Incidence and risk factors of pain crisis after hematopoietic cell transplantation for sickle cell disease.

ABSTRACT: Vaso-occlusive episodes (VOC) or pain crises are the most common indications for hematopoietic cell transplantation (HCT) for sickle cell disease (SCD). Elimination of pain crisis after HCT is an important patient-centered outcome and may improve understanding of the natural history of pain syndromes in SCD. We examined deidentified records of 763 patients followed-up for a median of 36.7 months (range, 0.3-168.6 months), with 69.6% patient's age <18 years at HCT, 83.3% patient's Karnofsky-Lansky performance score (KPS) ≥90, overall survival 92.9%, event-free survival 72.4%, graft failure (GF) 22.4%, AGVHD 21.4%, CGVHD 27%, and pain crisis 8.65%. On unadjusted logistic regression, increased risk of pain crisis after HCT was observed in patient's aged >10 years at HCT (range, 11-17 years; OR, 9.43; 95% CI, 3.20-27.79; P < .0001), in age ≥18 years (OR, 16.62; 95% CI, 5.85-47.16; P < .0001), in those with history of pain crisis 2 years before HCT (OR, 13.16; 95% CI, 4.08-42.42; P < .0001), alternate donors (haploidentical [OR, 4.80; 95% CI, 2.48-9.31; P < .0001], unrelated matched [OR, 2.71; 95% CI, 1.23-5.97; P = .0132], and mismatched unrelated [OR, 3.19; 95% CI, 1.44-7.05; P = .0041], and those with GF (n = 41 [5.37%]; OR, 7.15; 95% CI, 4.20-12.18; P < .0001). Pain crisis was less frequent with KPS of ≥90 (OR, 0.31; 95% CI, 0.18-0.55; P < .0001). Multivariable logistic regression models confirmed age at HCT, KPS, graft type, donor type, history of VOC 2 years before HCT, and GF as independent predictors of pain crisis after HCT and generated predictive models and nomograms for pain crisis after HCT for SCD, which can support shared decision making.

Pretreatment of Tribulus terrestris L. causes anti-ischemic cardioprotection through MAPK mediated anti-apoptotic pathway in rat.

The aim of the present investigation is the evaluation and elucidation of the mechanisms by which Tribulus terrestris L. methanol extract (TTM) devoid of fruit exhibits protection against cardiac ischemia in in vitro (H9c2 cell line) and in vivo (Wistar rat) model. Tribulus terrestris L. (TT) was used in this study to evaluate the efficacy against cardiac ischemia employing in vitro and in vivo models of myocardial ischemia. H9c2 cells were used for the in vitro induction of ischemia. Male Wistar rats (10 weeks old) weighing 180-220 g were used for the in vivo experiments. ECG and clinically relevant cardiac biomarkers like serum lactate dehydrogenase, serum creatinine kinase, serum creatinine kinase myocardial B fraction, serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase were analysed to evaluate efficacy in the rat. For elucidation of molecular mechanisms of its beneficial activity in vitro, expression of apoptotic markers like Bax, Bad, Bcl-2 and signalling pathways involving mitogen-activated protein kinases like p38α, JNK, and Akt were studied. Tribulus terrestris L. was found effective against cardiac ischemia in the rat which was evident from ECG and various cardiac biomarkers analysis. Tribulus terrestris L. was found to act through the mitogen-activated signalling pathway leading to prevention of apoptosis during ischemic insult. The beneficial effect of Tribulus terrestris L. against cardiac ischemia was seen both in in vitro and in vivo models via its anti-apoptotic potential.

Comparison of Conventional Techniques and Higher Imaging Modalities in the Evaluation of Relation between the Third Molar and Inferior Alveolar Nerve Canal: A Pilot Study.

CONTEXT: Mandibular third molars are the most commonly impacted teeth, and their surgical removal can be associated with inferior alveolar nerve (IAN) injury. To avoid the deleterious complication of nerve injury on patients, a thorough visualization of IAN and its localization are essential. AIMS AND OBJECTIVES: The aims and objectives of this study were to evaluate the efficacy of two conventional localization techniques in determining the relationship of mandibular third molars to IAN and to assess its reliability in comparison with computed tomography (CT). SETTINGS AND DESIGN: Panoramic radiograph (PR) was taken using Kodak 8000C Digital Panoramic and Cephalometric system. Intraoral periapical radiographs (IOPAs) were taken using Kodak 2200 Intraoral X-ray machine. CT scan images were taken using multidetector CT scans. MATERIALS AND METHODS: Two IOPAs (0° and -20° vertical angulation) and PR and CT scan images of thirty mandibular third molars were taken. Two combinations were used (i) a combination of two IOPAs and (ii) a combination of PR and IOPA (-20°). Tube-shift localization technique was applied to both these combinations to derive the relation between third molar and IAN canal as "in contact," "separate," "buccal," "lingual," and "in line with the apex" and the results were compared with CT images. STATISTICAL ANALYSIS: Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using SPSS software version 15.0. RESULTS: The combination of PR and IOPA radiographs showed 14 teeth to be in contact with IAN. This gave a sensitivity of 100%, specificity of 94.1%, PPV of 92.9%, and a NPV of 100% in determining the relation as "in contact" or "separate." 78.3%, 85.7%, 94.7%, and 54.5% were the sensitivity, specificity, PPV, and NPV in localizing it as "buccal," "lingual," or "in line with apex." These results were better than that of the combination of the two IOPAs. CONCLUSIONS: Localization using PR and IOPA could better deduce the relation between IAN and mandibular third molar.

Eugenol, a plant-derived phenolic nutraceutical, protects thiol (SH) group in myocardium from ROS-mediated oxidation under chemotherapeutic stress induced by arsenic trioxide - a in vivo model study.

Arsenic trioxide is an effective chemotherapeutic agent for the treatment of acute promyelocytic leukemia. The clinical usefulness of arsenic trioxide is narrow due to different organ toxicities. It is hypothesized that the generation of reactive oxygen species by arsenic trioxide leads to thiol-based oxidative damage in rat myocardium. In this study, the defensive effect of eugenol on thiol-based oxidative stress was investigated in arsenic trioxide-treated rats. Rats were orally administered with arsenic trioxide (4 mg/kg per day) alone and in combination with eugenol (5 mg/kg per day) for 30 days. Reduction in relative organ weight, total thiol level, protein thiol content, acid-soluble thiol content, thioredoxin activity, and protein content was witnessed in arsenic trioxide-treated rats. Additionally, the total antioxidant activity, tissue GSH level, and GSH/GSSG ratio were considerably diminished. However, the co-treatment of eugenol noticeably sheltered the arsenic trioxide-mediated cardiotoxicity. In conclusion, eugenol is a prospective phenolic compound, of natural origin, for protecting the thiol group in myocardium from oxidative stress by chemotherapeutic compounds.

An audit of febrile neutropenia cases from a rural cancer center in India.

BACKGROUND: Data of febrile neutropenia (FN) from rural cancer centers is sparse. We did a audit of outcome of patients with FN in the period of March 2013-August 2013. The aim was to help us to develop rational antibiotic usage policies. MATERIALS AND METHODS: Retrospective analysis of all consecutive patients presenting with FN. Data regarding demographic profile, tumor type, intent of treatment, chemotherapy regimen, blood culture susceptibility details, use of antibiotics, response to antibiotics and complications of FN were noted. SPSS (Statistical Product and Service Solutions) 16 was used for analysis. RESULTS: 67 patients had FN and there were 91 episodes. The median day of presentation with FN after start of chemotherapy was 10 days. The nadir absolute neutrophil count was 161.5 and nadir platelet count 1,00,000. The median multinational association for supportive care in cancer (MASCC) Score was 24. In accordance with MASCC there were 27 high risk FN and 64 low risk FN episodes. On multivariate analysis using logistic regression MASCC score strata was the only significant variable that predicted failure to 1st line antibiotics (P = 0.03) and mortality (P = 0.01). Nine patients (9.9%) had positive isolates on blood cultures. The blood culture isolates were predominantly Gram negative (66.7%). CONCLUSION: The importance of developing local guidelines for rational antibiotic usage is highlighted.