Prevalence and associated factors of impaired kidney functions among children and adolescents in India: insights from the Comprehensive National Nutrition Survey (CNNS) 2016-18.

BACKGROUND: Chronic kidney disease (CKD) is a significant public health problem. The burden of CKD in children and adolescents in India is not well described. We used data from the recent Comprehensive National Nutrition Survey (CNNS) to estimate the prevalence of impaired kidney function (IKF) and its determinants in children and adolescents between the ages of 5 and 19. METHODS: CNNS 2016-18 adopted a multi-stage sampling design using probability proportional to size sampling procedure after geographical stratification of urban and rural areas. Serum creatinine was tested once in 24,690 children and adolescents aged 5-19 years. The estimated glomerular filtration rate (eGFR) was derived using the revised Schwartz equation. The eGFR value below 60 ml/min/1.73 m2 is defined as IKF. Bivariate analysis was done to depict the weighted prevalence, and multivariable logistic regression examined the predictors of IKF. RESULTS: The mean eGFR in the study population was 113.3 + 41.4 mL/min/1.73 m2. The overall prevalence of IKF was 4.9%. The prevalence in the 5-9, 10-14, and 15-19 year age groups was 5.6%, 3.4% and 5.2%, respectively. Regression analysis showed age, rural residence, non-reserved social caste, less educated mothers, Islam religion, children with severe stunting or being overweight/obese, and residence in Southern India to be predictors of IKF. CONCLUSIONS: The prevalence of IKF among children and adolescents in India is high compared to available global estimates. In the absence of repeated eGFR-based estimates, these nationally representative estimates are intriguing and call for further assessment of socio-demographic disparities, genetics, and risk behaviours to have better clinical insights and public health preparedness.

Evaluating Cognitive Impairment in a Large Health Care System: The Cognition in Primary Care Program.

Background: The prevalence of Alzheimer's disease and related disorders (ADRD) is rising. Primary care providers (PCPs) will increasingly be required to play a role in its detection but lack the training to do so. Objective: To develop a model for cognitive evaluation which is feasible in primary care and evaluate its implementation in a large health system. Methods: The Cognition in Primary Care Program consists of web-based training together with integrated tools built into the electronic record. We implemented the program among PCPs at 14 clinics in a large health system. We (1) surveyed PCPs to assess the impact of training on their confidence to evaluate cognition, (2) measured the number of cognitive assessments they performed, and (3) tracked the number of patients diagnosed with mild cognitive impairment (MCI). Results: Thirty-nine PCPs completed the training which covered how to evaluate cognition. Survey response rate from those PCPs was 74%. Six months after the end of the training, they reported confidence in assessing cognition (mean 4.6 on 5-point scale). Cognitive assessments documented in the health record increased from 0.8 per month before the training to 2.5 in the six months after the training. Patients who were newly diagnosed with MCI increased from 4.2 per month before the training to 6.0 per month in the six months after the training. Conclusions: This model for cognitive evaluation in a large health system was shown to increase cognitive testing and increase diagnoses of MCI. Such improvements are essential for the timely detection of ADRD.

Multistable Protocells Can Aid the Evolution of Prebiotic Autocatalytic Sets.

We present a simple mathematical model that captures the evolutionary capabilities of a prebiotic compartment or protocell. In the model, the protocell contains an autocatalytic set whose chemical dynamics is coupled to the growth-division dynamics of the compartment. Bistability in the dynamics of the autocatalytic set results in a protocell that can exist with two distinct growth rates. Stochasticity in chemical reactions plays the role of mutations and causes transitions from one growth regime to another. We show that the system exhibits 'natural selection', where a 'mutant' protocell in which the autocatalytic set is active arises by chance in a population of inactive protocells, and then takes over the population because of its higher growth rate or 'fitness'. The work integrates three levels of dynamics: intracellular chemical, single protocell, and population (or ecosystem) of protocells.

Cannabis Use: An Uncommon Cause of Hypokalemia-Induced Acute Paralysis.

Severe hypokalemia can have life-threatening complications such as significant muscle weakness, ileus, rhabdomyolysis, and respiratory failure. Here, we report a case of a 33-year-old male who presented with worsening lower extremity weakness and falls after smoking marijuana for six months. Initial labs showed severe hypokalemia. EKG was remarkable for a first-degree AV block, widened QRS complex, and ST segment depression. Intravenous potassium replacement resulted in complete resolution of lower extremity motor weakness. Our case highlights the underdiagnosed association of marijuana use with clinically significant hypokalemia and the rare presentation of severe hypokalemia with acute paralysis.

Pulmonary haemorrhage and extensive arterial thrombosis with anabolic steroid abuse.

Anabolic-androgenic steroids (AASs) are commonly implicated in thromboembolic events but rarely cause diffuse alveolar haemorrhage. We report the case of a Caucasian man in his late 40s who was consuming supratherapeutic doses of AAS and presented with shortness of breath and haemoptysis. Chest imaging showed bilateral patchy infiltrates in the lungs with diffuse blood throughout the airways on bronchoscopy. Extensive infectious and autoimmune workup were unremarkable. The patient then developed right foot ischaemia and was found to have extensive aortic and bilateral lower extremity arterial thrombosis. Anticoagulation was attempted despite haemoptysis. Thrombectomy procedures were unsuccessful and the patient eventually developed worsening rhabdomyolysis requiring intubation and bilateral amputation. His clinical condition continued to worsen and he passed away 10 days after admission. This case highlights the rare synchronous occurrence of two life-threatening complications secondary to anabolic steroid abuse which can pose a significant diagnostic and therapeutic challenge for clinicians.

To evaluate serum cortisol levels in patients with alcohol withdrawal delirium v/s patients with delirium due to any other disorder.

Background: Delirium is an acute confusional state characterized by changes in the mental status, level of consciousness, impaired cognition, and inattention. It can develop within hours or days. Cortisol release from the hypothalamic-pituitary-adrenal axis (HPA) is vital for the host survival in stress. Biomarkers are used as an indicator of pathogenic processes or to assess the responses to a therapeutic intervention. To improve delirium recognition and care, investigators have identified possible biomarkers that may help in diagnosing individuals with delirium, assessing the severity of delirium. Cortisol has been suggested as biomarker for the diagnosis of delirium. Aims and Objectives: To evaluate and compare levels of serum cortisol in patients with alcohol withdrawal delirium with delirium due to other disorders. Materials and Methods: It was a cross-sectional prospective observational study. A total of 30 patients in Group A and 32 in Group B were included. The participants were evaluated based on delirium rating scale (DRS). Results: It was seen that in alcohol withdrawal delirium group, there was significant positive correlation between DRS score and serum cortisol level, i.e., with increase in DRS score, there was increase in serum cortisol levels and vice versa. Conclusion: Serum cortisol levels are associated and directly correlate with the occurrence and severity of delirium. Further studies are needed to elucidate the implications of this association for diagnosis and treatment.

SAEM GRACE: Dopamine antagonists and topical capsaicin for cannabis hyperemesis syndrome in the emergency department: A systematic review of direct evidence.

BACKGROUND: Adults with cannabis hyperemesis syndrome (CHS) are increasingly presenting to the emergency department (ED), and this systematic review will evaluate the direct evidence on the effectiveness of capsaicin and dopamine antagonists in its clinical management. METHODS: A bibliographic search was conducted to address the following population-intervention-control-outcome (PICO) question: (P) adults >18 years old with a diagnosis of acute CHS presenting to the ED; (I) dopamine antagonists (e.g., haloperidol, droperidol) and topical capsaicin; (C) usual care or no active comparator; and (O) symptoms improvement/resolution in ED, ED length of stay, admission rate, ED recidivism, need for rescue medication, and adverse events. This systematic review was conducted in accordance with PRISMA reporting recommendations. RESULTS: From 53 potentially relevant articles, seven articles were included: five observational studies and two randomized controlled trials, including a total of 492 patients. Five of these studies evaluated the efficacy of capsaicin cream (n = 386), and two examined dopamine antagonists (haloperidol, droperidol; n = 106). There was mixed evidence for the efficacy of capsaicin for reducing nausea and emesis. Both studies evaluating dopamine antagonists detected clinical benefit to usual care or no active comparator. CONCLUSIONS: There is limited direct evidence on the efficacy of dopamine antagonists or capsaicin for treating CHS in the ED. Current evidence is mixed for capsaicin and potentially beneficial for dopamine antagonists. Because of the small number of studies, small number of participants, lack of standardization of treatment administration, and risk of bias of the included studies, methodologically rigorous trials on both types of intervention are needed to directly inform ED management of CHS.

Long-Term Imaging and Clinical Outcomes of Surgical Left Atrial Appendage Occlusion With AtriClip.

Surgical left atrial appendage (LAA) occlusion with an AtriClip (AtriCure, West Chester, Ohio) is frequently performed for stroke prophylaxis in patients with atrial fibrillation (AF). We conducted a retrospective analysis of all patients with long-standing persistent AF who underwent hybrid convergent ablation and LAA clipping. Contrast-enhanced cardiac computed tomography was performed at 3 to 6 months after LAA clipping to assess the degree of complete closure and the residual LAA stump. A total of 78 patients (64 ± 10 years, 72% male) underwent LAA clipping as part of hybrid convergent AF ablation, from 2019 to 2020. Median size of AtriClip used was 45 mm. Mean LA size was 4.6 ± 1 cm. At 3-to-6 months follow-up computed tomography, 46.2% of patients (n = 36) had a residual stump proximal to the deployed LAA clip. Mean depth of residual stump was 3.95 ± 5.5 mm, with 19% of patients (n = 15) having a stump depth of ≥10 mm and 1 patient requiring more endocardial LAA closure owing to large stump depth. During 1-year follow-up, 3 patients developed stroke; device leak of 6 mm was noted in 1 patient; and none of the patients had a thrombus proximal to the clip. In conclusion, high incidence of residual LAA stump was observed with AtriClip. Larger studies with long-term follow-up are needed to better assess the thromboembolic implications of a residual stump after AtriClip placement.

Leveraging natural language processing to augment structured social determinants of health data in the electronic health record.

OBJECTIVE: Social determinants of health (SDOH) impact health outcomes and are documented in the electronic health record (EHR) through structured data and unstructured clinical notes. However, clinical notes often contain more comprehensive SDOH information, detailing aspects such as status, severity, and temporality. This work has two primary objectives: (1) develop a natural language processing information extraction model to capture detailed SDOH information and (2) evaluate the information gain achieved by applying the SDOH extractor to clinical narratives and combining the extracted representations with existing structured data. MATERIALS AND METHODS: We developed a novel SDOH extractor using a deep learning entity and relation extraction architecture to characterize SDOH across various dimensions. In an EHR case study, we applied the SDOH extractor to a large clinical data set with 225 089 patients and 430 406 notes with social history sections and compared the extracted SDOH information with existing structured data. RESULTS: The SDOH extractor achieved 0.86 F1 on a withheld test set. In the EHR case study, we found extracted SDOH information complements existing structured data with 32% of homeless patients, 19% of current tobacco users, and 10% of drug users only having these health risk factors documented in the clinical narrative. CONCLUSIONS: Utilizing EHR data to identify SDOH health risk factors and social needs may improve patient care and outcomes. Semantic representations of text-encoded SDOH information can augment existing structured data, and this more comprehensive SDOH representation can assist health systems in identifying and addressing these social needs.

Integrating patient voices into the extraction of social determinants of health from clinical notes: ethical considerations and recommendations.

Identifying patients' social needs is a first critical step to address social determinants of health (SDoH)-the conditions in which people live, learn, work, and play that affect health. Addressing SDoH can improve health outcomes, population health, and health equity. Emerging SDoH reporting requirements call for health systems to implement efficient ways to identify and act on patients' social needs. Automatic extraction of SDoH from clinical notes within the electronic health record through natural language processing offers a promising approach. However, such automated SDoH systems could have unintended consequences for patients, related to stigma, privacy, confidentiality, and mistrust. Using Floridi et al's "AI4People" framework, we describe ethical considerations for system design and implementation that call attention to patient autonomy, beneficence, nonmaleficence, justice, and explicability. Based on our engagement of clinical and community champions in health equity work at University of Washington Medicine, we offer recommendations for integrating patient voices and needs into automated SDoH systems.

Hypertension Control Cascade and Regional Performance in India: A Repeated Cross-Sectional Analysis (2015-2021).

Background The weak control cascade of hypertension from the time of screening till the attainment of optimal blood pressure (BP) control is a public health challenge, particularly in resource-limited settings. The study objectives were to (1) estimate the change in the rate of prevalence of hypertension, the yield of newly diagnosed cases, initiation of treatment, and attainment of BP control in the age group 15 to 49 years; (2) ascertain the magnitude and predictors of undiagnosed hypertension, lack of initiation of treatment, and poor control of those on antihypertensive therapy; and (3) estimate the regional variation and state-level performance of the hypertension control cascade in India. Methodology We analyzed demographic and health surveillance (DHS) data from India's National Family Health Survey Fifth Series (NFHS-5), 2019-2021, and NFHS-4 (2015-2016). The NFHS-5 sample comprised 695,707 women and 93,267 men in the age group of 15 to 49 years. Multiple logistic regressions were performed to find the associated predictors, and respective adjusted odds ratios (aORs) were reported. Results The prevalence of hypertension (cumulative previously diagnosed and new cases) among individuals aged 15 to 49 years was 22.8% (22.6%, 23.1%; n = 172,532), out of which 52.06% were newly diagnosed cases. In contrast, in NFHS-4, the prevalence of hypertension among individuals aged 15 to 49 years was 20.4% (20.2%, 20.6%; n = 153,384), of which 41.65% were newly diagnosed cases. In NFHS-5, 40.7% (39.8% and 41.6%) of the previously diagnosed cases were on BP-lowering medications compared to 32.6% (31.8%, 33.6%) in NFHS-4. Furthermore, in NFHS-5, controlled BP was observed in 73.7% (72.7% and 74.7%) of the patients on BP-lowering medication compared to 80.8% (80.0%, 81.6%) in NFHS-4. Females compared to males (aOR = 0·72 and 0·007), residents of rural areas (aOR = 0·82 and 0·004), and those belonging to the socially disadvantaged groups were not initiated on treatment despite awareness of their hypertension status indicative of poor treatment-seeking behavior. Furthermore, increasing age (aOR = 0·49, P < 0·001), higher body mass index (aOR = 0·51, P < 0·001), and greater waist-to-hip ratio (aOR = 0·78, P = 0·047) were associated with uncontrolled hypertension in patients on antihypertensive drug therapy. Conclusions Hypertension control cascade in India is largely ineffectual although screening yield and initiation of antihypertensive treatment have improved in NFHS-5 compared to NFHS-4. Identification of high-risk groups for opportunistic screening, implementing community-based screening, strengthening primary care, and sensitizing associated practitioners are urgently warranted.

Quality of sleep and disability associated with headache: migraine versus tension-type headache: A comparative study.

Background: One of the commonest and most frequently said, quoted and understood by even the least educated elements of our society is the neurological symptom of headache. The commonly diagnosed and studied headaches are Migraine and Tension type headache [TTH]. Headache has the power to reduce the very essence of a peaceful life and produce a disability in a person. Aims and Objectives: The aim of our study is to approach the subject with view of correlation of quality of sleep with the disability associated with migraine and compare it to TTH. Materials and Methods: For the same a cross-sectional study design was adopted and a consecutive sampling procedure was adopted. The sample was subjected to basic socio-demography, VAS, PSQI and HDI. Statistical analysis was done on the collected data. Results: Based on scales the results were evaluated using appropriate statistical methods. It was observed that there was a higher female preponderance in both migraine and TTH, there was severe disability associated and both headaches cause poor sleep quality. Conclusion: The current study concludes that headache is a debilitating illness which causes significant disability to a person.

A cross-sectional study to assess the caregiver burden and the quality of life of caregivers of the patients suffering with psychiatric illness.

Background: The impairment due to the psychiatric disorders makes the sufferer unable to become independent, therefore require long term support and care by their relatives. About 32% of years lived with disability (YLD) and about 13% of disability adjusted life-years (DALYs) is found in mental illness. Aims and Objectives: The aims were to study the socio-demographic profile, the caregiver burden and quality of life of the caregivers of the patients with different psychiatric illness. Also, to compare the burden and quality of life among caregivers of different psychiatric groups. Materials and Methods: It is a cross sectional study in which 120 caregivers of patients with psychiatric illnesses were included; divided into four groups (30 each): Anxiety, psychotic, mood and substance use disorders. After the consent, Zarit burden interview, socio demographic profile and quality of life -10 scales were used to assess the objectives. Results: The results revealed that maximum caregivers were males, and spouses in relation with the patient. Most of them were married and educated. Maximum had mild to moderate level of burden (49.1%), followed by moderate to severe level of burden in about 22.5% caregivers. Significant association was seen with the burden level. But no significant association was seen with the quality of life. Conclusion: Caregivers of the psychiatric patients have to suffer a lot and may land up into the psychiatric symptoms themselves.

Characterizing problematic internet use in a sample of heavy drinking emerging adults.

OBJECTIVE: Problematic internet use (PIU) is characterized by excessive or poorly controlled internet use resulting in impairment or distress. PIU is most prevalent during emerging adulthood, a period marked by an increase in psychiatric disorders, including substance use disorders (SUDs). In a sample of high-risk emerging adults, the aim of this study was to examine the relationship between PIU and quality of life (QoL), psychiatric disorders, and impulsivity. METHODS: Participants were a community sample of heavy drinking emerging adults in Hamilton, Ontario (N = 709). Measures included: PIU, QoL, eight psychiatric indicators, and three domains of impulsivity. All variables that were significantly associated with PIU were subsequently examined concurrently in structural equation models. RESULTS: PIU was negatively associated with physical QoL (ß = -0.27, p < .01) and social QoL (ß = -0.20, p < .01), but positively associated with environmental QoL (ß = 0.17, p < .01). For psychiatric conditions, PIU was positively associated with internalizing disorders (ß = 0.42, p < .01) but not SUD (ß = -0.01, p = .90). For impulsivity, PIU was positively associated with Lack of Perseverance (ß = 0.16, p < .01) and Negative Urgency (ß = 0.23, p < .01) but no other indicators. CONCLUSIONS: This study provides further evidence that PIU is associated with lower quality of life, selectively co-occurs with internalizing psychopathology, and is associated with certain impulsive traits. Lack of associations with SUD challenges conceptualizations of PIU as an alternative manifestation of externalizing psychopathology. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

FISH patterns of ROS1, MET, and ALK with a correlation of ALK immunohistochemistry in lung cancer: a case for introducing ALK immunohistochemistry 'Equivocal' interpretation category in the Ventana anti-ALK (D5F3) CDx assay - A tertiary cancer center experience.

Background: Mutations in ROS1, ALK, and MET genes are targetable alterations in non-small cell lung cancer (NSCLC). They can be evaluated by different techniques, most commonly fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Methods: We explored the prevalence of ROS1, ALK, MET mutations, discuss clinicopathological associations and FISH signal patterns on 413 consecutive cases of EGFR negative lung carcinoma from March 2016 to April 2017 using FISH for ALK, ROS1, and MET along with ALK (D5F3) IHC. Results: ROS1 gene rearrangement, ALK positivity (IHC and/or FISH), and MET amplification were seen in 18/358 (5%) cases, 76/392 cases (19.4%), and 10/370 (2.7%) cases, respectively. ALK FISH and ALK IHC were positive in 51/300 (17%) and 58/330 cases (17.57%), respectively, while 8/330 (2.4%) cases were ALK IHC "equivocal" of which 3/8 (37.5%) were ALK FISH positive. Of ALK FISH and IHC co-tested cases, 43/238 (18.07%) cases were positive by both techniques, while 15/43 (34.88%) of ALK positive cases showed discordant ALK FISH and IHC results. All ROS1 rearranged and MET amplified cases were adenocarcinoma. Signet ring cell histology was associated with 78.57% likelihood of being either ALK or ROS1 positive. Genomic heterogeneity was seen in 30% of MET amplified cases. Conclusions: ALK/ROS1/MET gene alterations were found in 25.18% of NSCLC cases. An ALK IHC "equivocal" interpretation category should be incorporated into practice. Atypical patterns of ROS1 and genomic heterogeneity need to be evaluated further for any clinical relevance.

Rapid spatial learning in cooperative and non-cooperative cichlids.

The number, duration and depth of social relationships that an individual maintains can impact social cognition, but the connection between sociality and other aspects of cognition has hardly been explored. To date, the link between social living and intelligence has been mainly supported by studies on primates, and far fewer tests connecting sociality to cognitive abilities have used other taxa. Here, we present the first comparative study in fishes that examines whether complex social living is associated with better performance on a cognitively demanding spatial task. Using three cooperative, group-living cichlid fish species and three of their non-cooperative, more solitary close relatives, we studied maze learning and employed a new statistical extension for the 'lme4' and 'glmmTMB' packages in R that allows phylogeny to be included as a random effect term. Across trials, the three cooperative and the three non-cooperative species completed the maze faster, made fewer mistakes, and improved their inhibitory control. Although fish improved their performance, we did not detect any differences in the extent of improvement between cooperative and non-cooperative species. Both the cooperative species and the non-cooperative species took similar amounts of time to complete the maze, had comparable numbers of mistakes, and exhibited similar inhibitory control while in the maze. Our results suggest that living and breeding in complex social groups does not necessarily imply enhancement of other forms of cognition nor, more specifically, an enhanced spatial learning capacity.

Phenotypic similarities within the morphologic spectrum of DICER1-associated sarcomas and pleuropulmonary blastoma: Histopathologic features guide diagnosis in the LMIC setting.

Extrapulmonary DICER1-associated sarcomas (DS) can harbor morphological features overlapping with pleuropulmonary blastoma. We report three children with intracranial and genital tract sarcomas, suspected to have DS based on a heterogeneous yet defining combination of spindle-cell sarcomatous and blastemal morphology, with rhabdomyomatous differentiation. Foci of immature cartilage at diagnosis (n = 2/3) and increased neuroepithelial differentiation at recurrence (n = 1) were noted. Morphological suspicion prompted somatic testing at reference centers, confirming likely biallelic, loss-of-function, and "hotspot" missense DICER1 variants in all three tumors. This can serve as a model for this diagnosis in resource-limited settings and has implications for germline testing, surveillance, and tumor management.

First-in-human phase I/Ib open-label dose-escalation study of GWN323 (anti-GITR) as a single agent and in combination with spartalizumab (anti-PD-1) in patients with advanced solid tumors and lymphomas.

BACKGROUND: GWN323 is an IgG1 monoclonal antibody (mAb) against the glucocorticoid-induced tumor necrosis factor receptor-related protein. This first-in-human, open-label phase I/Ib study aimed to investigate the safety and tolerability and to identify the recommended doses of GWN323 with/without spartalizumab, an anti-programmed cell death receptor-1 agent, for future studies. Pharmacokinetics, preliminary efficacy and efficacy biomarkers were also assessed. METHODS: Patients (aged ≥18 years) with advanced/metastatic solid tumors with Eastern Cooperative Oncology Group performance status of ≤2 were included. GWN323 (10-1500 mg) or GWN323+spartalizumab (GWN323 10-750 mg+spartalizumab 100-300 mg) were administered intravenously at various dose levels and schedules during the dose-escalation phase. Dose-limiting toxicities (DLTs) were assessed during the first 21 days in a single-agent arm and 42 days in a combination arm. Adverse events (AEs) were graded per National Cancer Institute-Common Toxicity Criteria for Adverse Events V.4.03 and efficacy was assessed using Response Evaluation Criteria in Solid Tumors V.1.1. RESULTS: Overall, 92 patients (single-agent, n=39; combination, n=53) were included. The maximum administered doses (MADs) in the single-agent and combination arms were GWN323 1500 mg every 3 weeks (q3w) and GWN323 750 mg+spartalizumab 300 mg q3w, respectively. No DLTs were observed with single-agent treatment. Three DLTs (6%, all grade ≥3) were noted with combination treatment: blood creatine phosphokinase increase, respiratory failure and small intestinal obstruction. Serious AEs were reported in 30.8% and 34.0%, and drug-related AEs were reported in 82.1% and 77.4% of patients with single-agent and combination treatments, respectively. Disease was stable in 7 patients and progressed in 26 patients with single-agent treatment. In combination arm patients, 1 had complete response (endometrial cancer); 3, partial response (rectal cancer, adenocarcinoma of colon and melanoma); 14, stable disease; and 27, disease progression. GWN323 exhibited a pharmacokinetic profile typical of mAbs with a dose-dependent increase in the pharmacokinetic exposure. Inconsistent decreases in regulatory T cells and increases in CD8+ T cells were observed in the combination arm. Gene expression analyses showed no significant effect of GWN323 on interferon-γ or natural killer-cell signatures. CONCLUSIONS: GWN323, as a single agent and in combination, was well tolerated in patients with relapsed/refractory solid tumors. The MAD was 1500 mg q3w for single-agent and GWN323 750 mg+spartalizumab 300 mg q3w for combination treatments. Minimal single-agent activity and modest clinical benefit were observed with the spartalizumab combination. TRIAL REGISTRATION NUMBER: NCT02740270.

Hysterectomy in India: Spatial and multilevel analysis.

OBJECTIVE: Using the unit-level data of women aged 15-49 years from National Family Health Survey-IV (2015-2016), the article maps the prevalence of hysterectomy across districts in India and examines its determinants. METHODS: Descriptive statistics, multivariate techniques, Moran's Index and Local indicators of Spatial Association were used to understand the objectives. The data were analysed in STATA 14.2, Geo-Da and Arc-GIS. RESULTS: In India, the prevalence of hysterectomy operation was 3.2%, the highest in Andhra Pradesh (8.9%) and the lowest in Assam (0.9%). Rural India had higher a prevalence than urban India. The majority of women underwent the operation in private hospitals. Hysterectomy prevalence ranged between 3% and 5% in 126 districts, 5% and 7% in 47 districts and more than 7% in 26 districts. Moran's Index (0.58) indicated the positive autocorrelation for the prevalence of hysterectomy among districts; a total of 202 districts had significant neighbourhood association. Variation in the prevalence of hysterectomy was attributed to the factors at the primary sampling unit, district and state level. Age, parity, wealth and insurance were positively associated with the prevalence of hysterectomy, whereas education and sterilization was negatively associated. CONCLUSION: Hysterectomy operation in India presented the geographical, socio-economic, demographic and medical phenomenon. The high prevalence of hysterectomy in many parts of the country suggested conducting in-depth studies, considering the life cycle approach and providing counselling and education to women about their reproductive rights and informed choice. Surveillance and medical audits and promoting the judicial use of health insurance can be of great help.

Immunohistochemical screening for mismatch repair protein deficiency in paediatric high-grade gliomas - institutional experience and review of literature.

PURPOSE: Immunohistochemical (IHC) testing for mismatch repair (MMR) deficiency (MMRD) is used as a screening tool to identify microsatellite instability in various cancers (especially colon). This not only identifies hereditary cancer syndromes like Lynch and constitutional mismatch repair deficiency (CMMRD) but also aids in prognostication and prediction of sensitivity to checkpoint inhibitor drugs. There are very few reported studies on MMRD status of pediatric high-grade gliomas (pHGG) and none from the Indian subcontinent. The aim of this study is to evaluate the frequency of MMRD in pHGG and to assess if there is a need for universal screening with immunohistochemistry. METHODS: Paraffin blocks of consecutive cases of pHGG (< 18 years) were retrieved from 2 centres, and IHC with four MMR antibodies - MLH1, PMS2, MSH2 and MSH6 - was performed using tissue microarray-based technique. RESULTS: Three out of nine cases (33%) studied showed loss of staining. One case had loss of MSH2 and MSH6 confirmed by gene sequencing. Eight of the cases were glioblastoma. One case of IDH1-mutated anaplastic astrocytoma showed loss of MLH1 and PMS2 staining. Isolated PMS2 loss was noted in 1 case, where the non-tumour cells also showed loss of staining, indicative CMMRD syndrome. This patient had prior colon cancer with isolated PMS2 loss and responded to check-point inhibitor therapy with nivolumab. CONCLUSION: Our study shows that the frequency of MMRD to be about one-third of pHGG. Universal IHC screening for MMRD in all pHGGs may benefit early diagnosis and play a role in therapeutic decisions. A larger multi-institutional study will help better assess the prevalence and treatment implications in MMRD tumours.