Pathological Complete Response as Outcome Modifier in Breast Cancer Patients and Brain Metastasis.

Breast cancer with brain metastases (BCBM) has dreadful outcomes. Various factors influencing outcomes are age, receptors status, number of distant metastases, performance status, leptomeningeal metastasis, chemotherapies, and whole brain radiation dose. This study aimed to find outcome-modifying factors in BCBM. Clinical, demographic, subtype, and pathological response of primary brain imaging characteristics of BCBM patients were correlated with brain metastasis-free interval and survival after brain metastasis was studied from January 2020 to March 2022. Triple-negative breast cancer (TNBC) patients had the earliest presentation for brain metastases (mean 45.4 years) vs luminal B (mean 57.93 years). Both brain metastasis-free interval (BMFI) and brain metastasis overall survival (BMOS) were maximum in HER2-positive subtype (mean 22.8 and 11.55 months) and least in TNBC patients (mean 9.8 and 2.12 months), respectively. Low-graded prognosis assessment (GPA) score and leptomeningeal metastasis were associated with the worst outcomes. BMFI and BMOS in patients with pathological complete response (PCR) were at 28.5 and 15.1 months, in partial response were 18.5 and 7.66 months, and with stable or progressive disease were 11 and 1.36 months, respectively. In the present study, PCR was the only modifiable parameter that changed breast cancer outcomes with brain metastasis and leptomeningeal metastasis was associated with the worst outcomes. Our study favors that PCR has prognostic importance.

Comparative metabolomics of MCF-7 and MCF-7/TAMR identifies potential metabolic pathways in tamoxifen resistant breast cancer cells.

OBJECTIVES: Breast cancer is the most common cancer and the leading cause of cancer-related death among women. An Estrogen Receptor (ER) antagonist called tamoxifen is used as an adjuvant therapy for ER-positive breast cancers. Approximately 40% of patients develop tamoxifen resistance (TAMR) while receiving treatment. Cancer cells can rewire their metabolism to develop resistant phenotypes, and their metabolic state determines how receptive they are to chemotherapy. METHODS: Metabolite extraction from human MCF-7 and MCF-7/TAMR cells was done using the methanol-methanol-water extraction method. After treating the dried samples with methoxamine hydrochloride in pyridine, the samples were derivatized with 2,2,2-Trifluoro-N-methyl-N-(trimethylsilyl)-acetamide, and Chlorotrimethylsilane (MSTFA + 1% TMCS). The Gas chromatography/mass spectrometry (GC-MS) raw data were processed using MSdial and Metaboanalyst for analysis. RESULTS: Univariate analysis revealed that 35 metabolites were elevated in TAMR cells whereas 25 metabolites were downregulated. N-acetyl-D-glucosamine, lysine, uracil, tyrosine, alanine, and o-phosphoserine were upregulated in TAMR cells, while hydroxyproline, glutamine, N-acetyl-L-aspartic acid, threonic acid, pyroglutamic acid, glutamine, o-phosphoethanolamine, oxoglutaric acid, and myoinositol were found to be downregulated. Multivariate analysis revealed a distinct separation between the two cell lines, as evidenced by their metabolite levels. The enriched pathways of deregulated metabolites included valine, leucine, and isoleucine degradation, Citric Acid Cycle, Warburg effect, Malate-Aspartate shuttle, glucose-alanine cycle, propanoate metabolism, and Phospholipid biosynthesis. CONCLUSION: This study revealed dysregulation of various metabolic processes in TAMR cells, which may be crucial in elucidating the molecular basis of the mechanisms underlying acquired tamoxifen resistance.

Regional and periodic asymmetries in the effect of Russia-Ukraine war on global stock markets.

This study aims to investigate regional and periodic asymmetries in the impact of the outbreak of the Russia-Ukraine war on global equity markets. Employing the event study methodology, the current study examines global stock market reactions within a 61-day window centred around the event day, i.e., February 24, 2022. MSCI equity indices of 47 sample countries have been utilized to ensure uniformity in the index development methodology. They provide broader coverage of global equity markets by including large and mid-cap companies, representing approximately 85% of the free float-adjusted market capitalization for each sampled country. The study extends the event window to 61 days to assess the enduring effects of the war over a relatively longer period. The research delineates regional and periodic asymmetries and posits that the impact of the war on a market is contingent upon its geographical proximity and trade relations with Russia and Ukraine. Additionally, the impact is stronger during a shorter window surrounding the event date but diminishes over the extended period.

Retrospective Analysis of Clinical Characteristics and Outcomes of Pregnant Women with SARS-CoV-2 Infections Admitted to Intensive Care Units in India (Preg-CoV): A Multicenter Study.

Aim: The aim was to examine the outcomes of pregnant women admitted to intensive care unit with coronavirus disease-2019 (COVID-19) infection during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in India. The primary outcome of the study was maternal mortality at day 30. The secondary outcomes were the intensive care unit (ICU) and hospital length of stay, fetal mortality and preterm delivery. Materials and methods: This was a retrospective multicentric cohort study. Ethical clearance was obtained. All pregnant women of the 15-45-year age admitted to ICUs with SARS-CoV-2 infection during 1st March 2020 to 31st October, 2021 were included. Results: Data were collected from nine centers and for 211 obstetric patients admitted to the ICU with a confirmed diagnosis of COVID-19. They were divided in to two groups as per their SpO2 (saturation of peripheral oxygen) level at admission on room air, that is, normal SpO2 group (SpO2 > 90%) and low SpO2 group (SpO2 < 90%). The mean age was (30.06 ± 4.25) years and the gestational age was 36 ± 8 weeks. The maternal mortality rate was10.53%. The rate of fetal death and preterm delivery was 7.17 and 28.22%, respectively. The average ICU and hospital length of stay (LOS) were 6.35 ± 8.56 and 6.78 ± 6.04 days, respectively. The maternal mortality (6.21 vs 43.48%, p < 0.001), preterm delivery (26.55 vs 52.17%, p = 0.011) and fetal death (5.08 vs 26.09%, p = 0.003) were significantly higher in the low SpO2 group. Conclusion: The overall maternal mortality among critically ill pregnant women affected with COVID-19 infection was 10.53%. The rate of preterm birth and fetal death were 28.22 and 7.17%, respectively. These adverse maternal and fetal outcomes were significantly higher in those admitted with low SpO2 (<90%) at admission compared with those with normal SpO2. How to cite this article: Sinha S, Paul G, Shah BA, Karmata T, Paliwal N, Dobariya J, et al. Retrospective Analysis of Clinical Characteristics and Outcomes of Pregnant Women with SARS-CoV-2 Infections Admitted to Intensive Care Units in India (Preg-CoV): A Multicenter Study. Indian J Crit Care Med 2024;28(3):265-272.

Adenomyoepithelial adenosis mimicking phylloides: A diagnostic dilemma.

Benign proliferative breast diseases are well recognized in young females. Benign biphasic proliferation of epithelial and myoepithelial cells has been observed, among which adeno-myoepithelial adenosis is one of the rare morphologies published in the literature with the tendency to recur and poses a risk for low-grade malignant transformation. Here, we report a case of a young female who had a history of recurrent breast lump mimicking phyllodes tumor and eventually diagnosed as adeno-myoepithelial adenosis on histopathological examination. Benign proliferative breast diseases are well recognized in young females. Benign biphasic proliferation of epithelial and myoepithelial cells has been observed, among which adeno-myoepithelial adenosis is one of the rare morphologies published in the literature with the tendency to recur and poses a risk for low-grade malignant transformation. Here, we report a case of a young female who had a history of recurrent breast lump mimicking phyllodes tumor and eventually diagnosed as adeno-myoepithelial adenosis on histopathological examination.

Host Response of Arabidopsis thaliana Interaction with Fungal Endophytes Involves microRNAs.

Plant and fungus interaction is a complex process involving many molecular factors determining the nature of relationship. The enigmatic methodology by which fungal endophytes are able to colonise a plant harmoniously is still inexplicable. Small RNAs have been identified as major regulatory elements under various biotic interactions. However, their role in endophytic plant-fungal interactions remain to be elucidated. Therefore, transcript expression data available on Gene Expression Omnibus for Arabidopsis thaliana was utilised for miRNAs identification under endophytism. The analysis predicted 15 miRNAs with differential expression of which the ath-miRNA398b modulation was significant. Application of psRNAtarget, C-mii, pmiREN, and TarDB provided a pool of 357 target genes for these miRNAs. Protein-protein interaction analysis identified major hub proteins, including BTB/POZ domain-containing protein, beta-Xylosidase-2 (AtBXL2), and Copper/Zinc Superoxide Dismutase-2 (AtSOD2). The quantitative real-time PCR validated the computational prediction and expression for selected target genes AtSOD2, AtBXL2, and AtRCA along with ath-miRNA398b under endophytism. Overall, results indicate that miRNAs have a significant role in regulating Arabidopsis thaliana-endophytic fungal interaction.

Greulich and Pyle atlas: a non-reliable skeletal maturity assessment method in the North Indian population.

Forensic age assessments are crucial in the evaluation of criminal responsibility and preventing false age claims. Of all the methods available, the Greulich and Pyle (GP) atlas is most commonly used for age estimation purposes. Therefore, the current study sought to analyze the reliability and applicability of the GP standard and, additionally, to determine any possible association between the socioeconomic status (SES), food habits, and estimated skeletal maturity in the North Indian population. The study included 627 (334 males and 293 females) healthy children up to 19 years of age with varying SES and food habits. The skeletal age (SA) was estimated by three different evaluators using the GP atlas. The chronological mean age (CA) and SA were compared in different age cohorts. A paired t-test and a Pearson chi-square test were applied to show the difference between CA and estimated SA and the association of skeletal maturity with SES and food habits. The estimated skeletal age in males was retarded by 0.142 years or 1.72 months (p ≤ 0.05), whereas in females, it was retarded by 0.259 years or 3.12 months (p ≤ 0.05). In males, the GP method has significantly underestimated SA in age cohorts 3-4, 4-5, 6-7, 7-8, 8-9, and 12-13, whereas it overestimated in 10-11 and 18-19 years. However, in females, the SA was significantly underestimated in age groups 10-11, 12-13, and 14-15, respectively. Estimated skeletal maturity had no significant association with SES and food habits. The current study concludes that the GP atlas may not be applicable to North India's population. The observed difference in assessed skeletal maturity may be due to geographical region, genetics, hormonal effects, etc., which require further investigation. Hence, population-specific standards are necessary to determine the bone age of Indian children accurately.

Early and mid-term outcomes of double-chambered right ventricle repair: An 8-year experience.

BACKGROUND/AIM: Double-chambered right ventricle is a rare and progressive condition that is characterised by obstruction of the right ventricular tract. Double-chambered right ventricle is usually associated with ventricular septal defect. Early surgical intervention is recommended in patients with these defects. Based on this background, the present study aimed to review early and midterm outcomes of primary repair after double-chambered right ventricle. METHODS: Between January 2014 and June 2021, 64 patients with a mean age of 13.42 ± 12.31 years underwent surgical repair for double-chambered right ventricle. The clinical outcomes of these patients were reviewed and assessed retrospectively. RESULTS: An associated ventricular septal defect was present in all the recruited patients; 48 (75%) patients of sub-arterial type, 15 (23.4%) of perimembranous, and 1 (1.6%) patient of muscular type. The patients were followed up for a mean period of 46.73 ± 27.37 months. During their follow-up, a significant decrease in the mean pressure gradient from 62.33 ± 5.52 mmHg preoperatively to 15.73 ± 2.94 mmHg postoperatively was observed (p < 0.001). Notably, there were no hospital deaths. CONCLUSIONS: The development of double-chambered right ventricle in association with ventricular septal defect results in an increased pressure gradient within the right ventricle. The defect needs correction in a timely manner. In our experience, the surgical correction of double-chambered right ventricle is safe and shows excellent early and mid-term results.

Low-temperature perception and modulations in Ocimum basilicum commercial cultivar CIM-Shishir: Biosynthetic potential with insight towards climate-smart resilience.

The newly released interspecific hybrid variety CIM-Shishir, resulting from a cross between Ocimum basilicum and Ocimum kilimandscharicum claims to be a multicut, lodging resistant, cold tolerant, high essential oil yielding with linalool rich variety. It has a purple-green stem and has a unique feature and advantage of better survival in the winter season than other O. basilicum varieties, illustrating its physiological mechanisms for cold tolerance. In this study, we subjected both the CIM-Shishir variety and a control plant to cold stress to investigate the impact of low temperatures on various physiological, trichome developments, secondary metabolite constitution aspects related to essential oil production, and gene expression. The analysis revealed a significantly higher density and altered morphology of trichomes on the leaf surface of the variety subjected to low temperatures, indicating its adaptation to cold conditions. Furthermore, when comparing the treated plants under low-temperature stress, it was observed that the relative electrolyte leakage and Malondialdehyde (MDA) contents substantially increased in the control in contrast to the CIM-Shishir variety. This finding suggests that CIM-Shishir exhibits superior cold tolerance. Additionally, an increase in proline content was noted in the variety exposed to low temperatures compared to the control. Moreover, the chlorophyll and anthocyanin content gradually increased with prolonged exposure to low-temperature stress in the newly developed variety, indicating its ability to maintain photosynthetic capacity and adapt to cold conditions. The activities of superoxide dismutase (SOD) also increased under low-temperature conditions in the CIM-Shishir variety, further highlighting its cold tolerance behaviour. In our research, we investigated the comprehensive molecular mechanisms of cold response in Ocimum. We analyzed the expression of key genes associated with cold tolerance in two plant groups: the newly developed hybrid variety known as CIM-Shishir Ocimum, which exhibits cold tolerance, and the control plants susceptible to cold climates that include WRKY53, ICE1, HOS1, COR47, LOS15, DREB5, CBF4, LTI6, KIN, and ERD2. These genes exhibited significantly higher expression levels in the CIM-Shishir variety compared to the control, shedding light on the genetic basis of its cold tolerance. The need for climate-smart, resilient high-yielding genotype is of high importance due to varied climatic conditions as this will hit the yield drastically and further to the economic sectors including farmers and many industries that are dependent on the bioactive constituents of Ocimum.

Early and Mid-Term Outcomes of Primary Repair After Atrioventricular Canal Defect: A Single-Center Eight-Year Experience.

BACKGROUND/AIM: Surgical repair techniques and management of patients with atrioventricular septal defect (AVSD) have progressed over the last few decades. Early and definitive interventions have become the choice of treatment for these patients. Based on this background, we aimed to review the early and mid-term outcomes of primary AVSD repair. METHODS: A total of 53 patients with a mean age of 3.45 ± 5.67 years underwent definitive repair for AVSD between January 2014 and June 2021. The clinical data including age, type of defect, associated co-anomalies, symptoms, pulmonary hypertension, etc. were collected and assessed retrospectively. Mitral regurgitation (MR) as a clinical outcome was assessed at 0, 1, 2, and 5 years. RESULTS: Among the recruited patients, 35 (66.1%) were male and 18 (33.9%) were female. Of 53 patients, repair for the complete defect was done in 38 (71.69%) patients, repair for intermediate/partial defect was done in 15 (23.1%) patients, and one patient underwent repair for incomplete type. Other associated co-anomalies were anterior mitral leaflet (12 (22.6%)), atrial and ventricular septal defect (VSD) (30 (56.6%)), and patent ductus arteriosus (PDA) (11 (20.8%)). Different procedures for surgical repair included patch closure, cleft repair, and polytetrafluoroethylene (PTFE) VSD closure. After repair, the mean follow-up period was 46.73 ± 27.37 months. Overall mortality was 3.78% (2/53), and two patients underwent reintervention due to symptomatic severe MR. CONCLUSIONS: A definitive and timely correction of AVSD shows satisfactory early and mid-term results.

Effect of Thyroidectomy on Tracheal Remodeling and Airway Physiology in Apparently Asymptomatic Patients with Goiter: A Prospective Study.

BACKGROUND: Tracheal airflow limitation is frequently reported in patients with goiter but is severely underestimated, and studies on how goiter and its treatment affect trachea are scarce. Moreover, the choice of the optimal treatment for individual patient with asymptomatic goiter is not straightforward. Therefore, in this study we aim to investigate the effect of goiter and subsequent thyroidectomy on tracheal anatomy and change in airflow in asymptomatic patient with goiter. METHODS: Seventy patients undergoing total/hemithyroidectomy (TT/HT) from Feb 2020 to Feb 2021 satisfying inclusion criteria were enrolled in the study. Neck radiograph (NR) and forced spirometry (FS) were performed preoperatively and on postoperative day 10 and 6 weeks and 3 months. RESULTS: Out of 70 patients, 84.3% patients were female, and mean duration and weight of goiter were 54.7 months and 72.21 gm, respectively. Of 70 patients, 57 were of benign pathology. Significant improvement in tracheal compression with moderate improvement in deviation was observed after surgery. Preoperative spirometry showed significant reduction in almost all parameters. After surgery, a weak improvement was observed at postoperative day 10 and 6 weeks; however, significant improvement in FEV1, PEFR, FEV1/FEV0.5, and FEF50%/FIF50% was observed at postoperative 3 months. Patient with right sided and those with ≥ 8 mm deviation were associated with poorer pulmonary function. Weak correlation was observed between neck NR and spirometry parameters. Weight of the thyroid gland significantly correlated with ratio of MVV/FEV1. CONCLUSION: Patients with asymptomatic goiter can have significant abnormal changes in airflow as evidenced by FS and NR. Thyroidectomy is followed by gradual restoration of tracheal deviation and compression with significant improvement in pulmonary airflow.

A Comparative Analysis of Liquid-Based Cytology and Conventional Smears in Fine-Needle Aspirates of Thyroid Lesions.

Background Palpable nodules in the thyroid are present in 4-7% of the general population. Fine-needle aspiration cytology is a safe and cost-effective method of choice for evaluating thyroid nodules. Aspirated samples can be manually spread directly onto the slide and stained in the conventional smear method. The liquid-cased cytology method has been recently introduced, which is an automated machine-based method, yielding a single slide with a clean background and greater preservation of cells and consuming less time for screening. This study aimed to compare the cytomorphological features and diagnostic accuracy of conventional smears and liquid-based cytology smears. Methodology This prospective study comprised 250 cases of thyroid lesions. Fine-needle aspiration cytology using conventional smears and liquid-based cytology smears was reported per the Bethesda system of reporting thyroid cytopathology. Detailed cytomorphological features were evaluated and compared in both techniques. Results The cellularity of conventional smears was significantly higher for scores 2+ and 3+ than paired liquid-based cytology smears (paired t-test, p < 0.001). The overall diagnostic efficacy of conventional smears and liquid-based cytology smears was equivalent in the majority of cases (n = 171, 68.4%). Conventional smears were better than liquid-cased cytology smears in 34 (13.6%) cases, and liquid-based cytology smears were better than conventional smears in eight (3.2%) cases. Liquid-based cytology smears showed a higher unsatisfactory rate compared to conventional Smears (15.6% vs. 5.2%). The sensitivity and specificity of conventional smears were 84.6% and 94.4%, respectively, compared to 68.7% and 92.4%, respectively, of liquid-based cytology smears. Conclusions Conventional smears are a cost-effective and easy method for diagnosing thyroid nodules. Liquid-based cytology smears can be used in association with conventional smears to enhance the accuracy of the evaluation of malignant thyroid nodules.

The multi-protein targeting potential of bioactive syringin in inflammatory diseases: using molecular modelling and in-silico analysis of regulatory elements.

Inflammation plays a crucial role in the onset or progression of a variety of acute and chronic diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) are the only available FDA-approved therapy. The therapeutic outcome of NSAIDs is still finite due to off-target effects and extreme side effects on other vital organs. Bioactive syringin has been manifested to hold anti-osteoporosis, cardiac hypertrophy, alter autophagy, anti-cancer, neuro-preventive effects, etc. However, its multi-protein targeting potential in inflammation mostly remains unexplored. In the present work, we have checked the multi-protein targeting potential of bioactive glycoside syringin in inflammatory diseases. Based on the binding score of protein-ligand complexes, glycoside syringin scored greater than -7 kcal/mol against 12 inflammatory proteins. Our molecular dynamic simulation study (200 ns) confirmed that bioactive syringin remained inside the binding cavity of inflammatory proteins (JAK1, TYK2, and COX1) in a stable conformation. Further, our co-expression analysis suggests that these genes play an essential role in multiple pathways and are regulated by multiple miRNAs. Our study demonstrates that bioactive glycoside syringin might be a multi-protein targeting potential against inflammatory diseases and could be further investigated utilizing different preclinical approaches.Communicated by Ramaswamy H. Sarma.

A rare triad in left atrial myxoma.

Atrial myxomas are the most common cardiac tumors, rarely presenting with both systemic embolization and intracranial aneurysms. A 34-year-old woman presented with acute limb ischemia of both lower limbs and right upper limb and on evaluation was diagnosed with left atrial myxoma and intracranial aneurysms. She underwent embolectomy and intracranial aneurysm repair followed by successful excision of left atrial myxoma after 4 weeks. This case is reported for the rare association of myxoma with intracranial aneurysm along with systemic embolization which has not been reported in the literature.

Effects of physical exercise on rehabilitation of cancer patients undergoing radiotherapy.

Background: According to the World Health Organization and American Cancer Society, cancer survivors should involve in mild-to-moderate intensity exercises and consume vegetarian diet. These lifestyle alterations show improvement in cancer recurrence, risk reduction, and quality of life (QOL). Objective: The purpose of this study was to study the effect of physical activity on health/behavioural changes among adult cancer survivors. Materials and Methods: The study is randomized controlled trial which included 100 patients (Group A - Exercise group - 50 patients and Group B - Control group - 50 patients). Assessment of cardiopulmonary fitness, endurance, and QOL was done. Results: Significant improvement in pulse rate, SpO2 and endurance, mental health, and social dimension was found in exercising group with no significant improvement in spiritual dimension. Conclusion: Remodelling the lifestyle by diet adjustment, strength training, and exercises alters the incidence and prognosis of cancer.

Acute Epigastric Pain: Unexpected Urologic Findings on Computed Tomography.

Mesenteric panniculitis is a relatively common condition encountered on cross-sectional imaging and is mostly asymptomatic. We present one such case where an underlying malignancy was brought to forefront due to associated mesenteric panniculitis presenting as acute abdomen.

Anthropometric Analysis of Distal Femur Parameters in the Eastern Uttar-Pradesh Population.

INTRODUCTION: Anthropometric measurements of the distal femoral fragment play a crucial role in prosthesis design during arthroplastic knee surgeries and offer valuable clues for stature estimation in forensic investigations. The present study is an attempt to assess various anthropometric parameters of the distal femur in this regard. MATERIALS AND METHODS: A total of 96 intact dry femora were anthropometrically assessed using digital Vernier calipers. The femoral length was measured using an osteometric table. The torsion angle was calculated with an analog goniometer. The various parameters studied included: medial condyle length and thickness, lateral condyle length and thickness, bicondylar width, intercondylar width, intercondylar depth, torsional angle, and femoral length. The data obtained were statistically analyzed using SPSS software (IBM Corp., Armonk, NY, USA). RESULTS: Mean medial condyle length was 57.38±4.47mm and thickness was 24.53±2.27mm. Mean lateral condyle length and thickness were found to be 58.49±4.3mm and 25.33±3.15mm respectively. Mean bicondylar width was 71.96±6.73mm, mean intercondylar width 21.86±2.71mm, and the intercondylar depth 27.04±2.59mm respectively. The average femur length was 41.87±3.31mm and the average torsion angle was 20.19°±6.99°. Significant correlations were observed between distal femoral parameters. Lateral condyle length showed maximum correlation with other parameters. Femur length was found to correlate significantly with all parameters except medial condyle thickness. Torsion angle was significantly correlated with lateral condyle length and femur length only. DISCUSSION: The findings of this study show considerable variation from those of other studies done within India. This proves that distal femoral anthropometry has regional variations. These data can aid sports physicians and orthopedic surgeons with implant designing and forensic experts during investigations.

Successful Management of a Very Unusual Coronary Pattern in Transposition of the Great Arteries.

Coronary artery anatomy is the key to a successful arterial switch operation in transposition of the great arteries. We came across an unusual coronary pattern in a child with transposition in which the three major coronary arteries were seen arising from all three aortic sinuses. This coronary pattern is the first of its kind in transposition, and this case report emphasizes the difficulty in translocating such a rare coronary pattern while performing an arterial switch operation.