Publications

BACKGROUND: Research output/efforts in a country should be reflective of the disease burden. India is a site for several national and multinational clinical trials. However, whether clinical trials performed in India reflect the disease burden is not well known.

OBJECTIVES: The aim of this study was to evaluate the relationship between disease burden and clinical trials performed in India.

MATERIALS AND METHODS: We extracted data on the disease burden from the World Health Organization (WHO) website and on characteristics of clinical trials performed in India from the Clinical Trial Registry of India (CRTI). The correlation between disease burden parameters of overall mortality, disability-adjusted life years (DALYs), years lost due to disability (YLD) and years of life lost (YLL), and the frequency of clinical trials associated with a particular disease was assessed. Additional subgroup analysis according to the number of trial centers, study phase, and medicine type was also performed.

RESULTS: Only 18% of clinical trials addressed top 10 diseases associated with 68.3% of overall mortality, and 8% of clinical trials addressed top 10 diseases associated with 52.3% of DALYs. Similarly, 16% of clinical trials addressed top 10 diseases associated with 53.2% YLDs. Furthermore, top 10 diseases associated with 65.9% of YLLs were addressed in only 8% of ongoing clinical trials. The overall correlation between any disease burden parameters with the diseases being explored in clinical trials was poor.

CONCLUSION: There is a mismatch between diseases for which clinical trials are happening in the India and the disease burden of India. Measures need to be taken to fulfill this gap between demand and need.

The United Network for Organ Sharing (UNOS) implemented a policy that requires patients with hepatocellular carcinoma seeking liver transplantation to wait six months before being granted Model for End-Stage Liver Disease exception points. We investigated the difference in resource utilization between patients who underwent liver transplantation before and after the present policy. We conducted a retrospective cohort study of adult liver transplants from 2013 to 2018. Patients were classified into prepolicy or postpolicy groups based on 964 days before or after the wait-time policy. We also retrieved national survival outcome data from United Network for Organ Sharing. Differences across compared groups for continuous variables were assessed using the independent sample t test, and the chi-squared test was used for binary variables. We found statistical differences in recipient age (P = 0.005), days on wait-list (P = 0.001), sustained virological response (P < 0.001), and hepatocellular carcinoma recurrence one year posttransplant (P = 0.04). There were statistically significant differences in the number of treatment days pretransplant and length of transplant admission stay, indicating an increase in resource utilization in the postpolicy group. No statistically significant differences were found between groups in one-year graft or patient survival despite an observed increase in resource utilization by the hepatocellular carcinoma postpolicy group.

Laterally located intracranial mature teratomas are rare entities. We report an extremely rare case of an extra-axial mature teratoma of the left petrous temporal bone in an infant who was managed surgically. This is the second reported case of a mature teratoma of the petrous temporal bone in an infant.

UNLABELLED: An elevation of serum inflammatory biomarkers in achalasia patients compared with controls recently was demonstrated. It has not been determined whether the elevation of inflammatory cytokines is unique to achalasia or occurs with other diseases involving the esophagus. The primary aim of our study was to compare the differences in plasma immunological profiles (TNF- α receptor, IL-6, IFN-γ, IL-12, IL-17, IL-22, and IL-23) of patients with achalasia, eosinophilic esophagitis (EoE), and gastroesophageal reflux disease (GERD). A secondary aim of this study was to classify these same plasma cytokine profiles in the three achalasia subtypes.

METHODS: Plasma from 53 patients with achalasia, 22 with EoE, and 20 with GERD (symptoms plus esophagitis or + reflux study) were analyzed.

EXCLUSION CRITERIA: malignancy, autoimmune condition, immunodeficiency disorder, and treatment with steroids/immune modulating drugs. Cytokine levels were assayed via multiplex enzyme-linked immunosorbent assay (ELISA).

RESULTS: Our key finding revealed significant elevations in IL- 6 (p = 0.0158) in achalasia patients compared with EoE patients. Overall, plasma inflammatory biomarker patterns were not different in the three subtypes of achalasia.

CONCLUSION: There were no differences between the cytokine levels of any of the measured biomarkers between the achalasia and GERD groups suggesting that luminal stasis does increase biomarker levels for any of the cytokines examined in our study. While these results are an early first step towards clarifying some aspects of the pathogenesis of achalasia, they bring about many more questions that require further investigation and expansion. Further investigation with a larger cohort and a broader panel of biomarkers is needed.

Basilar apex aneurysms constitute 5%-8% of all intracranial aneurysms. Microsurgical clipping of basilar tip aneurysms is still advocated for as it is safe, especially for unruptured basilar tip aneurysms which have a low risk of postoperative mortality or morbidity. Careful patient preparation is needed preoperatively because the risk of intraoperative rupture is significant. Good surgical techniques should be applied. The skill will need to be preserved as endovascular surgery becomes more popular. This is a case of basilar tip aneurysm managed by clipping through the anterior temporal approach, followed by a review of the literature.

BACKGROUND: The outcomes for patients with diffuse large B-cell lymphoma (DLBCL) with adverse clinical prognostic factors such as a high age-adjusted International Prognostic Index (aaIPI) are not optimal. In the current study, the authors performed a systematic review and meta-analysis to assess the totality of evidence pertaining to the efficacy of autologous hematopoietic stem cell transplantation (auto-HCT) consolidation for patients with DLBCL in first remission.

METHODS: The authors searched the Cochrane and MEDLINE/PubMed databases through December 1, 2018, for studies comparing conventional chemotherapy with rituximab (R-chemo) versus R-chemo and auto-HCT. Two authors independently reviewed all references for study inclusion and extracted data related to benefits (overall survival, progression-free survival, and response rates) and harms (treatment-related mortality and adverse events).

RESULTS: Four studies (1173 patients) met the inclusion criteria and were included in the current analysis. The median duration of follow-up ranged from 42 to 76 months. There was no difference noted with regard to the overall survival (hazard ratio, 1.01; 95% CI, 0.74-1.37), progression-free survival (hazard ratio, 0.77; 95% CI, 0.58-1.04), or response rates (risk ratio, 0.98; 95% CI, 0.92-1.04) between patients who received R-chemo and auto-HCT and those who received R-chemo alone. The risk of mortality and therapy failure was not found to be different when the analysis was limited to high aaIPI between the 2 groups. Although there was no difference noted with regard to the risk of treatment-related mortality, there was a significantly higher incidence of CTCAE grade 3 or 4 adverse events in patients who received R-chemo and auto-HCT compared with patients treated with R-chemo alone.

CONCLUSIONS: The findings from what to the authors' knowledge is the first meta-analysis performed in the rituximab era demonstrated no beneficial effect of upfront auto-HCT consolidation in patients with aggressive B-cell non-Hodgkin lymphoma, including high-risk clinical groups (high aaIPI).

Human T cell lymphotropic virus type 1 (HTLV1)-associated adult T cell leukemia/lymphoma (ATLL) is an aggressive malignant disorder. Intensive conventional chemotherapy regimens and autologous hematopoietic cell transplantation (HCT) have failed to improve outcomes in ATLL. Allogeneic HCT (allo-HCT) is commonly offered as front-line consolidation despite lack of randomized controlled trials. We performed a comprehensive search of the medical literature using PubMed/Medline, EMBASE, and Cochrane reviews on September 10, 2018. We extracted data on clinical outcomes related to benefits (complete response [CR], overall survival [OS], and progression-free survival [PFS]) and harms (relapse and nonrelapse mortality [NRM]), independently by 2 authors. Our search strategy identified a total of 801 references. Nineteen studies (n = 2446 patients) were included in the systematic review; however, only 18 studies (n = 1767 patients) were included in the meta-analysis. Reduced intensity conditioning regimens were more commonly prescribed (52%). Bone marrow (50%) and peripheral blood (40%) were more frequently used as stem cell source. The pooled post-allografting CR, OS, and PFS rates were 73% (95% confidence interval [CI], 57% to 87%), 40% (95% CI, 33% to 46%), and 37% (95% CI, 27% to 48%), respectively. Pooled relapse and NRM rates were 36% (95% CI, 28% to 43%) and 29% (95% CI, 21% to 37%), respectively. The heterogeneity among the included studies was generally high. These results support the use of allo-HCT as an effective treatment for patients with ATLL, yielding pooled OS rates of 40%, but relapse still occurs in over one-third of cases. Future studies should evaluate strategies to help reduce relapse in patients with ATLL undergoing allo-HCT.

BACKGROUND: Central nervous system (CNS) lymphoma is associated with poor outcomes. Autologous stem cell transplantation (ASCT) has been reported to improve outcomes when used as a consolidation strategy in primary CNS lymphoma (PCNSL) and as a salvage strategy in patients with disease relapse limited to the CNS. Herein, we describe our experience of using ASCT in PCNSL and secondary CNS lymphoma (SCNSL).

PATIENTS AND METHODS: We evaluated clinical outcomes of 18 patients from 2 major academic centers with a median age of 55 (range, 46-72) years. Thirteen patients had PCNSL and 5 patients had SCNSL. Most of the cases were in the first (CR1) or second (CR2) complete remission (CR1 = 7, CR2 = 7) at the time of ASCT. Carmustine with thiotepa (n = 12, 67%) was the most commonly prescribed preparative regimen.

RESULTS: The median follow-up from ASCT for surviving patients was 12 (range, 0.9-115) months. The 2-year progression-free survival (PFS) and overall survival (OS) were 74% (95% confidence interval [CI], 48%-99%) and 80% (95% CI, 55%-100%), respectively. Two-year non-relapse mortality was 0%. The 2-year cumulative incidence of relapse/progression was 27% (95% CI, 10%-72%). In subgroup analysis of PCNSL patients, 2-year PFS, OS, and relapse were 71% (95% CI, 38%-100%), 71% (95% CI, 38%-100%), and 29% (95% CI, 9%-92%), respectively.

CONCLUSION: In this retrospective study of patients with CNS lymphoma, consolidation with ASCT after high-dose methotrexate-based chemotherapy is safe and effective in reducing disease relapse.

BACKGROUND: Paediatric intubations are a relatively rare but critical procedure that requires adequate practice to achieve skillful performance. Simulation is a method to teach intubation skills in a safe environment. Rapid Cycle Deliberate Practice (RCDP), as a method of simulation debriefing, has been shown to improve pediatric resident resuscitation skills. It has not been demonstrated if RCDP can be effectively used in procedural skills training. The objective of this study was to determine if RCDP with feedback in real-time, as well as an opportunity to repeat the action, is superior to a simulation where no feedback is provided during the simulation and is instead provided after the simulation.

MATERIALS AND METHODS: This was a randomized controlled single-blinded study. All participants were videotaped during a simulated pre-assessment intubation, then received either the intervention (RCDP) or the control teaching (feedback after the simulation), followed by a post-assessment intubation. These videos were scored by two independent raters on an intubation checklist. The primary outcome was the change in score. The secondary outcome was intubation success.

RESULTS: Thirty-five students met the inclusion criteria. The RCDP group achieved a significantly higher score improvement in the preparation and post-procedure care categories. The overall score change in the RCDP group was significantly higher than in the control group, with a mean difference of -11.86 (CI -15.57 to -8.15, p<0.00001), but there was no significant improvement in intubation success.

CONCLUSION: Our study suggests that RCDP is an effective method to teach the procedural skill of intubation with an emphasis on procedural choreography. RCDP could be an appropriate method for debriefing learners in procedural skills training in this population.

OBJECTIVES: Percutaneous gastrostomy tube placement is performed in patients requiring long-term enteral nutrition. Although both endoscopic and fluoroscopic techniques may be used, there are inherent risks and potential complications associated with both procedures that are not generally known to referring physicians. The purpose of this study was to compare and contrast indications for placement and procedurally related complications between fluoroscopic and endoscopic gastrostomy tubes techniques at a tertiary care facility.

METHODS: A retrospective cohort study was performed. All consecutive patients with either percutaneous endoscopic (PEG) or percutaneous radiologic (PRG) gastrostomy tube placement between October 2011 and January 2013 were eligible for inclusion. Basic demographic information, American Society of Anesthesiologists score, procedure indication, laboratory data, and use of anticoagulation were recorded. Both direct and indirect procedural complications were documented if they occurred 30 days after gastrostomy tube placement, and were classified and scored based on severity and need for further intervention.

RESULTS: A total of 297 patients met the inclusion criteria, 150 of whom had gastrostomy tubes placed fluoroscopically and 147 of whom had them placed endoscopically. There was no statistically significant difference in direct complications within the first 30 days (PEG 6.8% vs PRG 8%); however, the type of complication observed varied between the two groups. Although superficial wound infections and buried bumpers were more common in the PEG group, bleeding was more common in the PRG group.

CONCLUSIONS: Placement of gastrostomy tubes either endoscopically or fluoroscopically is relatively safe with similar indications. Although the complication rate between the two groups was not significant, the types of procedural complications observed did vary.