Iodine and other factors associated with fertility outcome following oil-soluble contrast medium hysterosalpingography: a prospective cohort study.

Objective: To examine factors associated with fertility following hysterosalpingography (HSG) using an oil-soluble contrast medium (OSCM). Design: In a prospective cohort study on 196 women undergoing OSCM HSG, we showed that iodine excess was almost universal (98%) and mild subclinical hypothyroidism was frequent (38%). Here, we report the analyses of secondary outcomes examining factors associated with the likelihood of pregnancy following the HSG. Setting: Auckland, New Zealand (2019-2021). Sample: 196 women with primary or secondary infertility who underwent OSCM HSG. Methods: Baseline and serial urine iodine concentrations (UIC) and thyroid function tests were measured over six months following the HSG. Pregnancy and treatment with levothyroxine during the study period were documented. Results: Following OSCM HSG, pregnancy rates were 49% in women aged <40 years (77/158) but considerably lower (16%) among those ≥40 years (6/38). Similarly, live birth rates were markedly lower in women ≥40 years (17%; 1/6) versus <40 years (73%; 56/77). 29% of participants were iodine deficient at baseline despite advice recommending iodine fortification. Following HSG, the likelihood of pregnancy in women with moderate iodine deficiency was 64% higher than in women with normal iodine levels (p=0.048). Among women aged <40 years who had subclinical hypothyroidism (n=75), levothyroxine treatment was associated with higher pregnancy rates compared to untreated women [63% (26/48) vs 37% (10/27), respectively; p=0.047]. Conclusion: OSCM HSG was associated with higher pregnancy rates in women ≤40 than in those aged >40 years. Iodine deficiency was relatively common in this cohort, and increased iodine levels from OSCM exposure may contribute to the improved fertility observed with this procedure. Trial registration: This study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR: 12620000738921) https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000738921.

Periostin regulates lysyl oxidase through ERK1/2 MAPK-dependent serum response factor in activated cardiac fibroblasts.

Collagen crosslinking, mediated by lysyl oxidase, is an adaptive mechanism of the cardiac repair process initiated by cardiac fibroblasts postmyocardial injury. However, excessive crosslinking leads to cardiac wall stiffening, which impairs the contractile properties of the left ventricle and leads to heart failure. In this study, we investigated the role of periostin, a matricellular protein, in the regulation of lysyl oxidase in cardiac fibroblasts in response to angiotensin II and TGFß1. Our results indicated that periostin silencing abolished the angiotensin II and TGFß1-mediated upregulation of lysyl oxidase. Furthermore, the attenuation of periostin expression resulted in a notable reduction in the activity of lysyl oxidase. Downstream of periostin, ERK1/2 MAPK signaling was found to be activated, which in turn transcriptionally upregulates the serum response factor to facilitate the enhanced expression of lysyl oxidase. The periostin-lysyl oxidase association was also positively correlated in an in vivo rat model of myocardial infarction. The expression of periostin and lysyl oxidase was upregulated in the collagen-rich fibrotic scar tissue of the left ventricle. Remarkably, echocardiography data showed a reduction in the left ventricular wall movement, ejection fraction, and fractional shortening, indicative of enhanced stiffening of the cardiac wall. These findings shed light on the mechanistic role of periostin in the collagen crosslinking initiated by activated cardiac fibroblasts. Our findings signify periostin as a possible therapeutic target to reduce excessive collagen crosslinking that contributes to the structural remodeling associated with heart failure.

Anti-nuclear matrix protein 2 antibody-positive amyopathic dermatomyositis presenting in a patient with prostate cancer: A case report.

Nuclear matrix protein (NXP-2) positive amyopathic dermatomyositis (DM) may present without classic symptoms like muscle weakness, dysphagia, and edema, and mimic conditions like cutaneous lupus. Given DM's association with malignancy and interstitial lung disease, prompt and accurate diagnosis is important. Testing for myositis-specific antibodies aids diagnosis in ambiguous cases.

Expanding the phenotypic and genotypic spectrum of DYT-TUBB4A with seven patients from India.

BACKGROUND: Variants in the TUBB4A gene are associated with dystonia (DYT-TUBB4A), Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-ABC) and spastic paraplegia. Phenotypes intermediate to these three broad phenotypes are also observed. These are rare disorders, and data from diverse populations remains limited. We report seven Indian cases with dystonia phenotype related to TUBB4A mutation. CASES: Among these seven patients, age at onset ranged from 5 to 48 years. Five patients had cranio-cervical onset of dystonia. One patient had prominent parkinsonism with dystonia. Patients responded well to botulinum toxin injected for laryngeal, cervical and jaw dystonia. The patient with parkinsonism responded well to levodopa, albeit with development of dyskinesias. Apart from the common p.Arg2Gly variant in three patients with DYT-TUBB4A, other variants included p.Arg262Pro, p.Arg39Cys and p.Asp245Asn. CONCLUSIONS: We report the first collection of cases with TUBB4A mutation from India. We expand the phenotype to include levodopa-responsive parkinsonism. Indian patients, consistent with global literature, harbor prominent adductor dysphonia, cervical and jaw dystonia, which responds well to botulinum treatment.

Acute bilateral sensorineural hearing loss as presentation of leptomeningeal metastases.

We describe a rare occurrence of bilateral acute severe sensorineural hearing loss in a middle-aged man that heralded the diagnosis of metastatic gastric cancer.

Coaches Activating, Reaching, and Engaging Patients to Engage in Advance Care Planning: A Randomized Clinical Trial.

Importance: Advance care planning (ACP) remains low among patients with advanced cancer. Multilevel interventions compared with clinician-level interventions may be more effective in improving ACP. Objective: To evaluate whether a multilevel intervention could improve clinician-documented ACP compared with a clinician-level intervention alone. Design, Setting, and Participants: This randomized clinical trial, performed from September 12, 2019, through May 12, 2021, included adults with advanced genitourinary cancers at an academic, tertiary hospital. Data analysis was performed by intention to treat from May 1 to August 10, 2023. Intervention: Participants were randomized 1:1 to a 6-month patient-level lay health worker structured ACP education along with a clinician-level intervention composed of 3-hour ACP training and integration of a structured electronic health record documentation template (intervention group) or to the clinician-level intervention alone (control group). Main Outcome and Measures: The primary outcome was ACP documentation in the electronic health record by the oncology clinician within 12 months after randomization. Secondary, exploratory outcomes included shared decision-making, palliative care use, hospice use, emergency department visits, and hospitalizations within 12 months after randomization. Results: Among 402 participants enrolled in the study, median age was 71 years (range, 21-102 years); 361 (89.8%) identified as male. More intervention group participants had oncology clinician-documented ACP than control group participants (82 [37.8%] vs 40 [21.6%]; odds ratio [OR], 2.29; 95% CI, 1.44-3.64). At 12-month follow-up, more intervention than control group participants had palliative care (72 [33.2%] vs 25 [13.5%]; OR, 3.18; 95% CI, 1.91-5.28) and hospice use (49 [22.6%] vs 19 [10.3%]; OR, 2.54; 95% CI, 1.44-4.51). There were no differences in the proportion of participants between groups with an emergency department visit (65 [30.0%] vs 61 [33.0%]; OR, 0.87; 95% CI, 0.57-1.33) or hospitalization (89 [41.0%] vs 85 [46.0%]; OR, 0.82; 95% CI, 0.55-1.22). Intervention group participants had fewer hospitalizations than control group participants (mean [SD] number of hospitalizations per year, 0.87 [1.60] vs 1.04 [1.77]) and a lower risk of hospitalization (incidence rate ratio, 0.80; 95% CI, 0.65-0.98). Conclusions and Relevance: In this randomized clinical trial, a multilevel intervention improved oncology clinician-documented ACP compared with a clinician-level intervention alone for patients with genitourinary cancer. The intervention is one approach to effectively increase ACP among patients with cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03856463.

Clinical pharmacokinetics and pharmacodynamics of oral systemic nonbiologic therapies for psoriasis patients.

INTRODUCTION: Psoriasis is a chronic inflammatory immune condition. Treatments for psoriasis vary with disease severity, ranging from topicals to systemic biologic agents. The pharmacokinetic (PK) and pharmacodynamic (PD) properties of these therapies establish drug efficacy, toxicity, and optimal dosing to ensure therapeutic drug levels are sustained and adverse effects are minimized. AREAS COVERED: A literature search was performed on PubMed, Google Scholar, and Ovid MEDLINE for PK and PD, efficacy, and safety data regarding oral systemic nonbiologic therapies utilized for moderate-to-severe plaque psoriasis. The findings were organized into sections for each drug: oral acitretin, methotrexate, cyclosporine, apremilast, tofacitinib, and deucravacitinib. EXPERT OPINION: Some psoriasis patients may not respond to initial therapy. Ongoing research is evaluating genetic polymorphisms that may predict an improved response to specific medications. However, financial and insurance barriers, as well as limited genetic polymorphisms correlated with treatment response, may restrict the implementation of genetic testing necessary to personalize treatments. How well psoriasis patients adhere to treatment may contribute greatly to variation in response. Therapeutic drug monitoring may help patients adhere to treatment, improve clinical response, and sustain disease control.

Live vaccinations in dermatology for immunosuppressed patients: a narrative review.

Given the higher susceptibility to infectious disease in patients receiving immunosuppressive therapies for inflammatory dermatologic conditions, immunization is important in this population. While live vaccines protect against life-threatening diseases, they can be harmful in immunosuppressed patients given the risk of replication of the attenuated pathogen and adverse reactions. The utilization of live vaccines in immunosuppressed patients depends on multiple factors such as the vaccine and therapy regimen. To provide an overview of evidence-based recommendations for the use of live vaccines in patients receiving immunosuppressive therapies for dermatological conditions. A literature search of the PubMed database was performed using keywords live vaccine, live-attenuated vaccine, dermatology, immunosuppressed, and immunocompromised, and specific immunosuppressive therapies: corticosteroids, glucocorticoids, methotrexate, azathioprine, cyclosporine, mycophenolate mofetil, biologics. Relevant articles written in English were included. Using these keywords, 125 articles were reviewed, of which 28 were ultimately selected. Recommendations for live vaccines can be determined on a case-by-case basis. Measles, mumps, rubella, varicella (MMRV) vaccines may be safely administered to patients on low-dose immunosuppressive agents while the yellow fever vaccine is typically contraindicated. It may be safe to administer live MMRV boosters to children on immunosuppressive therapies and the live herpes zoster vaccine to patients on biologics. Given poor adherence to immunization guidelines in immunosuppressed patients, dermatologists have a critical role in educating patients and general practitioners regarding live vaccines. By reviewing a patient's vaccination history and following immunization guidelines prior to initiating immunosuppressive therapies, physicians can mitigate morbidity and mortality from vaccine-preventable diseases.

Community Pharmacist's Awareness, Knowledge and Attitude Towards use of Vitamin Supplements in Pimpri-Chinchwad Municipal Corporation (PCMC) Area of Pune, India: A Descriptive Cross Sectional Study.

Background: US FDA defines: dietary supplements is a product that intended to supplement a person's diet, it's generally consist of at least one or more of the following dietary ingredients, vitamin, minerals, a herb or other botanical and amino acid by increasing the daily consumptions of an extract metabolite concentration, constitute or combinations of these medication. Excessive and inappropriate use of medicines has been recognised as a public health problem resulting in increased likelihood of adverse drug event, drug interaction, and inappropriate drug prescribing and increased cost. Material and Methods: This was the cross-sectional study conducted in year 2022 at Pimpri Chinchwad (Pune). The total 250 questionaires are distributed and from that 226 response were received. Target population consist of community pharmacists working in the drug store in this area (n=226). Results: Data was represented in three domains of study i. e. awareness, knowledge and attitude. Correlation coefficient using Pearson's method were determined to evaluate strength of correlation between awareness-knowledge, Knowledge-attitude and awareness-attitude. Correlation coefficient were calculated by comparing most relevant and equal number of questions. Conclusion: The study demonstrated positive attitude among surveyed community pharmacists in Pune, India. There is lacuna in accurate and adequate awareness, knowledge and attitude of vitamin deficiency, efficiency, recommended daily allowance (RDA), toxicity and interactions among pharmacist as one of the stakeholders of healthcare in India. Few of the remedies viz. framing of guidelines, inclusion in formal education syllabus, continuous education, updation exams etc. may be of use.

Essential Tremor and Essential Tremor Plus Are Essentially Similar Electrophysiologically.

BACKGROUND: The merits of classifying the heterogeneous group of essential tremors into essential tremor (ET) and essential tremor plus (ETP) are debated. OBJECTIVES: We studied the electrophysiological and spiral characteristics of tremor in ET and ETP. METHODS: We reviewed standardized videos from a tremor database and clinically classified patients into ET, ETP, or dystonic tremor (DT). The following variables were derived from combined tri-axial accelerometry-surface electromyography (EMG)-peak frequency, total power, peak power, full width half maximum, tremor stability index and EMG-coherence. We analyzed hand-drawn spirals to derive mean deviation, tremor variability, inter-, and intra-loop widths. We compared these variables among the groups. RESULTS: We recruited 72 participants (81.9% male) with mean age 47.7 ± 16.1 years and Fahn-Tolosa-Marin Tremor Rating Scale total score 31.1 ± 14.1. Patients with ET were younger (P = 0.014) and had less severe tremor (P = 0.020) compared to ETP and DT. In ETP group, 48.6% had subtle dystonia. Peak frequency was greater in ETP (7.3 ± 0.3 Hz) compared to DT (6.1 ± 0.4 Hz; P = 0.024). Peak power was greater in ETP and DT for postural tremor. Rest tremor was recordable on accelerometry in 26.7% of ET. Other variables were similar among the groups. CONCLUSION: Electrophysiological evaluation revealed postural tremor of frequency 6 to 7 Hz in ET, ETP, and DT with subtle differences more severe tremor in ETP and DT, and higher frequency in ETP compared to DT. Our findings suggest a similar tremor oscillator in these conditions, supporting the view that these entities are part of a spectrum of tremor disorders, rather than distinct etiological entities.