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Background and Aim: A better understanding of the complex interplay between socioeconomic determinants and risk factors of high blood pressure (BP) has critical implications. Behavioral characteristics are strong candidates to act as mediators of the observed effects of socioeconomic determinants on BP; therefore, we aimed to investigate the mediating role of smoking and alcohol on the association between education, wealth index, sex, and hypertension using NFHS-5 data. Materials and Methods: We conducted a secondary analysis of the data collected from a nationally representative survey (NFHS-5 data) in India. We included 1,923,504 people aged 18 years and above who had all the necessary information for the analysis. We performed a mediation analysis using linear and logistic regression models to estimate the natural direct effect, total effects, and natural indirect effect of sex, education, and wealth index, and systolic BP (SBP) and diastolic BP (DBP), while maintaining behavioral habits (smoking and alcohol use) as mediator variables. Results: An equal distribution of males (51.4%) and females (48.6%) was seen, about 13.2% consumed alcohol, and 27.6% had used or smoked tobacco. Females had significantly lower SBP (β = −4.59, −4.67) and DBP (β = −2.07, −2.60) compared to males. Lower educational levels significantly influenced systolic (β = −2.89, −2.89) and diastolic (β = −1.15, −1.14) BP; people in the richer and richest quintile had significantly higher systolic (β = 0.60, 0.59) and diastolic (β = 0.43, 0.43) BP. Mediation analysis showed partial mediation by alcohol and tobacco, which was statistically significant (P < 0.001). Conclusion: These results will help in developing targeted interventions to address the unique risk factors and challenges faced by different population subgroups.

Background: The cardiovascular disease (CVD) risk prediction charts, updated by the World Health Organization for 21 regions in 2019. These charts—lab and non-lab versions—estimate a person’s overall CVD risk; the non-lab version is intended for low-resource environments. Objectives: Using the “non-lab” and “lab” versions of the WHO CVD risk prediction charts, we sought to estimate the burden of ten-year risk of a fatal or non-fatal CVD event in a tertiary care hospital of Puducherry and to assess the agreement between them. Materials and Methods: We included 255 doctors working in a tertiary care hospital in Puducherry. Age, gender, systolic blood pressure, and smoking status are all factors used in both charts. Moreover, a lab chart requires a person’s total cholesterol and diabetes mellitus status, whereas a non-lab chart requires a person’s body mass index. Proportions (95% confidence intervals) were used to portray the population at various CVD risk levels. Using Cohen’s Kappa, the degree of agreement between the lab and non-lab charts was assessed (k). Results: The majority of the study participants had 20% in both the charts, which shows the better health-seeking behaviour of doctors. A good level of agreement was shown by the 95.2% (95%CI = 91.7 – 97.4 ) concordance in the risk categorization between the two charts (k = 0.934). Conclusion: When data are available and there is strong agreement between non-lab and lab-based charts, it is practical to apply WHO-updated CVD risk prediction charts.

BackgroundWe hypothesized that a gender difference in clinical response may exist to adjuvant CTLA4 blockade with ipilimumab versus high-dose IFNα (HDI). We investigated differences in candidate immune biomarkers in the circulation and tumor microenvironment (TME).Patients and methodsThis gender-based analysis was nested within the E1609 trial that tested adjuvant therapy with ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus HDI in high risk resected melanoma. We investigated gender differences in treatment efficacy with ipi3 and ipi10 versus HDI while adjusting for age, stage, ECOG performance (PS), ulceration, primary tumor status and lymph node number. Forest plots were created to compare overall survival (OS) and relapse free survival (RFS) between ipi and HDI. Gene expression profiling (GEP) was performed on tumors of 718 (454 male, 264 female) patients. Similarly, serum and peripheral blood mononuclear cells (PBMC) samples were tested for soluble and cellular biomarkers (N = 321 patients; 109 female and 212 male).ResultsThe subgroups of female, stage IIIC, PS = 1, ulcerated primary, in-transit metastasis demonstrated significant improvement in RFS and/or OS with ipi3 versus HDI. Female gender was significant for both OS and RFS and was further explored. In the RFS comparison, a multivariate Cox regression model including significant variables indicated a significant interaction between gender and treatment (P = 0.024). In peripheral blood, percentages of CD3+ T cells (P = 0.024) and CD3+ CD4+ helper T cells (P = 0.0001) were higher in females compared to males. Trends toward higher circulating levels of IL1β (P = 0.07) and IL6 (P = 0.06) were also found in females. Males had higher percentages of monocytes (P = 0.03) with trends toward higher percentages of regulatory T cells (T-reg). Tumor GEP analysis supported enhanced infiltration with immune cells including gammadelta T cells (P = 0.005), NK cells (P = 0.01), dendritic cells (P = 0.01), CD4+ T cells (P = 0.03), CD8+ T cells (P = 0.03) and T-reg (P = 0.008) in the tumors of females compared to males and a higher T-effector and IFNγ gene signature score (P = 0.0244).ConclusionFemale gender was associated with adjuvant CTLA4 blockade clinical benefits and female patients were more likely to have evidence of type1 immune activation within the TME and the circulation. Trial registration ClinicalTrials.gov NCT01274338. Registered 11 January 2011, https://www.Clinicaltrialsgov/ct2/show/NCT01274338.

BackgroundMelanoma of unknown primary (MUP) represents a poorly understood group of patients both clinically and immunologically. We investigated differences in prognosis and candidate immune biomarkers in patients with unknown compared with those with known primary melanoma enrolled in the E1609 adjuvant trial that tested ipilimumab at 3 and 10 mg/kg vs high-dose interferon-alfa (HDI).Patients and methodsMUP status was defined as initial presentation with cutaneous, nodal or distant metastasis without a known primary. Relapse-free survival (RFS) and overall survival (OS) rates were estimated by the Kaplan-Meier method. Stratified (by stage) log-rank test was used to compare RFS and OS by primary tumor status. Gene expression profiling (GEP) was performed on the tumor biopsies of a subset of patients. Similarly, peripheral blood samples were tested for candidate soluble and cellular immune biomarkers.ResultsMUP cases represented 12.8% of the total population (N=1699) including 11.7% on the ipilimumab arms and 14.7% on the HDI arm. Stratifying by stage, RFS (p=0.001) and overall survival (OS) (p=0.009) showed outcomes significantly better for patients with unknown primary. The primary tumor status remained prognostically significant after adjusting for treatment and stage in multivariate Cox proportional hazards models. Including only ipilimumab-treated patients, RFS (p=0.005) and OS (p=0.023) were significantly better in favor of those with unknown primary. Among patients with GEP data (n=718; 102 MUP, 616 known), GEP identified pathways and genes related to autoimmunity, inflammation, immune cell infiltration and immune activation that were significantly enriched in the MUP tumors compared with known primaries. Further investigation into infiltrating immune cell types estimated significant enrichment with CD8 +and CD4+T cells, B cells and NK cells as well as significantly higher major histocompatibility complex (MHC)-I and MHC-II scores in MUP compared with known primary. Among patients tested for circulating biomarkers (n=321; 66 unknown and 255 known), patients with MUP had significantly higher circulating levels of IL-2R (p=0.04).ConclusionPatients with MUP and high-risk melanoma had significantly better prognosis and evidence of significantly enhanced immune activation within the TME and the circulation, supporting the designation of MUP as a distinct prognostic marker in patients with high-risk melanoma.

PurposeNeoadjuvant immunotherapy may improve the clinical outcome of regionally advanced operable melanoma and allows for rapid clinical and pathologic assessment of response. We examined neoadjuvant pembrolizumab and high-dose IFNα-2b (HDI) therapy in patients with resectable advanced melanoma.Patients and methodsPatients with resectable stage III/IV melanoma were treated with concurrent pembrolizumab 200 mg i.v. every 3 weeks and HDI 20 MU/m2/day i.v., 5 days per week for 4 weeks, then 10 MU/m2/day subcutaneously 3 days per week for 2 weeks. Definitive surgery followed, as did adjuvant combination immunotherapy, completing a year of treatment. Primary endpoint was safety of the combination. Secondary endpoints included overall response rate (ORR), pathologic complete response (pCR), recurrence-free survival (RFS), and overall survival (OS). Blood samples for correlative studies were collected throughout. Tumor tissue was assessed by IHC and flow cytometry at baseline and at surgery.ResultsA total of 31 patients were enrolled, and 30 were evaluable. At data cutoff (October 2, 2019), median follow-up for OS was 37.87 months (range, 33.2-43.47). Median OS and RFS were not reached. Radiographic ORR was 73.3% [95% confidence interval (CI): 55.5-85.8], with a 43% (95% CI: 27.3-60.1) pCR rate. None of the patients with a pCR have had a recurrence. HDI and pembrolizumab were discontinued in 73% and 43% of patients, respectively. Correlative analyses suggested that intratumoral PD-1/PD-L1 interaction and HLA-DR expression are associated with pCR (P = 0.002 and P = 0.008, respectively).ConclusionsNeoadjuvant concurrent HDI and pembrolizumab demonstrated promising clinical activity despite high rates of treatment discontinuation. pCR is a prognostic indicator.See related commentary by Menzies et al., p. 4133.

The activity of daily living (ADL) related to stair climbing is one of the most compromised ADLs among the elders. It requires good muscle strength, balance, and range of motion (ROM) in the lower limb. We aimed to investigate the effects of Yoga complemented with physiotherapy (Intervention group) compared to only physiotherapy (control group) on lower limb muscle strength, balance, and ROMs among elders with ADL limitation in stair climbing. Sixty-five community-dwelling elders with compromised stair climbing were enrolled. Elders who consented to yoga along with physiotherapy were enrolled in the intervention arm. Data were collected and analyzed following 12 weeks of intervention. Endline assessment showed that the intervention group had more improvement in all test scores and ROMs as compared to the control group, although there were improvements in both arms as compared to baseline. Considering the beneficial effects of both interventions, yoga can be added to gain additional advantages. Trial Registration: Indian Clinical Trials Registry number CTRI/2021/08/035825.

We report a patient with Sweet syndrome involving the pulmonary system in the context of myelodysplastic syndrome. Although Sweet syndrome may involve a variety of organ systems, the pulmonary system is rarely affected and can result in poor clinical outcomes, including acute respiratory distress syndrome. Both cutaneous and pulmonary symptoms respond well to systemic corticosteroid therapy and early diagnosis and treatment can improve the prognosis. Our case highlights the importance of collaboration between hematologists, dermatologists, and pulmonologists to facilitate effective diagnosis, triage, and treatment of these patients.

Key Clinical Message Hydroxychloroquine (HCQ) has been reported to cause pustular drug eruptions such as acute generalized exanthematous pustulosis (AGEP) and putular psoriasis (PP). Clinical differentitation of these entities is often difficult. This case emphasizes characteritics of AGEP and PP as well as the need for clinicans to proactively follow‐up these patients to monitor for the more aggressive outcome of PP.