The Impact of the Association Between Nonalcoholic Fatty Liver Disease and Intrahepatic Cholestasis of Pregnancy on Maternal and Fetal Outcomes.

Backgroundː Intrahepatic cholestasis of pregnancy (ICP), a hepatic condition that causes severe itching in late pregnancy, is linked to nonalcoholic fatty liver disease (NAFLD) due to disrupted bile acid balance. It poses maternal risks such as preterm labor and gestational diabetes and fetal risks such as preterm birth and respiratory distress. The study examined NAFLD's impact on ICP in pregnant women, highlighting management and research implications. Methodsː This retrospective study examined pregnant women (≥18 years) with ICP, assessing fatty liver with follow-up ultrasounds. Participants were divided into ICP only and ICP with fatty liver (FL) groups, excluding heavy alcohol users and incomplete data. Maternal age, medical history, and comorbidities were evaluated alongside abdominal ultrasounds to identify FL. Resultsː In this study of 43 pregnant women, the mean maternal age was 27 years. Patients with ICP and FL had significantly higher bile acid levels than those with ICP alone. However, no significant differences were found between the two groups regarding the history of gestational diabetes mellitus (GDM), dyslipidemia, polycystic ovarian syndrome (PCOS), parity, and hypothyroidism. Among women with ICP and FL, 51.85% underwent lower segment cesarean section (LSCS), while 43.75% with ICP without FL underwent LSCS. Conclusionsː ICP with FL did not show significant adverse effects on maternal and neonatal outcomes, including mode of delivery, gestational age, maternal complications, neonatal intensive care unit (NICU) admissions, and low birth weight (LBW) with asphyxia. However, additional research is required to fully comprehend the relationship between ICP, NAFLD, and their impact on pregnancy outcomes.

Brachytherapy for Oral Cavity Cancers in the Era of Intensity-Modulated Radiotherapy: Save it or Shelve it.

Head and neck cancer treatment includes a multidisciplinary approach involving all specialties. Surgery and radiotherapy are equally effective in controlling small tumors. Intensity-modulated radiotherapy (IMRT) and interstitial brachytherapy (ISBT) play an important role in the treatment of head and neck cancers. Both are proved to be highly conformal techniques of radiotherapy. Our aim is to compare dosimetric aspects of ISBT alone, IMRT alone, and IMRT combined with ISBT in early stage node negative oral cavity cancer. Ten cases of histopathologically proven early stage node negative oral cavity cancer were treated with external beam therapy followed by interstitial brachytherapy boost or ISBT alone. All these patients had undergone computerized tomography (CT) planning for brachytherapy. Retrospectively, these images were utilized, and three sets of plans were done for each patient's CT image set. Group A was IMRT alone plans, groups B had combined IMRT with ISBT boost, and group C was ISBT alone plans. Dosimetric details such as target coverage, dose to critical organs, and conformity index were compared between the three sets of plans. The mean values of the doses to the critical organs with IMRT alone and IMRT with ISBT boost were brainstem 10.40 Gy and 9.20 Gy, spinal cord 19.20 Gy and 16.10 Gy, mandible 62.99 Gy and 66.50 Gy, and I/L and C/L parotids were 6.03 Gy and 5.50 Gy and 5.70 Gy and 5.10 Gy where as in ISBT alone plans mean values were brainstem 1.30 Gy, spinal cord 1.40 Gy, mandible 36.50 Gy, I/L, and C/L parotids were 1.60 Gy and 1.00 Gy. Conformity index (CI) between IMRT and ISBT plans were 0.8580 and 0.7140 respectively. With comparable CI values, doses to critical organs appear to be in favor of ISBT plans as opposed to IMRT, and this was found to be statistically significant. Brachytherapy shows a dosimetric advantage over IMRT in this setting and could be translated to a benefit in terms of toxicities, organ preservation, and cosmesis in the actual clinical scenario. However, whether this would translate to significant benefit in terms of clinical outcome needs to be still verified.

Tolerance of Radical Radiotherapy Among Elderly Head and Neck Cancer Patients.

Head and neck cancers usually occur in the elderly age group and about half of the cases occur at the age > 60 years with majority detected in an advanced stage with increased morbidity and decreasing compliance to therapy. Since there are limited data available for the adequate treatment of elderly head and neck cancer patients, we proposed a study to analyze tolerance and response based on age, site, modality of treatment received, and implication of nutrition vs weight loss during treatment. Fifty-five patients were enrolled in this study, which was conducted between November 2015 and April 2017, and those who met the eligibility criteria were evaluated with a detailed history and physical examination, and biochemical, pathological, and radiological investigations. Patients were staged based on TNM staging and treated as per the standard guidelines. Patients were assessed with the weekly routine blood investigation, weight loss, and toxicity. The response was assessed after 6 weeks and documented as per RECIST criteria. 52/55 (94.5%) patients completed the treatment, and 48/55 (92.3%) had a complete response at 6 weeks (p value 0.000) with a mean treatment duration of 46.67 days and mean weight loss of 5.44 kg with 55.4% having GR-II mucositis, 40% having GRIII mucositis at the time of completion of treatment. Sixty-eight percent having GRII and 38.2% having GR I dermatitis and 80% had moderate pain. Subgroup analysis was done based on age, site, and treatment modality. Patients were also assessed for nutrition vs weight loss. We concluded that elderly patients tolerate and respond well to radical treatment with acceptable toxicities; hence, age should not be a barrier to decide treatment.

Synchronous presentation of tuberculosis and hepatocellular carcinoma in a cirrhotic patient: a case report.

Tuberculosis (TB) is a common opportunistic infection which may be reactivated in immunocompromised patients. The incidence of hepatocellular carcinoma (HCC) is on the rise with healthcare resulting in increased longevity of people. Reactivation of TB has been reported with liver-directed therapies for HCC like transarterial chemoembolisation (TACE) and transarterial radio-embolisation (TARE). However, the co-occurrence of both TB and HCC in the same patient without any such history is rarely found. Only three isolated case reports have been published previously. We report the case of an elderly hepatitis C virus-related chronic liver disease patient who developed two different nodular liver lesions with multiple intra-abdominal lymphadenopathy, one such nodule being confirmed as HCC and another as TB along with nodal TB.

Adjuvant radiotherapy in carcinoma buccal mucosa; more conformal the best: Is it so?

INTRODUCTION: Since 1980s, computerization has made improvements in radiation therapy delivery from conventional two-dimensional to three-dimensional conformal radiotherapy (2DCRT to 3DCRT) to intensity-modulated radiotherapy (IMRT) and its newer versions. This small study is aimed to compare the existing techniques for planning target volume (PTV) and organ at risk (OAR) dose distribution parameters in postoperative buccal mucosa cases. MATERIALS AND METHODS: Ten post operative cases of early stage carcinoma buccal mucosa in whom only post operative bed irradiation was indicated was enrolled and was planned with conventional, 3DCRT and IMRT techniques to get 95% PTV coverage and dose received by organs at risk were recorded and evaluated. RESULTS: Mean and standard deviation values for PTV 95% for IMRT, 3DCRT, and conventional plans were 96.4 ± 1.8, 95.1 ± 1.9, and 91 ± 2.7, respectively. Dose received by OARs was high in conventional technique when compared to the other two. Maximum dose received by 1 cc of brain (46.2 ± 7.9 and 60.8 ± 3.8) (priority was given for PTV coverage) and mean dose received by the same eye (13.6 ± 1.4 and 22 ± 2.4) were less in IMRT when compared to 3DCRT. However, maximum dose received by 1 cc of brainstem (29.7 ± 7.6 and 14.1 ± 9.5), optic chiasma (29.2 ± 4.2 and 12 ± 2.1), spinal cord (31.8 ± 3 and 20.9 ± 4.2), and the same-side optic nerve (22 ± 6.9 and 11.7 ± 9.4) and mean dose received by opposite-side parotid (8.7 ± 1.1 and 1.7 ± 0.4) and submandibular gland (18.6 ± 1.7 and 3.2 ± 0.9) were more with IMRT when compared to 3DCRT. CONCLUSION: In postoperative cases of early-stage carcinoma buccal mucosa, it is good enough to treat with 3DCRT technique. Here, the target area will be well lateralized, and 3DCRT technique can give good target coverage and less dose to OARs, especially the only remaining major salivary glands.

Molecular Marker as a Prognostic Indicator in Head and Neck Cancer Patients.

Head and neck cancer forms the major burden of cancer in the developing countries. Despite advancement in the treatment approach of head and neck cancer in terms of surgery, chemotherapy and radiotherapy overall long-term survival remains low due to uncontrollable persistent and recurrent disease. This low survival rate has demanded for the need for newer treatment approaches and prognostic markers. In a previously published study "impact of molecular predictors on the response rates in head and neck Cancer patients" by Koushik et al. assessed the impact of molecular markers like HPV, P53, and EGFR status along with other prognostic factors like tobacco use, age, sex, and socioeconomic status on response to treatment of head and neck cancer patients. Our present study is intent to provide update of the impact of those molecular markers on survival. Objective of our study is to correlate the HPV, EGFR, and P53 status with the survival rate of the head and neck cancer patients. Twenty-five histologically proven head and neck cancer patients were assessed for HPV, EGFR, and P53 status who underwent chemoradiation to a dose of 66 Gy in 33 fraction along with weekly cisplatin of 40 mg/m2, and all treated patients were followed up to a minimum of 3 years and analyzed for the survival. We found that 3-year survival for complete responders after treatment is 61.5% and partial responders, 57.1%; stable disease is 33.3%, and progressive disease is 0%. A 3-year survival for HPV-positive patients is 57.4% (p = 0.973), EGFR-mutated patients is 47.62% (p = 0.593), and P53-mutated patients is 57.89% (p = 0.378).

Enhanced photoelectrochemical activity of Co-doped ß-In2S3 nanoflakes as photoanodes for water splitting.

This work is primarily focused on indium sulfide (ß-In2S3) and cobalt (Co)-doped ß-In2S3 nanoflakes as photoanodes for water oxidation. The incorporation of cobalt introduces new dopant energy levels increasing visible light absorption and leading to improved photo-activity. In addition, cobalt ion centers in ß-In2S3 act as potential catalytic sites to promote electro-activity. 5 mol% Co-doped ß-In2S3 nanoflakes when tested for photoelectrochemical water splitting exhibited a photocurrent density of 0.69 mA cm-2 at 1.23 V, much higher than that of pure ß-In2S3.

Optimal technique of radiotherapy for carcinoma cervix in developing countries: Dosimetric and logistic comparison.

PURPOSE: Carcinoma cervix is the most common malignancy affecting women in developing countries. Radical radiotherapy is the mainstay of treatment in more than 90% of patients. The present study is a dosimetric and logistic comparison of various techniques of radiotherapy, namely two-dimensional conventional radiotherapy (2DCRT), three-dimensional conformal radiotherapy (3DCRT), and intensity-modulated radiotherapy (IMRT). METHODS: All the patients underwent contrast-enhanced computed tomography (CT) scans for simulation. 2DCRT, 3DCRT, and IMRT plans were generated in 24 patients and dosimetrically compared. Radiotherapy treatment time involved in each technique was analyzed in 27 treated patients. RESULTS: The planning target volume (PTV) coverage was best in 3DCRT technique with a median coverage of 99.9% as compared to IMRT (99.3%) and 2DCRT (82.2%). There was progressive sparing of all the organs at risk in IMRT as compared to 3DCRT. The total planning time was longest in IMRT (332.1 min) and shortest in 2DCRT (11.7 min). The mean treatment time for the delivery of each fraction of 2DCRT, 3DCRT, and IMRT were 14.3, 13.6, and 24.7 min, respectively. CONCLUSION: 3DCRT technique is the most optimal technique for radical radiotherapy of cervical cancers with optimum PTV coverage, acceptable planning time, and minimal treatment time as compared to IMRT. 2DCRT technique should be limited to the setting where CT simulation is unavailable.

Brachytherapy in Head and Neck Cancers: "Are We Doing It or Are We Done with It".

We performed an e-Survey and reviewed the literature on the prevalence of use of brachytherapy in head and neck cancers in order to understand the patterns of care and probable application of this modality. A five-point questionnaire was prepared and sent to 300 oncologists through a web-based survey engine. This was done in preparation for my lecture on "Ongoing Research and Potential Research Avenues" in IBSCON held in Chennai in August 2016. SPSS software was used for the statistical analysis. Of a total of 300 emails that were sent out for the survey, 120 replies were received, which is 40%. Among the results of various questions, (i) 65% of the oncologists felt that there were > 300 ongoing studies in brachytherapy and out of them only 10-20 were on head and neck brachytherapy; (ii) 58% of the responders felt that external beam radiotherapy (EBRT) advances followed by lack of training and experience are the reasons for declining role of brachytherapy; (iii) among the responders, numbers of head and neck brachytherapy performed stand third after gynecological and breast brachytherapy. This survey shows that brachytherapy in head and neck cancers is an essential tool, but seldom practiced. If no path-breaking event happens, we may be dealing with it as a dying art.

Quantification of Dose-Volume and Dose-Length Parameters for Cervical Esophageal Stricture in Head and Neck Irradiation with the 3DCRT and IMRT Technique.

PURPOSE: To quantify and compare dose-volume and dose-length parameters of cervical esophagus between three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT) and to correlate with incidence of cervical strictures in head and neck cancer irradiation with radical intent. MATERIALS AND METHODS: Forty consecutive head and neck cancer patients who received radical radiation therapy, either with 3DCRT (n = 20) or IMRT (n = 20), between December 2011 and August 2012 were retrospectively analyzed and followed up for at least 4 years post-treatment completion. RESULTS: The volumes of cervical esophagus receiving ≥54 Gy (V54) and ≥60 Gy (V60) and lengths receiving circumferential dose of ≥50 Gy (L50) and ≥54 Gy (L54) were significantly higher in patients treated with IMRT as compared to 3DCRT (P ≤ .05). At the end of minimum 4 years' post-treatment, nine patients had documented symptomatic strictures; three patients were treated with 3DCRT and six patients with IMRT technique. CONCLUSION: IMRT technique in entire-neck irradiation is associated with increased spillage dose to the cervical esophagus, and thereby increased risk for late sequelae. The cervical esophagus has to be considered as an organ at risk and constraints need to be given in IMRT planning, particularly for lower-neck irradiation.

Accelerated Radiation Therapy Using Weekend Boost with Concurrent Cisplatin in Head and Neck Squamous Cell Cancers: An Indian Institutional Experience.

PURPOSE: The purpose of the study was to evaluate the feasibility and efficacy of an accelerated radiotherapy schedule using weekend boost in terms of tumor response, compliance, and acute toxicities for head and neck squamous cell carcinoma, and to report long-term clinical outcomes. MATERIALS AND METHODS: Twenty-six patients with stages III-IV head and neck squamous cell carcinoma receiving radical chemoradiotherapy were accrued prospectively into the study. External beam radiation therapy to a total dose of 66-70 Gy in 33-35 fractions, 1.8-2.0 Gy per fraction along with concurrent weekly cisplatin was planned. Radiation regimen included delivery of six fractions per week, with boost field delivered as the sixth fraction on the weekend. The compliance, tumor response, and toxicities were recorded. Survival curves were estimated using the Kaplan-Meier method. RESULTS: Twenty-one of 26 patients (81%) completed treatment as planned and five patients died during the course of treatment. Sixteen patients (62%) completed treatment in less than 44 days and, at the end of 3 months' follow-up, 18 patients (69%) showed complete response and two patients (8%) showed partial response. The 2- and 5-year actuarial disease-free survival were 90% and 65%, respectively, and 2- and 5-year actuarial overall survival were 60% and 38%, respectively. CONCLUSION: Accelerated fractionation using weekend boost, along with concurrent weekly concurrent cisplatin, is an effective and promising approach with favorable impact on initial tumor response, comparable results, and acceptable toxicities.

Patient-specific 3D FLAIR for enhanced visualization of brain white matter lesions in multiple sclerosis.

PURPOSE: To improve the conspicuity of white matter lesions (WMLs) in multiple sclerosis (MS) using patient-specific optimization of single-slab 3D fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). MATERIALS AND METHODS: Sixteen MS patients were enrolled in a prospective 3.0T MRI study. FLAIR inversion time and echo time were automatically optimized for each patient during the same scan session based on measurements of the relative proton density and relaxation times of the brain tissues. The optimization criterion was to maximize the contrast between gray matter (GM) and white matter (WM), while suppressing cerebrospinal fluid. This criterion also helps increase the contrast between WMLs and WM. The performance of the patient-specific 3D FLAIR protocol relative to the fixed-parameter protocol was assessed both qualitatively and quantitatively. RESULTS: Patient-specific optimization achieved a statistically significant 41% increase in the GM-WM contrast ratio (P < 0.05) and 32% increase in the WML-WM contrast ratio (P < 0.01) compared with fixed-parameter FLAIR. The increase in WML-WM contrast ratio correlated strongly with echo time (P < 10-11 ). Two experienced neuroradiologists indicated substantially higher lesion conspicuity on the patient-specific FLAIR images over conventional FLAIR in 3-4 cases (intrarater correlation coefficient ICC = 0.72). In no case was the image quality of patient-specific FLAIR considered inferior to conventional FLAIR by any of the raters (ICC = 0.32). CONCLUSION: Changes in proton density and relaxation times render fixed-parameter FLAIR suboptimal in terms of lesion contrast. Patient-specific optimization of 3D FLAIR increases lesion conspicuity without scan time penalty, and has potential to enhance the detection of subtle and small lesions in MS. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:557-564.

Impact of Molecular Predictors on the Response Rates in Head and Neck Cancer Patients - an Observational Study.

Squamous cell carcinoma of head and neck region account for more than 25 % of male and more than 10 % of female cancers in India (1). Head and neck cancer treatment includes a multidisciplinary approach involving all specialties. Concurrent chemo-radiation is the standard of care in most of the subsites (2). Inspite of the multi-disciplinary approach, a plateau has been reached in terms of results with 5 year survival of locally advanced disease of around 30 % (3). In order to improve outcomes, there has been considerable interest in molecular profiling of head and neck cancers 4-10. However there is still significant paucity in terms of Indian data, hence the need for the study. The objectives are to assess the HPV-p16, EGFR and p53 status, to correlate HPV-p16, EGFR and p53 status with the response rates, to correlate HPV-p16,EGFR and p53 status with other factors like age, sex, tobacco use. Twenty five consecutive cases of histopathologically proven head and neck cancers were accrued. All patients were treated with external radiation to a dose of 66Gy in 33 fractions along with concurrent weekly cisplatin chemotherapy at a dose of 40mg/sqm. HPV-p16, EGFR and p53 mutation analysis was done on paraffin embedded histopathological blocks. PCR technique used for HPV-p16, EGFR and p53 status detection. Response assessment was done based on RECIST criteria. Correlation of HPV, EGFR and p53 status on response was done. The EGFR positivity rate was 84 %, the p53 positivity rate was 76 % and the HPV p-16 positivity rate was 28 %. Out of 25 patients, 13(52%) had complete response, 7(28 %) had partial response, 3(12 %) had stable disease and 2(8 %) had progressive disease. On correlation of molecular profile with response, there was no statistical significance between EGFR status and response (p 0.5) or HPV-p16 and response (p 0.8). However, p53 positivity was approaching significance with respect to good response (p 0.07).

Cortical Thickness in Mild Traumatic Brain Injury.

Magnetic resonance imaging data were acquired at ∼24 h and ∼3 months post-injury on mild traumatic brain injury (mTBI; n = 75) and orthopedic injury (n = 60) cohorts. The mTBI subjects were randomly assigned to a treatment group with atorvastatin or a non-treatment mTBI group. The treatment group was further divided into drug and placebo subgroups. FreeSurfer software package was used to compute cortical thickness based on the three dimensional T1-weighted images at both time-points. Cross-sectional analysis was carried out to compare cortical thickness between the mTBI and control groups. Longitudinal unbiased templates were generated for all subjects and cortical thickness measurements were compared between baseline and follow-up scans in the mTBI group. At baseline, significant reduction in cortical thickness was observed in the left middle temporal and the right superior parietal regions in the mTBI group, relative to the control group (p = 0.01). At follow-up, significant cortical thinning was again observed in the left middle temporal cortex in the mTBI group. Further analysis revealed significant cortical thinning only in the non-treatment group relative to the control group. In the follow-up, small regions with significant but subtle cortical thinning and thickening were seen in the frontal, temporal, and parietal lobes in the left hemisphere in the non-treatment group only. Our results indicate that cortical thickness could serve as a useful measure in identifying subtle changes in mTBI patients.

A study of the clinical profile of acute pancreatitis and its correlation with severity indices.

BACKGROUND: Acute pancreatitis is a common disease with wide clinical variation and its incidence is increasing. Acute pancreatitis may vary in severity, from mild self-limiting pancreatic inflammation to pancreatic necrosis with life-threatening sequelae. Severity of acute pancreatitis is linked to the presence of systemic organ dysfunctions and/or necrotizing pancreatitis. AIM AND OBJECTIVES: The present study was aimed to assess the clinical profile of acute pancreatitis and to assess the efficacy of various severity indices in predicting the outcome of patients. METHODOLOGY: This was a prospective study done in Sri Ramachandra Medical College and Hospital from April 2012-September 2014. All patients with a diagnosis of acute pancreatitis were included in this study. Along with routine lab parameters, serum amylase, lipase, lipid profile, calcium, CRP, LDH, CT abdomen, CXR and 2D Echo was done for all patients. RESULTS: A total of 110 patients were analysed. 50 patients required Intensive care, among them 9 patients (18%) died. 20 patients (18.2%) had MODS, 15 patients (13.6%) had pleural effusion, 9 patients (8.2%) had pseudocyst, 2 patients(1.8%) had hypotension, 2 patients(1.8%) had ARDS and 2 patients(1.8%) had DKA. In relation to various severity indices, high score of CRP, LDH and CT severity index was associated with increased morbidity and mortality. 15 patients (13.6%) underwent open necrosectomy surgery, 3 patients (2.7%) underwent laparoscopic necrosectomy and 7 patients (6.4%) were tried step up approach but could not avoid surgery. Step up approach and surgery did not have a significant reduction in the mortality. CONCLUSION: Initial assessment of severity by CRP, LDH and lipase could be reliable indicators of outcome in acute pancreatitis.

Effect of in-painting on cortical thickness measurements in multiple sclerosis: A large cohort study.

A comprehensive analysis of the effect of lesion in-painting on the estimation of cortical thickness using magnetic resonance imaging was performed on a large cohort of 918 relapsing-remitting multiple sclerosis patients who participated in a phase III multicenter clinical trial. An automatic lesion in-painting algorithm was developed and implemented. Cortical thickness was measured using the FreeSurfer pipeline with and without in-painting. The effect of in-painting was evaluated using FreeSurfer's paired analysis pipeline. Multivariate regression analysis was also performed with field strength and lesion load as additional factors. Overall, the estimated cortical thickness was different with in-painting than without. The effect of in-painting was observed to be region dependent, more significant in the left hemisphere compared to the right, was more prominent at 1.5 T relative to 3 T, and was greater at higher lesion volumes. Our results show that even for data acquired at 1.5 T in patients with high lesion load, the mean cortical thickness difference with and without in-painting is ∼2%. Based on these results, it appears that in-painting has only a small effect on the estimated regional and global cortical thickness. Hum Brain Mapp 36:3749-3760, 2015. © 2015 Wiley Periodicals, Inc.

A prospective dosimetric and clinical comparison of acute hematological toxicities in three-dimensional conformal radiation therapy and intensity modulated radiation therapy with concurrent chemotherapy in carcinoma cervix.

BACKGROUND AND OBJECTIVES: Acute hematological toxicities are an important cause of morbidity in patients receiving concurrent chemoradiation to pelvis in carcinoma cervix. The objective of this study was to evaluate the role of intensity-modulated radiotherapy (IMRT) in reducing the dose to the bone marrow as compared with three-dimensional conformal radiotherapy (3DCRT) and hence its impact on reducing the acute hematological toxicities. MATERIALS AND METHODS: Eleven consecutive patients treated with IMRT and 12 patients treated with 3DCRT to the whole pelvis along with concurrent chemotherapy were selected. Bone marrow was delineated. V10 Gy, V20 Gy, V95%, and Dmean of bone marrow were recorded. Weekly blood counts were recorded and graded as per Common Terminology Criteria version 4.0 for all the patients. RESULTS: The dose to the bone marrow V20 Gy was 206.78 ± 57.10 cc (75%) and 251.70 ± 40.45 cc (91%) for IMRT and 3DCRT, respectively (P = 0.04) and V95% was 23.30 ± 8.34% and 46.76 ± 6.71% for IMRT and 3DCRT, respectively (P = 0.001). The grade of toxicities during each week did not show the difference in either arm. However, the total count and Neutrophil counts during the 2nd week showed statistical significance between IMRT and 3DCRT. CONCLUSION: IMRT significantly reduces the dose to the bone marrow as compared to 3DCRT. The reduction of the dose did not translate into a decrease in acute hematological toxicities. Concurrent platinum-based chemotherapy is the probable cause for the hematological toxicities.

Approaches for plasma membrane wounding and assessment of lysosome-mediated repair responses.

Rapid plasma membrane repair is essential to restore cellular homeostasis and improve cell survival after injury. Several mechanisms for plasma membrane repair have been proposed, including formation of an intracellular vesicle patch, reduction of plasma membrane tension, lesion removal by endocytosis, and/or shedding of the wounded membrane. Under all conditions studied to date, plasma membrane repair is strictly dependent on the entry of calcium into cells, from the extracellular medium. Calcium-dependent exocytosis of lysosomes is an important early step in the plasma membrane repair process, and defects in plasma membrane repair have been observed in cells carrying mutations responsible for serious lysosomal diseases, such as Chediak-Higashi (Huynh, Roth, Ward, Kaplan, & Andrews, 2004) and Niemann-Pick Disease type A (Tam et al., 2010). A functional role for release of the lysosomal enzyme acid sphingomyelinase, which generates ceramide on the cell surface and triggers endocytosis, has been described (Corrotte et al., 2013; Tam et al., 2010). Therefore, procedures for measuring the extent of lysosomal fusion with the plasma membrane of wounded cells are important indicators of the cellular repair response. The importance of carefully selecting the methodology for experimental plasma membrane injury, in order not to adversely impact the membrane repair machinery, is becoming increasingly apparent. Here, we describe physiologically relevant methods to induce different types of cellular wounds, and sensitive assays to measure the ability of cells to secrete lysosomes and reseal their plasma membrane.

ESCRT: nipping the wound in the bud?

Rapid repair of plasma membrane wounds is critical for cellular survival. Exocytic patches, membrane tension reduction and endocytosis were previously proposed to mediate resealing. A recent study implicating the ESCRT complex adds to the growing evidence that repair involves removal of damaged plasma membrane, and not simply patching the wound.