Sorting lung tumor volumes from 4D-MRI data using an automatic tumor-based signal reduces stitching artifacts.

PURPOSE: To investigate whether a novel signal derived from tumor motion allows more precise sorting of 4D-magnetic resonance (4D-MR) image data than do signals based on normal anatomy, reducing levels of stitching artifacts within sorted lung tumor volumes. METHODS: (4D-MRI) scans were collected for 10 lung cancer patients using a 2D T2-weighted single-shot turbo spin echo sequence, obtaining 25 repeat frames per image slice. For each slice, a tumor-motion signal was generated using the first principal component of movement in the tumor neighborhood (TumorPC1). Signals were also generated from displacements of the diaphragm (DIA) and upper and lower chest wall (UCW/LCW) and from slice body area changes (BA). Pearson r coefficients of correlations between observed tumor movement and respiratory signals were determined. TumorPC1, DIA, and UCW signals were used to compile image stacks showing each patient's tumor volume in a respiratory phase. Unsorted image stacks were also built for comparison. For each image stack, the presence of stitching artifacts was assessed by measuring the roughness of the compiled tumor surface according to a roughness metric (Rg). Statistical differences in weighted means of Rg between any two signals were determined using an exact permutation test. RESULTS: The TumorPC1 signal was most strongly correlated with superior-inferior tumor motion, and had significantly higher Pearson r values (median 0.86) than those determined for correlations of UCW, LCW, and BA with superior-inferior tumor motion (p < 0.05). Weighted means of ratios of Rg values in TumorPC1 image stacks to those in unsorted, UCW, and DIA stacks were 0.67, 0.69, and 0.71, all significantly favoring TumorPC1 (p = 0.02-0.05). For other pairs of signals, weighted mean ratios did not differ significantly from one. CONCLUSION: Tumor volumes were smoother in 3D image stacks compiled using the first principal component of tumor motion than in stacks compiled with signals based on normal anatomy.

Telmisartan Plus Amlodipine as the Preferred Initial Combination in Newly Diagnosed Indian Patients with Hypertension: An Expert Consensus Statements.

INTRODUCTION: Hypertension (HTN) remains one of the most important risk factors for cardiovascular (CV) diseases and a leading cause of mortality worldwide. Despite improvement in detection and treatment, poor blood pressure (BP) control rates are observed globally. The situation in India is alarming with only 22.5% of patients maintaining their BP under control. Initiating early and effective treatment for HTN helps control BP within normal limits and reduces associated health risks. In India, currently, there are no guidelines on the choice of dual combination treatment that can be considered an initial treatment for newly diagnosed HTN patients to achieve effective BP control and reduce CV risks. OBJECTIVE: To provide consensus recommendations for preferred initial combinations in newly diagnosed Indian patients with HTN. METHODOLOGY: A core group of 100 experts with HTN expertise conceptualized and formulated the four key questions based on answerability, effectiveness, potential for translation to clinical practice, novelty, and potential impact on the healthcare burden. A mix of Delphi and Child Health and Nutrition Research Initiative (CHNRI) methods was adopted for acceptance or refusal of recommendations. Likert scale 1-9 was used for scoring. A score of ≥7 was considered "statement accepted," >6.50 "near to acceptance" and <6.50 "not accepted." A vote of ≥7 by at least two-thirds of the experts (66.66%) was mandatory for acceptance of the recommendation. CONCLUSION: Combination therapy could be necessary for a majority of newly diagnosed Indian patients for effective BP control. It can manage HTN with better clinical outcomes. Based on mean rating scores from experts, telmisartan plus amlodipine can be considered the preferred initial combination in the management of newly diagnosed Indian patients with HTN to achieve better BP control and improve CV outcomes.

Clinical characteristics and 30-day outcomes in patients with acute decompensated heart failure: Results from Indian College of Cardiology National Heart Failure Registry (ICCNHFR).

BACKGROUND: Acute decompensated heart failure (ADHF) is a challenging medical emergency with high mortality and its prevalence is increasing in India. There is paucity of data on ADHF in the country. METHODS: Indian College of Cardiology National Heart Failure Registry (ICCNHFR) is an on-going observational registry on ADHF contributed by 22 hospitals across India; and we present the in-hospital and 30-day outcomes of ADHF patients enrolled from August 2018 to July 2019. Major objective included capturing demographics, comorbid conditions, aetiology, prescription patterns and assessing clinical outcomes. RESULTS: Of 5269 patients (mean age: 61.90 ± 13.85 years) enrolled in this study, males were predominant (67.09%). Mean duration of hospitalization was 5.74 ± 4.74 days. Ischemic heart disease was the most common (75.44%) aetiology. Abnormal electrocardiogram readings were found in most patients (89.86%). LVEF of ˂40% was found in 68.29% of patients. In-hospital mortality rates were 6.98%. The 30-day cumulative mortality was 12.35% and 30-day rehospitalization rate was 7.98%. At discharge, all guideline-based medical therapy (GDMT) were prescribed only to 24.99% of patients and 23.72% adhered to the prescription until 30 days. Older age, high serum creatinine levels and poor LVEF contributed to high mortality and rehospitalization. CONCLUSION: Patients with ADHF were younger and predominantly males. Usage of GDMT in ADHF patients was low (24.99%) and the in-hospital mortality was high. Older age, high serum creatinine levels, poor LVEF contributed for 30-day mortality and rehospitalization. This data on ADHF, could help in developing strategies to improve outcomes for HF patients in India.

Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer.

BACKGROUND: We have carried out a study to determine the scope for reducing heart doses in photon beam radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC). MATERIALS AND METHODS: Baseline VMAT plans were created for 20 LA-NSCLC patients following the IDEAL-CRT isotoxic protocol, and were re-optimized after adding an objective limiting heart mean dose (MDHeart). Reductions in MDHeart achievable without breaching limits on target coverage or normal tissue irradiation were determined. The process was repeated for objectives limiting the heart volume receiving ≥ 50 Gy (VHeart-50-Gy) and left atrial wall volume receiving ≥ 63 Gy (VLAwall-63-Gy). RESULTS: Following re-optimization, mean MDHeart, VHeart-50-Gy and VLAwall-63-Gy values fell by 4.8 Gy and 2.2% and 2.4% absolute respectively. On the basis of associations observed between survival and cardiac irradiation in an independent dataset, the purposefully-achieved reduction in MDHeart is expected to lead to the largest improvement in overall survival. It also led to useful knock-on reductions in many measures of cardiac irradiation including VHeart-50-Gy and VLAwall-63-Gy, providing some insurance against survival being more strongly related to these measures than to MDHeart. The predicted hazard ratio (HR) for death corresponding to the purposefully-achieved mean reduction in MDHeart was 0.806, according to which a randomized trial would require 1140 patients to test improved survival with 0.05 significance and 80% power. In patients whose baseline MDHeart values exceeded the median value in a published series, the average MDHeart reduction was particularly large, 8.8 Gy. The corresponding predicted HR is potentially testable in trials recruiting 359 patients enriched for greater MDHeart values. CONCLUSIONS: Cardiac irradiation in RT of LA-NSCLC can be reduced substantially. Of the measures studied, reduction of MDHeart led to the greatest predicted increase in survival, and to useful knock-on reductions in other cardiac irradiation measures reported to be associated with survival. Potential improvements in survival can be trialled more efficiently in a population enriched for patients with greater baseline MDHeart levels, for whom larger reductions in heart doses can be achieved.

Combining immunotherapy and radiotherapy in lung cancer.

Immunotherapy has become standard of care in advanced non-small cell lung cancer (NSCLC) in a number of settings. Radiotherapy remains an important and potentially curative treatment for localized and locally advanced NSCLC not amenable to surgery. While the principal cytotoxic effect of ionizing radiation is via DNA damage, the effect on tumour microenvironment, promoting dendritic cell presentation of tumour-derived antigens to T cells stimulating the host adaptive immune system to mount an immune response against tumours cells, has become of particular interest when combining immunomodulating agents with radiation. The 'abscopal effect' of radiation where non-irradiated metastatic lesions may respond to radiation may be immune-mediated, via radiation primed anti-tumour T cells. Immune priming by radiation offers the potential for increasing the efficacy of immunotherapy and this is subject to on-going clinical trials underpinned by immunological bioassays. Increasing understanding of the interaction between tumour, radiation and immune cells at a molecular level provides a further opportunity for intervention to enhance the potential synergy between radiation and immunotherapy. Applying the potential efficacy of combination therapy to clinical practice requires caution particularly to ensure the safety of the two treatment modalities in early phase clinical trials, many of which are currently underway. We review the biological basis for combining radiation and immunotherapy and examine the existing pre-clinical and clinical evidence and the challenges posed by the new combination of treatments.

Confronting system barriers for ST- elevation MI in low and middle income countries with a focus on India.

Our previous research found seven specific factors that cause system delays in ST-elevation Myocardial infarction management in developing countries. These delays, in conjunction with a lack of organized STEMI systems of care, result in inefficient processes to treat AMI in developing countries. In our present opinion paper, we have specifically explored the three most pertinent causes that afflict the seven specific factors responsible for system delays. In doing so, we incorporated a unique strategy of global STEMI expertise. With this methodology, the recommendations were provided by expert Indian cardiologist and final guidelines were drafted after comprehensive discussions by the entire group of submitting authors. We expect these recommendations to be utilitarian in improving STEMI care in developing countries.

Percutaneous reconstruction of chronic total occlusion of brachiocephalic vein using transseptal needle in dialysis-dependent patient.

Placement of a dialysis catheter substantially increases the risk of central vein stenosis. 52-year-old female with end-stage renal disease and a right brachial-cephalic hemodialysis access presented with right arm swelling. The chronic total occlusion of right brachiocephalic vein was refractory to wire traversal. Sharp recanalization of the central venous occlusion was done with transseptal needle retrogradely. The track was balloon dilated and stented. When the conventional catheters and guide wires options fail, sharp recanalization technique may be used to salvage a precious dialysis access.

Radiotherapy for a benign cause of cauda equina compression in a known case of breast carcinoma.

A woman underwent breast conservation surgery and axillary clearance for T1N1M0 breast carcinoma, followed by adjuvant chemotherapy, radiotherapy and hormone therapy. At 3-year follow-up she presented with lumbar back pain and developed bilateral lower limb weakness. MRI spine demonstrated an expansile lesion at L1 causing cauda equina compression. The mass, unusually, was centred on the spinous process; metastases typically involve pedicles. The patient underwent surgical decompression with complete resolution of neurological signs. Histology revealed Masson tumour (intravascular papillary endothelial hyperplasia), a benign vascular lesion. Pain recurrence 9 months later prompted imaging demonstrating recurrent mass. Preoperative embolisation and re-excision was undertaken for recurrent Masson tumour. Recurrence of these lesions is rare and it was felt residual disease was likely. Radiotherapy has been used in isolated cases; therefore, she was treated with adjuvant radiotherapy, the first reported case of radiation in management of extracranial Masson tumour, and remains well 3 years later.

Management of febrile neutropenia in solid tumours and lymphomas using the Multinational Association for Supportive Care in Cancer (MASCC) risk index: feasibility and safety in routine clinical practice.

GOALS OF WORK: Febrile neutropenia (FN) represents a spectrum of severity in which low-risk patients can be defined using the Multinational Association for Supportive Care in Cancer (MASCC) risk index. However, despite publication in 2000, there remains limited published literature to date to support the use of MASCC risk assessment in routine clinical practice and eligibility for early hospital discharge. In this study, we present our experience with the routine use of the MASCC risk index to determine the management of FN in our institution. PATIENTS AND METHODS: Patients treated for solid tumours or lymphomas with low-risk FN (MASCC score >/ or =21) were eligible for oral antibiotics (ciprofloxacin plus either co-amoxiclav or doxycycline) and for early hospital discharge irrespective of first or subsequent episode. The primary outcome was rate of resolution of FN without serious medical complications (SMC). Secondary outcomes were the "success" of antibiotic therapy without treatment modifications, duration of hospitalisation and rate of readmissions. RESULTS: A total of 100 FN episodes occurring in 83 patients were treated over a 6-month period. Ninety of these episodes were low-risk (90%), of which 75 received oral antibiotics (83.3%) and 3 (3.3%) experienced SMC, and the success rate was 94.5% [95% confidence interval (CI) 89.6-99.3%] in low-risk episodes. The median duration of hospitalisation was 2.5 days (25th centile: 1.0 day; 75th centile: 5.0 days) in low-risk compared to 6.5 days (25th centile: 5.3 days; 75th centile: 9.3 days) in high-risk episodes (p = 0.003); 2 days for low-risk episodes treated with oral antibiotics compared to 4 days for low-risk receiving intravenous antibiotics (p = 0.015). Positive predictive value for the MASCC index was 96.7% (95% CI 95.0-98.6%). CONCLUSION: The MASCC risk index is both feasible and safe when used in standard clinical practice to guide the management of FN in patients with solid tumours and lymphomas. Patients predicted to have low risk can be managed safely with oral antibiotics and early hospital discharge.