Incidence and clinical profile of brain metastasis treated with whole brain radiotherapy in a tertiary hospital in eastern India: A retrospective audit.

Introduction: Management of brain metastases (BM) is witnessing marked advancement worldwide and modern technologies with better outcomes are gradually being adopted in developing countries. However, data regarding current practice in this field is lacking from the Indian subcontinent prompting us to plan the current study. Materials and Methods: A retrospective, single institutional audit was performed on 112 patients with solid tumors metastasizing to the brain treated over the last 4 years at a tertiary care center in eastern India, of which 79 were ultimately evaluable. Demography, patterns of incidence, and overall survival (OS) were determined. Results: The prevalence of BM was 5.65% among all patients with solid tumors. The median age was 55 years with a slight male preponderance. Lung followed by breast were the most common primary subsites. Multiple BM (54%), left-sided (61%), and frontal lobe lesions (54%) were the more common. Metachronous BM was found in 76% of patients. All patients received whole brain radiation therapy (WBRT). The median OS for the entire cohort was 7 months (95% confidence interval [CI]: 4 - 19 months). The median OS for lung and breast primaries were 6.5 and 8 months and for recursive partitioning analysis (RPA) classes I, II, and III the OS were 11.5, 7, and 3 months, respectively. Median OS did not differ by number of or other sites of metastases. Conclusions: The outcomes from our series about BM from solid tumors in patients from eastern Indian are in congruence to those available in the literature. Patients with BM are still largely treated with WBRT in resource-limited settings.

Epidemiological challenges in pandemic coronavirus disease (COVID-19): Role of artificial intelligence.

World is now experiencing a major health calamity due to the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus clade 2. The foremost challenge facing the scientific community is to explore the growth and transmission capability of the virus. Use of artificial intelligence (AI), such as deep learning, in (i) rapid disease detection from x-ray or computed tomography (CT) or high-resolution CT (HRCT) images, (ii) accurate prediction of the epidemic patterns and their saturation throughout the globe, (iii) forecasting the disease and psychological impact on the population from social networking data, and (iv) prediction of drug-protein interactions for repurposing the drugs, has attracted much attention. In the present study, we describe the role of various AI-based technologies for rapid and efficient detection from CT images complementing quantitative real-time polymerase chain reaction and immunodiagnostic assays. AI-based technologies to anticipate the current pandemic pattern, prevent the spread of disease, and face mask detection are also discussed. We inspect how the virus transmits depending on different factors. We investigate the deep learning technique to assess the affinity of the most probable drugs to treat COVID-19. This article is categorized under:Application Areas > Health CareAlgorithmic Development > Biological Data MiningTechnologies > Machine Learning.

Impact of maternal substance use on offspring's cardiovascular health.

Substance use (SU) during pregnancy is on the rise, posing significant risks to the developing fetus. The adverse impact of maternal alcohol and nicotine use during the perinatal period on offspring health has been well established, including their associations with adverse cardiovascular health in offspring. However, limited studies examine the impact of other well-known SU utilized during pregnancy on offspring's cardiovascular health. This review summarizes the proposed mechanism of action of four commonly utilized substances: cocaine, marijuana, methamphetamine, and opioids, and their cardiovascular impact. Furthermore, we will review the current understanding of the adverse impact of substance use during pregnancy on offspring's cardiovascular system based on existing studies. This review will also highlight possible molecular mechanisms underlying the in-utero adverse programming of offspring's cardiovascular system secondary to SU in pregnancy and address the gaps in current understanding of how SU adversely impacts the developing cardiovascular system of offspring in utero.

Cytogenetic Abnormalities in Multiple Myeloma: Incidence, Prognostic Significance, and Geographic Heterogeneity in Indian and Western Populations.

Multiple myeloma (MM) is a genetically complex and heterogeneous neoplasm in which cytogenetics is a major factor playing an important role in the risk stratification of disease. High-risk MM based upon cytogenetic classification includes primary IGH translocations t(4;14), t(14;16), t(14;20), and secondary progressive aberrations such as gain/amp(1q), 1p deletion, del(17p), and hypodiploidy. Several studies have proved that interphase FISH can detect primary as well as secondary cryptic aberrations very efficiently in lowest 5-10% abnormal plasma cell population. The present large-scale study was undertaken to evaluate the incidence of cytogenetic abnormalities, to analyse the correlation of conventional karyotyping with FISH, and to seek the geographic heterogeneity in the incidence of primary as well as secondary aberrations in our Indian versus Western populations. We conducted prospective studies of 1,104 patients consecutively referred from the primary, secondary, and tertiary oncology centres from all over India. Interphase FISH was performed on isolated plasma cells. Karyotype analysis was done as per ISCN 2016 and 2020. FISH could detect cytogenetic abnormalities in 67.6% of the cases with an incidence of 59% non-hyperdiploidy. The incidence of IGH translocation was 26% versus literature frequency of 40-50% which was mainly due to a low incidence (6%) of t(11;14) in contrast to 15-20% in other series. Additionally, the association of secondary progressive aberrations in the hyperdiploid group rather than the non-hyperdiploid group in our patients is not a common finding. A biallelic inactivation of TP53 as an ultra-high risk factor was detected in old-aged patients. These observations disclose the novel findings and strongly indicate the racial disparity which leads to geographic heterogeneity. In contrast to FISH, conventional karyotyping could detect MM-related aberrations in 50% of cases, of which 44% revealed highly complex karyotypes with common aberrations of chromosome 1q. Overall, FISH was found to be a novel, easy approach with high success rate and capability of detection of all cytogenetic abnormalities that add valid information for the risk stratification of disease. This, in future, in combination with mutation profile and gene expression profile will help in further refinement of disease and identification of actionable targets.

Perception of Oncology Evaluated by Medical Students (P.O.E.M.S)-a Single Institutional Study.

Rising incidence of cancer coupled with lack of structured oncology teaching in the undergraduate (UG) medical curriculum could be detrimental by generating unmet needs in the proper care of cancer patients in the future. To determine the orientation amongst undergraduate medical students regarding Oncology as a specialization and future career option, a cross-sectional, single institutional study was conducted amongst 950 undergraduate students by using an online survey over 2 months. The perception of the subject of Oncology as a career option and the opinion regarding the need for inclusion in the undergraduate curriculum were assessed. Students themselves or those with first-degree relatives as cancer survivors were excluded. A total of 317 responses (33.4%) met the inclusion criteria. Majority were MBBS students from semesters 6 to 9. Even though students ranked the future prospect of Oncology 7.5 on 10, only 6% of the respondents actually wanted to pursue it as a career option stating high mortality amongst cancer patients (63.6%) and emotional burnout (49.7%) as the primary limitations. On a brighter note, better job opportunity due to increasing global cancer incidence (61%) and opportunity for research (42.8%) were thought to be the promising features of the specialization. Majority (51.3%) wanted the inclusion of Oncology in the undergraduate curriculum. Due to limited exposure in the undergraduate curriculum, there is a lack of knowledge and interest regarding the scope of Oncology as a future career option. We therefore advocate revision of the undergraduate curriculum to include Oncology.

SUMO fosters assembly and functionality of the MutSγ complex to facilitate meiotic crossing over.

Crossing over is essential for chromosome segregation during meiosis. Protein modification by SUMO is implicated in crossover control, but pertinent targets have remained elusive. Here we identify Msh4 as a target of SUMO-mediated crossover regulation. Msh4 and Msh5 constitute the MutSγ complex, which stabilizes joint-molecule (JM) recombination intermediates and facilitates their resolution into crossovers. Msh4 SUMOylation enhances these processes to ensure that each chromosome pair acquires at least one crossover. Msh4 is directly targeted by E2 conjugase Ubc9, initially becoming mono-SUMOylated in response to DNA double-strand breaks, then multi/poly-SUMOylated forms arise as homologs fully engage. Mechanistically, SUMOylation fosters interaction between Msh4 and Msh5. We infer that initial SUMOylation of Msh4 enhances assembly of MutSγ in anticipation of JM formation, while secondary SUMOylation may promote downstream functions. Regulation of Msh4 by SUMO is distinct and independent of its previously described stabilization by phosphorylation, defining MutSγ as a hub for crossover control.

Effect of carboplatin dose capping on survival in recurrent breast, ovary and head and neck cancers: a single institutional retrospective study.

INTRODUCTION: Carboplatin based regimens are an integral part of chemotherapy regimens for recurrent head and neck cancers (rHNC), triple negative breast cancers (rTNBC) and ovarian cancers (rOC). Dose reduction/capping of carboplatin remains a controversial aspect of such regimens in patients with moderate creatinine clearance (50 ml/min to 125 ml/min), especially in resource limited setting. The authors, therefore, looked into the magnitude of difference in outcome this makes in the above mentioned subsites. METHODS: This single institutional retrospective study was performed with a total of 120 patients divided equally into Group A (patients receiving capped dose) and Group B (patients receiving uncapped dose). Further matching was performed with respect to age, sex, body surface area, weight, and primary malignancy subsite and baseline creatinine clearance. Patients in Group A had received 450 mg (for AUC 6 regimens) and 150 mg (for AUC 2 regimens) of carboplatin while patients in Group B received the actual calculated dose of carboplatin determined by the Calvert formula. Median progression free survival (mPFS) and median overall survival (mOS) were the co-primary outcome measures. RESULTS: At a median follow-up of 24 months, compared to Group A, Group B had a higher mPFS and mOS by 4 months (p < .001) and 5.5 months (p < .001), respectively. Statistically significant difference in outcome favouring Group B extends to all primary tumour subsites, with mPFS difference being 3.1 months (rHNC), 5.1 months (rTNBC) and 4.5 months (rOC) and mOS difference being 4.2 months (rHNC), 3 months (rTNBC) and 5.6 months (rOC). It was also found that capping had a statistically significant detriment in distal failure (p = .042) compared to locoregional failure (p = .842). A higher proportion of hematotoxicity was found in Group B, however, it was not statistically significant and well manageable. CONCLUSIONS: Blatant dose capping of carboplatin should be avoided probably with more caution in patients with distant disease recurrence compared to their counterparts with locoregional failure.

Noncovalent Association and Partitioning of Some Perfume Components at Infinite Dilution with Myelin Basic Protein Pseudophase in Normal Saline.

Myelin basic protein (MBP), one of the major protein constituents of the myelin sheath, possesses unique ligand-binding features. We present a novel equilibrium headspace gas chromatographic technique to examine the thermodynamics of noncovalent interactions between common perfume components: Lilial, Hedione, Hexylcinnamic aldehyde, and Versalide with MBP monomers and its hexameric MBP-pseudophase. A general theoretical model is used to calculate the critical aggregation concentration (cac) of MBP, perfume component binding constants with monomeric MBP, K11, and MBP as pseudophase, Kn1, and free energies for perfume component binding with monomeric MBP, ΔGb,11, and MBP as pseudophase, ΔGb,n1. In addition, the pseudophase-water partition coefficients, Kx, the free energies of transfer of perfume from bulk water to the MBP-pseudophase, ΔGt, and the intra-aggregate activity coefficients, γm∞, at infinite dilution were also determined. The cac value measured by the method of fractional distribution is a unique and precise approach in understanding the aggregation phenomenon. Within the experimental error, the 1:1 binding free energies did not differ by more than 1 kJ/mol among the perfume components but favored the MBP pseudophase binding by 6 kJ/mol. Therefore, that protein aggregation can enhance the binding of small molecules is probably a general conclusion. While the magnitudes of K11, Kn1, ΔGb, Kx, and ΔGt show weak trends, the γm∞ values show a strong and distinct trend in interaction, spanning 4 orders of magnitude among the perfume components.

A new open-access platform for measuring and sharing mTBI data.

Despite numerous research efforts, the precise mechanisms of concussion have yet to be fully uncovered. Clinical studies on high-risk populations, such as contact sports athletes, have become more common and give insight on the link between impact severity and brain injury risk through the use of wearable sensors and neurological testing. However, as the number of institutions operating these studies grows, there is a growing need for a platform to share these data to facilitate our understanding of concussion mechanisms and aid in the development of suitable diagnostic tools. To that end, this paper puts forth two contributions: (1) a centralized, open-access platform for storing and sharing head impact data, in collaboration with the Federal Interagency Traumatic Brain Injury Research informatics system (FITBIR), and (2) a deep learning impact detection algorithm (MiGNet) to differentiate between true head impacts and false positives for the previously biomechanically validated instrumented mouthguard sensor (MiG2.0), all of which easily interfaces with FITBIR. We report 96% accuracy using MiGNet, based on a neural network model, improving on previous work based on Support Vector Machines achieving 91% accuracy, on an out of sample dataset of high school and collegiate football head impacts. The integrated MiG2.0 and FITBIR system serve as a collaborative research tool to be disseminated across multiple institutions towards creating a standardized dataset for furthering the knowledge of concussion biomechanics.

Achieving Perfect Hand Washing: an Audit Cycle with Surgical Internees.

The aim of this study is to achieve 100% compliance in surgical hand antisepsis along with identification of areas of worst compliance and efficacies of various interventions best suited to deal with them. This audit was performed over 6 days in a tertiary care hospital in Calcutta, India, with 42 surgical internees. Compliance to ideal hand washing technique was recorded after each attempt with the first attempt as baseline. Video demonstration, personal demonstration by a consultant, and individual instruction were used as subsequent interventions to achieve 100% compliance. The baseline level of compliance was found to be 33.59%. A total of 6 attempts was required to achieve 100% compliance, with the increase in compliance being statistically significant (p = 0.0294). Personal instruction was found to be the most effective intervention. Hand washing technique was the criterion that needed the most number of attempts (n = 6) to rectify. This study found video-based instruction and individual guidance effective teaching tools for surgical hand disinfection and gave novel data regarding the reasons responsible for poor compliance to proper hand washing in a general surgical setting. This study demonstrated the efficiency of audit cycles in the improvement of surgical hand washing and can be the preferred mode of intervention in future studies aimed at achieving ideal hand antisepsis.

Efficacy of Chronomodulated Chemotherapy for Palliation of Hematemesis in Inoperable Gastric Cancer: A Single-Institutional Retrospective Study.

CONTEXT: Aside abdominal discomfort and pain, upper gastrointestinal bleeding (UGIB) significantly disgraces the quality of life (QoL), especially in inoperable gastric cancer patients. Although, in early stages, it is infrequent and often ignored, but in advanced stages, its aggressiveness often deteriorates patient's hemoglobin (Hb) level and performing status. AIM: The aim of this study is to correlate the change in (1) the frequency of episodes of UGIB, (2) its severity in terms of Common Terminology Criteria for Adverse Events (CTCAE) grade for UGIB, and (3) Hb level with the successful completion of successive cycles of palliative chemotherapy where it becomes invariably the only modality to palliate the cancer disease. SETTING AND DESIGN: This single-institutional retrospective observational study included seventy gastric carcinoma patients with a chief complaint of frequent hematemesis. They were divided according to the cause behind inoperability or irresectability: (1) Metastatic disease, (2) locally advanced irresectable disease, (3) uncontrolled comorbidities, (4) poor GC (PGC), and (5) refused to give surgical consent. SUBJECTS AND METHODS: Following baseline evaluation and prechemotherapy workups, patients were subjected to three-weekly chronomodulated modified EOX regimen. Relevant parameters, i.e., (1) average episodes per-week (AEP) score, (2) Hb, and (3) average CTCAE grade value for UGIB were recorded after every cycle. RESULTS: At 12-week follow-up, there was a significant decrease in mean AEP score from baseline (from 2.6691 ± 0.7047 to 1.5033 ± 0.6272) for the entire cohort (P < 0.001). Maximum benefit in terms of mean Hb (increase by 1.0737% above baseline) took place for PGC group (P < 0.001). Mean CTCAE grade value for the entire cohort decreased from baseline by 0.6428, which was statistically significant with a P < 0.001. CONCLUSIONS: PGC group was maximally benefited considering all three parameters. Though surgery defines the mainstay of treatment for gastric carcinoma, yet in inoperable cases, only chronomodulated chemotherapy significantly affects the severity of UGIB and thus may improve QoL.

Sexual functioning in females with depression in remission receiving escitalopram.

Background & objectives: Sexual functioning is a strong determinant of quality of life. Sexual dysfunction has been widely reported due to depressive disorder as well as selective serotonin reuptake inhibitors. Thus, treatment with antidepressants can culminate in a double-edged sword, leading to drug discontinuation and symptom relapse. The objective of this study was to assess the sexual functioning of sexually active females with depression, currently in remission, receiving escitalopram and to compare with healthy controls. Methods: Fifty female patients with depression, currently in remission, with self-reported normal pre-morbid sexual function and receiving escitalopram for at least three months, were assessed on female sexual function index (FSFI) questionnaire and compared with healthy controls. Results: Half of the patients (n=25, 50%) in group A were found to have sexual dysfunction (FSFI score <26.55), while, 90 per cent (n=45) had decreased desire, 86 per cent (n=43) had decreased arousal, 54 per cent (n=27) had decreased lubrication, 68 per cent (n=34) had decreased orgasm, 62 per cent (n=31) had decreased satisfaction and 32 per cent (n=16) had pain during sexual activity. Patients receiving escitalopram had significantly higher sexual dysfunction as compared to healthy controls in mean total FSFI score (P < 0.001) and all mean domain scores of FSFI except pain. Interpretation & conclusions: A significant proportion of sexually active females with depression currently in remission, receiving escitalopram, reported dysfunction in all domains of sexual function; thus, routine screening for sexual dysfunction during follow up is advisable for early identification and prompt treatment.

A Field Fire Ulcer.

Basal cell carcinoma (BCC) is the most common skin cancer, mostly affecting areas of the skin exposed to UV radiation. Though metastasis is rare, the tumour may be locally invasive with a high recurrence rate. Pathophysiology involves neoplastic transformation of the pluripotent cells of the epidermis and follicular epithelium. 'Field fire BCC' is an uncommon type of BCC, showing concomitant crusting, ulceration and scarring which spreads peripherally with a central area of regression.

Stratification of phaco-trabectome surgery results using a glaucoma severity index in a retrospective analysis.

BACKGROUND: To stratify the outcomes of phacoemulsification combined with trabectome surgery using a new glaucoma severity index. METHODS: This is a retrospective, observational cohort study that included open angle glaucoma patients with visually significant cataract that had phacoemulsification combined with trabectome surgery. Exclusion criteria were follow-up less than 12 months, any other surgeries or diagnosis of neovascular or active uveitic glaucoma. Patients were stratified into four groups according to the Glaucoma Index (GI) that incorporated preoperative intraocular pressure (IOP), number of medications and visual field status. The primary outcome measures were IOP reduction and the success rate at 12 months. We examined the relationship between GI group and IOP and medications at one year with a linear regression analysis and survival with log-rank testing. RESULTS: Of 1374 patients, a total of 498 cases with 12 month follow-up were included in the study after applying the exclusion criteria. At one year, IOP of GI groups 1 through 4 was reduced by 2.9 ± 4.4, 3.6 ± 5.0, 3.9 ± 5.3, and 9.2 ± 7.6 mmHg for. Individuals in the next higher GI group had a 1.69 ± 0.2 mmHg larger IOP decrease. The success rate was 98%, 93%, 96% and 88% at one year for GI groups 1 to 4 (p < 0.05). CONCLUSIONS: A substantial IOP reduction was seen in subjects with more advanced glaucoma suggesting that the trabecular meshwork is the primary impediment to outflow and its ablation benefits those eyes relatively more than in mild glaucoma. A larger IOP reduction can be expected in individuals with a higher GI group that indicates a clinically more challenging glaucoma.