Bench-to-bedside imaging in brain metastases: a road to precision oncology.

Radiology has seen tremendous evolution in the last few decades. At the same time, oncology has made great strides in diagnosing and treating cancer. Distant metastases of neoplasms are being encountered more often in light of longer patient survival due to better therapeutic strategies and diagnostic methods. Brain metastasis (BM) is a dismal manifestation of systemic cancer. In the present scenario, magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography (PET) are playing a big role in providing molecular information about cancer. Lately, molecular imaging has emerged as a stirring arena of dynamic imaging techniques that have enabled clinicians and scientists to noninvasively visualize and understand biological processes at the cellular and molecular levels. This knowledge has impacted etiopathogenesis, detection, personalized treatment, drug development, and our understanding of carcinogenesis. This article offers insight into the molecular biology underlying brain metastasis, its pathogenesis, imaging protocols, and algorithms. It also discusses disease-specific molecular imaging features, focusing on common tumors that spread to the brain, such as lung, breast, colorectal cancer, melanoma, and renal cell carcinoma. Additionally, it covers various targeted treatment options, criteria for assessing treatment response, and the role of artificial intelligence in diagnosing, managing, and predicting prognosis for patients with brain metastases.

Post-treatment imaging of gliomas: challenging the existing dogmas.

Gliomas are the commonest malignant central nervous system tumours in adults and imaging is the cornerstone of diagnosis, treatment, and post-treatment follow-up of these patients. With the ever-evolving treatment strategies post-treatment imaging and interpretation in glioma remains challenging, more so with the advent of anti-angiogenic drugs and immunotherapy, which can significantly alter the appearance in this setting, thus making interpretation of routine imaging findings such as contrast enhancement, oedema, and mass effect difficult to interpret. This review details the various methods of management of glioma including the upcoming novel therapies and their impact on imaging findings, with a comprehensive description of the imaging findings in conventional and advanced imaging techniques. A systematic appraisal for the existing and emerging techniques of imaging in these settings and their clinical application including various response assessment guidelines and artificial intelligence based response assessment will also be discussed.

Anatomical categorization of isolated non-focal dystonia: novel and existing patterns using a data-driven approach.

According to expert consensus, dystonia can be classified as focal, segmental, multifocal, and generalized, based on the affected body distribution. To provide an empirical and data-driven approach to categorizing these distributions, we used a data-driven clustering approach to compare frequency and co-occurrence rates of non-focal dystonia in pre-defined body regions using the Dystonia Coalition (DC) dataset. We analyzed 1,618 participants with isolated non-focal dystonia from the DC database. The analytic approach included construction of frequency tables, variable-wise analysis using hierarchical clustering and independent component analysis (ICA), and case-wise consensus hierarchical clustering to describe associations and clusters for dystonia affecting any combination of eighteen pre-defined body regions. Variable-wise hierarchical clustering demonstrated closest relationships between bilateral upper legs (distance = 0.40), upper and lower face (distance = 0.45), bilateral hands (distance = 0.53), and bilateral feet (distance = 0.53). ICA demonstrated clear grouping for the a) bilateral hands, b) neck, and c) upper and lower face. Case-wise consensus hierarchical clustering at k = 9 identified 3 major clusters. Major clusters consisted primarily of a) cervical dystonia with nearby regions, b) bilateral hand dystonia, and c) cranial dystonia. Our data-driven approach in a large dataset of isolated non-focal dystonia reinforces common segmental patterns in cranial and cervical regions. We observed unexpectedly strong associations between bilateral upper or lower limbs, which suggests that symmetric multifocal patterns may represent a previously underrecognized dystonia subtype.

Imaging Analytics using Artificial Intelligence in Oncology: A Comprehensive Review.

The present era has seen a surge in artificial intelligence-related research in oncology, mainly using deep learning, because of powerful computer hardware, improved algorithms and the availability of large amounts of data from open-source domains and the use of transfer learning. Here we discuss the multifaceted role of deep learning in cancer care, ranging from risk stratification, the screening and diagnosis of cancer, to the prediction of genomic mutations, treatment response and survival outcome prediction, through the use of convolutional neural networks. Another role of artificial intelligence is in the generation of automated radiology reports, which is a boon in high-volume centres to minimise report turnaround time. Although a validated and deployable deep-learning model for clinical use is still in its infancy, there is ongoing research to overcome the barriers for its universal implementation and we also delve into this aspect. We also briefly describe the role of radiomics in oncoimaging. Artificial intelligence can provide answers pertaining to cancer management at baseline imaging, saving cost and time. Imaging biobanks, which are repositories of anonymised images, are also briefly described. We also discuss the commercialisation and ethical issues pertaining to artificial intelligence. The latest generation generalist artificial intelligence model is also briefly described at the end of the article. We believe this article will not only enrich knowledge, but also promote research acumen in the minds of readers to take oncoimaging to another level using artificial intelligence and also work towards clinical translation of such research.

Trends of surgical-care delivery during the COVID-19 pandemic: A multi-centre study in India (IndSurg Collaboration).

Context: The COVID-19 pandemic and subsequent lockdowns adversely affected global healthcare services to varying extents. To accommodate its added burden, emergency services were affected along-with elective surgeries. Aims: To quantify and analyze the trends of essential surgeries and bellwether procedures during the waxing and waning of the pandemic, across various hospitals in India. Settings and Design: Multi-centric retrospective study. Methods and Material: A research consortium led by World Health Organization (WHO) Collaboration Center (WHOCC) for Research in Surgical Care Delivery in Low-and Middle-Income countries, India, conducted this study with 5 centers. All surgeries performed during April 2020 (Wave I), November 2020 (Recovery I), and April 2021 (Wave II) were compared with those performed in April 2019 (pre-pandemic period). Statistical Analysis Used: Microsoft Excel 2019 and SPSS Version 20. Results: The total number of surgeries reduced by 77% during Wave I, which improved to a 52% reduction in Recovery I compared to the pre-pandemic period. However, surgeries were reduced again during Wave II to 68%, but the reduction was less compared to Wave I. Emergency and essential surgeries were affected along with the elective ones but to a lesser extent. Conclusions: The present study has quantified the effects of the pandemic on surgical-care delivery across a timeline and documented a reduction in overall surgical volumes during the peaks of the pandemic (Wave I and II) with minimal improvement as the surge of COVID-19 cases declined (Recovery II). The surgical volumes improved during the second wave compared to the first one which may be attributable to better preparedness. Cesarean sections were affected the least.

Imaging of Neck Nodes in Head and Neck Cancers - a Comprehensive Update.

Cervical lymph node metastases from head and neck squamous cell cancers significantly reduce disease-free survival and worsen overall prognosis and, hence, deserve more aggressive management and follow-up. As per the eighth edition of the American Joint Committee on Cancer staging manual, extranodal extension, especially in human papillomavirus-negative cancers, has been incorporated in staging as it is important in deciding management and significantly impacts the outcome of head and neck squamous cell cancer. Lymph node imaging with various radiological modalities, including ultrasound, computed tomography and magnetic resonance imaging, has been widely used, not only to demonstrate nodal involvement but also for guided histopathological evaluation and therapeutic intervention. Computed tomography and magnetic resonance imaging, together with positron emission tomography, are used widely for the follow-up of treated patients. Finally, there is an emerging role for artificial intelligence in neck node imaging that has shown promising results, increasing the accuracy of detection of nodal involvement, especially normal-appearing nodes. The aim of this review is to provide a comprehensive overview of the diagnosis and management of involved neck nodes with a focus on sentinel node anatomy, pathogenesis, imaging correlates (including radiogenomics and artificial intelligence) and the role of image-guided interventions.

Imaging of brain metastasis in non-small-cell lung cancer: indications, protocols, diagnosis, post-therapy imaging, and implications regarding management.

Increased survival (due to the use of targeted therapies based on genomic profiling) has resulted in the increased incidence of brain metastasis during the course of disease, and thus, made it essential to have proper imaging guidelines in place for brain metastasis from non-small-cell lung cancer (NSCLC). Brain parenchymal metastases can have varied imaging appearances, and it is pertinent to be aware of the various molecular risk factors for brain metastasis from NSCLC along with their suggestive imaging appearances, so as to identify them early. Leptomeningeal metastasis requires additional imaging of the spine and an early cerebrospinal fluid (CSF) analysis. Differentiation of post-therapy change from recurrence on imaging has a bearing on the management, hence the need for its awareness. This article will provide in-depth literature review of the epidemiology, aetiopathogenesis, screening, detection, diagnosis, post-therapy imaging, and implications regarding the management of brain metastasis from NSCLC. In addition, we will also briefly highlight the role of artificial intelligence (AI) in brain metastasis screening.

Glioma radiogenomics and artificial intelligence: road to precision cancer medicine.

Radiogenomics refers to the study of the relationship between imaging phenotypes and gene expression patterns/molecular characteristics, which might allow improved diagnosis, decision-making, and predicting patient outcomes in the context of multiple diseases. Central nervous system (CNS) tumours contribute to significant cancer-related mortality in the present age. Although historically CNS neoplasms were classified and graded based on microscopic appearance, there was discordance between two histologically similar tumours that showed varying prognosis and behaviour, attributable to their molecular signatures. These led to the incorporation of molecular markers in the classification of CNS neoplasms. Meanwhile, advancements in imaging technology such as diffusion-based imaging (including tractography), perfusion, and spectroscopy in addition to the conventional imaging of glial neoplasms, have opened an avenue for radiogenomics. This review touches upon the schema of the current classification of gliomas, concepts behind molecular markers, and parameters that are used in radiogenomics to characterise gliomas and the role of artificial intelligence for the same. Further, the role of radiomics in the grading of brain tumours, prediction of treatment response and prognosis has been discussed. Use of automated and semi-automated tumour segmentation for radiotherapy planning and follow-up has also been discussed briefly.

Oral metronomic chemotherapy after definitive chemoradiation in esophageal squamous cell carcinoma: a randomized clinical trial.

BACKGROUND: Improving outcomes in locally advanced esophageal/GEJ squamous cell cancer (SCC) is an unmet need. We investigated the addition of oral metronomic chemotherapy (OMC) following definitive chemoradiotherapy (CRT). MATERIALS AND METHODS: This was a randomized open-label integrated phase II/III study in patients with SCC of esophagus/GEJ following definitive CRT who had no radiologic evidence of progression, and no endoscopically detected disease. Randomization was 1:1 to OMC (celecoxib 200 mg twice daily and methotrexate 15 mg/m2 weekly) for 12 months or observation. The primary endpoint for the phase II portion was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. P ≤ 0.2 for PFS was required to proceed to phase III. RESULTS: Between Jan 2016 and Dec 2019, we enrolled 151 patients for the phase II portion, 75 to OMC and 76 to observation. The tumor originated in the upper thoracic esophagus in 79% patients. Concurrent CRT consisted of median 63 Gy in a median of 35 fractions; concurrent chemotherapy was weekly paclitaxel + carboplatin in 91%. OMC was started at a median of 2.6 months (IQR 2.3-2.8) from CRT completion. Grade 3 or higher toxicities occurred in 18 patients (24%) in the OMC arm and 9 (12%) in the observation arm; P = 0.071. Median PFS was 25 months (95% CI, 17-58) in the OMC arm and was not attained [NA] (95% CI, 25-NA) in the observation arm; HR, 1.51, 95% CI, 1-2; P = 0.073. Median OS was 36 months (95% CI, 23-NA) in the OMC arm, and not attained (95% CI, NA-NA) in the observation arm; HR, 1.77; 95% CI, 1-2.9; P = 0.023. CONCLUSION: Oral metronomic methotrexate and celecoxib in patients who have not progressed radiologically and have no endoscopic evidence of disease following radical CRT for locally advanced esophageal/GEJ SCC does not improve outcomes and may lower survival. [Funded by the TMC-Research Administration Council (TRAC); CHROME study (CHemoRadiotherapy followed by Oral Metronomic therapy in Esophageal cancer); ctri.nic.in number: CTRI/2015/09/006204]. TRIAL REGISTRATION NUMBER: CTRI/2015/09/006204.

Childhood oral lichen planus: a case series with review of literature.

BACKGROUND: Oral Lichen Planus (OLP) is a chronic autoimmune mucocutaneous condition, the exact etiology of which is still unknown. It is known to occur chiefly in adults and has a reported prevalence of 0.5-2% in general population and < 2-3% of total in pediatric population. OLP is considered as Oral Potentially Malignant Disorder with a malignant transformation rate of 1-2% in adults. Its occurrence in children is a rare finding with few cases reported in the literature. As a result, it gets misdiagnosed by the general practitioner and hence, there is a need to consider OLP in differential diagnosis of white lesions of oral cavity even in children. Therefore, in this paper, we present six cases of childhood OLP along with their management and follow-up. CASE SERIES: We present here six patients aged between 11 and 13 years who presented either as incidental finding or as symptomatic lesions and were diagnosed with OLP. Symptomatic patients were treated with topical steroid ointment and both the symptomatic and asymptomatic patients were followed-up. We have also presented literature review of childhood OLP reported in PubMed, Medline and google scholar from 1980 till December 2020. CONCLUSION: OLP is unusual in children and is often left untreated due to low awareness among the patients. Can be often misdiagnosed and should be considered in differential diagnosis of any white lesion of oral cavity. Any such lesions must be correctly diagnosed in time to institute appropriate management and follow-up.

Cardiac sympathetic denervation for catecholaminergic polymorphic ventricular tachycardia.

Catecholaminergic polymorphic ventricular tachycardia (CPVT), a rare inheritable fatal arrhythmogenic disorder, is difficult to diagnose and is a challenge to manage. A 21-years-old man presented with recurrent exertional syncope and complex multifocal ventricular ectopy. CPVT was diagnosed based on the clinical criteria, despite the absence of some classical findings. The patient underwent cardiac sympathetic denervation (CSD) after lifestyle modification and pharmacological management were ineffective. CSD proved to be effective. The patient did not have any exertional symptoms or recurrence of syncope at follow-up period of 1 year. The present case report adds to the growing evidence in favour of CSD for CPVT.

Prevalence of growth hormone deficiency in patients with unexplained chronic fatigue after undergoing bone marrow transplantation in adulthood.

PURPOSE: Many patients who undergo bone marrow transplantation (BMT) in adulthood experience unexplained chronic fatigue which can have a major impact on their health-related quality of life (QoL). Pre-BMT treatment regimens increase the risk of developing acquired growth hormone deficiency (GHD), which results in a clinical syndrome with decreased energy and has additionally been linked to metabolic syndrome. METHODS: Using the gold-standard insulin hypoglycemic test (IHT), we evaluated the prevalence of GHD in 18 post-BMT adult patients with unexplained chronic fatigue, as well as the correlation between peak serum GH response and QoL scores, the metabolic syndrome, and insulin resistance. Peak serum GH cut-point less than 3.0 ug/L was used for the diagnosis of severe GHD. The Fatigue Severity Scale and Quality of Life in Adult GHD Assessment questionnaires were used to quantify fatigue symptoms. RESULTS: The prevalence of severe GHD within this sample of 18 patients was 50%. A trend between lower peak serum GH response and higher fatigue and QoL-AGHDA scores was observed. CONCLUSIONS: GHD may represent a remediable contributor to post-BMT chronic fatigue in adults, further studies are needed to evaluate the potential role of screening and GH replacement therapy in this vulnerable patient population. IMPLICATIONS FOR CANCER SURVIVORS: GHD may be a treatable explanation for disabling post-BMT fatigue pending results of intervention studies.

Appropriate THI model and its threshold for goats in semi-arid regions of India.

The present study was attempted to identify an appropriate THI model and threshold THI for goats of semi-arid regions of India. Sixty non-pregnant goats each from Jamunapari and Barbari breeds were selected for the study. The study was conducted from last week of February to first week of June, during which average THI ranged between 53 and 92. Pulse rate (PR), respiration rate (RR) and rectal temperature (RT) were recorded at 1430 h on alternate days from six goats of each breed randomly during the experiment. Nine THI models were used to calculate THI. An appropriate THI model was predicted on the basis of correlation between THIs calculated from each model and physiological responses. The data of physiological parameters were linked to the THI calculated from identified THI model and threshold THI for each parameter was determined using segmented regression analysis (SegReg Software). The THI models; THI1{(1.8 × Tdb+32)-[(0.55-0.0055 × RH) × (1.8 × Tdb-26.8)]} and THI8{(0.8 × Tdb)+[(RH/100) × (Tdb-14.4)]+46.4)} were found to be equally appropriate for assessing environmental heat stress. Threshold THIs with respect to PR, RR and RT in Jamunapari goat were 71.78, 75.14 and 85.94, respectively and in Barbari goats, threshold THIs for PR and RR were 79.48 and 84.40, respectively. A threshold THI could not be identified for RT in Barbari goats. It can be concluded that THI1 and THI8 were the appropriate THI models for measuring environmental heat stress in goats. Results suggested that PR is the first physiological parameter which alters after the onset of heat stress and is followed by changes in RR and RT. On the basis of differential threshold THIs, it can be concluded that Barbari is better adapted than Jamunapari goats in semi-arid regions of India.

Current Clinical Evidence of Trimetazidine in the Management of Heart Disease in Patients with Diabetes.

Diabetes Mellitus (DM) is a global heath burden and the leading cause for cardiovascular (CV) disease. The differential presentation of CV disease in DM is related to the metabolic derangements leading to deterioration of myocardial cell function and its serious consequences. Therefore, there is a need for early and effective treatment intervention for this myocardial cell metabolic dysfunction. DM and myocardial ischemia (MI) share a common metabolic dysregulation mediated via increased fatty acid oxidation that makes the diabetic heart susceptible to myocardial ischemia and reduced myocardial performance during ischemia compared to non-diabetic heart. Modulation of myocardial free fatty acid metabolism should be the key target for metabolic interventions in patients with Diabetic CV complications. Trimetazidine, a fatty acid metabolic modulator, has shown to improve CV outcomes in diabetes. The present review summarizes the clinical evidence and relevance of trimetazidine as an anti-anginal and antiischemic agent in patients with DM. Evidence suggested that trimetazidine could significantly improve clinical outcomes in patients with angina or heart failure and diabetes. Administering trimetazidine in patients with diabetes undergoing re-vascularization could also provide significant clinical benefits. Current clinical practice guidelines also recommend trimetazidine as a first-line agent for selected patients or as a second-line treatment option for angina patients.

Signatures of a Spin-1/2 Cooperative Paramagnet in the Diluted Triangular Lattice of Y_{2}CuTiO_{6}.

We present a combination of thermodynamic and dynamic experimental signatures of a disorder driven dynamic cooperative paramagnet in a 50% site diluted triangular lattice spin-1/2 system: Y_{2}CuTiO_{6}. Magnetic ordering and spin freezing are absent down to 50 mK, far below the Curie-Weiss scale (-θ_{CW}) of ∼134 K. We observe scaling collapses of the magnetic field and temperature dependent magnetic heat capacity and magnetization data, respectively, in conformity with expectations from the random singlet physics. Our experiments establish the suppression of any freezing scale, if at all present, by more than 3 orders of magnitude, opening a plethora of interesting possibilities such as disorder stabilized long range quantum entangled ground states.

Study of the Prevalence of Congenital Coronary Anomalies of Origin from the Opposite or Non-coronary Sinus in patients undergoing Invasive Coronary Angiography.

OBJECTIVES: 1. To study the incidence and clinical features of patients with Congenital Coronary Anomalies of Origin from Oppossite or Non-coronary Sinus; 2. To study the course of these Anomalous Coronary Artery Origins with CT Coronary Angiography. METHODS: A Cross Sectional Observation study was conducted at Department of Cardiology, in a tertiary Hospital for a period of 3 years. Patients undergoing Coronary Angiography (CAG) were screened and patients having Anomalous Coronary Origin from the Opposite or Non-Coronary Sinus of Valsalva were selected. CT Cronary Angiography was done in all such patients and the course of the anomalous artery was studied. RESULTS: During the 3 years period of study, total of 5241 CAGs were conducted of which 42 (0.8%) patients were found to have Anomalous Coronary Artery Origin as per the inclusion criteria. Out of the 42 cases, Anomalous origin of RCA from Left Corornary Cusp was the commonest with 23(0.43%) cases, followed by Anomalous Origin of LCX from Right Coronary or RCC with 17 (0.32%) cases. Other anomalies of origin were quite rare (n=2) which included Anomalous origin of Left Main from RCA (n=1) and Dual origin of LAD (n=1). CT Coronary Angiography showed that of the 23 patients with Anomalous Origin of RCA from Left side,27.4% had Inter-Arterial course and 56.1% had Retro-Aortic course. Of the 17 patients with Anomalous Origin of LCX from Right sinus, 88.23% had Retro-Aortic course. CONCLUSIONS: This study showed that anomalous origin of Coronary Artery from the opposite sinus is quite rare with RCA from Left Sinus and LCX from Right sinus comprised the vast majority of cases. Most of these anomalous Coronaries have on benign course as defined on CT Coronary Angiography. However, it is important to recognize to delineate the origin and course as it can have significant clinical, therapeutic and prognostic implications.

Radiation therapy strategies for skull-base malignancies.

INTRODUCTION: The management of skull base malignancies continues to evolve with improvements in surgical technique, advances in radiation delivery and novel systemic agents. METHODS: In this review, we aim to discuss in detail the management of common skull base pathologies which typically require multimodality therapy, focusing on the radiotherapeutic aspects of care. RESULTS: Technological advances in the administration of radiation therapy have led to a wide variety of different treatment strategies for the treatment of skull base malignances, with outcomes summarized herein. CONCLUSION: Radiation treatment plays a key and critical role in the management of patients with skull base tumors. Recent advancements continue to improve the risk/benefit ratio for radiotherapy in this setting.

Correction to: Cesarean delivery to prevent anal incontinence: a systematic review and meta-analysis.

The original article can be found online.

How have advances in genetic technology modified movement disorder nosology?

The role of genetics and its technological development have been fundamental in advancing the field of movement disorders, opening the door to precision medicine. Starting from the revolutionary discovery of the locus of the Huntington's disease gene, we review the milestones of genetic discoveries in movement disorders and their impact on clinical practice and research efforts. Before the 1980s, early techniques did not allow the identification of genetic alteration in complex diseases. Further advances increasingly defined a large number of pathogenic genetic alterations. Moreover, these techniques allowed epigenomic, transcriptomic and microbiome analyses. In the 2020s, these new technologies are poised to displace phenotype-based classifications towards a nosology based on genetic/biological data. Advances in genetic technologies are engineering a reversal of the phenotype-to-genotype order of nosology development, replacing convergent clinicopathological disease models with the genotypic divergence required for future precision medicine applications.