PCOS stratification for precision diagnostics and treatment.

Globally, polycystic ovarian syndrome (PCOS) affects approximately 10% of fertile women, leading to great health and economic burden. PCOS is a heterogenous illness that can cause infertility, irregular menstrual cycles, acne, and hirsutism, among other symptoms. The clinical diagnosis is primarily a diagnosis of exclusion if one or more of the three primary symptoms, namely, oligo- or anovulation, hyperandrogenism, and polycystic ovarian morphology, are present. Obesity and PCOS are often coexisting disorders that may be bidirectionally causally related. Phenotypic heterogeneity throughout the reproductive lifespan, such as the overlap of PCOS symptoms with regular fluctuations in a woman's menstrual cycle and metabolism during the menarche and menopausal transition, further complicates diagnosis. PCOS etiology is mostly unknown and complex, likely due to the fact that it is a group of disorders with overlapping metabolic and reproductive problems. Evidence-based, common, standardized guidelines for PCOS diagnosis and treatment are urgently needed. Genomics and clinical data from populations across diverse ages and ethnicities are urgently needed to build efficient machine learning models for the stratification of PCOS. PCOS subtype-specific strategies for early screening, an accurate diagnosis, and management throughout life will optimize healthcare resources and reduce unnecessary testing. This will pave the way for women to be able to take the best possible care of their own health using the latest clinical expertise combined with their unique needs and preferences.

Duration of birth depression and neurodevelopmental outcomes after whole-body hypothermia for hypoxic ischemic encephalopathy in India, Sri Lanka and Bangladesh - an exploratory analysis of the HELIX trial.

Background: Effect of duration of birth depression on neurodevelopmental outcomes in low- and middle-income countries (LMICs) is not known. We examined the association of birth depression with brain injury, neurodevelopmental outcomes, and hypothermia after hypoxic ischemic encephalopathy (HIE) in south Asia. Methods: We compared cerebral magnetic resonance (MR) at 2 weeks, and adverse outcomes (death or moderate or severe disability) at 18 months in 408 babies with moderate or severe HIE who had long birth depression (positive pressure ventilation (PPV) >10 min or Apgar score<6 at 10 min or cord pH < 7.0) and short birth depression (PPV for 5-10 min or Apgar score<6 at 5 min, but ≥6 at 10 min). Findings: Long depression group (n = 201) had more severe HIE (32.8% versus 6.8%), mortality (47.5% versus 26.4%), death or disability at 18 months (62.2% versus 35.4%) (all p < 0.001), MR injury (Odds ratio; 95% CI) to basal ganglia (2.4 (1.3, 4.1); p = 0.003), posterior limb of internal capsule (2.3 (1.3, 4.3); p < 0.001) and white matter (1.7 (1.1, 2.7); p = 0.021), and lower thalamic N-acetylaspartate levels (7.69 ± 1.84 versus 8.29 ± 1.60); p = 0.031) than short depression group (n = 207). Three babies had no heartbeat at 5 min, of which 1 died and 2 survived with severe disability. No significant interaction between the duration of birth depression and whole-body hypothermia was seen for any of the MR biomarker or clinical outcomes. Interpretation: Long birth depression was associated with more brain injury and adverse outcomes than short depression. Effect of hypothermia was not modified by duration of birth depression. Funding: National Institute for Health Research.

Evaluation of 'Normal' Cognitive Functions and Correlation With MRI Volumetry: Towards a Definition of Vascular Cognitive Impairment.

Introduction It is important to establish criteria to define vascular cognitive impairment (VCI) in India as VCI is an image-based diagnosis and magnetic resonance imaging (MRI) changes resulting from age with prevalent vascular risk factors may confound MRI interpretation. The objective of this study was to establish normative community data for MRI volumetry including white matter hyperintensity volume (WMHV), correlated with age-stratified cognitive scores and vascular risk factors (VRFs), in adults aged 40 years and above.  Methods We screened 2651 individuals without known neurological morbidity, living in Mumbai and nearby rural areas, using validated Marathi translations of Kolkata Cognitive Battery (KCB) and geriatric depression score (GDS). We stratified 1961 persons with GDS ≤9 by age and cognitive score, and randomly selected 10% from each subgroup for MRI brain volumetry. Crude volumes were standardized to reflect percentage of intracranial volume.  Results MRI volumetry studies were done in 199 individuals (F/M = 90/109; 73 with body mass index (BMI) ≥25; 44 hypertensives; 29 diabetics; mean cognitive score 76.3). Both grey and white matter volumes decreased with increasing age. WMHV increased with age and hypertension. Grey matter volume (GMV) decreased with increasing WMHV. Positive predictors of cognition included standardized hippocampal volume (HCV), urban living, education, and BMI, while WMHV and age were negative predictors. Urban dwellers had higher cognitive scores than rural, and, paradoxically, smaller HCV.  Conclusion In this study of MRI volumetry correlated with age, cognitive scores and VRFs, increasing age and WMHV predicted lower cognitive scores, whereas urban living and hippocampal volume predicted higher scores. Age and WMHV also correlated with decreasing GMV. Further study is warranted into sociodemographic and biological factors that mutually influence cognition and brain volumes, including nutritional and endocrine factors, especially at lower cognitive score bands. In this study, at the lower KCB score bins, the lack of laboratory data pertaining to nutritional and endocrine deficiencies is a drawback that reflects the logistical limitations of screening large populations at the community level. Our volumetric data which is age and cognition stratified, and takes into account the vascular risk factors associated, nevertheless constitutes important baseline data for the Indian population. Our findings could possibly contribute to the formulation of baseline criteria for defining VCI in India and could help in early diagnosis and control of cognitive decline and its key risk factors.

Ipsilateral renal dysgenesis or agenesis with tubulocystic anomalies of the mesonephric duct.

Tubulocystic anomalies of the mesonephric duct (MND) are a rare group of related entities with a perplexing clinical presentation. Ultrasound is a useful screening investigation, which can help identify a dysplastic kidney or point to renal agenesis and identify cystic or tubulocystic changes in the structures derived from the ureteric bud or MND. Further evaluation with MRI can help in characterisation and direct management. The presence of a dysplastic kidney or absence of a kidney should prompt further evaluation for associated ureteric abnormalities such as ectopic insertion or ureterocoele, which could lead to a diagnosis of tubulocystic anomaly of the MND. Contribution: The authors describe two cases, briefly outline the diagnostic approach and summarise the literature on management. Reporting radiologists should be aware of these entities.

Insights into Sex and Gender Differences in Brain and Psychopathologies Using Big Data.

The societal implication of sex and gender (SG) differences in brain are profound, as they influence brain development, behavior, and importantly, the presentation, prevalence, and therapeutic response to diseases. Technological advances have enabled speed up identification and characterization of SG differences during development and in psychopathologies. The main aim of this review is to elaborate on new technological advancements, such as genomics, imaging, and emerging biobanks, coupled with bioinformatics analyses of data generated from these technologies have facilitated the identification and characterization of SG differences in the human brain through development and psychopathologies. First, a brief explanation of SG concepts is provided, along with a developmental and evolutionary context. We then describe physiological SG differences in brain activity and function, and in psychopathologies identified through imaging techniques. We further provide an overview of insights into SG differences using genomics, specifically taking advantage of large cohorts and biobanks. We finally emphasize how bioinformatics analyses of big data generated by emerging technologies provides new opportunities to reduce SG disparities in health outcomes, including major challenges.

A Case of Tracheitis Sicca with Obstructive Tracheal Crusting In A 7 Year Old Boy.

Tracheitis sicca is a rare condition where there is drying and crusting of tracheal mucosa which may lead to tracheal obstruction and respiratory distress. Reported here is a case of young boy, who presented with cough, cold and respiratory distress worsening over a period of 5 days. On admission the patient was administered with dexamethasone and was intubated. However, saturation was not maintained despite assisted ventilation, and multiple episodes of self extubation always presented with stridor. Hence, otorhinolaryngology reference was taken and decision was taken to perform laryngotracheobronchoscopy. Endoscopy done showed extensive crusting in the trachea causing complete obstruction of airway above the level of carina. The crusting was meticulously removed, sent for culture, and the obstruction was relieved. The patient maintained saturation after the procedure, and was ultimately extubated and discharged.

Whole-Body Hypothermia, Cerebral Magnetic Resonance Biomarkers, and Outcomes in Neonates With Moderate or Severe Hypoxic-Ischemic Encephalopathy Born at Tertiary Care Centers vs Other Facilities: A Nested Study Within a Randomized Clinical Trial.

Importance: The association between place of birth and hypothermic neuroprotection after hypoxic-ischemic encephalopathy (HIE) in low- and middle-income countries (LMICs) is unknown. Objective: To ascertain the association between place of birth and the efficacy of whole-body hypothermia for protection against brain injury measured by magnetic resonance (MR) biomarkers among neonates born at a tertiary care center (inborn) or other facilities (outborn). Design, Setting, and Participants: This nested cohort study within a randomized clinical trial involved neonates at 7 tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh between August 15, 2015, and February 15, 2019. A total of 408 neonates born at or after 36 weeks' gestation with moderate or severe HIE were randomized to receive whole-body hypothermia (reduction of rectal temperatures to between 33.0 °C and 34.0 °C; hypothermia group) for 72 hours or no whole-body hypothermia (rectal temperatures maintained between 36.0 °C and 37.0 °C; control group) within 6 hours of birth, with follow-up until September 27, 2020. Exposure: 3T MR imaging, MR spectroscopy, and diffusion tensor imaging. Main Outcomes and Measures: Thalamic N-acetyl aspartate (NAA) mmol/kg wet weight, thalamic lactate to NAA peak area ratios, brain injury scores, and white matter fractional anisotropy at 1 to 2 weeks and death or moderate or severe disability at 18 to 22 months. Results: Among 408 neonates, the mean (SD) gestational age was 38.7 (1.3) weeks; 267 (65.4%) were male. A total of 123 neonates were inborn and 285 were outborn. Inborn neonates were smaller (mean [SD], 2.8 [0.5] kg vs 2.9 [0.4] kg; P = .02), more likely to have instrumental or cesarean deliveries (43.1% vs 24.7%; P = .01), and more likely to be intubated at birth (78.9% vs 29.1%; P = .001) than outborn neonates, although the rate of severe HIE was not different (23.6% vs 17.9%; P = .22). Magnetic resonance data from 267 neonates (80 inborn and 187 outborn) were analyzed. In the hypothermia vs control groups, the mean (SD) thalamic NAA levels were 8.04 (1.98) vs 8.31 (1.13) among inborn neonates (odds ratio [OR], -0.28; 95% CI, -1.62 to 1.07; P = .68) and 8.03 (1.89) vs 7.99 (1.72) among outborn neonates (OR, 0.05; 95% CI, -0.62 to 0.71; P = .89); the median (IQR) thalamic lactate to NAA peak area ratios were 0.13 (0.10-0.20) vs 0.12 (0.09-0.18) among inborn neonates (OR, 1.02; 95% CI, 0.96-1.08; P = .59) and 0.14 (0.11-0.20) vs 0.14 (0.10-0.17) among outborn neonates (OR, 1.03; 95% CI, 0.98-1.09; P = .18). There was no difference in brain injury scores or white matter fractional anisotropy between the hypothermia and control groups among inborn or outborn neonates. Whole-body hypothermia was not associated with reductions in death or disability, either among 123 inborn neonates (hypothermia vs control group: 34 neonates [58.6%] vs 34 [56.7%]; risk ratio, 1.03; 95% CI, 0.76-1.41), or 285 outborn neonates (hypothermia vs control group: 64 neonates [46.7%] vs 60 [43.2%]; risk ratio, 1.08; 95% CI, 0.83-1.41). Conclusions and Relevance: In this nested cohort study, whole-body hypothermia was not associated with reductions in brain injury after HIE among neonates in South Asia, irrespective of place of birth. These findings do not support the use of whole-body hypothermia for HIE among neonates in LMICs. Trial Registration: ClinicalTrials.gov Identifier: NCT02387385.

Integrated analysis of robust sex-biased gene signatures in human brain.

BACKGROUND: Sexual dimorphism is highly prominent in mammals with many physiological and behavioral differences between male and female form of the species. Accordingly, the fundamental social and cultural stratification factors for humans is sex. The sex differences are thought to emerge from a combination of genetic and environmental factors. It distinguishes individuals most prominently on the reproductive traits, but also affects many of the other related traits and manifest in different disease susceptibilities and treatment responses across sexes. Sex differences in brain have raised a lot of controversy due to small and sometimes contradictory sex-specific effects. Many studies have been published to identify sex-biased genes in one or several brain regions, but the assessment of the robustness of these studies is missing. We therefore collected huge amount of publicly available transcriptomic data to first estimate whether consistent sex differences exist and further explore their likely origin and functional significance. RESULTS AND CONCLUSION: In order to systematically characterise sex-specific differences across human brain regions, we collected transcription profiles for more than 16,000 samples from 46 datasets across 11 brain regions. By systematic integration of the data from multiple studies, we identified robust transcription level differences in human brain across to identify male-biased and female-biased genes in each brain region. Firstly, both male and female-biased genes were highly conserved across primates and showed a high overlap with sex-biased genes in other species. Female-biased genes were enriched for neuron-associated processes while male-biased genes were enriched for membranes and nuclear structures. Male-biased genes were enriched on the Y chromosome while female-biased genes were enriched on the X chromosome, which included X chromosome inactivation escapees explaining the origins of some sex differences. Male-biased genes were enriched for mitotic processes while female-biased genes were enriched for synaptic membrane and lumen. Finally, sex-biased genes were enriched for drug-targets and more female-biased genes were affected by adverse drug reactions than male-biased genes. In summary, by building a comprehensive resource of sex differences across human brain regions at gene expression level, we explored their likely origin and functional significance. We have also developed a web resource to make the entire analysis available for the scientific community for further exploration, available at https://joshiapps.cbu.uib.no/SRB_app/.

Sex and gender differences are present across many organs in humans and have biological and social origins. The differences in brain raise a lot controversy due to small and sometimes contradictory results and its societal implications. In this study, we set out to discern the consistency of sex differences in brain by collecting a huge amount of publicly available transcriptomic data and further explore their likely origin and functional significance. We identified robust sex-biased genes in human brain with female-biased genes enriched for X chromosome genes. We also noted that male- and female-biased genes were enriched for distinct biological processes. Finally, sex-biased genes were enriched for androgen response elements. In summary, our analysis suggests sex-chromosomes and androgens as likely sources of sex differences in brain. Finally, we noted that age affects gene expression in brain more than sex.

Multi-omics and machine learning for the prevention and management of female reproductive health.

Females typically carry most of the burden of reproduction in mammals. In humans, this burden is exacerbated further, as the evolutionary advantage of a large and complex human brain came at a great cost of women's reproductive health. Pregnancy thus became a highly demanding phase in a woman's life cycle both physically and emotionally and therefore needs monitoring to assure an optimal outcome. Moreover, an increasing societal trend towards reproductive complications partly due to the increasing maternal age and global obesity pandemic demands closer monitoring of female reproductive health. This review first provides an overview of female reproductive biology and further explores utilization of large-scale data analysis and -omics techniques (genomics, transcriptomics, proteomics, and metabolomics) towards diagnosis, prognosis, and management of female reproductive disorders. In addition, we explore machine learning approaches for predictive models towards prevention and management. Furthermore, mobile apps and wearable devices provide a promise of continuous monitoring of health. These complementary technologies can be combined towards monitoring female (fertility-related) health and detection of any early complications to provide intervention solutions. In summary, technological advances (e.g., omics and wearables) have shown a promise towards diagnosis, prognosis, and management of female reproductive disorders. Systematic integration of these technologies is needed urgently in female reproductive healthcare to be further implemented in the national healthcare systems for societal benefit.

Decreased Speech Comprehension and Increased Vocal Efforts Among Healthcare Providers Using N95 Mask.

AIM: N95 masks are recommended for the healthcare providers (HCPs) taking care of patients with coronavirus disease 2019. However, the use of these masks hampers communication. We aimed to evaluate the effect of N95 masks on speech comprehension among listeners and vocal efforts (VEs) of the HCPs. MATERIALS AND METHODS: This prospective study involved 50 HCPs. We used a single observer with normal hearing to assess the difficulty in comprehension, while VE was estimated in HCPs. The speech reception threshold (SRT), speech discrimination score (SDS), and VEs were evaluated initially without using N95 mask and then repeated with HCPs wearing N95 mask. RESULTS: The use of masks resulted in a statistically significant increase in mean SRT [4.25 (1.65) dB] and VE [2.6 (0.69)], with simultaneous decrease in mean SDS [19.2 (8.77)] (all p-values < 0.0001). Moreover, demographic parameters including age, sex, and profession were not associated with change in SRT, SDS, and VE (all p-values > 0.05). CONCLUSION: Though use of N95 masks protects the HCPs against the viral infection, it results in decreased speech comprehension and increased VEs. Moreover, these issues are universal among the HCPs and are applicable to the general public as well.

Pancreatic Neoplasms: CT Evaluation of the Uncommon Presentations of Common Lesions and Common Presentations of the Uncommon Lesions!

Pancreatic masses are commonly encountered entities in radiology practice. Pancreatic ductal adenocarcinomas (PDAC) are the commonest pancreatic malignancies that typically present as infiltrative hypodense focal masses in the pancreatic head, which are hypoattenuating to the pancreatic parenchyma on pancreatic parenchymal and venous phases. However, there are various atypical imaging features of PDACs that create a diagnostic dilemma like tumor in body or tail, diffuse glandular involvement, isoattenuating tumors, cystic changes, or calcifications. Also, few relatively uncommon pancreatic malignancies like pancreatic neuroendocrine tumors, cystic pancreatic tumors, pancreatic lymphoma, and pancreatic metastases present with overlapping features. Accurate radiological characterization of pancreatic masses is important for optimal management and prognostication. Thus, it is imperative for radiologists to be aware of all the uncommon presentations of common pancreatic lesions and common presentations of uncommon pancreatic lesions to avoid erroneous interpretations and establishing the correct diagnosis.

Prevalence of Voice Disorders in Indian Female Secondary School Teacher Population-A Cross Sectional Study.

Teachers are the backbone of any civilized society as they are the keepers of knowledge, wisdom and values. Lack of infrastructure, manpower and resources makes voice the most important tool for a teacher. Teachers need to speak loudly for long periods often under unfavourable circumstances. Increased vocal effort and incorrect phonation techniques can lead to vocal fold tissue damage and vocal fold pathologies and hence voice problems producing adverse effects on teaching performance. To study the prevalence of voice disorders in Indian female secondary school teacher population. To identify the risk factors for the development of voice disorders. A multicentric, cross-sectional observational study of 200 teachers were conducted in 4 schools over a period of 2 years. Female teachers who gave consent and were willing for follow up were included in the study. Details were collected using a structured questionnaire. Subjective analysis by VHI, perceptual analysis by GRABS score, acoustic analysis and direct visualization using Hopkins 70° rigid laryngoscope were done.The prevalence of voice disorders was 18.5%. Risk factors identified were age group 41-60 years, repeated respiratory allergies, comorbidities, constitutional symptoms, increased number of years of teaching and number of lecture hours per week. VHI, GRABS, Acoustic analysis findings were consistent with Rigid Laryngoscopic finding making them effective tools in the assessment of voice.

Effective cataract surgical coverage in adults aged 50 years and older: estimates from population-based surveys in 55 countries.

BACKGROUND: Cataract is the leading cause of blindness globally. Effective cataract surgical coverage (eCSC) measures the number of people in a population who have been operated on for cataract, and had a good outcome, as a proportion of all people operated on or requiring surgery. Therefore, eCSC describes service access (ie, cataract surgical coverage, [CSC]) adjusted for quality. The 74th World Health Assembly endorsed a global target for eCSC of a 30-percentage point increase by 2030. To enable monitoring of progress towards this target, we analysed Rapid Assessment of Avoidable Blindness (RAAB) survey data to establish baseline estimates of eCSC and CSC. METHODS: In this secondary analysis, we used data from 148 RAAB surveys undertaken in 55 countries (2003-21) to calculate eCSC, CSC, and the relative quality gap (% difference between eCSC and CSC). Eligible studies were any version of the RAAB survey conducted since 2000 with individual participant survey data and census population data for people aged 50 years or older in the sampling area and permission from the study's principal investigator for use of data. We compared median eCSC between WHO regions and World Bank income strata and calculated the pooled risk difference and risk ratio comparing eCSC in men and women. FINDINGS: Country eCSC estimates ranged from 3·8% (95% CI 2·1-5·5) in Guinea Bissau, 2010, to 70·3% (95% CI 65·8-74·9) in Hungary, 2015, and the relative quality gap from 10·8% (CSC: 65·7%, eCSC: 58·6%) in Argentina, 2013, to 73·4% (CSC: 14·3%, eCSC: 3·8%) in Guinea Bissau, 2010. Median eCSC was highest among high-income countries (60·5% [IQR 55·6-65·4]; n=2 surveys; 2011-15) and lowest among low-income countries (14·8%; [IQR 8·3-20·7]; n=14 surveys; 2005-21). eCSC was higher in men than women (148 studies pooled risk difference 3·2% [95% CI 2·3-4·1] and pooled risk ratio of 1·20 [95% CI 1·15-1·25]). INTERPRETATION: eCSC varies widely between countries, increases with greater income level, and is higher in men. In pursuit of 2030 targets, many countries, particularly in lower-resource settings, should emphasise quality improvement before increasing access to surgery. Equity must be embedded in efforts to improve access to surgery, with a focus on underserved groups. FUNDING: Indigo Trust, Peek Vision, and Wellcome Trust.

Primary CNS lymphoma in Immunocompetent patients: Appearances on Conventional and Advanced Imaging with Review of literature.

Primary central nervous system lymphoma (PCNSL) constitutes about 3% of all primary brain tumors and nearly 1 to 3% of all Non Hodgkin Lymphomas. In the recent years the incidence of primary CNS lymphoma is increasing in immunocompetent patients. As PCNSL are chemosensitive as well as radiosensitive, its early and accurate diagnosis is imperative for optimal management. Contrast enhanced Magnetic Resonance Imaging (MRI) is the recommended imaging modality for PCNSL; however, contrast enhanced Computed Tomography (CE-CT) is done in cases where MRI is contraindicated. Advanced imaging techniques like DWI (diffusion weighted imaging), MRS (MR Spectroscopy), MR perfusion, DTI (Diffusion tensor imaging) are important in diagnosis and help in its differentiation from other tumors.

Aberrant signaling of immune cells in Sjögren's syndrome patient subgroups upon interferon stimulation.

Background: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease, characterized by mononuclear cell infiltrates in the salivary and lacrimal glands, leading to glandular atrophy and dryness. Patient heterogeneity and lack of knowledge regarding its pathogenesis makes pSS a difficult disease to manage. Methods: An exploratory analysis using mass cytometry was conducted of MAPK/ERK and JAK/STAT signaling pathways in peripheral blood mononuclear cells (PBMC) from 16 female medication free pSS patients (8 anti-Sjögren's syndrome-related antigen A negative/SSA- and 8 SSA+) and 8 female age-matched healthy donors after stimulation with interferons (IFNs). Results: We found significant differences in the frequencies of memory B cells, CD8+ T central and effector memory cells and terminally differentiated CD4+ T cells among the healthy donors and patient subgroups. In addition, we observed an upregulation of HLA-DR and CD38 in many cell subsets in the patients. Upon IFNα2b stimulation, slightly increased signaling through pSTAT1 Y701 was observed in most cell types in pSS patients compared to controls, while phosphorylation of STAT3 Y705 and STAT5 Y694 were slightly reduced. IFNγ stimulation resulted in significantly increased pSTAT1 Y701 induction in conventional dendritic cells (cDCs) and classical and non-classical monocytes in the patients. Most of the observed differences were more prominent in the SSA+ subgroup, indicating greater disease severity in them. Conclusions: Augmented activation status of certain cell types along with potentiated pSTAT1 Y701 signaling and reduced pSTAT3 Y705 and pSTAT5 Y694 induction may predispose pSS patients, especially the SSA+ subgroup, to upregulated expression of IFN-induced genes and production of autoantibodies. These patients may benefit from therapies targeting these pathways.

Hyperplastic Anterior Choroidal Artery-A Rare Variant Detected on MR Angiography.

Introduction The anterior choroidal artery is a branch of the terminal internal carotid artery (ICA) that is often an incidentally detected anomaly. The hyperplastic variant has been linked with an increased risk of aneurysms. We explore the role of magnetic resonance (MR) angiography in the detection of this variant and its impact of presentation of patients. Patient Presentation A 62-year-old diabetic and hypertensive male came to the casualty with complaints of giddiness, left-sided weakness, and loss of coordination for the last 2 to 3 days. He was provisionally diagnosed with a posterior circulation stroke. Management and Outcome Magnetic resonance imaging of brain revealed an acute infarct in the right thalamus and the midbrain. Time-of-flight angiography sequences were done that showed hypoplasia of the A1 segment of the left anterior cerebral artery, fetal origin of the right posterior cerebral artery, narrowing of the left ICA, and a hyperplastic left anterior choroidal artery. He was managed conservatively with antiplatelets. He later underwent a digital subtraction angiography that revealed significant narrowing of the left ICA for which he was advised carotid stenting. However, the patient was unwilling for the procedure and was discharged on oral medication with stable vitals. Conclusion Anatomical variations in the intracranial vasculature impact ischemia territory and the approach to intracranial pathology. Hyperplastic anterior choroidal artery results from the abnormal persistence of fetal pattern of vascular supply. It is important to recognize the presence of a hyperplastic anterior choroidal artery as it impacts both disease presentation and management of these patients. MR angiography allows for noninvasive and reliable detection of these anomalies in patients without the risks associated with radiation or contrast exposure in conventional/computed tomography angiography.

Phase 1 clinical trial for intravenous administration of mesenchymal stem cells derived from umbilical cord and placenta in patients with moderate COVID-19 virus pneumonia: results of stage 1 of the study.

OBJECTIVE: Mesenchymal stem cells can serve as a therapeutic option for COVID-19. Their immunomodulatory and anti-inflammatory properties can regulate the exaggerated inflammatory response and promote recovery of lung damage. METHOD: Phase-1, single-centre open-label, prospective clinical trial was conducted to evaluate the safety and efficacy of intravenous administration of mesenchymal stem cells derived from umbilical cord and placenta in moderate COVID-19. The study was done in 2 stages with total 20 patients. Herein, the results of stage 1 including first 10 patients receiving 100 million cells on day 1 and 4 with a follow up of 6 months have been discussed. RESULTS: No adverse events were recorded immediately after the administration of MSCs or on follow up. There was no deterioration observed in clinical, laboratory and radiological parameters. All symptoms of the study group resolved within 10 days. Levels of inflammatory biomarkers such as NLR, CRP, IL6, ferritin and D-dimer improved in all patients after intervention along with improved oxygenation demonstrated by improvement in the SpO2/FiO2 ratio and PaO2/FiO2 ratio. None of the patients progressed to severe stage. 9 out of 10 patients were discharged within 9 days of their admission. Improvements were noted in chest x-ray and chest CT scan scores at day 7 in most patients. No post-covid fibrosis was observed on chest CT 28 days after intervention and Chest X ray after 6 months of the intervention. CONCLUSION: Administration of 100 million mesenchymal stem cells in combination with standard treatment was found to be safe and resulted in prevention of the cytokine storm, halting of the disease progression and acceleration of recovery in moderate COVID-19. This clinical trial has been registered with the Clinical Trial Registry- India (CTRI) as CTRI/2020/08/027043. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=43175.