Optimization of Deep Learning Based Brain Extraction in MRI for Low Resource Environments.

Brain extraction is an indispensable step in neuro-imaging with a direct impact on downstream analyses. Most such methods have been developed for non-pathologically affected brains, and hence tend to suffer in performance when applied on brains with pathologies, e.g., gliomas, multiple sclerosis, traumatic brain injuries. Deep Learning (DL) methodologies for healthcare have shown promising results, but their clinical translation has been limited, primarily due to these methods suffering from i) high computational cost, and ii) specific hardware requirements, e.g., DL acceleration cards. In this study, we explore the potential of mathematical optimizations, towards making DL methods amenable to application in low resource environments. We focus on both the qualitative and quantitative evaluation of such optimizations on an existing DL brain extraction method, designed for pathologically-affected brains and agnostic to the input modality. We conduct direct optimizations and quantization of the trained model (i.e., prior to inference on new data). Our results yield substantial gains, in terms of speedup, latency, through-put, and reduction in memory usage, while the segmentation performance of the initial and the optimized models remains stable, i.e., as quantified by both the Dice Similarity Coefficient and the Hausdorff Distance. These findings support post-training optimizations as a promising approach for enabling the execution of advanced DL methodologies on plain commercial-grade CPUs, and hence contributing to their translation in limited- and low- resource clinical environments.

The federated tumor segmentation (FeTS) tool: an open-source solution to further solid tumor research.

Objective.De-centralized data analysis becomes an increasingly preferred option in the healthcare domain, as it alleviates the need for sharing primary patient data across collaborating institutions. This highlights the need for consistent harmonized data curation, pre-processing, and identification of regions of interest based on uniform criteria.Approach.Towards this end, this manuscript describes theFederatedTumorSegmentation (FeTS) tool, in terms of software architecture and functionality.Main results.The primary aim of the FeTS tool is to facilitate this harmonized processing and the generation of gold standard reference labels for tumor sub-compartments on brain magnetic resonance imaging, and further enable federated training of a tumor sub-compartment delineation model across numerous sites distributed across the globe, without the need to share patient data.Significance.Building upon existing open-source tools such as the Insight Toolkit and Qt, the FeTS tool is designed to enable training deep learning models targeting tumor delineation in either centralized or federated settings. The target audience of the FeTS tool is primarily the computational researcher interested in developing federated learning models, and interested in joining a global federation towards this effort. The tool is open sourced athttps://github.com/FETS-AI/Front-End.

Bedaquiline, Delamanid, Linezolid and Clofazimine for Treatment of Pre-extensively Drug-Resistant Tuberculosis.

BACKGROUND: Treatment success rates for multidrug-resistant tuberculosis (MDR-TB) remain low globally. Availability of newer drugs has given scope to develop regimens that can be patient-friendly, less toxic, with improved outcomes. We proposed to determine the effectiveness of an entirely oral, short-course regimen with Bedaquiline and Delamanid in treating MDR-TB with additional resistance to fluoroquinolones (MDR-TBFQ+) or second-line injectable (MDR-TBSLI+). METHODS: We prospectively determined the effectiveness and safety of combining two new drugs with two repurposed drugs - Bedaquiline, Delamanid, Linezolid, and Clofazimine for 24-36 weeks in adults with pulmonary MDR-TBFQ+ or/and MDR-TBSLI+. The primary outcome was a favorable response at end of treatment, defined as two consecutive negative cultures taken four weeks apart. The unfavorable outcomes included bacteriologic or clinical failure during treatment period. RESULTS: Of the 165 participants enrolled, 158 had MDR-TBFQ+. At the end of treatment, after excluding 12 patients due to baseline drug susceptibility and culture negatives, 139 of 153 patients (91%) had a favorable outcome. Fourteen patients (9%) had unfavorable outcomes: four deaths, seven treatment changes, two bacteriological failures, and one withdrawal. During treatment, 85 patients (52%) developed myelosuppression, 69 (42%) reported peripheral neuropathy, and none had QTc(F) prolongation >500msec. At 48 weeks of follow-up, 131 patients showed sustained treatment success with the resolution of adverse events in the majority. CONCLUSION: After 24-36 weeks of treatment, this regimen resulted in a satisfactory favorable outcome in pulmonary MDR-TB patients with additional drug resistance. Cardiotoxicity was minimal, and myelosuppression, while common, was detected early and treated successfully.

Prevalence of latent structural heart disease in Nepali schoolchildren.

BACKGROUND: The present study aimed to quantify the burden of structural heart disease in Nepali children. METHODS: We performed a school-based cross-sectional echocardiographic screening study with cluster random sampling among children 5-16 years of age. RESULTS: Between December 2012 and January 2019, 6573 children (mean age 10.6 ± 2.9 years) from 41 randomly selected schools underwent echocardiographic screening. Structural heart disease was detected in 14.0 per 1000 children (95% CI 11.3-17.1) and was congenital in 3.3 per 1000 (95% CI 2.1-5.1) and rheumatic in 10.6 per 1000 (95% CI 8.3-13.4). Rates of rheumatic heart disease were higher among children attending public as compared to private schools (OR 2.8, 95% CI 1.6-5.2, p = 0.0001). CONCLUSION: Rheumatic heart disease accounted for three out of four cases of structural heart disease and was more common among children attending public as compared to private schools.

Impact of COVID-19 pandemic on pediatric cardiac services in India.

BACKGROUND: COVID-19 pandemic has disrupted pediatric cardiac services across the globe. Limited data are available on the impact of COVID.19 on pediatric cardiac care in India. AIMS: The aims are to study the impact of COVID-19 pandemic on the care of children with heart disease in India in terms of number of outpatient visits, hospitalizations, catheter-based interventions, and cardiac surgeries. SETTINGS AND DESIGN: This is a retrospective, multicentric, observational study. METHODS: We collected monthly data on the number and characteristics of outpatient visits, hospitalizations, catheter-based interventions, and cardiac surgeries and major hospital statistics, over a period of 5 months (April to August 2020), which coincided with the first wave of COVID-19 pandemic in India and compared it with data from the corresponding months in 2019. RESULTS: The outpatient visits across the 24 participating pediatric cardiac centers decreased by 74.5% in 2020 (n = 13,878) as compared to the corresponding period in 2019 (n = 54,213). The reduction in the number of hospitalizations, cardiac surgeries, and catheterization procedures was 66.8%, 73.0%, and 74.3%, respectively. The reduction in hospitalization was relatively less pronounced among neonates as compared to infants/children (47.6% vs. 70.1% reduction) and for emergency surgeries as compared to elective indications (27.8% vs. 79.2%). The overall in-hospital mortality was higher in 2020 (8.1%) as compared to 2019 (4.8%), with a higher postoperative mortality (9.1% vs. 4.3%). CONCLUSIONS: The current COVID-19 pandemic significantly impacted the delivery of pediatric cardiac care across India with two-third reduction in hospitalizations and cardiac surgeries. In an already resource-constrained environment, the impact of such a massive reduction in the number of surgeries could be significant over the coming years. These findings may prove useful in formulating strategy to manage subsequent waves of ongoing COVID-19 pandemic.

Effectiveness of Systematic Echocardiographic Screening for Rheumatic Heart Disease in Nepalese Schoolchildren: A Cluster Randomized Clinical Trial.

Importance: Echocardiographic screening allows for early detection of subclinical stages of rheumatic heart disease among children in endemic regions. Objective: To investigate the effectiveness of systematic echocardiographic screening in combination with secondary antibiotic prophylaxis on the prevalence of rheumatic heart disease. Design, Setting, and Participants: This cluster randomized clinical trial included students 9 to 16 years of age attending public and private schools in urban and rural areas of the Sunsari district in Nepal that had been randomly selected on November 17, 2012. Echocardiographic follow-up was performed between January 7, 2016, and January 3, 2019. Interventions: In the experimental group, children underwent systematic echocardiographic screening followed by secondary antibiotic prophylaxis in case they had echocardiographic evidence of latent rheumatic heart disease. In the control group, children underwent no echocardiographic screening. Main Outcomes and Measures: Prevalence of the composite of definite or borderline rheumatic heart disease according to the World Heart Federation criteria in experimental and control schools as assessed 4 years after intervention. Results: A total of 35 schools were randomized to the experimental group (n = 19) or the control group (n = 16). After a median of 4.3 years (interquartile range [IQR], 4.0-4.5 years), 17 of 19 schools in the experimental group (2648 children; median age at follow-up, 12.1 years; IQR, 10.3-12.5 years; 1308 [49.4%] male) and 15 of 16 schools in the control group (1325 children; median age at follow-up, 10.6 years; IQR, 10.0-12.5 years; 682 [51.5%] male) underwent echocardiographic follow-up. The prevalence of definite or borderline rheumatic heart disease was 10.8 per 1000 children (95% CI, 4.7-24.7) in the control group and 3.8 per 1000 children (95% CI, 1.5-9.8) in the experimental group (odds ratio, 0.34; 95% CI, 0.11-1.07; P = .06). The prevalence in the experimental group at baseline had been 12.9 per 1000 children (95% CI, 9.2-18.1). In the experimental group, the odds ratio of definite or borderline rheumatic heart disease at follow-up vs baseline was 0.29 (95% CI, 0.13-0.65; P = .008). Conclusions and Relevance: School-based echocardiographic screening in combination with secondary antibiotic prophylaxis in children with evidence of latent rheumatic heart disease may be an effective strategy to reduce the prevalence of definite or borderline rheumatic heart disease in endemic regions. Trial Registration: ClinicalTrials.gov Identifier: NCT01550068.

Unroofed coronary sinus: An unusual interatrial communication and a rare childhood entity.

Unroofed coronary sinus, an unusual form of interatrial communication, is a rare cardiac anomaly. It is not a true defect of the atrial septum. It is described as a partial (focal or fenestrated) or complete absence of the roof of the coronary sinus, resulting in a communication between the coronary sinus and left atrium. It is presumably the least common variety of defects associated with interatrial shunting. Such defects are often difficult to diagnose and may even be overlooked during surgery for complex congenital heart disease. In most cases, they are associated with a persistent left superior vena cava, pulmonary or tricuspid atresia, and hearts with isomeric right atrial appendages. We report a case of this unusual form of interatrial communication without any associated anomalies in a 7-year-old girl child who presented to us with exertional dyspnea.

Establishing Cardiac Surgery in Eastern Nepal: Early Results.

BACKGROUND: Only few dedicated cardiac centres provide cardiac surgery service in Nepal. We are the only government affiliated centre outside the capital providing this service. In this study, we aim to present our early results of cardiac surgery. METHODS: This retrospective study was conducted at B P Koirala Institute of Health Sciences with objective of analysing the early results of cardiac surgery in the patients operated from July 2016 to March 2017.The data were analysed for patient demographics, type of surgery and cardiac disease, mortality, hospital and intensive care unit stay, valve related complications. RESULTS: Total 51 major cardiac surgeries (42 on pump and nine off pump) were performed. There were 27 (53%) males and 24 (47%) females with median age of 36 years (range: 1 to 70 years).The cardiac diseases consisted of 28 rheumatic heart disease, 12 congenital heart diseases, five coronary artery disease, five chronic constrictive pericarditis and one left atrial myxoma. The mean cardiopulmonary bypass and cross clamp times were 106 ±35 and 80±26 minutes respectively. The mean intensive care unit and hospital stay was 4±2 and 8±3 days respectively. Two (4%) patients required re-exploration for mediastinal bleeding. There was no prosthetic valve thrombosis or infection.Two patients (4%) had superficial wound infections.There were four (7.8%) in hospital mortalities. Remaining 47 patients (91.8%) are in NYHA class I aftermean follow up duration of five months. CONCLUSIONS: Our early result of cardiac surgery is encouraging and has established the safety and feasibility of starting open heart surgery in other parts of Nepal.

Primary mucoepidermoid carcinoma of the lung with prominent clear cells.

Mucoepidermoid carcinoma of the lung is a rare malignancy of salivary gland-type origin. We report a case of a 21-year-old man with a right mainstem bronchus mass composed predominantly of clear cells. This case represents a rare primary pulmonary low-grade mucoepidermoid carcinoma positive for MAML2 rearrangement by fluorescence in situ hybridization with a prominent clear cell component.

microRNA-10b is a prognostic biomarker for melanoma.

Malignant melanoma is an aggressive form of skin cancer. Recently, drug therapy of advanced disease has been revolutionized by new agents. More therapeutic options, coupled with the desire to extend treatment to the adjuvant setting mean that prognostic biomarkers that can be assayed from formalin-fixed paraffin-embedded clinical would be valuable. microRNAs have potential to fill this need. We analyzed 377 microRNAs in 79 primary melanomas and 32 metastases using a split sample discovery strategy. From a discovery analysis using 40 thick primary melanomas (20 cases with metastasis and 20 controls without metastasis at 5 years), microRNA expression was measured by quantitative RT-PCR (QRT-PCR). MiR-10b emerged as a candidate prognostic microRNA. This was confirmed in an independent validation set of thick primary melanomas (20 cases with metastasis and 19 controls without metastasis at 5 years). In the combined discovery and validation cohorts (n=79), miR-10b expression showed a 3.7-fold increase in expression between cases and controls (P=0.005) and showed a trend of increasing expression between primary melanomas and their matched metastases (P<0.001). In situ hybridization showed expression was in melanoma cells and correlated with expression measured by QRT-PCR (P=0.0005). We used the combined discovery and validation samples to verify the prognostic value of additional candidate microRNAs identified from other studies, and proceeded to analyze miR-200b. We demonstrated that miR-10b and miR-200b showed independent prognostic value (P=0.002 and 0.047, respectively) in multivariable analysis alongside known clinico-pathological prognostic features (eg, Breslow thickness) using a Cox proportional hazards regression model. Furthermore, the addition of these microRNAs to the clinico-pathological features led to an improved regression model with better identification of aggressive thick melanomas. Taken together, these data suggest that miR-10b is a new prognostic microRNA for melanoma and that there could be a place for microRNA analysis in stratifying melanoma for therapy.

Unruptured Sinus of Valsalva Aneurysm Obstructing the Left Ventricular Outflow Tract: An Uncommon Presentation in Childhood.

Congenital aneurysms of the sinus of Valsalva are uncommon abnormalities that are usually silent and slowly progressive without symptoms of cardiac dysfunction unless catastrophic rupture occurs. However, in rare cases, unruptured aneurysms can produce symptoms resulting from compression of adjacent structures, ventricular outflow tract obstruction, heart block, and coronary and valvular insufficiency. We report a case of a single unruptured sinus of Valsalva aneurysm producing left ventricular outflow tract obstruction in an 8-year-old boy who presented with chest pain on exertion.

Survivorship in Non-Small Cell Lung Cancer: Challenges Faced and Steps Forward.

Improvements in curative therapies and the advent of screening have led to increased numbers of non-small cell lung cancer (NSCLC) survivors. Most survivors have undergone invasive treatment (surgery, radiation therapy, and/or chemotherapy) and carry a higher comorbidity burden than survivors of other cancers. Overall quality of life (QOL) and health-related quality of life (HRQOL) suffer during the treatment phase, with the potential for long-term decline, and both clinical characteristics and treatment impact these measures. Physical and mental components of HRQOL seem to be most at risk for decline. The issues faced by survivors include physical symptoms such as respiratory issues, fatigue, hearing loss, neuropathy, and postsurgical pain; psychological distress leading to depression, financial issues, and poor compliance with recommended guidelines; and fear or risk of recurrence and secondary malignancies. This article summarizes the major issues faced by NSCLC survivors and suggests appropriate management. Future collaborative efforts are needed to further elucidate the complex issues that affect overall QOL and HRQOL in NSCLC survivors and to develop appropriate interventions in this large and diverse survivor population.

Disparities in access to video-assisted thoracic surgical lobectomy for treatment of early-stage lung cancer.

BACKGROUND: Video-assisted thoracic surgical (VATS) lobectomy was originally described in 1992 and has slowly gained increasing acceptance. This study documents current utilization and outcomes for VATS versus open lobectomy in three Mid-Atlantic states. SUBJECTS AND METHODS: Inpatient discharge claims data were queried for all lobectomies performed for cancer in the Mid-Atlantic United States (New Jersey, New York, and Pennsylvania) between October 2007 and December 2008. Associations between sociodemographic factors and likelihood of undergoing VATS were tested with multiple logistic regressions. Outcomes were compared using two-sample t tests. RESULTS: There were 5489 lobectomies included. Forty-seven percent of patients were men, and 62% were ≥65 years old. Thirty-two percent (1741 of 5489) were VATS lobectomies. Men were less likely to undergo VATS (odds ratio 0.86, P=.004); those ≥65 years old were more likely to undergo VATS (odds ratio 1.34, P=.009). Uninsured patients underwent VATS less often (odds ratio 0.46, P=.01). Patients from rural areas were less likely to undergo VATS (odds ratio 0.67, P=.001), although travel distances for both groups were similar. A total of 44% of these hospitals (125 of 284) performed only open lobectomies. Patients without private insurance or Medicare were less likely to undergo a VATS lobectomy (P=0.01). In general, the likelihood of VATS lobectomy increased as hospital lobectomy volume increased. VATS patients had a shorter median length of stay (5 versus 6 days, P<.001) and a higher rate of discharge to home (92.5% versus 89.5%, P<.001). Mean total hospital costs were less for VATS patients ($49,948 versus $56,280, P<.001). In-hospital mortality was less for VATS patients (1.2% versus 2.1%, P=.013). CONCLUSION: For the period studied, patients in rural areas, in low-volume hospitals, who had Medicaid, or with lower median incomes underwent VATS lobectomy less often.

Relationship between upper airway obstruction and gastroesophageal reflux in a dog model.

The association between gastroesophageal reflux (GER) and upper airway obstruction in children is recognized but not well understood. Our objective was to determine if the creation of a model of upper airway obstruction in dogs would cause GER and to determine if the GER is related to intrathoracic pressure changes. Five dogs underwent evaluation with esophageal manometry and pH probe at baseline and 1 week after creation of an upper airway obstruction. Airway obstruction was created by placement of a fenestrated cuffed tracheostomy tube, which was then capped and the cuff was inflated, requiring the animals to breathe via the fenestrations. The negative inspiratory pressure (Pes) (+/- SD) increased from 11.8 +/- 4.8 cm H(2)O at baseline to 17.6 +/- 4.9 cm H(2)O 1 week after creation of an airway obstruction (p = .029). None of the dogs had GER at baseline with a reflux index (RI) value of 0.0; however, 1 week after creation of airway obstruction, three out of five dogs had GER, with a mean RI value of 21.2 +/- 21.2. There was a significant (p = .023) correlation (r = .928) of the changes in Pes and RI values following airway obstruction. Upper airway obstruction (UAO) does cause GER in this canine model. Severity of GER is significantly correlated with Pes changes.

Open heart surgery in patients 85 years and older.

BACKGROUND: There has been an increase in the number of elderly patients considered for cardiac surgery. Several reports have documented acceptable morbidity and mortality in patients 80 years and older. The results from surgical patients 85 years and older were analyzed. METHODS: The records of 89 consecutive patients 85 years and older having cardiac operations between June 1993 and May 1999 were retrospectively reviewed. For purposes of statistical analysis follow-up was considered as a minimum of one office visit to the surgeon, cardiologist, or internist at least 1 month postoperatively. RESULTS: Eighty-seven patients underwent coronary artery grafting and two patients had mitral valve replacement. Follow-up was 100% complete. The operative mortality rate was 12.3%; probability of in-hospital death was 8.2%; risk-adjusted mortality rate was 3.2%. The complication rate was 31.5%. The actuarial 1-, 3-, and 5-year survivals were as follows: 75%, 67%, and 40%. Multivariate predictors of 30-day mortality were preoperative EF, less than 30% (p = 0.029) and postoperative renal failure (p = 0.0039). CONCLUSIONS: Cardiac surgery can be performed in patients 85 years and older with good results. There is an associated prolonged hospital stay for elderly patients. Consistent successful outcomes can be expected in this patient population with selective criteria identifying risk factors.