Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.

BACKGROUND: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODS: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS: A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONS: In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).

Novel Management of Ocular Surface Inflammation in Patients With Ocular Graft-Versus-Host Disease in the Setting of Cataract Surgery.

PURPOSE: To report the outcomes of cataract surgery in patients with ocular graft-versus-host disease (oGVHD) using a novel preoperative immunomodulatory regimen in a collaborative subspecialty care setting. METHODS: Retrospective case series of patients with oGVHD who underwent cataract surgery using a novel preoperative immunomodulatory regimen in a collaborative care setting. A preoperative regimen consisting of pooled human immune globulin 1%, autologous serum 50%, and methylprednisolone 1% eye drops was prescribed. Outcome measures included visual acuity (VA), ocular surface disease index (OSDI) score, lissamine green staining, and complications with a minimum of 2 years of follow-up. RESULTS: Thirty-five eyes from 20 patients with oGVHD were studied. The mean age was 59 years (range 30-70 years). A healthy comparison group included 35 eyes from 24 patients with a mean age of 63 years (range 44-74 years). At the 2-year follow-up, the mean corneal staining score was 2.3/15, the mean OSDI score was 37.5, and the mean VA was 20/30 (logarithm of the minimal angle of resolution 0.17). The global complication rate was 2.8% at the last follow-up with no difference versus a healthy comparison group. CONCLUSIONS: A collaborative care model improving ocular surface health before cataract surgery with dry eye and cataract subspecialists can optimize outcomes in patients with oGVHD.

Recombinant Deoxyribonuclease I Eye Drops for Ocular Graft Versus Host Disease: Results of a Randomized Clinical Trial.

OBJECTIVE: We have previously shown that neutrophil extracellular traps (NETs) are present on the ocular surface of patients with ocular graft versus host disease (oGVHD), contributing to inflammation and surface disease. Therefore, we performed a clinical trial using deoxyribonuclease I (DNAase) eye drops to test the hypothesis that reducing the abundance of NETs from the ocular surface will reduce signs and symptoms of oGVHD. METHODS: A prospective, phase I or II, randomized, placebo-controlled, double-masked clinical trial was performed to determine the safety and preliminary efficacy of DNAase (0.1%) eye drops four times daily for 8 weeks in patients with oGVHD (n=58). Intent-to-treat analysis was performed to determine the change in safety outcome measures (drug tolerability and proportion of adverse events) and efficacy outcome measures (ocular surface disease index [OSDI] score and corneal staining) between baseline and week 8. RESULTS: Tolerability and adverse events were similar in the vehicle and DNAase groups. Within the DNAase group (but not the vehicle group), corneal staining showed a statistically significant and clinically meaningful reduction at week 8 (3.50 [2.75; 5.00]) compared with baseline (5.00 [3.00; 7.00]). The OSDI score also showed a statistically significant clinically meaningful reduction of 18.4 (9.16; 33.1) ( P <0.001) at week 8 compared with baseline (45.5 [31.8; 50.0]) within the DNAase group. The proportion of eyes that had improvement in subjective global assessment (SGA) and mucous discharge was significantly greater in the DNAase group (55.6% and 57.7% at weeks 4 and 8, respectively; P <0.0001 at both time points) as compared with the vehicle group (35.7% and 34.0% at weeks 4 and 8, respectively). CONCLUSIONS: Treatment of patients with oGVHD using DNAase eye drops is safe and demonstrates preliminary efficacy. Deoxyribonuclease I eye drops can potentially reduce the severity of signs and symptoms of ocular surface disease in patients with oGVHD.

"Window of Opportunity" in Ocular Graft-Versus-Host Disease Treatment: Results of a Longitudinal Study and Case Reports.

OBJECTIVE: To perform a longitudinal study for determining the development of ocular graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplant (HSCT) and report cases that illustrate the "window of opportunity" concept in oGVHD treatment. METHODS: Patients (n=61) were examined at prescheduled clinic visits before HSCT and three-month intervals after HSCT for 2 years. The presence or absence of oGVHD was determined using the international chronic oGVHD consensus group diagnostic criteria. Ocular surface washings (OSW) were obtained at each visit and analyzed for cytokine levels. RESULTS: In the longitudinal study, 26.2% (n=16; progressed group) developed either probable (11.5%, n=7) or definite oGVHD (14.8%, n=9). In the progressed group, clinically significant changes in signs (corneal staining and Schirmer I test) and symptoms at the post-HSCT visit as compared with the pre-HSCT visit occurred at 9 months. Significant differences in clinical signs and symptoms (whether average post-HSCT values or changes in values over pre-HSCT levels) between the progressed and nonprogressed groups occurred at a 9-month visit or later. In the progressed group, 55.6% of eyes that had negative matrix metalloproteinase 9 (MMP-9) test at pre-HSCT turned MMP-9 positive at 3 to 6 months post-HSCT. In the progressed group, interleukin 8 levels in OSW were significantly increased at 6 months post-HSCT. In the case reports, the "window of opportunity" was detected by MMP-9 turning positive, early corneal staining, interleukin 8 increase in OSW, and peripheral corneal epithelial thinning, which resolved with treatment initiation. CONCLUSIONS: A "window of opportunity" exists before patients developing symptomatic tear-deficient dry eye after HSCT for initiating treatment that may preempt oGVHD development; however, larger-scale longitudinal studies are needed for definitive recommendations.

Optimizing nutrients from fly ash-amended soil through microbial-assisted phytoremediation using response surface methodology.

Nutrients are vital ingredients to boost plant health. The availability of nutrients is limited in fly ash (FA) waste to properly implement phytoremediation. The research explored the integration of microbes and treated wastewater irrigation in phytoremediation to provide the necessary nutrients for plant growth in fly ash-amended soils. The Box-Behnken method was used to design the experimental layout for the pot study. Response surface methodology (RSM) was applied as the optimization approach to model predictions for nutrient accumulation. The implemented pot study attained the highest morphological indicators with a plastochron index of 33.40, an absolute growth rate of 2.63 cm/day, and a leaf area of 2681.68 cm2 and attained maximum biomass of 24.91 g for the treatments that included a mid-range of the variables. The combination of FA 14.98%, microbial dose 4.07 mL, and treated wastewater as the irrigation source was found to be the optimized combination for nitrogen and phosphorus accumulation of 212.4 and 8.867 mg/L.

Comparison of the effectiveness and safety of 2 aspirin doses in secondary prevention of cardiovascular outcomes in patients with chronic kidney disease: A subgroup analysis of ADAPTABLE.

BACKGROUND: Among patients with established cardiovascular disease, the ADAPTABLE trial found no significant differences in cardiovascular events and bleeding rates between 81 mg and 325 mg of aspirin (ASA) daily. In this secondary analysis from the ADAPTABLE trial, we studied the effectiveness and safety of ASA dosing in patients with a history of chronic kidney disease (CKD). METHODS: ADAPTABLE participants were stratified based on the presence or absence of CKD, defined using ICD-9/10-CM codes. Within the CKD group, we compared outcomes between patients taking ASA 81 mg and 325 mg. The primary effectiveness outcome was defined as a composite of all cause death, myocardial infarction, or stroke and the primary safety outcome was hospitalization for major bleeding. Adjusted Cox proportional hazard models were utilized to report differences between the groups. RESULTS: After excluding 414 (2.7%) patients due to missing medical history, a total of 14,662 patients were included from the ADAPTABLE cohort, of whom 2,648 (18%) patients had CKD. Patients with CKD were older (median age 69.4 vs 67.1 years; P < .0001) and less likely to be white (71.5% vs 81.7%; P < .0001) when compared to those without CKD. At a median follow-up of 26.2 months, CKD was associated with an increased risk of both the primary effectiveness outcome (adjusted HR 1.79 [1.57, 2.05] P < .001 and the primary safety outcome (adjusted HR 4.64 (2.98, 7.21), P < .001 and P < .05, respectively) regardless of ASA dose. There was no significant difference in effectiveness (adjusted HR 1.01 95% CI 0.82, 1.23; P = .95) or safety (adjusted HR 0.93; 95% CI 0.52, 1.64; P = .79) between ASA groups. CONCLUSIONS: Patients with CKD were more likely than those without CKD to have adverse cardiovascular events or death and were also more likely to have major bleeding requiring hospitalization. However, there was no association between ASA dose and study outcomes among these patients with CKD.

Dofetilide use is not associated with increased mortality in patients with left ventricular hypertrophy and atrial fibrillation.

BACKGROUND: Left ventricular hypertrophy (LVH) is common in patients with atrial fibrillation (AF), however, many antiarrhythmic drugs (AADs) are contraindicated. US guidelines recommend avoiding pure class III antiarrhythmics such as dofetilide in patients with significant LVH due to concern for an increased risk of death, however, clinical data is lacking. We sought to determine if dofetilide use was associated with increased mortality in patients with LVH. METHODS: Patients ≥18 years of age with AF and LVH ≥ 1.4 cm were included. A group of patients treated with dofetilide and a control group of patients without a history of AAD use were propensity matched. The primary outcome was all-cause mortality at 3 years and secondary outcomes were total number of all-cause hospitalizations and hospitalizations related to AF. RESULTS: There were 359 patients in each of the groups. Baseline variables were well-matched. The primary outcome of all-cause mortality occurred in 7% of patients in the dofetilide group and 12% of patients in the control group (hazard ratio: 0.90, 95% confidence interval: 0.53-1.53). Total all-cause hospitalizations were higher in the control group but hospitalizations for AF were no different. CONCLUSIONS: In a propensity-matched cohort of 718 patients with AF and LVH, dofetilide was not associated with increased mortality at 3 years. Our study adds to prior data demonstrating the safety of dofetilide in this population despite guideline recommendations against its use. Given the limited options for AF management in LVH patients, dofetilide may be reasonable for symptomatic AF management.

Response assessment by positron emission tomography-computed tomography as compared with contrast-enhanced computed tomography in childhood Hodgkin lymphoma can reduce the need for radiotherapy in low- and middle-income countries.

INTRODUCTION: The InPOG-HL-15-01, a multicentric prospective study, used a risk-stratified and response-based approach with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) backbone to treat children and adolescents with newly diagnosed Hodgkin lymphoma (HL) and reduce the use of radiation therapy (RT). Children/adolescents with bulky disease or inadequate response at early response assessment (ERA) after two cycles of chemotherapy were assigned to receive RT. For ERA, positron emission tomography computed tomography (PET-CT) was recommended but not mandatory in view of limited access. This study aimed to compare the impact of using contrast-enhanced computed tomography (CECT) and PET-CT on treatment decisions and outcomes. METHODOLOGY: 396 patients were enrolled and 382 had an ERA at the assigned time point. Satisfactory response was defined as Deauville score 3 or less for patients undergoing PET-CT and complete response (CR)/very good partial response (VGPR) for patients undergoing CECT. Outcomes of interest incorporate 5 year event-free survival (EFS), EFS including abandonment (EFSa), and overall survival (OS). RESULTS: At ERA, satisfactory response was documented in 277 out of 382 (72.5%) participants and this was significantly higher in PET-CT (151 out of 186, 81.2%) as compared with CECT-based assessments (126 out of 196, 64.3%) respectively (p value < .001). Amongst the 203 patients with nonbulky disease (wherein the indication for RT was entirely dependent on ERA), 96 out of 114 (84.2%) and 61 out of 89 (68.5%) patients achieved a satisfactory response according to the PET-CT and CECT (p value = .008) respectively and hence a lesser proportion of patients in the PET-CT arm received RT. Despite a lower usage of RT the 5 year OS of both groups, ERA based on CECT (91.8%) versus PET-CT (94.1%) was comparable (p value = .391) and so was the 5 year EFS (86.7 vs. 85.5%, p value = .724). CONCLUSION: Use of PET-CT as the modality for ERA is more likely to indicate a satisfactory response as compared with CECT and thereby decreases the need for RT in response-based treatment algorithm for HL-afflicted children. The reduction in the application of RT did not impact the overall outcome and plausibly would lower the risk of delayed toxic effects.

Targeted left ventricular lead positioning to the site of latest activation in cardiac resynchronization therapy: a systematic review and meta-analysis.

AIMS: Several studies have evaluated the use of electrically- or imaging-guided left ventricular (LV) lead placement in cardiac resynchronization therapy (CRT) recipients. We aimed to assess evidence for a guided strategy that targets LV lead position to the site of latest LV activation. METHODS AND RESULTS: A systematic review and meta-analysis was performed for randomized controlled trials (RCTs) until March 2023 that evaluated electrically- or imaging-guided LV lead positioning on clinical and echocardiographic outcomes. The primary endpoint was a composite of all-cause mortality and heart failure hospitalization, and secondary endpoints were quality of life, 6-min walk test (6MWT), QRS duration, LV end-systolic volume, and LV ejection fraction. We included eight RCTs that comprised 1323 patients. Six RCTs compared guided strategy (n = 638) to routine (n = 468), and two RCTs compared different guiding strategies head-to-head: electrically- (n = 111) vs. imaging-guided (n = 106). Compared to routine, a guided strategy did not significantly reduce the risk of the primary endpoint after 12-24 (RR 0.83, 95% CI 0.52-1.33) months. A guided strategy was associated with slight improvement in 6MWT distance after 6 months of follow-up of absolute 18 (95% CI 6-30) m between groups, but not in remaining secondary endpoints. None of the secondary endpoints differed between the guided strategies. CONCLUSION: In this study, a CRT implantation strategy that targets the latest LV activation did not improve survival or reduce heart failure hospitalizations.

Impact of minimal residual disease on relapse in childhood acute lymphoblastic leukemia: Lessons learnt from a tertiary cancer center in India.

Prognostic predictive value of end of induction minimal residual disease (EOI-MRD) is well established in acute lymphoblastic leukemia (ALL). We evaluated the factors likely to affect EOI-MRD positivity (>0.01%) by flow cytometry and relapse in different BFM-95 (Berlin-Frankfurt-Munich) risk groups among children and adolescents. In this retrospective study, data of 223 newly diagnosed patients with ALL was analyzed. Association between demographic and pretreatment characteristics with EOI-MRD was assessed. Risk factors for relapse were analyzed using univariate and multivariate Cox regression. Proportion of the SR (standard risk), MR (moderate risk), and HR (high risk) patients was 18.8%, 60.9%, 20.3%, respectively. Positive EOI-MRD among these risk groups was observed in 11.9%, 18.3%, and 55.5% patients respectively (p value <.01%). MRD positivity was more likely to be associated with older age (>10 years) and BFM-HR patients (p value .0008 and <.0001). Thirty-four (15.2%) patients relapsed in the whole cohort. On univariate analysis, statistically significant factors for RFS (relapse-free survival) included hyperleukocytosis, high-risk cytogenetics, NCI (National Cancer Institute) high risk, poor day-8 prednisolone response, BFM-HR and positive EOI-MRD status. Of all these only EOI-MRD retained its impact by multivariate analysis. Positive EOI-MRD significantly predicted relapse in BFM-MR with 5-year RFS of 88.0% and 68.4% (p value .02). Five-year RFS of EOI-MRD negative and positive groups were 86.4% and 65.5%, respectively (p value .004). EOI-MRD is a powerful tool to predict relapse in children and adolescent with ALL especially in BFM-MR. Application of MRD in HR patients needs to be redefined in conjunction with other variables.

Response surface method for optimization of process variables for bioaccumulation of metals with Jatropha curcas on fly ash-amended soil.

Heavy metal contamination is a serious rising issue with the dumping of fly ash (FA). A recent focus of researches and practices tends towards reutilization of FA with bioremediation technique using various plants. The present research aimed to investigate optimum metal extraction in fly ash-amended soil using microbes and treated wastewater with Jatropha curcas plant using response surface methodology (RSM). The Box-Behnken design was used to determine the optimum condition for maximum metal remediation with three levels and three variables, viz., fly ash percentage (5, 12.5, 20%), microbial dose (0.5, 5.25, 10 ml), and contaminant level of water to irrigate the plant (freshwater, treated wastewater, untreated wastewater). The approach adopted was to set fly ash percentage as "maximum," microbial dose as "minimum," and contaminant level of water to irrigate the plant as "in range." The outcome of the present research provided the best prediction models, integrated the process variables, and developed rotational curves for analyzing metal remediation in 360° rotation for Fe, Mn, Zn, Cu, and Al as responses of interest. The optimum conditions for maximum bioremediation from fly ash-amended soils by bioaccumulation on Jatropha curcas plant worked out as 13.866% fly ash, 4.088 ml microbial dose, and treated wastewater as type of water to irrigate the plant that bioaccumulated Fe, Mn, Zn, Cu, and Al as to 26.904, 0.760, 0.160, 0.162, and 12.895 mg/l.

Hodgkin Lymphoma in Children Under 5 Years: Do They Behave Differently?

The median age of presentation for Hodgkin lymphoma (HL) is lower in developing countries with a higher proportion under 5 years of age possibly attributable to the high prevalence of Epstein-Barr virus-driven disease. It is unclear whether the clinical presentation and outcomes of this cohort are different with concern regarding late effects being most pronounced in this age group. We report the outcome of children under 5 years of age enrolled in the InPOG-HL-15-01, the first multicentric collaborative study for newly diagnosed children and adolescents with HL from India. Thirty-five (9%) of the study population was younger than 5 years with a striking male preponderance of 34:1. They were less likely to have bulky disease, mediastinal or splenic involvement. The outcomes appear to be at least as favorable as in the older patient group. Efforts need to be made to evolve treatment strategies that spare this very young cohort from potential late effects.

Metabolic syndrome in childhood cancer survivors: delta BMI a risk factor in lower-middle-income countries.

PURPOSE: Metabolic syndrome (MetSyn) is an important late effect of childhood cancer. The combination of rising obesity and high prevalence of under-nutrition at diagnosis makes this a unique population to study in LMIC (lower middle-income countries). METHODS: Children ≤ 18 years of age at cancer diagnosis, in a single center in a LMIC, who were disease free and had completed treatment at least 2 years prior to study were included. MetSyn was defined using International Federation for Diabetes criteria for Asian Indians. Logistic regression analyses were carried out to evaluate the influence of various risk factors, including delta BMI (increase in body mass index from diagnosis to evaluation), on MetSyn. RESULTS: A high prevalence of MetSyn (12.2%), central obesity (33%), and dyslipidemia (61.8%) were found in a cohort of 500 Asian Indian childhood cancer survivors (CCS) at a median follow-up age of 17 years. Multivariable analysis revealed older age at diagnosis ≥ 10 years, OR 2.9 (1.6-5); longer survival duration ≥ 10 years, OR 2.2 (1.3-3.8); high BMI at diagnosis, OR 3.2 (1.5-6.9); and large delta BMI ≥ 50, OR 3.15(1.7-5.9) to be independent predictors of MetSyn. Patients who were underweight or normal at diagnosis with large delta BMI ≥ 50 had very high odds (OR, 12.5, 1.7-92) of developing MetSyn compared to those with lower delta BMI. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: A high prevalence of MetSyn was observed in CCS with early age at onset. Timely screening and early intervention are proven to be beneficial and delta BMI could be a useful screening tool for LMIC.

Sustainable amelioration of fly ash dumps linking bio-energy plantation, bioremediation and amendments: A review.

Disposal of fly ash in dumps is posing serious environmental problem causing air pollution, groundwater contamination, and loss of valuable land making it unproductive dumpsites. Cultivation of plants using bioremediation technique is looked upon as one of the sustainable remedial solution to these fly ash dumpsites. In recent years, researches on the plantation of bio-energy crops over the fly ash dumpsites is creating renewed interest, as it serves remediation along with distinct energy outcomes creating a win-win situation. The issue of the slow growth of plants, due to lack of nutrients and microbial activities is being resolved through advances in bioremediation research done in conjunction with organic matter, microbial inoculants, and inclusion of wastewater. New researches are being done with different plants and microbes in the matrix combination and use wastewater to supplement nutrients requirement to find eco-friendly & sustainable solutions. The present paper critically reviews the research on bioremediation and amendments with specific to bio-energy plantation on fly ash dumps.

To investigate the knowledge, attitude and practices regarding tuberculosis case notification among public and private doctors practicing of modern medicine in South Delhi.

In India, tuberculosis (TB) notification has been required since 2012. Notwithstanding, notification rates remain low. Non-reporting of tuberculosis cases not only results in an underestimation of cases, but also impedes the country's TB control strategy. Our research aims to assess practitioners' awareness, perception, and practice of tuberculosis case notification, as these factors can help reduce the TB burden. A cross-sectional study of 142 physicians was conducted between August 2018 and December 2019. Doctors were interviewed and given evaluation forms. Seventy-seven percent of the 142 physicians polled worked in medicine-related specialties, while 33% worked in surgery. Public sector physicians (64.7%) knew more about the Nikshay App than private practitioners (40.8%). The vast majority of public-sector doctors were only notified through their hospital's National Tuberculosis Elimination Programme (NTEP) center. However, the majority of private practitioners (47.8%) notified cases directly through the hospital, the local District Tuberculosis Officer (DTO) or NTEP medical officer (24 percent), or the Nikshay portal (28%), whereas the majority of public sector doctors notified only through the hospital NTEP center (85.9%). The primary reasons for non-notification are the high patient load on doctors, a lack of understanding about Nikshay App and its functionality, technological difficulties in using the Nikshay App, and the stigma associated with tuberculosis. The Nikshay App must be popularized as a notification mechanism through the NTEP program. To increase notification rates, practitioners must overcome the challenges they face. In terms of notification, more seminars and training, particularly hands-on training, should be held on a regular basis.

Ventricular pacing and myocardial function in patient with congenital heart block.

INTRODUCTION: Pacing-induced cardiomyopathy (PICM) is a potential complication of chronic right ventricular (RV) pacing, but its characterization in adult patients is often complicated by pre-existing cardiomyopathy. This study investigated the incidence of PICM in patients with congenital heart block (cHB) who have conduction disease from birth without confounding pre-existing cardiac conditions. METHODS AND RESULTS: This retrospective cohort analysis included 42 patients with cHB and baseline left ventricular ejection fraction (LVEF) ≥50%. Kaplan-Meier analysis was used to assess freedom from cardiomyopathy (defined as LVEF <50%) between paced and nonpaced patients. Patients were 26 ± 3 years old at first presentation, 64% were women and baseline LVEF was 60.0 ± 0.2%. Median follow-up from birth was 35 (interquartile range [IQR]: 20-42) years with a median of 6.7 years (IQR: 3.6-9.2) at our institution. Thirty-two patients received pacing at mean age 21 ± 3 years. Patients receiving a pacemaker (PM) were significantly more likely to develop a cardiomyopathy (p = .021) and no patient developed a cardiomyopathy in the absence of a PM. Four patients who developed a new cardiomyopathy were upgraded to biventricular pacing, leading to stabilization or improvement of LVEF. CONCLUSION: In a relatively young and healthy cHB cohort, RV pacing is associated with a higher risk of developing a cardiomyopathy. These data confirm the deleterious effects of RV pacing on myocardial function in patients without pre-existing structural cardiac disease and has clinical implications to the management of patients with cHB.

Treating early-stage Hodgkin lymphoma in resource-limited settings: InPOG-HL-15-01 experience.

BACKGROUND: Hodgkin lymphoma (HL) in childhood is an eminently curable disease. Excellent outcomes can be achieved even in resource-limited settings and increasingly, the focus is on limiting long-term toxicity. Contemporary treatment incorporates a risk-stratified, response-adapted approach using multiagent chemotherapy with or without low-dose radiotherapy (RT). Many developing countries continue to use ABVD (adriamycin, bleomycin, vinblastin, and dacarbazine)-based regimen owing to limited acute toxicity, cost, and ease of delivery. We report outcomes of children with early-stage HL using limited cycles of ABVD-based treatment in the first prospective multicentric collaborative study from India InPOG-HL-15-01. METHODS: Children <18 years with biopsy-proven HL were enrolled. Patients with stages I and IIA with or without bulky disease were classified as having early-stage disease. Patients were planned to receive four cycles of ABVD subject to satisfactory early response assessment (ERA) scheduled after two cycles of chemotherapy. RT was limited to patients with bulky disease or those with suboptimal ERA. RESULTS: Four hundred ten patients were enrolled over 30 months from 27 centers. One hundred thirty-four were classified as having early-stage disease. Fifty-three (40%) of these had bulky disease. One hundred ten (83%) of this cohort achieved complete or very good partial ERA. Fifty-four (40%) received RT. At a median of 52 months since diagnosis, 5-year event-free survival (EFS) and overall survival (OS) is 94% and 95.5%, respectively. Treatment-related mortality and abandonment were <1%. CONCLUSION: Limited cycles of ABVD with RT to selected patients is a very effective option for patients with early-stage disease in resource-limited settings.

Management of systemic fungal infections in the presence of a cardiac implantable electronic device: A systematic review.

Evidence to inform the management of systemic fungal infections in the setting of a cardiac implantable electronic devices (CIED), such as a permanent pacemaker or implantable cardioverter-defibrillator, is scant and limited to case reports and series. The available literature suggests high morbidity and mortality. To better characterize the shared experience of these cases and their outcomes, we performed a systematic review. We investigated all published reports of systemic fungal infections-fungemia and fungal vegetative disease-in the context of CIED, drawing from PubMed, EMBASE, and the Cochrane database of systematic reviews, inclusive of patients who received treatment between January 2000 and May 2020. Exclusion criteria included presence of ventricular assist device and concurrent bacteremia, bacterial endocarditis, bacterial vegetative infection, or viremia. Among 6261 screened articles, 48 cases from 41 individual studies were identified. Candida and Aspergillus species were the most commonly isolated fungi. There was significant heterogeneity in antifungal medication selection and duration. CIED extraction-either transvenous or surgical-was associated with increased survival to hospital discharge (92%) and clinical recovery at latest follow-up (81%), compared to cases where CIED extraction was deferred (56% and 40%, respectively). Importantly, there were no prospective data, and the data were limited to individual case reports and one small case series. In summary, CIED extraction is associated with improved fungal clearance and patient survival. Reported antifungal regimens are heterogeneous and nonuniform. Prospective studies are needed to verify these results and define optimal antifungal regimens.

IAP Chemotherapy Regimen Is a Viable and Cost-effective Option in Children and Adolescents With Osteosarcoma: A Comparative Analysis With MAP Regimen on Toxicity and Survival.

BACKGROUND: Cisplatin and doxorubicin are integral components of chemotherapy regimens in the treatment of osteosarcoma. Choice of third agent high-dose methotrexate (HDMTX) or an alkylating agent such as ifosfamide is debatable. The present study compared the impact of MAP (HDMTX-doxorubicin-cisplatin) and IAP (ifosfamide-doxorubicin-cisplatin) chemotherapy regimens on toxicity and survival in children and adolescents with osteosarcoma. MATERIALS AND METHODS: This was a retrospective study including patients 18 years and younger with osteosarcoma during the study period. Clinical, demographic, chemotherapy regimen, and surgical details and treatment-related toxicity were retrieved from hospital medical records. Prognostic factors affecting overall survival (OS) and event-free survival (EFS) were analyzed. RESULTS: Among 102 patients included in the study, 59 (57.8%) and 43 (42.2%) patients were treated with MAP and IAP regimens, respectively. Two groups were comparable in terms of pretreatment characteristics and surgical treatment. Overall, 95.9% patients underwent limb salvage surgery. There was a statistically increased incidence in supportive care admissions and delay in starting the next cycle of chemotherapy in the MAP group. Among the MAP cohort, the 5-year OS and EFS were 62% and 55% compared with 47% and 44%, respectively, in the IAP cohort (P=0.143 and 0.316, respectively). On univariate and multivariate analyses, statistically significant factors affecting EFS of the whole group included tumor size, stage, site of metastasis, histologic necrosis, and type of surgery. CONCLUSIONS: OS and EFS with both regimens were similar. However, the MAP regimen was associated with a statistically significant increase in incidence of supportive care admissions, delay in next cycle of chemotherapy, and predicted higher cost of treatment.

Maternal focal atrial tachycardia during pregnancy: A systematic review.

INTRODUCTION: The presentation and optimal management of maternal focal atrial tachycardia (AT) during pregnancy are unknown. The objective of this study is to conduct a comprehensive summary of the existing evidence. METHODS AND RESULTS: A systematic review of all reported cases of maternal focal AT during pregnancy was performed. The primary search queried PubMed using the MeSH terms "supraventricular tachycardia" and "pregnancy." A stepwise ancillary search included article bibliographies, citations listed by the Google internet search engine, and PubMed using the MeSH terms "atrial tachycardia" and "pregnancy." In total, 28 citations that described 32 patients were retrieved. A case from our institution was added. Detailed information was available for 30 patients. Clinical characteristics at presentation included a mean ± standard deviation of 28.3 ± 5.7 years for maternal age and 24.6 ± 7.7 weeks for gestation age. Suspected tachycardia-induced cardiomyopathy was present in 20 of 30 (67%) patients and left ventricular ejection fraction improved in 15 of 15 (100%) patients with follow-up measurements. Medication failure was common. Focal AT resolved spontaneously after delivery in eight of nine (89%) patients treated with only medications. Automaticity was suggested by discrete electrograms at sites of origin and lack of reported inducibility and termination with programmed stimulation in all patients who underwent electrophysiology studies. There were nine cases of successful catheter ablation with zero fluoroscopy since 2010. CONCLUSIONS: Automaticity is the dominant mechanism for patients with maternal focal AT during pregnancy. Catheter ablation with zero fluoroscopy is an emerging therapy for medically refractory cases.