Impact of high MELD scores on CMV viremia following liver transplantation.

INTRODUCTION: Advanced liver disease or cirrhosis is associated with an increased risk of infections; however, the impact of high pretransplant model for end-stage liver disease (MELD) score on cytomegalovirus (CMV) viremia after liver transplantation is unknown. METHODS: This single-center, retrospective, cohort study evaluated CMV high-risk (CMV immunoglobulin G D+/R-) liver transplant recipients who received valganciclovir prophylaxis for 3 months between 2009 and 2019. Patients were stratified by pretransplant MELD score of <35 (low MELD) and ≥35 (high MELD). The primary outcome was 12-month CMV viremia, and secondary outcomes included CMV resistance and tissue invasive disease, mortality, biopsy-proven acute rejection (BPAR), leukopenia, and thrombocytopenia. Multivariable Cox proportional-hazards modeling was used to assess the association of MELD score with the time to CMV viremia. RESULTS: There were 162 and 79 patients in the low and high MELD groups, respectively. Pretransplant MELD score ≥35 was associated with an increased risk of CMV viremia (hazard ratio [HR] 1.73; confidence interval 1.06-2.82, p = .03). CMV viremia occurred at 162 ± 61 days in the low MELD group and 139 ± 62 days in the high MELD group. Although BPAR occurred early at 30 days (13-59) in the low-MELD group and at 18 days (11-66) in the high-MELD group (p = .56), BPAR was not associated with an increased risk of CMV viremia (HR 1.55 [0.93-2.60], p = .1). DISCUSSION: MELD scores ≥35 were associated with an increased hazards of CMV viremia. In liver transplant recipients with MELD scores ≥35 who are CMV high-risk, additional CMV intervention may be warranted.

The Impact of Treatment Delay on Hepatitis C Liver Transplant Outcomes.

Background: Direct-acting antivirals for the treatment of hepatitis C virus (HCV) have improved outcomes in liver transplant recipients (LTRs). However, the timing of HCV treatment and approach to treating rejection have not been well described. Additionally, pharmacists' roles in these comprehensive areas have not been investigated. Methods: This single-center, retrospective, cohort review compared 1-year graft and patient survival between HCV-positive and HCV-negative LTRs. Secondary endpoints included 1-year rejection rates, HCV sustained virologic response and time to HCV treatment. Results: Ninety-two HCV Nucleic Acid Amplification Test (NAT)-positive LTRs were matched 1:1 to HCV-seronegative LTRs. One-year graft and patient survival were similar between groups. HCV-positive LTRs were more likely to experience biopsy-proven acute rejection (BPAR), and despite treatment with pulse steroids, there was no impact on graft survival or occurrence of fibrosing cholestatic hepatitis (FCH). Time to HCV treatment was 5.4-6.4 months post-transplant, with no treatment failures or impact on graft or patient survival. Conclusions: No difference was seen in graft survival at 1 year between HCV-positive and HCV-seronegative LTRs. Delayed time to treatment of HCV and treatment of rejections in the HCV-positive cohort did not impact outcomes. However, pharmacist-driven protocols could ensure more efficient initiation of HCV treatment in the future.

Adverse childhood experiences and substance misuse in young people in India: results from the multisite cVEDA cohort.

BACKGROUND: Adverse childhood experiences (ACEs) increases vulnerability to externalising disorders such as substance misuse. The study aims to determine the prevalence of ACEs and its association with substance misuse. METHODS: Data from the Consortium on Vulnerability to Externalising Disorders and Addictions (cVEDA) in India was used (n = 9010). ACEs were evaluated using the World Health Organisation (WHO) Adverse Childhood Experiences International Questionnaire whilst substance misuse was assessed using the WHO Alcohol, Smoking and Substance Involvement Screening Test. A random-effects, two-stage individual patient data meta-analysis explained the associations between ACEs and substance misuse with adjustments for confounders such as sex and family structure. RESULTS: 1 in 2 participants reported child maltreatment ACEs and family level ACEs. Except for sexual abuse, males report more of every individual childhood adversity and are more likely to report misusing substances compared with females (87.3% vs. 12.7%). In adolescents, family level ACEs (adj OR 4.2, 95% CI 1.5-11.7) and collective level ACEs (adj OR 6.6, 95% CI 1.4-31.1) show associations with substance misuse whilst in young adults, child level ACEs such as maltreatment show similar strong associations (adj OR 2.0, 95% CI 1.1-3.5). CONCLUSION: ACEs such as abuse and domestic violence are strongly associated with substance misuse, most commonly tobacco, in adolescent and young adult males in India. The results suggest enhancing current ACE resilience programmes and 'trauma-informed' approaches to tackling longer-term impact of ACEs in India. FUNDING: Newton Bhabha Grant jointly funded by the Medical Research Council, UK (MR/N000390/1) and the Indian Council of Medical Research (ICMR/MRC-UK/3/M/2015-NCD-I).

The Impact of Atherosclerotic Cardiovascular Risk on Graft Failure in Deceased-Donor Renal Transplantation.

INTRODUCTION: Pretransplant cardiovascular risk may be amplified after renal transplant, but little is known about its impact on graft outcomes. RESEARCH QUESTION: The purpose of this study was to determine if pretransplant cardiovascular risk was associated with graft outcomes. DESIGN: This retrospective study included deceased-donor renal transplant recipients from 2010-2015. Atherosclerotic cardiovascular disease risk for patients without prior disease was calculated and patients were categorized into high (score >20%), intermediate (7.5-20%), and low risk (<7.5%). Patients with and without prior cardiovascular disease were also compared. The main endpoint was graft failure at 3-years post-transplant. Other outcomes included major adverse cardiovascular events, biopsy-proven rejection, and mortality. RESULTS: In patients without prior atherosclerotic cardiovascular disease (N = 115), graft failure rates (4.5% vs 11.3% vs 12.5%; (P = 0.64) and major adverse cardiovascular events (9.1% vs 13.2% vs 5.0%; P = 0.52) were similar in the high, intermediate, and low risk groups. In those with prior disease (N = 220), rates of primary nonfunction (6.8% vs 1.7%; P = 0.04), major adverse cardiovascular events (7.3% vs 2.6%; P = 0.01), and heart failure (10.9% vs 3.5%; P = 0.02) were higher than those without cardiovascular; rates of major adverse cardiovascular events and heart failure were insignificant after adjusting for age, gender, and race. Other outcomes were not different. Outcomes did not differ based on pretransplant cardiovascular risk. DISCUSSION: Pretransplant atherosclerotic cardiovascular disease was associated with increased early graft failure but similar outcomes at 3-years, suggesting cardiac risk alone should not exclude transplantation.

The Correlation of Endothelial Nitric Oxide Synthase (eNOS) Polymorphism and Other Risk Factors with Aneurysmal Subarachnoid Hemorrhage: A Case-Control Study.

OBJECTIVE: Endothelial nitric oxide synthase gene (eNOS) polymorphism is an association with cerebral aneurysm formation, rupture, and vasospasm and plays a role in the a functional outcome. PATIENTS AND METHODS: The aim of the study was to evaluate the role of eNOS gene polymorphism and further assess the predictors of outcome in the aneurysmal subarachnoid hemorrhage (aSAH). A prospective case-control study was conducted from 2009 to 2012 among those who presented with aSAH. A serum sample was collected from aSAH patients along with age and sex-matched healthy controls. The frequency of polymorphism of eNOS gene and other factors (demographic and aneurysmal) were correlated with functional outcome at six month of follow-up. RESULTS: 100 patients with aSAH and 100 healthy controls were enrolled in the cohort. The mean age of the patient group was 51.61 years and control group was 45.81 years with a male:female ratio of 1:1.38 and 1:1.08 for patients and controls, respectively. Among all eNOS polymorphisms, 4BB (65%) 24-VNTR, TT (71%) of T-786C, and GG (71%) of G947T were the most common and frequency was similar in the control group. The occurrences of hypertension, smoking, diabetes were 32%, 37%, and 7% respectively in the patient group. Maximum patients were in WFNS grade 1 (53%) followed by 23% grade 2 and only 10% in grade 4. Fisher grade 3 (57%) was the most common followed by Fisher grade 4 (28%). Most aneurysms (97%) were in anterior circulation. 83% of the aneurysms were clipped and 10% underwent coiling. Size-wise most of the aneurysms were in the middle group (6-9 mm) followed by bigger group (>10 mm) (37%); only 6% aneurysms were in the small aneurysm (<6 mm) group. 33% of the patients had evidence of vasospasm. TT of G894T polymorphism (60%) had the highest incidence of vasospasm. Univariate analysis showed smoking (OR: 3.19, CI: 1.19-8.84, P = 0.01), 4AA (OR: 12.15, CI: 1.13-624.9, P = 0.03) variety of 24-VNTR polymorphism, CC (OR: 15.39, CI: 1.60-762.8, P = 0.01) variety of T786C polymorphism, Fisher grade 4 (OR: 3.43, CI: 1.24-9.68, P = 0.01), WFNS grade (poor vs. good) (OR: 3.42, CI: 1.17-10.12, P = 0.02), vasospasm (OR: 3.84, CI: 1.42-10.75, P = 0.006), intraoperative rupture (OR: 4.77, CI: 1.55-15.27, P = 0.004) were significantly related with unfavorable outcome at 6 months follow-up. In regression analysis, smoking (CI: 0.06-0.69, P = 0.01), Fisher grade 4 (CI: 0.09-1.00, P = 0.05), and intraoperative rupture (CI: 0.05-0.89, P = 0.03) were correlated with an unfavorable outcome at 6 months follow-up. CONCLUSION: The eNOS gene polymorphism, smoking, clinical grade (WFNS), Fisher grade, intraoperative rupture, and vasospasm play a role in functional outcome after the treatment of cerebral aneurysms.

Clinical outcomes of valganciclovir prophylaxis in high-risk (D+/R-) renal transplant recipients experiencing delayed graft function.

BACKGROUND: Cytomegalovirus (CMV) outcomes with valganciclovir prophylaxis in renal transplant recipients experiencing delayed graft function (DGF) are unclear. METHODS: This single center, retrospective, cohort study of CMV high-risk (D+/R- with alemtuzumab induction) deceased donor renal transplant recipients receiving valganciclovir prophylaxis assessed CMV outcomes in patients experiencing DGF (n = 72) versus those with immediate graft function (IGF; n = 66). RESULTS: Cytomegalovirus viremia by 12 months occurred at similar rates in the IGF and DGF groups (30.3% vs 26.4%, respectively, P = 0.71) with 89.7% (35/39) of all cases classified as CMV disease. The median time to CMV viremia post transplant was day 141 and 138 in the IGF and DGF groups, respectively (P = 0.30). The incidence of biopsy-proven acute rejection (BPAR) was higher in the DGF group (18.1% vs 4.6%, P = 0.02) with BPAR preceding CMV in only 1 patient. There was no significant difference in graft loss (1.5% vs 4.2%, P = 0.62) or patient survival (98.5% vs 95.8%, P = 0.62) at 1 year between the IGF and DGF groups, respectively. CONCLUSION: Valganciclovir prophylaxis in patients experiencing DGF yielded similar CMV outcomes up to 1-year post transplant when compared to use in patients with IGF.

Transcriptome profiling reveals PDZ binding kinase as a novel biomarker in peritumoral brain zone of glioblastoma.

PURPOSE: Peritumoural brain zone (PT) of glioblastoma (GBM) is the area where tumour recurrence is often observed. We aimed to identify differentially regulated genes between tumour core (TC) and PT to understand the underlying molecular characteristics of infiltrating tumour cells in PT. METHODS: 17 each histologically characterised TC and PT tissues of GBM along with eight control tissues were subjected to cDNA Microarray. PT tissues contained 25-30% infiltrating tumour cells. Data was analysed using R Bioconductor software. Shortlisted genes were validated using qRT-PCR. Expression of one selected candidate gene, PDZ Binding Kinase (PBK) was correlated with patient survival, tumour recurrence and functionally characterized in vitro using gene knock-down approach. RESULTS: Unsupervised hierarchical clustering showed that TC and PT have distinct gene expression profiles compared to controls. Further, comparing TC with PT, we observed a significant overlap in gene expression profile in both, despite PT having fewer infiltrating tumour cells. qRT-PCR for 13 selected genes validated the microarray data. Expression of PBK was higher in PT as compared to TC and recurrent when compared to newly diagnosed GBM tumours. PBK knock-down showed a significant reduction in cell proliferation, migration and invasion with increase in sensitivity to radiation and Temozolomide treatment. CONCLUSIONS: We show that several genes of TC are expressed even in PT contributing to the vulnerability of PT for tumour recurrence. PBK is identified as a novel gene up-regulated in PT of GBM with a strong role in conferring aggressiveness, including radio-chemoresistance, thus contributing to recurrence in GBM tumours.

Predictors of Surgical Outcomes of Traumatic Peripheral Nerve Injuries in Children: An Institutional Experience.

AIM: This study was undertaken to address the epidemiological characteristics, operative details, and surgical outcome of peripheral nerve injuries in children treated in a tertiary hospital in India (NIMHANS, Bangalore). MATERIALS AND METHODS: This is a retrospective study of epidemiology, operative findings, and surgical outcomes over the period of 2000-2016. Our series includes 102 children with peripheral nerve injuries of various causes. RESULTS: Intramuscular injections were the most common cause (52.9%), followed by entrapment (15.6%). The most common nerve involved was the sciatic nerve (54.9%), followed by the common peroneal nerve (13.7%), the ulnar nerve (10.8%), and the radial nerve (10.8%). Perineural adhesion was the most common intraoperative finding (74.5%), followed by a neuroma in continuity (14.7%) and gap (10.8%). Most of the children with peripheral adhesion underwent external and internal neurolysis (75.5%). Follow-up was available for 67 children. The median follow-up period was 7 months (range 3-36). The outcome was assessed according to MRC grading. Favorable functional improvement was noted in 76.1% of the children. Age less than 10 years (p = 0. 06), injury before 6 months (p = 0.03), and MRC motor grade (<3) (p = 0. 01) were positive predictive factors related to the final outcome. CONCLUSION: Early surgical intervention, age less than 10 years, and incomplete motor palsy were the best predictors of a superior functional outcome. This study can serve as a guide to determine the epidemiology, duration of intervention, and surgical outcome of traumatic peripheral nerve injuries in the pediatric population.

Efficacy and safety of short course adjuvant trastuzumab combination chemotherapy in breast cancer.

BACKGROUND: The adjuvant short course 9-week trastuzumab combination therapy for human epidermal receptor 2 positive breast cancer patients may often be considered as a cost-effective and safe option and has important implications for the Indian subcontinent as well as other developing countries. However, such regimens of shorter duration trastuzumab therapy like FinHer, offered in view of economic constraints, may not be able to achieve globally comparable cure rates in early breast cancer especially with high-risk women with more than 3 lymph node positive. METHODS AND MATERIAL: Outcome of 21 patients with HER2 positive breast cancer was treated with short course trastuzumab combination chemotherapy in the adjuvant setting was studied. RESULTS: Out of 21 patients 15 are alive and disease free with a follow up of up to 73 months (median follow up 42 months).

A rare case of multiple brain abscess and probably disseminated phaeohyphomycosis due to Cladophialophora bantiana in an immunosuppressed individual from India.

Cladophialophora bantiana, a dematiaceous neurotropic mold causes rare and lethal brain abscess, commonly in immunocompetent hosts. We report a rare and probably a case of disseminated infection with this black mold in an immunosuppressed individual from India. A 55-year-old diabetic male presented with severe headache, blurred-vision, behavioural abnormalities, eye-pain and ear-discharge. He was undergoing treatment for hypertension, prostatomegaly and obstructive pulmonary disease. He was on steroids for the past six years for uveitis. Haematology reports indicated elevated WBC and platelet count. He was negative for HIV, hepatitis, autoimmune antibodies and tumour markers. CD4 count was within normal limits. Brain magnetic resonance imaging revealed multiple ring-enhancing lesions and oedema in the left tempero-parietal region. Chest X-ray showed irregular consolidations in right paracardiac region and confluence in both lungs. Positron Emission Tomography of whole body revealed multiple lesions in brain, lungs, lymph nodes and C3-vertebrae. Histopathology of the lung lesion showed non-tuberculous infectious pathology and brain lesions showed necrosis with occurrence of pigmented hyphal fungi. The pus aspirated during surgical excision of brain lesions grew black mold, identified as C. bantiana. Although patient was started on intravenous Voriconazole, he succumbed to the infection after 7 days. The lesion was initially suspected to be of tuberculous etiology, and the lesions in lungs were also suggestive of malignancy, which was however ruled out by histopathological examination. Such diagnostic dilemmas are common in the infection caused by Cladophialophora, which can cause treatment delay and death. Early diagnosis is therefore mandatory for the rapid treatment and survival of patients.

Successful treatment of primary cerebral mucormycosis: Role of microbiologist.

Fungal brain abscess is rare with a rapidly progressive disease with fulminant course and invariably fatal outcome, unless diagnosed early and treated rapidly. We report a 56-year-old woman diagnosed to have fungal abscess who recovered completely following amphotericin B treatment. She presented with weakness of the right hand, deviation of mouth to left and aphasia for 2 days. Computed tomography of the brain revealed a left frontal capsuloganglionic hypodense lesion. Stereotactic biopsy was performed, and microbiological confirmation of non-septate fungal hyphae from pus from aspirate within 2 h helped initiate timely and appropriate treatment leading to cure. Histopathology and culture later confirmed mucormycosis.

Clinical, electrophysiological, imaging, pathological and therapeutic observations among 18 patients with Rasmussen's encephalitis.

We studied the clinical, electrophysiological, imaging and pathological features of 18 patients with Rasmussen's encephalitis (RE). This descriptive study included 18 patients (six males, 12 females) with RE who were evaluated for demographic and phenotypic details, electroencephalogram (EEG) results, MRI results, pathological features, virological markers and outcome. Radiological staging as per Bien et al. and pathological staging in accordance with Robitaille et al. were performed. Simple partial seizures were the most common initial manifestation. During the disease course, epilepsia partialis continua (EPC) developed in 15/18 (83.3%) and hemiparesis in 17/18 (94.4%) patients. EEG revealed hemispheric slowing (100%), interictal epileptiform discharges (100%) and ictal pattern (44.4%). Brain MRI revealed unihemispheric focal cortical atrophy (100%), white matter changes (88.2%), basal ganglia-ipsilateral caudate and putamen involvement (50.0%) and progression of atrophy on serial MRI (100%). Unusual presentations in this series included late onset (n=1), and isolated lingual EPC (n=1). Diagnostic biopsies in two patients revealed Robitaille stage 3 disease. The six hemispherotomy specimens showed stage 2 disease in one, stage 3 in three and stage 4 in two cases. Heterogeneity in disease stage in the different neuroanatomical regions and within the same cortical segment reflected progression of immune-mediated damage. Immunomodulation provided only temporary benefit. Patients who underwent functional hemispherotomy had reduction in seizure frequency and improved quality of life. The clinical, EEG and MRI findings are in accordance with the established literature. MRI staging was concordant with Robitaille pathological staging. Immunomodulation did result in transient reduction in seizure frequency while surgery in six produced reasonable benefit.

Dexmedetomidine anesthesia enhances spike generation during intra-operative electrocorticography: A promising adjunct for epilepsy surgery.

BACKGROUND: Anesthetic-induced suppression of cortical electrical activity is a major concern during epilepsy surgery. Dexmedetomidine (Dex) has been recently evaluated in a few small series for its effect on the electrocorticographic spikes intra-operatively. METHODS: In this prospective study, electrocorticogram (ECoG) was monitored during dexmedetomidine infusion in 34 patients (M:F=23:11, age=29.2 ± 10.9 years; duration of epilepsy=15.3 ± 8.9 years) undergoing anterior temporal lobe resection with amygdalo-hippocampectomy for drug-resistant mesial temporal lobe epilepsy (Right: 18, Left: 16). Anesthesia was induced with thiopental/propofol and maintained with oxygen-N2O-isoflurane. ECoG was recorded for 5 min after the end tidal MAC of N2O and isoflurane were decreased to zero; anesthesia was maintained with O2:Air=50:50, vecuronium and fentanyl. ECoG was recorded using a 4-contact strip electrode for: (a) 5 min prior to dexmedetomidine (PreDEX), (b) 5 min during dexmedetomidine infusion (DEX; 1 µg/kg) and (c) 5 min after stopping dexmedetomidine (PostDEX). RESULTS: The ECoG spikes were manually counted in all the channels. The mean spike rate in the 2 channels with maximum spikes (MAX CH A and MAX CH B) was normalized to a 3-min duration. RM-ANOVA and post hoc comparison of three phases were used to compare the spike rates. The mean spike rate during Dex phase was higher compared to preDEX (MAX CH B: p=0.007 and MAX CH A: p=0.079) and PostDEX (MAX CH B: p=0.17, MAX CH A: p=0.79) phases. The spike rate increased in 67.6% patients, while 11.8% patients showed ≤ 25% reduction and 20.6% patients showed >25% reduction in spike frequency. CONCLUSION: Dexmedetomidine is useful during intra-operative ECoG recording in epilepsy surgery as it enhances or does not alter spike rate in most of the cases, without any major adverse effects.

Hemodynamic effects of dexmedetomidine during intra-operative electrocorticography for epilepsy surgery.

BACKGROUND: Dexmedetomidine, a predominant alpha-2-adrenergic agonist has been used in anesthetic practice to provide good sedation. The drug is being recently used in neuroanesthesia during awake surgery for brain tumors and in functional neurosurgery. MATERIALS AND METHODS: This prospective study analyzed the hemodynamic effects of dexmedetomidine infusion during electrocorticography in patients undergoing surgery for mesial temporal sclerosis. Dexmedetomidine infusion was administered during intra-operative electrocorticography recording, 15 minutes after the end tidal MAC of N2O and isoflurane were decreased to zero. Anesthesia was maintained with O2 : air mixture = 50:50, vecuronium and fentanyl. Heart rate (HR), mean arterial pressure (MAP) and end tidal carbon dioxide (ETCO2) were recorded across at induction, 2 min prior to dexmedetomidine (PreDEX), 5 min during dexmedetomidine infusion (DEX; 1 µg/kg), 5 min after stopping dexmedetomidine and 10 minutes after stopping dexmedetomidine. RESULTS: Forty patients with mesial temporal sclerosis (M: F = 27:13, mean age = 28.15 ± 10.9 years; duration of epilepsy = 12.0 ± 7.9 years) underwent anterior temporal lobe resection with amygdalohippocampectomy for drug-resistant epilepsy. Infusion of dexmedetomidine caused a transient fall in HR in 87.5% of patients and an increase in MAP in 62.5% of patients, which showed a tendency to revert back towards PreDEX values within 10 min after stopping the infusion. Sixty-five percent of the patients showed ≤25% reduction and 10% of them showed >25% reduction in HR. 47.5% of the patients showed ≤25% increase and 15% of them showed >25% increase in MAP. These changes were over a narrow range and within physiological limits. CONCLUSION: The infusion of dexmedetomidine for a short period causes reduction of HR and increase in MAP in patients, however the variations are within acceptable range.

Clinico-pathological factors influencing surgical outcome in drug resistant epilepsy secondary to mesial temporal sclerosis.

BACKGROUND: Mesial temporal sclerosis (MTS) is the most common cause of drug resistant epilepsy amenable for surgical treatment and seizure control. METHODS: This study analyzed the outcome of patients with MTS following anterior temporal lobectomy and amygdalohippocampectomy (ATL-AH) over 10 years and correlated the electrophysiological and radiological factors with the post operative seizure outcome. RESULTS: Eighty seven patients were included in the study. Sixty seven (77.2%) patients had an Engel Class 1 outcome, 9 (11.4%) had Class 2 outcome. Engel's class 1 outcome was achieved in 89.9% at 1 year, while it reduced slightly to 81.9% at 2 years and 76.2% at 5 year follow up. Seventy seven (88.5%) patients had evidence of hippocampal sclerosis on histopathology. Dual pathology was observed in 19 of 77 specimens with hippocampal sclerosis, but did not influence the outcome. Factors associated with an unfavorable outcome included male gender (p=0.04), and a higher frequency of pre-operative seizures (p=0.005), whereas the presence of febrile seizures (p=0.048) and loss of hippocampal neurons in CA4 region on histopathology (p=0.040) were associated with favorable outcome. The effect of CA4 loss on outcome is probably influenced by neuronal loss in other subfields as well since isolated CA4 loss was rare. Abnormal post operative EEG at the end of 1 week was found to be a significant factor predicting unfavorable outcome (p=0.005). On multivariate analysis, the pre-operative seizure frequency was the only significant factor affecting outcome. CONCLUSIONS: The present study observed excellent seizure free outcome in a carefully selected cohort of patients with MTS with refractory epilepsy. The presence of dual pathology did not influence the outcome.

Single agent weekly paclitaxel as neoadjuvant chemotherapy in locally advanced breast cancer: a feasibility study.

AIM: To study the toxicity profile and response rates of weekly paclitaxel given as neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer. MATERIALS AND METHODS: The study was planned as a single arm, prospective phase II study. Twenty-six patients with locally advanced breast cancer were enrolled in the study from December 2006 to October 2007. These patients underwent NACT with weekly paclitaxel at 100 mg/m(2) for 8 consecutive weeks followed by surgery. This was followed by anthracycline-based chemotherapy for three to four cycles followed by radiation. The patients received standard adjuvant hormonal therapy. The patients were carefully monitored for side-effects using common toxicity criteria. The clinical and pathological response rates were documented. The response rates were descriptively stated. RESULTS: The median age of the patients was 52 years (30-67 years) and the median tumour size was 7 cm (2.5-15 cm). Of the 208 planned weekly cycles, 207 could be given. The rates of grade 3-4 neutropenia, thrombocytopenia and neuropathy were 4, 12 and 4%, respectively. A complete clinical response was observed in 10 patients (38.5%) and a completed pathological response, defined as the absence of invasive cancer from the breast and axillary nodes, was seen in 11.5% of patients. Breast-conserving surgery was possible in 23% of patients. CONCLUSION: The regimen of weekly single agent paclitaxel is feasible in patients with locally advanced breast cancer with acceptable toxicity. It resulted in a pathological response rate that was comparable with other regimens in this group of advanced stage patients. Considering the efficacy and low toxicity of this regimen, it is worth exploring in larger studies.

Density functional theory investigations on the structure and dissolution mechanisms for cellobiose and xylan in an ionic liquid: gas phase and cluster calculations.

Density functional theory (DFT) calculations have been carried out for cellobiose and xylan chosen as models for cellulose and hemicellulose, respectively, in gas phase, implicit and explicit solvent (water, methanol, and the ionic liquid, 1,3-dimethylimidazolium acetate) media using plane wave and atom centered basis set approaches in order to find out lowest energy conformers and configurations. Geometry, vibrational properties, and (1)H and (13)C NMR chemical shift values have been discussed under all three conditions. Calculations predict that inter- and intramolecular hydrogen bonding play an important role in the dissolution processes. In the gas phase and in implicit solvent, the anti-anti conformer of cellobiose and the anti-syn conformer of xylan are the most stable due to the formation of a large number of intramolecular hydrogen bonds. However, in the cluster calculations containing ion pairs of the ionic liquid (IL) surrounding the cellulosic units, the anti-syn conformer of cellobiose is more stable as intramolecular hydrogen bonds are substituted by intermolecular ones formed with the ions of the IL. The complexes of cellobiose (or of xylan) with the ions of the ionic liquid are stable with large negative binding energies ranging between -21 and -55 kcal mol(-1). The predicted (1)H NMR values of the lowest energy cellobiose conformers are in good agreement with the experimental value. Xylan binds stronger with the IL than cellobiose does by 20 kcal mol(-1). Furthermore, the two pentose rings in xylan are rotated by 60° to each other in contrast to their coplanarity in cellobiose, which can explain the higher solubility and the amorphous nature of hemicellulose in ionic liquids. The fewer number of hydroxyl groups in xylan (relative to cellobiose) does not affect the number of cations present in its first solvation shell while the number of anions is reduced.

Clinical, neuroimaging and pathological features of 5-nitroimidazole-induced encephalo-neuropathy in two patients: Insights into possible pathogenesis.

We report two patients manifesting with involvement of central and peripheral nervous system with brain magnetic resonance imaging (MRI) changes and pathological features of neuropathy possibly due to harmful and chronic use of various nitroimidazole group of medications for recurrent diarrheal illness. Patient 1, a 21-year-old man with obsessive-compulsive disorder, impulsive behavior and harmful use of substance (tinidazole), had developed encephalopathy and biopsy-proven neuropathy with partial remission. The MRI of brain showed involvement of bilateral caudate, lentiform and dentate nuclei, and splenium, with contrast enhancement of the caudate and putaminal lesions and restricted diffusion of the splenial lesion. Patient 2 was a 50-year-old woman with irritable bowel syndrome and was on harmful use of tinidazole and metronidazole. She manifested with encephalopathy, ataxia, and neuropathy. Her MRI of brain revealed involvement of bilateral putamen, dentate nuclei and periventricular white matter with restricted diffusion. Sural nerve biopsy revealed evidence of vasculitic neuropathy. At follow-up, there was definite, though incomplete, recovery in both the patients. The MRI alterations improved completely in patient 2 and substantially in patient 1. Increasing awareness among the physicians may enable early recognition of potentially reversible neurotoxicity and avoid unwarranted prescription of such medications.