Neuropsychological Rehabilitation for Epilepsy in India: Looking Beyond the Basics.

BACKGROUND: Neuropsychological Rehabilitation (NR) helps manage cognitive deficits in epilepsy. As internationally developed programs have limited applicability to resource-limited countries, we developed a program to bridge this gap. This 6-week caregiver-assisted, culturally suitable program has components of (1) psychoeducation, (2) compensatory training, and, (3) cognitive retraining and is called EMPOWER (Indigenized Home Based Attention and Memory Rehabilitation Program for Adult Patients with Drug Refractory Epilepsy). Its efficacy needs to be determined. METHODS: We carried out an open-label parallel randomized controlled trial. Adults aged 18-45 years with Drug Refractory Epilepsy (DRE), fluency in Hindi and or English, with impaired attention or memory (n = 28) were randomized to Intervention Group (IG) and Control Group (CG). The primary outcomes were objective memory (Auditory Verbal Learning Test), patient and caregiver reported everyday memory difficulties (Everyday Memory Questionnaire-Revised), number of memory aids in use, depression (Hamilton Depression Rating Scale), anxiety (Hamilton Anxiety Rating Scale) and quality of life (Quality of Life in Epilepsy-31). Intention to treat was carried out for group analysis. In the absence of norms necessary for computing Reliable Change Indices (RCIs), a cut-off of +1.0 Standard Deviation (SD) was utilized to identify clinically meaningful changes in the individual analysis of objective memory. A cut-off of 11.8 points was used for quality of life. Feedback and program evaluation responses were noted. RESULTS: The majority of the sample comprised DRE patients with temporal lobe epilepsy who had undergone epilepsy surgery. Group analysis indicated improved learning (p = 0.013), immediate recall (p = 0.001), delayed recall (p < 0.001), long-term retention (p = 0.031), patient-reported everyday memory (p < 0.001), caregiver-reported everyday memory (p < 0.001), anxiety (p = 0.039) and total quality of life (p < 0.001). Individual analysis showed improvement in 50 %, 64 %, 71 %, 57 %, and 64 % of patients on learning, immediate recall, delayed recall, long-term retention, and total quality of life respectively. Despite improvements, themes indicative of a lack of awareness and understanding of cognitive deficits were identified. Overall, the program was rated favorably by patients and caregivers alike. CONCLUSION: NR shows promise for patients with DRE, however larger studies are warranted. The role of cognition in epilepsy needs to be introduced at the time of diagnosis to help lay the foundation for education and acceptance.

Topical Diclofenac for Prevention of Capecitabine-Associated Hand-Foot Syndrome: A Double-Blind Randomized Controlled Trial.

PURPOSE: Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting cyclooxygenase-2 (COX-2) that is upregulated because of the underlying associated inflammation. However, systemic side effects of celecoxib have limited routine prescription. Topical diclofenac inhibits COX-2 locally with minimal risk of systemic adverse events. Therefore, we conducted this study to assess the efficacy of topical diclofenac in the prevention of capecitabine-induced HFS. METHODS: In this single-site phase III randomized double-blind trial, we enrolled patients with breast or GI cancer who were planned to receive capecitabine-based treatment. Participants were randomly assigned in a 1:1 ratio to receive topical diclofenac or placebo gel for 12 weeks or until the development of HFS, whichever occurred earlier. The primary end point was the incidence of grade 2 or 3 HFS (Common Terminology Criteria for Adverse Events version 5), which was compared between the two groups using simple logistic regression. RESULTS: In total, 264 patients were randomly assigned to receive topical diclofenac gel (n = 131) or placebo (n = 133). Grade 2 or 3 HFS was observed in 3.8% of participants in the diclofenac group compared with 15.0% in the placebo group (absolute difference, 11.2%; 95% CI, 4.3 to 18.1; P = .003). Grade 1-3 HFS was lower in the diclofenac group than in the placebo group (6.1% v 18.1%; absolute risk difference, 11.9%; 95% CI, 4.1 to 19.6). Capecitabine dose reductions because of HFS were less frequent in the diclofenac group (3.8%) than in the placebo group (13.5%; absolute risk difference, 9.7%; 95% CI, 3.0 to 16.4). CONCLUSION: Topical diclofenac prevented HFS in patients receiving capecitabine. This trial supports the use of topical diclofenac to prevent capecitabine-associated HFS.

Elucidating the Role of miRNA-326 Modulating Hedgehog Signaling in Pancreatic Carcinoma.

BACKGROUND AND AIM: Pancreatic ductal adenocarcinoma (PDAC) is one of the lethal malignancies worldwide characterized by poor prognosis. MicroRNAs (miRNAs) function as the key regulators in carcinogenesis and may act as noninvasive biomarkers in various malignancies including PDAC. The present study aimed to elucidate the role of miR-326, a known modulator of hedgehog (Hh) pathway in PDAC. MATERIALS AND METHODS: miR-326 circulating levels were assessed in 105 PDAC patients, 31 with chronic pancreatitis (CP) and 36 healthy controls by quantitative Polymerase chain reaction. The expression of miR-326 and smoothened (SMO) was checked in surgical PDAC tissue. SMO protein expression was analyzed by immunohistochemistry in different groups. Finally, the role of miR-326 as a modulator of Hh pathway was assessed in vitro. RESULTS: Our results demonstrate that miR-326 is downregulated in both blood and tissue of PDAC patients as compared with controls. In contrast, the target gene/protein expression of SMO is upregulated in PDAC. Moreover, the tumor stromal expression of SMO was found to be clinically associated with lymph-node metastasis and vascular encasement in PDAC. Overexpression of miR-326 in Panc1 cell line was found to induce downregulation of SMO suggesting the tumor suppressor role of miR-326 in PDAC. CONCLUSIONS: Taken together, miR-326 acts as a tumor suppressor in PDAC by modulating Hh pathway. It may be a promising target for the development of efficient drug therapies for the treatment of PDAC.

Randomized Controlled Trial of Neoadjuvant Short-Course Radiotherapy Followed by Consolidation Chemotherapy Versus Long-Course Chemoradiotherapy in Locally Advanced Rectal Cancer: Comparison of Overall Response Rates.

BACKGROUND: Management of locally advanced rectal cancer (LARC) is evolving with current emphasis on the addition of chemotherapy to short course radiotherapy (SCRT). We primarily aimed to analyse the difference in overall response rates between SCRT with sequential chemotherapy and standard long-course chemoradiotherapy (LCCRT)in LARC. METHODS: After randomization, patients in arm A received 45 Gy in 25 fractions over 5 weeks with concurrent capecitabine while patients in arm B received 25 Gy in 5 fractions over 1 week followed by 3 cycles of CAPOX (capecitabine and oxaliplatin) chemotherapy. Clinical and radiological response assessment was made after the completion of neoadjuvant treatment, a week prior to surgery. Adjuvant chemotherapy was added to complete 6 months of peri-operative chemotherapy. Surgery was performed between 8 and 10 weeks of completion of radiation treatment in both arms. RESULTS: Of the 33 patients recruited in this study between February 2020 to July 2021, 17 patients were randomized to arm A and 16 to arm B. The rates of complete tumour regression were 23.1% in arm A versus 35.7% in arm B (p-value = 0.683). Pathological complete response (pCR) rate was 20% arm A versus 30% in arm B (0.446). A higher number of patients in arm B experienced grade 3 diarrhoea, whereas acute skin toxicity was seen only in arm A. SCRT had fewer treatment interruptions compared to LCCRT. CONCLUSIONS: SCRT followed by three cycles of CAPOX chemotherapy in the neoadjuvant setting is comparable to LCCRT in terms of tumour response. This may be a better alternative regimen with fewer treatment interruptions in a resource-limited setting.

Impact of Topical Cyclosporine-A or Topical Chloroquine on Post-LASIK Ocular Surface Stability - A Randomized Controlled Trial.

PURPOSE: To compare effect of topical cyclosporine-A 0.05% (CsA) and chloroquine phosphate 0.03% (CHQ) as an adjunct to standard therapy in maintaining post-laser assisted in situ keratomileusis (LASIK) ocular surface stability. METHODS: Randomized controlled trial on 100 eyes undergoing femtosecond-LASIK randomized into three groups: 33 eyes in Group I (Standard Treatment group), 34 eyes in Group II (CsA group) and 33 eyes in Group III (CHQ group). Standard treatment included topical moxifloxacin, topical prednisolone and carboxymethyl cellulose. Group II received topical CsA 0.05% twice daily for three months and group III received topical CHQ 0.03% twice daily for three months in addition to standard treatment. Primary outcome measure was change in ocular surface disease index (OSDI) at 6 months. Secondary outcome measures were tear break up time (TBUT), Schirmer-I score, tear film osmolarity, tear film MMP-9 and visual acuity. Follow-up was performed at postoperative 1, 3 and 6 months. RESULTS: At 6 months, OSDI score, MMP-9, tear osmolarity, TBUT and Schirmer score were significantly better in both CsA and CHQ groups as compared with controls (p < 0.001). OSDI, Tear osmolarity, TBUT, MMP-9 levels were comparable in CsA and CHQ group (p > 0.05). In CsA group, tear film MMP-9 levels at 6 months were comparable to preoperative baseline (p = 0.09). There was no significant change in the Schirmer score from baseline in the CsA group; in addition, the Schirmer score was significantly better than the CHQ group at 6 months (p = 0.02). Visual acuity was comparable in all three groups. Adverse effects including burning sensation, stinging, pain and redness were reported by ten patients (CsA group- 3, CHQ group-7; p = 0.28). CONCLUSION: Both CsA and CHQ are useful adjuncts to standard therapy in maintaining ocular surface stability after refractive surgery. Cyclosporine A has more potent and sustained anti-inflammatory effect with less ocular irritative effects.

Serum Trace Elements in Children with Well-Controlled and Drug Refractory Epilepsy Compared to Controls: An Observational Study.

Background: Trace elements have been implicated in pathogenesis of epilepsy. Studies till date have shown altered levels of serum trace elements in children with epilepsy. Objective: The objective of the current was to estimate serum levels of trace elements in children with well-controlled and drug refractory epilepsy and compare it with controls. Methodology: In a tertiary care teaching hospital of North India, serum selenium, copper, zinc, and iron were estimated in well-controlled and drug refractory epileptic children aged 2-12 years and compared with age and gender matched controls. Results: A total of 106 children with epilepsy (55 drug refractory and 51 well controlled) and 52 age and gender matched controls were included in the study. Serum selenium and copper were significantly decreased in cases compared to controls. After classifying epilepsy into well-controlled and drug refractory cases, only in the latter the significant difference for serum selenium and copper levels remained compared to controls. Additionally, in the drug refractory cases, serum iron levels were significantly reduced compared to controls. Conclusions: Serum trace elements are altered in children with epilepsy (more so in the drug refractory group) compared to controls. Monitoring of serum trace elements in children with epilepsy should be considered. Up to one-third of epilepsy is drug refractory of which only another third are amenable to surgery. It is worth investigating the therapeutic potential of altered micronutrient status in these patients.

Comparison of Modified Rose Method of Thyroid Palpation Versus Other Methods for the Detection of Retrosternal and Nodular Goitre.

Objectives: This is a diagnostic test research study to evaluate the various existing methods of thyroid examination and their comparison with the novel modified Rose method. It also aims to measure inter-examiner variation in clinical findings based on the level of education and training, as compared to ultrasonography. Methodology: This cross-sectional study was conducted at a tertiary care hospital with 83 patients presenting to surgery OPD with neck swelling. Each patient was examined by one trained Junior Resident and a Surgery Consultant with all the four methods and with ultrasonography. Data was analysed by Stata-14, agreement between the two categorical variables was assessed by Kappa. In case of continuous variable agreement was assessed by Intra class correlation and Bland-Altman plot. Results: Modified Rose method by the consultant has the highest sensitivity (98%) and diagnostic odds (210) as compared to others but its specificity ranges from 46.7-91.1% to diagnose retro-sternal extension of a goiter. It has 93.98% agreement for identification of nodules. It has a high specificity (Consultant - 100%, Resident - 95.5%) with relatively lower sensitivity (Consultant - 94%, Resident - 86.8%) to diagnose solitary thyroid nodule (STN) but the sensitivity and specificity for diagnosing a multinodular goitre (MNG) was high. However, the highest sensitivity to diagnose STN was highest with Crile's method, but specificity was low. Lahey's method was a better clinical method to palpate lymph nodes compared to the other three. Conclusion: Examination in modified Rose's position is a better method of clinical examination of thyroid especially in patients with occult substernal extension. Lahey's method is a better method to examine cervical lymph nodes.

Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study.

Introduction: The objective of the study was to evaluate the clinical profile and outcome of patients with secondary hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. Materials and methods: A prospective observational study was conducted where critically ill adult patients presenting with fever and bicytopenia were evaluated according to the HLH-2004 diagnostic criteria for the presence of secondary HLH. The underlying trigger, clinical profile, treatment, and outcome of patients with HLH were analyzed. Results: Of the 76 critically ill patients with fever and bicytopenia, 33 (43%) patients were diagnosed with HLH. The following triggers for HLH were identified: bacterial infections (23%), fungal infections (10%), viral infections (10%), parasitic infections (10%), autoimmune diseases (13%), and malignancy (8%). A total of 78% of the HLH cases received steroids, but the use of steroids was not associated with improvement in mortality. Conclusion: There is a high prevalence of HLH in patients presenting with fever and bicytopenia in critically ill adult patients. Infections were identified as the most common trigger of HLH. How to cite this article: Fazal F, Gupta N, Soneja M, Mitra DK, Satpathy G, Panda SK, et al. Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study. Indian J Crit Care Med 2022;26(5):564-567.

Effect of Yoga on Clinical Outcomes and Quality of Life in Patients With Vasovagal Syncope (LIVE-Yoga).

OBJECTIVES: This study aims to determine the impact of yoga as an adjunct to standard therapy versus standard therapy alone on the symptomatic burden in patients with recurrent vasovagal syncope (VVS). BACKGROUND: There is a significant reduction in the quality of life (QoL) of patients with recurrent VVS. Existing management therapies have been largely ineffective. Recent trials have demonstrated the efficacy of yoga in diseases with autonomic imbalance, suggesting its possible utility in VVS. METHODS: Patients with recurrent VVS were randomized to receive either a specialized yoga training program in addition to current guideline-based therapy (intervention arm, group 1) or current guideline-based therapy alone (control arm, group 2). The primary outcome was a composite of the number of episodes of syncope and presyncope at 12 months. Secondary outcomes included QoL assessment by World Health Organization Quality of Life Brief Field questionnaire (WHOQoL-BREF) scores and Syncope Functional Status Questionnaire scores at 12 months, head up tilt test, and heart rate variability at 6 weeks. RESULTS: A total of 55 patients underwent randomization. The mean number of syncopal or presyncopal events at 12 months was 0.7 ± 0.7 in the intervention arm compared to 2.52 ± 1.93 in the control arm (P < 0.01). In the intervention arm, 13 (43.3%) patients remained free of events versus 4 (16.0%) patients in the control arm (P = 0.02). QoL at 12 months showed significant improvement of all Syncope Functional Status Questionnaire scores and 2 domains of WHOQoL-BREF scores (P < 0.05). CONCLUSIONS: Yoga as adjunctive therapy is superior to standard therapy alone in reducing the symptomatic burden and improving QoL in patients with recurrent VVS.

Autophagy-associated HMGB-1 as a novel potential circulating non-invasive diagnostic marker for detection of Urothelial Carcinoma of Bladder.

Urothelial carcinoma of bladder (UBC), a highly prevalent urological malignancy associated with high mortality and recurrence rate. Standard diagnostic method currently being used is cystoscopy but its invasive nature and low sensitivity stresses for identifying predictive diagnostic marker. Autophagy, a cellular homeostasis maintaining process, is usually dysregulated in cancer and its role is still enigmatic in UBC. In this study, 30 UBC patients and healthy controls were enrolled. Histopathologically confirmed tumor and adjacent normal tissue were acquired from patients. Molecular expression and tissue localization of autophagy-associated molecules (HMGB-1, RAGE, beclin, LC-3, and p62) were investigated. Serum HMGB-1 concentration was measured in UBC patients and healthy controls. ROC curves were plotted to evaluate diagnostic potential. Transcript, protein, and IHC expression of HMGB-1, RAGE, beclin, and LC-3 displayed upregulated expression, while p62 was downregulated in bladder tumor tissue. Serum HMGB-1 levels were elevated in UBC patients. Transcript and circulatory levels of HMGB-1 showed positive correlation and displayed a positive trend with disease severity. Upon comparison with clinicopathological parameters, HMGB-1 emerged as molecule of statistical significance to exhibit association. HMGB-1 exhibited optimum sensitivity and specificity in serum. The positive correlation between tissue and serum levels of HMGB-1 showcases serum as a representation of in situ scenario, suggesting its clinical applicability for non-invasive testing. Moreover, optimum sensitivity and specificity displayed by HMGB-1 along with significant association with clinicopathological parameters makes it a potential candidate to be used as diagnostic marker for early detection of UBC but requires further validation in larger cohort.

Substance use and its associated factors among school students.

Background: . There is lack of comprehensive data on substance use and associated factors among school students in Delhi, India. Methods: . We used a cluster sampling method based on sections of classes in schools to conduct this study in two government-run schools in Delhi. All enrolled students from 8th, 9th and 11th grades participated (n = 405). The WHO Student Drug Use questionnaire was administered in a single session for a class section for assessing substance use. Results: . The participation rate was 90.6%. The rates of past 12 months' use of tobacco, alcohol, cannabis and inhalants were 22%, 12.1%, 12.1% and 8.6%, respectively, while rates for 'sedatives and tranquillizers' were 4.9%, opium 2.7% and other opioids 1.2%. Lifetime use of heroin was reported by two students and use in the past 12 months by one student. Multiple substance use was high. Higher age was associated with the use of alcohol and cannabis. According to logistic regression model results, use by a family member significantly increased the probability of using tobacco (adjusted odds ratio [AOR] 11.3; 95% confidence interval (CI) 3.4-37.8) and alcohol (AOR 3.75; 95% CI 5.1-1059.3). Similarly, use by peers significantly increased the probability of tobacco (AOR 7.7; 95% CI 2.0-29.8) and cannabis use (AOR 5.7; 95% CI 1.5-21.5). Having poor harm perception significantly increased the chances of inhalant use by students (AOR 5.5; 95% CI 1.5-20.1). Conclusion: . The study results bring to attention the prevalent and important problem of substance use among schoolchildren. We recommend that (i) intervention strategies for school settings are important and need to factor in the use of illicit substances (cannabis); (ii) psychosocial intervention by trained school counsellors in school settings is the mainstay for intervention for cannabis and inhalants; and (iii) heroin users should be referred to healthcare facilities for detoxification.

Growth Outcome and Jaw Functions Are Better After Gap Arthroplasty Plus Costochondral Graft Reconstruction Than Gap Arthroplasty Alone in Pediatric Temporomandibular Joint Ankylosis Patients: A Cluster Randomized Controlled Trial.

PURPOSE: It is not known if the muscle matrix that becomes functional after gap arthroplasty (GA) in temporomandibular joint ankylosis (TMJA), induces growth of the mandible or the reconstructive arthroplasty with costochondral graft (CCG) is responsible for growth. The study aimed to evaluate the mandibular growth and functional outcome with the use of CCG/GA in the management of pediatric TMJA. METHODS: The investigators designed a cluster randomized controlled trial on pediatric (3 to 16 years) TMJA patients. Treatment applied (CCG and GA), was the primary predictor variable. Patients were divided into CCG and GA groups. The primary outcome variable was growth. Secondary outcome variables included etiology and duration of ankylosis, maximal incisal opening (MIO), reankylosis, occlusion, laterotrusion, chin deviation, facial asymmetry, occlusal tilt, and complications. The distance condylion (Co) to gnathion (Gn) was used to measure mandibular length. Ramal height was measured from Co- gonion (Go). Lower facial height was measured from the anterior nasal spine to Gn. Generalized estimating equations were used to calculate the regression coefficient adjusted for the cluster. The patient was considered as a cluster and the unit of analysis was joint. RESULTS: Fifty-six {n = 28 in each group, (n = 33 joint in the CCG group and n = 31 joints in GA group)} patients were analyzed. The median follow-up was 33-months (31.93 ± 15.24) in the CCG group and 32-months (32.85 ± 17.84) in the GA group. Intergroup comparison between the CCG and GA group showed a statistically significant difference in mandibular length (CCG = 77.51 ± 9.31 and GA = 66.66 ± 8.32 mm, P < .001), ramal height (CCG = 44.21 ± 7.3 and GA = 31.87 ± 8.4 mm, P < .001), and statistically insignificant difference in lower facial height (CCG = 52.53 ± 6.1 and GA = 50.19 ± 6.3 mm, P = 0.14) at follow-up. Statistically, significant improvement was seen in MIO in both groups (<.001). CONCLUSIONS: The results of the present study concluded that growth and jaw functions were better in reconstructive arthroplasty with CCG than GA in pediatric TMJA.

Can costochondral grafts fulfil ramus-condyle unit reconstruction goals in children with temporomandibular joint ankylosis?

The purpose of this study was to analyse whether costochondral grafts (CCG) fulfil temporomandibular joint (TMJ) reconstructive goals in children with TMJ ankylosis. A total of 23 patients (12 male, 11 female, aged 3-16 years) with unilateral or bilateral TMJ ankylosis operated on between January 2014 to April 2018 were included in the study. Maximal incisal opening (MIO), frequency of reankylosis, and growth of CCG, were evaluated at one month and six months for one year, and after that once yearly. Mouth opening changes with time were assessed by the Friedman test and growth was compared at follow up and analysed using the paired t test. Mean (range) follow up was 18 (12-48) months. Study results revealed follow up MIO at 12 months was highly significant (p=0.001). Out of 27 CCG studied, only one graft had undergone re-ankylosis. Based on the predetermined criteria using condylion to gnathion (Co-Gn) measurement in the posteroanterior cephalogram, CCG were categorised into optimum, sub-optimum, and overgrowth. However, long-standing TMJ ankylosis cases still displayed mandibular asymmetry at the end of the study, even with "optimal growth" radiographically. Overall comparison between the immediate postoperative and last follow up Co-Gn measurements in either unilateral or bilateral cases was not significant. CCG with functional matrix maintained the growth of the mandible and MIO in TMJ ankylosis. It can be concluded that CCG partially fulfils reconstructive goals; however, patients need to be followed up till the end of puberty for a substantive conclusion.

Measurement of Serum EGFR mRNA Expression is a Reliable Predictor of Treatment Response and Survival Outcomes in Non- Small Cell Lung Cancer.

BACKGROUND: EGFR over-expression plays a key role in the development and progression of lung cancer. However, its status as a prognostic biomarker for survival outcomes is unclear. OBJECTIVES: To evaluate the prognostic utility of serum EGFR mRNA expression in Non-Small cell lung cancer (NSCLC) for treatment response and survival. METHODS: EGFR mRNA levels were determined in serum using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Based on ROC curve, a cut off value of 16.0-fold increase was selected to categorize patients into low EGFR (≤ 16.0) and high EGFR (> 16.0) groups. RESULTS: A total of 350 subjects were included (78.3% males), with mean (± SD) age of 57.1 (± 11.2) years, and including 247 (70.6%) adenocarcinoma (ADC). Majority (73.1%) had metastatic (stage IV) disease. Patients had higher pre-treatment serum EGFR mRNA levels than controls [median fold-increase (min, max), 16.2 (1.9, 66.7). Serum EGFR mRNA levels significantly reduced in those who achieved objective response and disease control. Significantly longer OS and PFS was observed in subjects having baseline EGFR mRNA expression ≤ 16.0 fold- increase compared to those with > 16.0 fold- increase [median (95% CI) OS: 25.0 (14.9, NR) versus 7.7 (6.3, 8.9) months; HR (95% CI) 2.9 (2.3, 4.0), p < 0.001; and PFS: 9.9 (7.1, 11.5) versus 6.0 (4.1, 7.5) months; HR (95% CI) 1.8 (1.3, 2.4), p < 0.001]. CONCLUSION: Serum EGFR mRNA expression is a useful parameter for predicting treatment response and survival outcomes in NSCLC.

Therapeutic bronchoscopic interventions for nonmalignant central airway obstruction provide rapid and sustained improvement in symptoms and functional status.

BACKGROUND: Central airway obstruction (CAO) is a potentially lethal condition that requires urgent endobronchial intervention and may occur due to several nonmalignant causes. The effect of these interventions on clinically relevant outcomes such as symptomatic and functional status over a period of time is, however, sparsely studied. MATERIALS AND METHODS: Consecutive patients with CAO due to nonmalignant causes and undergoing various therapeutic bronchoscopy procedures were evaluated. Symptoms were assessed using the Visual Analog Scale (VAS) and Speiser score, and functional status was assessed using the 6-min walk test, spirometry, and St. George Respiratory Questionnaire (SGRQ) score at baseline and after 48 h, 4 weeks, and 12 weeks postprocedure. RESULTS: Over 2 years, 31 patients with CAO due to nonmalignant etiology underwent 41 therapeutic bronchoscopic procedures. Majority of procedures (96.8%) were done using the rigid bronchoscope under general anesthesia. Postintubation tracheal stenosis was the most common indication (32.2%). The various procedures included, controlled radial expansion balloon dilatation of the stenotic airway (53.6%), deployment of silicone stents (19.5%), and mechanical debulking of airway tumors (16.1%). Significant improvement occurred in dyspnea and cough scores and in the Speiser score from baseline to 48 h postprocedure, and further improved at 4 weeks and 12 weeks. Similarly, the 6 min walk distance, forced expiratory volume in 1 s, and SGRQ scores progressively improved from baseline to 12 weeks. Complications occurred in 26.8% of total procedures, with no procedure-related mortality. CONCLUSION: Therapeutic bronchoscopy interventions provide rapid and sustained benefits in symptoms and functional status of participants with CAO of nonmalignant etiology, with an acceptable safety profile.

Ketamine mouthwash versus placebo in the treatment of severe oral mucositis pain in children with cancer: A randomized double-blind placebo-controlled trial.

BACKGROUND AND AIMS: Oral mucositis (OM) is a common and distressing toxicity in children on chemotherapy. There are a limited number of safe and effective therapeutic options available for OM. Ketamine oral rinse has shown promising results in a few studies in adults. This randomized, double-blind placebo-controlled trial aimed to test the efficacy of ketamine mouthwash in reducing chemotherapy-induced severe OM pain in children. METHODS: Children aged 8-18 years with severe OM were randomized to a single dose of ketamine mouthwash (4 mg/mL solution; dose 1 mg/kg) or a placebo. A sample size of 44 patients was determined. Pain score (6-point faces scale) was noted at baseline and 15, 30, 45, 60, 120, 180, and 240 min. The outcome variables were a reduction in pain score, need for rescue medications, and adverse events. RESULTS: The baseline characteristics were comparable in the two groups. The mean OM pain at 60 min decreased by 1.64 points (CI 1.13-2.14) in the ketamine group and 1.32 points (CI 0.76-1.87) in the placebo group (P = 0.425), with a group difference of 0.32 points. Rescue pain medication (at 60 min) was required in 13.6% in the ketamine group and 18.2% in the placebo group (P = 1.000). No significant adverse events were observed. CONCLUSIONS: Among children on cancer chemotherapy with severe OM, ketamine mouthwash at a dose of 1 mg/kg did not significantly reduce OM pain. It did not decrease the need for rescue pain medications. Further research is warranted to test higher doses of ketamine for a clinically significant effect.

NOVEL USE OF FLUORESCEIN DYE IN DETECTION OF ORAL DYSPLASIA AND ORAL CANCER.

BACKGROUND: India is now regarded as the country with one of the highest incidence of oral cancer in the world. Considering poor survival in cases with late diagnosis, early detection can reduce morbidity and mortality of cancer patients and may impede malignant transformation in cases of oral potentially malignant disorders (OPMD). Most of the diagnostic aids are expensive and not available for mass screenings in developing countries. There is a need to develop a sensitive and affordable technique for screening of oral cancer, which can be accurate even in hands of health care workers with limited experience. Fluorescein dye has been used for tumour detection in colon, stomach, breast and brain. However, its utility in the diagnosis of oral cancer and OPMD has not yet been explored. METHODS: This is the first study to report the role of fluorescein in the detection of oral cancer and OPMD. The present cross sectional study was conducted at a tertiary care dental centre. It included 100 individuals presenting with 42 OPMDs, 40 oral squamous cell carcinoma (OSCC) and 18 controls. RESULTS: The sensitivity and specificity for the fluorescein detection method for OPMDs and OSCC was found to be 96.6% and 52.4% respectively. The positive predictive value was 73.7% and the negative predictive value was 91.7% for the fluorescein method. The likelihood ratios stood at 2.03 for a positive test and 0.066 for a negative test. CONCLUSION: We conclude that fluorescein staining along with blue light is likely to improve detection of early oral cancers and dysplasia and can play a vital role in mass screening programmes of oral cancer.

Diabetes mellitus in pheochromocytoma and paraganglioma: Prevalence, dynamics of insulin secretion / sensitivity and predictors of remission.

BACKGROUND AND AIMS: Pheochromocytoma and paraganglioma (PPGL) are associated with dysglycemia and diabetes mellitus (DM) much of which improves post operatively. In this study, we set out to ascertain pre and post-operative prevalence of DM in patients with PPGL based on oral glucose tolerance test (OGTT) and HbA1c and to evaluate effect of insulin secretion and sensitivity indices on DM pre-operatively. METHODS: Clinical and anthropometric data collection, HbA1c, 75 g OGTT with serum insulin estimation were done pre-operatively (n = 34) and at follow-up after successful surgery (n = 24) in patients with PPGL. RESULTS: Pre and post-operative prevalence of DM were 48%(18/37) and 17% (4/24) respectively. Comparison of patients with highest (Q4) and lowest (Q1) quartiles of insulinogenic index (IGI),a parameter of insulin secretion, revealed trends towards higher prevalence of DM in patients with lower IGI (Q4 to Q1: 29% versus 71%,n = 28, p = 0.24)but no association was observed with HOMA-IR (Q4 to Q1:50% versus 57%, n = 28, p = 1.00), an insulin sensitivity index. DM remitted in 77% patients post-operatively, predicted by duration of DM of<3 years. CONCLUSION: There is high prevalence of DM in PPGL, with marked remission post-operatively, especially predicted by shorter duration of DM. Impaired insulin secretion is more strongly associated with pre-operative DM than increased insulin resistance.

Histotyping of Indian thymomas: A clinicopathologic study from north India.

Background & objectives: Thymomas are rare, but most common anterior mediastinal lesions. The histomorphologic spectrum of thymic epithelial tumours (TETs) in Indian population has not been explored in depth. This study was aimed to assess the histomorphology of TETs in the Indian patients and correlate clinical parameters with pathological features. Methods: It was a retrospective study conducted in a tertiary referral hospital in north India. All morphologically confirmed cases of TETs since 2009 were included. Clinical details and histology slides were reviewed using the Modified Masaoka-Koga staging system and WHO 2015 classification. Clinicopathological correlation and survival analysis were done. A comparative review from other published Indian studies was performed. Results: A total of 219 cases of TETs (138 resections and 81 biopsies) were identified. The most common histomorphologic type was B2, and the most frequent stage was I. Types A/AB were common in older age (P<0.01). Clinically, higher stage tumours were found mostly in men (P<0.01), and these were Type B thymomas (P<0.01). Myasthenia gravis was more common in women (P<0.02) and in lower stages (P<0.05). Survival analysis revealed significant association between recurrence and tumour stage. Although thymic carcinoma was diagnosed on biopsy, no resectable case was identified. Interpretation & conclusions: Our findings showed that the thymomas in Indian patients were most commonly Stage I tumours of B2 and AB histotypes. Resected thymic carcinomas were conspicuously absent in our study. More studies need to be done to establish the frequency and biology of TETs from India.

Arthroscopic and 3D CT Scan Evaluation of Femoral Footprint of the Anterior Cruciate Ligament in Chronic ACL Deficient Knees.

The outcome of single-bundle anterior cruciate ligament (ACL) reconstruction depends largely on the anatomic placement of bone tunnel. The lateral intercondylar ridge (LIR) and bifurcate ridge (BR) are useful bony landmarks for femoral tunnel placement. The purpose of our study was to compare the bony landmarks of ACL footprint on femur by three-dimensional computed tomography (3D CT) scan and arthroscopy in chronic ACL-deficient knees. Fifty patients above 18 years of age who were diagnosed of having ACL tear were selected for the study. All the cases were more than 6 months old since the injury. Preoperative 3D CT scan of the affected knee was obtained for each of them. They underwent single-bundle anatomic ACL reconstruction. Measurements were done on the preoperative 3D CT and arthroscopy to quantify the position of the LIR and BR. The proximodistal distance of lateral femoral condyle was 21.41+/-2.5 mm on CT scan and 22.02+/-2.02 mm on arthroscopy. On preoperative 3D CT scan, the midpoint of the LIR was found to be located at a mean distance of 11.17±2.11 mm from the proximal margin of the lateral femoral condyle. On arthroscopy, it was at 10.18+/-1.52 mm from the proximal margin the lateral femoral condyle. The "bifurcate ridge"(BR) was not visible in any of the cases during arthroscopy or CT scan. We concluded that LIR is an easily identifiable bony landmark on arthroscopy in all cases. It can also be identified on CT scans. BR is not identified both on arthroscopy and CT scans in chronic ACL tears. The arthroscopic measurements of bony landmarks are quite close to those of CT scan. Midpoint of LIR is at 52.185% of the proximodistal distance on CT scan evaluation and it is at 46.21% on arthroscopic evaluation.