5-yr BMD changes. Some HSA parameters have predictive value for hip fracture risk in postmenopausal osteoporotic women. Strontium ranelate improves some HSA parameters, through the BMD increase.     

Identification of rheumatoid arthritis patients with vertebral fractures using bone mineral density and trabecular bone score

The aim of this study was to test bone mineral density (BMD), trabecular bone score (TBS), and their combination, for detection of rheumatoid arthritis (RA) patients with vertebral fractures (VFs). One hundred eighty-five women aged 56.0 ± 13.5 yr, with RA since 15.5 ± 9.9 yr were studied. Lumbar spine, total hip, and femoral neck BMD were assessed by dual-energy X-ray absorptiometry (DXA). TBS was calculated from anteroposterior image of lumbar spine BMD. VFs from T4 to L4 were evaluated using Vertebral Fracture Assessment software on DXA device. The proportions of patients with VF and T-scores ≤-2.5 were only 24.2%, 21.2%, and 33.3% at lumbar spine, total hip, and femoral neck, respectively. T-scores were significantly lower in patients with VF than in patients without VF, the largest difference being observed at femoral neck (p=0.0001). TBS was significantly lower in patients with VF vs without VF (p=0.0001). The areas under the curves were 0.621, 0.704, 0.703, 0.719, and 0.727 for lumbar spine BMD, TBS, lumbar spine BMD+TBS, total hip BMD, and femoral neck BMD, respectively. The threshold of 1.173 for TBS had the best sensitivity (63%) and specificity (74%). TBS measured at the lumbar spine has a better discrimination value than lumbar spine BMD, and similar to femoral neck BMD, for prediction of presence of VF in patients with RA. In RA subjects with osteopenia, the proportion of patients with VF was higher in the lowest tertile of TBS when compared with the highest tertile. In this population, at low risk according to BMD, TBS could help to detect patients with VF.     

The evolution of the hypervariable region-1 of hepatitis C virus may predict liver fibrosis outcome after renal transplantation

The aim of our study was to assess hepatitis C virus (HCV) evolution and long term liver histology outcome in anti-HCV(+)/RNA(+) renal-transplant (RT) patients. Fifty-five anti-HCV(+)/RNA(+) RT patients underwent every 3-4 years after transplantation liver biopsies (LB) (2 LBs, N = 55; 3 LBs, N = 44; 4 LBs, N = 10). The hypervariable region (HVR)-1 of the HCV genome from all patients was characterized over time. Overall, the rate of liver fibrosis progression was 0.07 +/- 0.03 Metavir units/year. We identified three groups of patients: those in whom liver fibrosis remained stable (group I, N = 21), those with progressing liver fibrosis (group II, N = 21), and those with a regression in liver fibrosis (group III, N = 13). Initial fibrosis stage and high diversification of the HVR-1 of HCV genome between the transplantation and the first liver biopsy were independent factors associated with liver fibrosis regression. In conclusion, in this study, after renal transplantation, HCV infection is not harmful upon liver histology in more than fifty percent of the patients. The diversification of the HVR-1 of the HCV genome might be used to predict liver fibrosis outcome.