Posterior-Scleritis: Case Report of an Uncommon Immune-Related Adverse Event in the Treatment of Advanced Endometrial Cancer

As Immune checkpoint inhibitors are being expanded for use in gynecologic malignancies, rare immune-related adverse events are more frequently being reported. Here we describe a 63-year-old with Stage IIIB mismatch repair deficient uterine adenocarcinoma who underwent six cycles of carboplatin and paclitaxel with partial response but persistent disease. She was then started on single agent pembrolizumab. After six cycles of pembrolizumab, she developed bilateral vision changes and was diagnosed with posterior scleritis. Pembrolizumab was held and she was treated with oral prednisone, with rapid resolution of symptoms. One month after completion of prednisone, vision changes were again reported and she was restarted on a longer oral prednisone course. She then underwent definitive surgical management consisting of a total laparoscopic hysterectomy and bilateral salpingo-oophorectomy, with final pathology of benign endometrial hyperplasia. She has completed her steroid course without any symptoms. Given her complete pathologic response, she was subsequently placed into surveillance and is currently without evidence of disease. Prompt recognition and treatment of this rare immune-related adverse event led to the prevention of potential permanent, debilitating outcomes

Whole exome re-sequencing implicates CCDC38 and cilia structure and function in resistance to smoking related airflow obstruction

Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality and, whilst smoking remains the single most important risk factor, COPD risk is heritable. Of 26 independent genomic regions showing association with lung function in genome-wide association studies, eleven have been reported to show association with airflow obstruction. Although the main risk factor for COPD is smoking, some individuals are observed to have a high forced expired volume in 1 second (FEV1) despite many years of heavy smoking. We # hypothesised that these ‘‘resistant smokers’’ may harbour variants which protect against lung function decline caused by smoking and provide insight into the genetic determinants of lung health. We undertook whole exome re sequencing of 100 heavy smokers who had healthy lung function given their age, sex, height and smoking history and applied three complementary approaches to explore the genetic architecture of smoking resistance. Firstly, we identified novel functional variants in the ‘‘resistant smokers’’ and looked for enrichment of these novel variants within biological pathways. Secondly, we undertook association testing of all exonic variants individually with two independent control sets. Thirdly, we undertook gene-based association testing of all exonic variants. Our strongest signal of association with smoking resistance for a non-synonymous SNP was for rs10859974 (P = 2.3461024) in CCDC38, a gene which has previously been reported to show association with FEV1/FVC, and we demonstrate moderate expression of CCDC38 in bronchial epithelial cells. We identified an enrichment of novel putatively functional variants in genes related to cilia structure and function in resistant smokers. Ciliary function abnormalities are known to be associated with both smoking and reduced mucociliary clearance in patients with COPD. We suggest that genetic influences on the development or function of cilia in the bronchial epithelium may affect growth of cilia or the extent of damage caused by tobacco smoke

KNOWLEDGE, ATTITUDE, AND PRACTICES OF SELF-MEDICATION AMONG THE STUDENTS OF PRIVATE UNIVERSITY

Objectives: Self-medication is becoming very common in our routine life which is an unhealthy and risky practice in a few instances. The present study was carried out to determine the knowledge, attitude, and practice of self-medication among students of Charotar University of Science and Technology (CHARUSAT). Methods: A pre-validated questionnaire was prepared and distributed among the students. Data was collected and analyzed using Microsoft Excel and the results expressed as counts and percentages. Results: A total of 431 students participated voluntarily in the study. The most common reason for taking self-medication was found in 70% of total students. We found that the source of information of the drugs used for self-medication was “previous prescription (57%)” and source of drugs was “medical store (66%).” Only (46%) students accepted the fact that they always visited a qualified practitioner whenever they felt ill. Most of the students took self-medication for headache (82%) followed by cough, cold, and sore throat (62%) and fever (57%). Of total 431 students, most of the students took analgesics (78%) as self-medication followed by lozenges (50%). Conclusion: Self-medication was common in nearly 70% of university students. They provided the reason that “no needs to visit the doctor for minor illness.” Cough and cold preparations were taken by 82% population as self-medication

Classical cannabinoid receptors as target in cancer-induced bone pain: a systematic review, meta-analysis and bioinformatics validation

Abstract To test the hypothesis that genetic and pharmacological modulation of the classical cannabinoid type 1 (CB1) and 2 (CB2) receptors attenuate cancer-induced bone pain, we searched Medline, Web of Science and Scopus for relevant skeletal and non-skeletal cancer studies from inception to July 28, 2022. We identified 29 animal and 35 human studies. In mice, a meta-analysis of pooled studies showed that treatment of osteolysis-bearing males with the endocannabinoids AEA and 2-AG (mean difference [MD] − 24.83, 95% confidence interval [95%CI] − 34.89, − 14.76, p < 0.00001) or the synthetic cannabinoid (CB) agonists ACPA, WIN55,212-2, CP55,940 (CB1/2-non-selective) and AM1241 (CB2-selective) (MD − 28.73, 95%CI − 45.43, − 12.02, p = 0.0008) are associated with significant reduction in paw withdrawal frequency. Consistently, the synthetic agonists AM1241 and JWH015 (CB2-selective) increased paw withdrawal threshold (MD 0.89, 95%CI 0.79, 0.99, p < 0.00001), and ACEA (CB1-selective), AM1241 and JWH015 (CB2-selective) reduced spontaneous flinches (MD − 4.85, 95%CI − 6.74, − 2.96, p < 0. 00001) in osteolysis-bearing male mice. In rats, significant increase in paw withdrawal threshold is associated with the administration of ACEA and WIN55,212-2 (CB1/2-non-selective), JWH015 and AM1241 (CB2-selective) in osteolysis-bearing females (MD 8.18, 95%CI 6.14, 10.21, p < 0.00001), and treatment with AM1241 (CB2-selective) increased paw withdrawal thermal latency in males (mean difference [MD]: 3.94, 95%CI 2.13, 5.75, p < 0.0001), confirming the analgesic capabilities of CB1/2 ligands in rodents. In human, treatment of cancer patients with medical cannabis (standardized MD − 0.19, 95%CI − 0.35, − 0.02, p = 0.03) and the plant-derived delta-9-THC (20 mg) (MD 3.29, CI 2.24, 4.33, p < 0.00001) or its synthetic derivative NIB (4 mg) (MD 2.55, 95%CI 1.58, 3.51, p < 0.00001) are associated with reduction in pain intensity. Bioinformatics validation of KEGG, GO and MPO pathway, function and process enrichment analysis of mouse, rat and human data revealed that CB1 and CB2 receptors are enriched in a cocktail of nociceptive and sensory perception, inflammatory, immune-modulatory, and cancer pathways. Thus, we cautiously conclude that pharmacological modulators of CB1/2 receptors show promise in the treatment of cancer-induced bone pain, however further assessment of their effects on bone pain in genetically engineered animal models and cancer patients is warranted

Measuring stigma in chronic pain: preliminary investigation of instrument psychometrics, correlates, and magnitude of change in a prospective cohort attending interdisciplinary treatment

Chronic pain is a potentially stigmatizing condition. However, stigma has received limited empirical investigation in people with chronic pain. Therefore, we examined the psychometric properties of a self-report questionnaire of stigma in people with chronic pain attending interdisciplinary treatment. Secondarily, we undertook an exploratory examination of the magnitude of change in stigma associated with interdisciplinary treatment in a prospective observational cohort. Participants attending interdisciplinary treatment based on acceptance and commitment therapy completed the Stigma Scale for Chronic Illness 8-item version (SSCI-8; previously developed and validated in neurological samples), and measures of perceived injustice, pain acceptance, and standard pain outcomes before (n = 300) and after treatment (n = 247). A unidimensional factor structure and good internal consistency were found for the SSCI-8. Total SSCI-8 scores were correlated with pain intensity, indices of functioning, and depression in bivariate analyses. Stigma scores were uniquely associated with functioning and depression in multiple regression analyses controlling for demographic factors, pain intensity, pain acceptance, and perceived injustice at baseline. SSCI-8 total scores did not significantly improve after treatment, although an exploratory subscale analysis showed a small improvement on internalized stigma. In contrast, scores on perceived injustice, pain acceptance, and pain outcomes improved significantly. Taken together, these data support the reliability and validity of the SSCI-8 for use in samples with chronic pain. Further research is needed optimize interventions to target stigma at both the individual and societal levels

QQ plots for SKAT and AMELIA analyses using primary controls.

<p>QQ plots for SKAT and AMELIA analyses using primary controls.</p

QQ plots of single-variant association test statistics for all exonic variants (A) and for exonic variants with MAF>5% (B).

<p>QQ plots of single-variant association test statistics for all exonic variants (A) and for exonic variants with MAF>5% (B).</p

Flowchart describing each of the 3 main analytical pathways used to explore the genetic architecture of smoking resistance.

<p>Analyses are described in full in the methods. MAF: minor allele frequency.</p