Unraveling disparities: Probing gender, race, and geographic inequities in pulmonary heart disease mortality in the United States: An extensive longitudinal examination (1999-2020) leveraging CDC WONDER data.

This comprehensive study delves into the epidemiological landscape of Pulmonary Heart Disease (PHD) mortality in the United States from 1999 to 2020, leveraging the extensive CDC WONDER database. PHD encompasses conditions affecting the right side of the heart due to lung disorders or elevated pressure in the pulmonary arteries, including pulmonary hypertension, pulmonary embolism, and chronic thromboembolic pulmonary hypertension (CTEPH). Analyzing data from death certificates, demographic characteristics, and geographical segmentation, significant trends emerge. The age-adjusted mortality rates (AAMRs) for PHD-related deaths show a fluctuating pattern, initially decreasing from 1999 to 2006, followed by a steady increase until 2020. Male patients consistently exhibit higher AAMRs than females, with notable disparities observed among racial/ethnic groups and geographic regions. Non-hispanic (NH) Black or African American individuals, residents of specific states like Colorado and the District of Columbia, and those in the Midwest region demonstrate elevated AAMRs. Furthermore, nonmetropolitan areas consistently manifest higher AAMRs than metropolitan areas. These findings underscore the urgent need for intensified prevention and treatment strategies to address the rising mortality associated with PHD, particularly among vulnerable populations. Insights from this study offer valuable guidance for public health initiatives aimed at reducing PHD-related mortality and improving outcomes nationwide.

Punicalagin improves inflammation and oxidative stress in rat model of pelvic inflammatory disease.

Pelvic inflammatory disease (PID) is one of the major public health concerns accounting for 30% of infertility and 50% of ectopic pregnancy cases due to severe inflammation and fibrosis. Punicalagin® are known to exhibit potent anti-inflammatory activity. The aim of this study was to demonstrate the anti-inflammatory and antioxidant effects of Punicalagin®, against pelvic inflammatory disease in rats. Female Sprague Dawley rats (n = 24) were divided into 6 groups (n = 4) as control, PID, prophylactic (low dose and high dose) and therapeutic group (low dose and high dose). PID model was constructed by implanting the rat cervix with mixed microbe (Escherichia Coli and Staphylococcus Aureus) solution. Prophylactic group was gavaged with 3 mg/kg (low dose) and 6 mg/kg (high dose) Punicalagin® daily starting one day before PID induction and therapeutic group was gavaged with 3 mg/kg (low dose) and 6 mg/kg (high dose) Punicalagin® daily starting 1 day after confirmation of PID model. Rats were sacrificed at the end of experiment and samples from upper genital tract were collected for ELISA, antioxidant assay and histopathological examination. According to results, obvious signs of inflammation and oxidative stress including infiltration of neutrophils and significantly raised levels of cytokines, and oxidative stress markers were observed in PID group when compared to control group. Punicalagin® significantly decreased the levels of IL-1ß, catalase and lipid peroxidation in both prophylactic and therapeutic groups when compared to PID group. Punicalagin® also decreased the infiltration of leucocytes in uterus of prophylactic and therapeutic group when compared to PID group, as determined by histological examination. On basis of these results, we concluded that Punicalagin® showed anti-inflammatory and antioxidant potential in rat model of pelvic inflammatory disease and could be used as possible therapeutic agent in treatment of PID.

Cross-cultural adaptation and psychometric validation of the brief assessment of recovery capital (BARC-10) scale into Bangla.

Recovery capital is a construct central to the substance use disorder treatment and recovery field. Lack of structured instrument for its assessment in the local context necessitated the translation of the English self-assessment version of the "Brief Assessment of Recovery Capital" (BARC-10) scale to Bangla and the study of its psychometric properties. The objective was to develop a culturally adapted and validated Bangla version of the BARC-10 scale for substance use disorders patients. This study conducted in the period of January 2021 to March 2022 in the department of Psychiatry of a tertiary hospital and central drug addiction treatment center. Initially BARC-10 questionnaire was translated into Bangla (T1 and T2) by 2 separate translators and then synthesis of a single version (T12) was done based on the previous translations. After that 2 back translations (BT1 and BT2) were done by 2 more translators based on the synthesized version (T12). By reviewing all these forward and backward translations, an expert committee made the pre-final version after making some linguistic modification. Then data collection was done among 100 subjects who were selected purposively. Reliability was assessed by Cronbach alpha. Content validity, face validity and Construct validity by factor analysis were measured. Internal consistency measured by Cronbach alpha found was 0.846. No significant change in Cronbach alpha was observed following deleting any item. Confirmatory factor analysis revealed a good fit to data by a chi-square/df value1.33, RMSEA value 0.058. Kaiser-Meyer-Olkin value (.840) showed sampling adequacy. Exploratory factor analysis of the principal component identified 2 factors which had eigenvalues of more than 1. Scree plot also revealed similar factors. These 2 factors together explained 53.1% of the variance. All items were loaded under 2 factors after varimax rotation. The validated Bangla version of the BARC-10 demonstrated high internal reliability and validity. It can potentially be applied in "recovery-oriented" deaddiction service.

Neurokinin B Administration Induces Dose Dependent Proliferation of Seminal Vesicles in Adult Rats.

BACKGROUND: Neurokinin B; an endogenous decapeptide, mediates its reproductive physiological actions through gonadotropin releasing hormone. Despite the potential role of Neurokinin B on seminal vesicles, its effects on seminal vesicles in adult male mammals remain elusive. We aimed to investigate the potentials of variable doses of Neurokinin B, its agonist and antagonist on histomorphology and expression of NK3R on seminal vesicles, and secretory activity of seminal vesicles in adult male rats. METHODS: Adult male Sprague Dawley rats (n=10 in each group) were administered intraperitoneally with Neurokinin B in three variable doses: 1 µg, 1 ηg and 10 ρg while, Senktide (Neurokinin B agonist) and SB222200 (Neurokinin B antagonist) in 1 µg doses consecutively for 12 days. After 12 days of peptide treatment, half of the animals (n=05) in each group were sacrificed while remaining half (n=05) were kept for another 12 days without any treatment to investigate treatment reversal. Seminal vesicles were dissected and excised tissue was processed for light microscopy, immunohistochemistry and estimation of seminal fructose levels. RESULTS: Treatment with Neurokinin B and Senktide significantly increased while SB222200 slightly decrease the seminal vesicles weight, epithelial height and seminal fructose levels as compared to control. Light microscopy revealed increased epithelial height and epithelial folding as compared to control in all Neurokinin B and Senktide treated groups while decreased in SB222200. Effects of various doses of Neurokinin B, Senktide and SB222200 on seminal vesicles weight, epithelial height, seminal fructose levels and histomorphology were reversed when rats were maintained without treatments. Immuno-expression of Neurokinin B shows no change in treatment and reversal groups. CONCLUSION: Continuous administration of Neurokinin B and Senktide effect positively while SB222200 have detrimental effects on cellular morphology, epithelial height and seminal fructose levels in seminal vesicles. Effects of peptide treatments depicted a reversal towards control group when rats were kept without any treatment.

Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortium.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. It remains unclear how MIS-C phenotypes vary across SARS-CoV-2 variants. We aimed to investigate clinical characteristics and outcomes of MIS-C across SARS-CoV-2 eras. Methods: We performed a multicentre observational retrospective study including seven paediatric hospitals in four countries (France, Spain, U.K., and U.S.). All consecutive confirmed patients with MIS-C hospitalised between February 1st, 2020, and May 31st, 2022, were included. Electronic Health Records (EHR) data were used to calculate pooled risk differences (RD) and effect sizes (ES) at site level, using Alpha as reference. Meta-analysis was used to pool data across sites. Findings: Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the Alpha era, 111 (19%) in the Delta era, and 104 (17%) in the Omicron era. Compared with patients admitted in the Alpha era, those admitted in the Delta era were younger (ES -1.18 years [95% CI -2.05, -0.32]), had fewer respiratory symptoms (RD -0.15 [95% CI -0.33, -0.04]), less frequent non-cardiogenic shock or systemic inflammatory response syndrome (SIRS) (RD -0.35 [95% CI -0.64, -0.07]), lower lymphocyte count (ES -0.16 × 109/uL [95% CI -0.30, -0.01]), lower C-reactive protein (ES -28.5 mg/L [95% CI -46.3, -10.7]), and lower troponin (ES -0.14 ng/mL [95% CI -0.26, -0.03]). Patients admitted in the Omicron versus Alpha eras were younger (ES -1.6 years [95% CI -2.5, -0.8]), had less frequent SIRS (RD -0.18 [95% CI -0.30, -0.05]), lower lymphocyte count (ES -0.39 × 109/uL [95% CI -0.52, -0.25]), lower troponin (ES -0.16 ng/mL [95% CI -0.30, -0.01]) and less frequently received anticoagulation therapy (RD -0.19 [95% CI -0.37, -0.04]). Length of hospitalization was shorter in the Delta versus Alpha eras (-1.3 days [95% CI -2.3, -0.4]). Interpretation: Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in Delta and Omicron eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time. Funding: None.

Effects of different progesterone levels on reproductive outcomes in assisted reproductive technologies: from molecular basis to treatment strategies.

PURPOSE: The aim of this narrative review is to offer an overview about the role of progesterone levels on pregnancy outcome in patients undergoing assisted reproductive technologies (ARTs). METHODS: A detailed computerized search of the literature was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science) to determine the importance of elevated progesterone levels at different stages of the cycle for pregnancy rates in the in vitro fertilization (IVF) cycle. Our review also provides information on the differences between elevated progesterone levels and their interpretation in normal and in poorly responding women. RESULTS: After careful evaluation, our search strategy yielded a total of 15 included articles, showing the possible factors that may have had an impact on the increased progesterone level before human chorionic gonadotropin (HCG) injection and the different thresholds above which the pregnancy rate was lower. Furthermore, increased progesterone on cycle day 2 or 3 could serve as a marker for increased progesterone in the late follicular phase, which is associated with a lower pregnancy rate. CONCLUSION: Despite the literature data that support the negative effect of elevated progesterone on fresh cycles, due to lack of randomized controlled trials, the value of measuring progesterone in daily practice is questionable. Available evidence supports the detrimental effect of elevated progesterone in different subgroups of women, although there is still the need for defining different thresholds and durations of high progesterone exposure. The need for various thresholds for different cohorts of women, the inter-assay variability is making this decision harder.

Chemoimmunotherapy vs. Immunotherapy for First Line Treatment of Advanced Non-small Cell Lung Cancer With a PD-L1 Expression ≥50% or ≥90.

BACKGROUND: Evidence about the comparative effectiveness of chemoimmunotherapy vs. immunotherapy alone in patients with advanced non-small cell lung cancer (aNSCLC) and high PD-L1 expression (≥50%) or very high PD-L1 expression (≥90%) is limited because of the lack of head-to-head clinical trials. OBJECTIVE: To compare survival in aNSCLC patients receiving first-line chemoimmunotherapy vs. immunotherapy in both the PD-L1 expression ≥50% or ≥90% subgroups, accounting for potential confounders that may influence physician decision-making. METHODS: This cohort study used a nationwide electronic health record derived database to identify newly diagnosed cases of aNSCLC patients with PD-L1 expression of ≥50% who initiated first-line systemic therapy between October 2016 and October 2021. The exposure of interest was first-line therapy with chemoimmunotherapy or immunotherapy among patients with PD-L1 expression ≥50% or ≥90%. Survival was assessed using Kaplan-Meier curves and Cox regression. Propensity score-based inverse probability of weighting (IPW) was used to control for confounding. Because of nonproportionality of hazards, we estimated hazard ratios over the first 6 months and after 6 months for the overall cohort, and over the first 12 months and after 12 months for a subgroup of persons with a PD-L1 expression ≥90%. RESULTS: We identified 3086 subjects who met inclusion criteria, of whom 32% received chemoimmunotherapy and 68% received immunotherapy alone. Chemoimmunotherapy was associated with no survival advantage vs. immunotherapy alone during the entire follow-up period (IPW-adjusted Hazard Ratio [aHR] 0.98, 95% CI, 0.86-1.12), but was associated with a survival benefit during the first 6 months (aHR 0.74, 95% CI, 0.61-0.90). Similarly, in the subgroup of patients with a PD-L1 expression ≥90%, chemoimmunotherapy was associated with no overall survival advantage during the entire follow-up period (aHR 0.99, 95% CI, 0.87-1.22), but was associated with a survival benefit during the first 12 months (aHR 0.74, 95% CI, 0.57-0.97). CONCLUSION: Chemoimmunotherapy was not associated with an overall benefit over immunotherapy alone, although was associated with an early survival advantage in both the overall cohort and the subgroup of patients with a PD-L1 expression ≥90%. Future studies should focus on identifying the characteristics of higher risk patients that may benefit from the addition of chemotherapy.

Effects of Oral Lipid-Based nutritional supplements on appetite, energy intake, and lipid profile of moderately underweight children.

Oral lipid-based nutritional supplements (LNS) are designed to ensure dietary adequacy and to improve malnourishment in children. Therefore, this study investigated the effects of 4 weeks of LNS on appetite, energy intake, and lipid profile of moderately underweight children (5-10 years old) with BMI-Z score between -2 and - 3 SDS, recruited in a single-blind randomized control trial. In addition to the regular dietary intake, fasting blood samples, anthropometric measurements, energy intake, and appetite responses were obtained before and after 4 weeks of LNS (535 kcal) or PLACEBO (92 kcal). After 4 weeks of supplementation mean energy intake (kcal) (p < .001), body weight (kg) (p < .001), BMI (kg/m2) (p < .01), mid-upper arm circumference (cm) (p < .01), total cholesterol (mg/dl) (p < .01) and fasting glucose (mg/dl) (p < .01) were raised significantly in the LNS group as compared to the PLACEBO group. No significant changes were detected in appetite responses (p > 0.05). In conclusion, LNS increases the overall energy intake, but does not affect the appetite but may induce hyperglycemia and hyperlipidemia.

The short-term impact of high energy nutritional supplements on energy balance in underweight primi-gravidae: A randomized controlled trial.

OBJECTIVE: To determine the impact of high-energy nutritional supplements on appetite, appetite regulators, energy intake and macronutrients level among underweight primigravidae. Methods: The single-blind randomised controlled trial was conducted from April 26, 2018, to August 10, 2019, in tertiary care hospitals of Khyber Pakhtunkhwa province of Pakistan, after approval from the ethics review committee of Khyber Medical University, Peshawar, and comprised underweight primigravidae who were randomly allocated to high energy nutritional supplement group A and placebo group B. Appetite questionnaires were filled and blood samples were obtained in fasting state, at 30, 60, 120, 210 and 270 minutes to measure blood glucose, insulin, peptide YY and cholecystokinin. Breakfast and lunch were served at 30 minutes and 210 minutes after supplementation, respectively. Data was analysed using SPSS 20. RESULTS: Of the 36 subjects, 19(52.8%) were in group A and 17(47.2%) were in group B. The overall mean age was 18.66 ± 2.5 years. Energy intake in group A was significantly higher than group B (p<0.001), and so were mean protein and fats (p<0.001). The subjective appetite perceptions for 'hunger' and 'desire to eat' were significantly lower (p<0.001) before lunch in group A. Plasma concentrations of appetite hormones corresponded to the appetite perceptions and were significantly higher in group A after breakfast and lunch for peptide YY, cholecystokinin and insulin compared to group B (p<0.001). CONCLUSIONS: High-energy nutritional supplement was found to have short-term suppressive effect on energy intake and appetite. Trial registration: ClinicalTrials.gov Identifier: ISRCTN 10088578. Registered on 27 March 2018. https://www.isrctn.com/ ISRCTN10088578.

Antibiotic spectrum index as an antimicrobial stewardship tool in paediatric intensive care settings.

OBJECTIVES: Antibiotic spectrum index (ASI) is a recently developed antimicrobial stewardship (AMS) tool that aims to classify antibiotics based on activity against clinically relevant bacterial pathogens. METHODS: We utilised ASI in a 2-year retrospective study between April 2019 and April 2021 in four paediatric intensive care units of a specialist UK children's hospital to quantify antibiotic use based on age, presence of immunosuppression and AMS input. We then compared ASI to days of therapy (DOT) to determine the utility of this AMS metric. We have made changes to Gerber's original ASI list and score of antibiotics to align with prescribing and resistance patterns in the UK. RESULTS: Median ASI/antibiotic days increased with age: for infants under 1 year of age 4.1 (IQR 4.0-4.3), for children 1-5 years 4.4 (IQR 4.0-4.6) and for children over 5 years 4.5 (IQR 4.1-4.6). Immunocompromised patients received much broader-spectrum antibiotics than immunocompetent patients throughout the whole study period. Patients who had AMS input had a higher ASI compared with those who did not throughout the whole period, likely due to more complex patients being discussed on such rounds. CONCLUSIONS: Our results show a complex picture of changing antibiotic consumption and prescribing in a large specialist paediatric hospital in the UK with a long-standing AMS programme before and throughout the COVID-19 pandemic. ASI shows less variability than DOT and can potentially be used to identify patient groups and time periods where broader-spectrum antibiotics are used to help guide further AMS efforts.

Association of vitamin D deficiency and vitamin D receptor (VDR) gene single-nucleotide polymorphism (rs7975232) with risk of preeclampsia.

BACKGROUND: Preeclampsia has a multifactorial-yet-elusive etiology. Recent reports suggest a link between preeclampsia and vitamin D (VD) metabolic axis. Genetic variations like single-nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) gene can alter the metabolic role of VD, which have been shown by several genetic association studies. However, there is discordance among these studies. OBJECTIVE: The current study aimed to investigate the association of VDR gene polymorphism (ApaI) and VD deficiency with risk of developing preeclampsia. PATIENTS AND METHOD: In this case-control study, 40 preeclamptic and 40 normotensive pregnant women were compared for VD status and VDR gene polymorphism. Serum 25-hydroxyvitamin-D [25(OH) D] level was determined by enzyme-linked immunosorbent assay (ELISA) and VDR gene polymorphism Apa1 was analyzed by Allele specific polymerase chain reaction (AS-PCR) using sequence specific primers. RESULTS: Serum levels of 25(OH) D were very low but comparable in both preeclamptic and normotensive pregnant women. The difference between the two groups were not statistically significant (p = .423). VDR gene polymorphism ApaI (rs7975232) was found not to have significant association with the risk of developing preeclampsia. The frequencies of wild genotype (GG) in preeclamptic and normotensive women were 27.5% and 22.5% respectively. A total of 25% of preeclamptic women had mutant homozygous genotype (TT) and 17.5% of normotensive women had mutant homozygous genotype. The frequency of mutant heterozygous genotype (GT) in preeclamptic patients was 47.5% and in normotensive women was 60%. The variation of wild and mutant genotypes between the two groups was not statistically significant (p > .05). CONCLUSION: This study showed that VDR gene polymorphism (ApaI) and VD deficiency are not associated with the risk of preeclampsia.

The effects of tobacco and cannabis use on semen and endocrine parameters in infertile males.

Substances such as tobacco and cannabis can negatively modulate seminal parameters and sex hormones and lead to fertility problems in males. The present study aimed to determine the effect of cigarettes, dipping tobacco, and cannabis on semen parameters and sex hormones in infertile males. A total of 160 infertile healthy participants (cigarette smokers n = 40, dipping tobacco users n = 40, cannabis users n = 40 and infertile controls n = 40) were included in the study. Fasting blood samples were collected from all the participants using the aseptic technique, and semen samples were collected by masturbation following sexual abstinence of 2-7 days. The levels of serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined using ELISA. The serum level of FSH was significantly higher in cannabis users relative to the control group (p = 0.043). A mild non-significant decrease in sperm count, serum LH and testosterone levels were observed in all drug users compared to controls. In conclusion, chronic use of tobacco and cannabis mildly modulates semen and hormonal parameters in infertile males.

The Impact of Vaping on Primary Spontaneous Pneumothorax Outcomes.

INTRODUCTION: Cigarette smoking is associated with primary spontaneous pneumothorax (PSP). Electronic cigarettes (E-cigarettes) are touted as a healthier alternative to cigarettes; however, the impact E-cigarette use has on PSP management is not known. The goal of this study was to determine if E-cigarette use is associated with inferior outcomes after PSP, compared to never smokers and cigarette smokers. METHODS: We conducted a retrospective cohort study of patients in a large tertiary care hospital system in an urban area who presented with PSP from September 2015 through February 2019. Primary spontaneous pneumothorax patients were identified from the institutional Society of Thoracic Surgeon (STS) database. Patients with pneumothoraces from traumatic, iatrogenic, and secondary etiologies were excluded. Baseline clinical and demographic data and outcomes including intervention(s) required, length of stay, and recurrence were evaluated. RESULTS: Identified were 71 patients with PSP. Seventeen (24%) had unverifiable smoking history. Of the remaining, 7 (13%) currently vaped, 27(50%) currently smoked cigarettes, and 20(37%) were never smokers. Mean age was 33 years; 80% male. All vapers required tube thoracostomy vs 74% of current smokers and 75% of never smokers. Vaping was associated with increased odds of recurrence compared to never smokers (OR 2.00, 95% CI 0.35,11.44). Vapers had the shortest median time to recurrence after initial hospitalization (10 d[4,18] v 20 d[5,13] cigarette smokers v 27 d[13 275] never smokers, P < .001). CONCLUSION: Vaping may complicate PSP outcomes. As vaping use increases, especially among adolescents, it is imperative that the manner of tobacco use is documented and considered when caring for patients, especially those with pulmonary problems.

Treatment with combined resveratrol and myoinositol ameliorates endocrine, metabolic alterations and perceived stress response in women with PCOS: a double-blind randomized clinical trial.

PURPOSE: The present study aimed to assess whether treatment with combined resveratrol and myoinositol is more effective in ameliorating the altered parameters associated with PCOS when compared to the combined metformin and pioglitazone therapy. METHOD: One hundred and ten obese, oligo-anovulatory PCOS women, aged 20-35 years were randomly assigned into two treatment arms. Participants in arm-1 (n = 55), received combination of metformin and pioglitazone (500 mg and 15 mg, respectively), twice daily, while those in arm-2 (n = 55) received combination of resveratrol and myoinositol (1000 mg and 1000 mg, respectively) twice daily for 12 weeks. Evaluations performed at baseline were repeated after 3 months of therapy. The endocrine and metabolic derangements were assessed by measuring serum levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), adiponectin and insulin using ELISA. Cohen's perceived stress scale (PSS) was employed as a subjective measure of stress. RESULTS: Pre-treatment PCOS women in both the arms (arm-1 and arm-2) had remarkably elevated serum testosterone and insulin concentrations, low serum adiponectin and high perceived stress response scores. The treatment reduced the altered endocrine indices in arm-2 (resveratrol and myoinositol) participants, manifested by statistically significant reduction in serum testosterone level (p = 0.001) and notably increased serum adiponectin level (p = 0.001). Interestingly, the hormonal profile, including serum LH and FSH levels also decreased (p < 0.001) along with a marked reduction in the ovarian volume (p = 0.001) in arm-2 participants. There was a significant reduction in weight (<0.001), BMI (p < 0.001) and an improvement in waist-hip ratio (p < 0.001) in arm-2 participants compared to arm-1 group. The PSS scores of the arm-2 subjects improved significantly (p < 0.001) whereas, the Ferrimen-Gallwey score was improved in both the arms (arm-1 and arm-2; p = 0.010 and 0.008 respectively) however, the change was highly significant in arm-2. Interestingly, the menstrual regularity was 81.4% in arm-2 while 18.2% in arm-1. We conclude that the therapeutic intervention with combined resveratrol and myoinositol is more effective in ameliorating altered endocrine, metabolic indices and stress burden and could be of clinical importance in high risk group of obese, oligo-anovulatory married PCOS affected women. TRIAL REGISTRATION: ClinicalTials.gov Trial No: NCT04867252. Registered 24 April, 2021, https://clinicaltrials.gov/ct2/show/NCT04867252.

Temporal Trends in Internal vs. External Referrals for TAVR in a Large Academic Center: Patients Characteristics and Outcomes.

Background: Since transcatheter aortic valve replacement (TAVR) first became approved for inoperable patients followed by high, intermediate-, and low-risk patients, referrals to TAVR centers have rapidly increased. The purpose of this study was to investigate referral patterns to a large academic TAVR center in the state of North Carolina and evaluate differences between externally and internally referred patients. Methods: Data for all patients who underwent TAVR at our institution between November 2014 and March 2020 were pulled from the Transcatheter Valve Therapy Registry. The electronic medical record was used to determine the referral source. The descriptive statistical analysis was performed using Excel (Microsoft, Redmond, Washington). Results: 491 patients underwent TAVR at our institution between November 2014 and March 2020. Half of the patients were referred by a cardiologist within the same health system (N = 250, 50.9%). Other referral sources included a cardiologist external to the health system (N = 210, N = 42.8%) and a surgeon or proceduralist (such as urologist, surgeon, or gastroenterologist) during the workup for another procedure (N = 26, 5.3%). Over time, there was a trend toward an increasing proportion of patients referred by a cardiologist external to our system, but this trend did not reach statistical significance (20.0% in 2014, 29.2% in 2015, 30.7% in 2016, 53.0% in 2017, 36% in 2018, 48.4% in 2019, and 56.8% in 2020, p=0.06 using the Mann-Kendall trend test). Externally referred patients were less likely to have private insurance and were more likely to have a reduced ejection fraction and had a higher mean gradient across the valve. Postprocedure, externally referred patients were more likely to have the procedure under moderate sedation and less likely to be discharged home. Conclusions: This study presents the referral pattern to a large TAVR center in North Carolina. Over time, there was an increase in external referrals suggesting that TAVR is increasingly adopted as an important component of the management of aortic valve stenosis. Internally and externally referred patients have differences in baseline demographic and clinical characteristics which may have an impact on clinical outcomes.

The Translational Role of miRNA in Polycystic Ovary Syndrome: From Bench to Bedside-A Systematic Literature Review.

MicroRNAs (miRNAs) are small, non-coding RNAs that are essential for the regulation of post-transcriptional gene expression during tissue development and differentiation. They are involved in the regulation of manifold metabolic and hormonal processes and, within the female reproductive tract, in oocyte maturation and folliculogenesis. Altered miRNA levels have been observed in oncological and inflammatory diseases, diabetes or polycystic ovary syndrome (PCOS). Therefore, miRNAs are proving to be promising potential biomarkers. In women with PCOS, circulating miRNAs can be obtained from whole blood, serum, plasma, urine, and follicular fluid. Our systematic review summarizes data from 2010-2021 on miRNA expression in granulosa and theca cells; the relationship between miRNAs, hormonal changes, glucose and lipid metabolism in women with PCOS; and the potential role of altered miRNAs in fertility (oocyte quality) in PCOS. Furthermore, we discuss miRNAs as a potential therapeutic target in PCOS and as a diagnostic marker for PCOS.

Association Between Survival and Very High Versus High PD-L1 Expression in Patients Receiving Pembrolizumab as First-line Treatment for Advanced Non-Small Cell Lung Cancer.

BACKGROUND: A prior study found that, among advanced non-small cell lung cancer (aNSCLC) patients with PD-L1 expression 50% to 100% receiving immunotherapy as monotherapy, PD-L1 expression ≥ 90% was associated with longer survival. We sought to replicate this finding using real-world data from community oncology practices across the US. METHODS: Retrospective cohort study of aNSCLC patients who initiated pembrolizumab monotherapy for first line and had a PD-L1 expression ≥ 50% using a nationwide, deidentified longitudinal electronic health record-derived real-world database. The exposure of interest was very high PD-L1 expression, which was defined as ≥ 90%, compared to high PD-L1 expression, defined as 50% to 89%. The primary outcome was overall survival, measured from initiation of pembrolizumab to date of death, with censoring at last healthcare encounter. Multiple imputation was used to impute missing covariates. Propensity score-based inverse probability weighting (IPW) was used to address confounding in Kaplan-Meier curves and Cox proportional hazard regression models. RESULTS: The cohort included 1952 aNSCLC patients receiving first-line pembrolizumab monotherapy. Half of cohort members were female, median age was 73 years (interquartile range, 65-80), 71% had non-squamous histology, 94% had a history of smoking, and 46% had very high PD-L1 expression. Median overall survival in the propensity score-weighted sample was 15.84 months for very high PD-L1 expression and 12.72 months for high PD-L1 expression. Having a very high PD-L1 expression was associated with lower hazard of mortality (IPW hazard ratio 0.79, 95% CI 0.69-0.91). CONCLUSIONS: In this large national US cohort, patients with very high PD-L1 expression (≥ 90%) aNSCLC receiving first-line pembrolizumab experienced better median survival than those with high PD-L1 expression (50% to 89%).

QoS-Aware Cost Minimization Strategy for AMI Applications in Smart Grid Using Cloud Computing.

Cloud computing coupled with Internet of Things technology provides a wide range of cloud services such as memory, storage, computational processing, network bandwidth, and database application to the end users on demand over the Internet. More specifically, cloud computing provides efficient services such as "pay as per usage". However, Utility providers in Smart Grid are facing challenges in the design and implementation of such architecture in order to minimize the cost of underlying hardware, software, and network services. In Smart Grid, smart meters generate a large volume of different traffics, due to which efficient utilization of available resources such as buffer, storage, limited processing, and bandwidth is required in a cost-effective manner in the underlying network infrastructure. In such context, this article introduces a QoS-aware Hybrid Queue Scheduling (HQS) model that can be seen over the IoT-based network integrated with cloud environment for different advanced metering infrastructure (AMI) application traffic, which have different QoS levels in the Smart Grid network. The proposed optimization model supports, classifies, and prioritizes the AMI application traffic. The main objective is to reduce the cost of buffer, processing power, and network bandwidth utilized by AMI applications in the cloud environment. For this, we developed a simulation model in the CloudSim simulator that uses a simple mathematical model in order to achieve the objective function. During the simulations, the effects of various numbers of cloudlets on the cost of virtual machine resources such as RAM, CPU processing, and available bandwidth have been investigated in cloud computing. The obtained simulation results exhibited that our proposed model successfully competes with the previous schemes in terms of minimizing the processing, memory, and bandwidth cost by a significant margin. Moreover, the simulation results confirmed that the proposed optimization model behaves as expected and is realistic for AMI application traffic in the Smart Grid network using cloud computing.

Very high PD-L1 expression as a prognostic indicator of overall survival among patients with advanced non-small cell lung cancer receiving anti-PD-(L)1 monotherapies in routine practice.

PURPOSE: Programmed death or ligand-1 (PD-(L)1) pathway inhibitors confer improved survival as the first-line treatment for advanced non-small cell lung cancer (aNSCLC) in patients with PD-L1 expression (PD-L1 + e ≥ 50%) compared to platinum-doublet chemotherapy and have become a standard therapy. Some recent evidence suggests that among aNSCLC patients with PD-L1 + e of ≥50% receiving pembrolizumab monotherapy, very high levels of PD-L1 + e (≥90%) may be associated with better outcomes. We sought to assess whether very high PD-L1 + e (≥90%) compared to high PD-L1 + e (50%-89%) is associated with an overall survival benefit in aNSCLC patients receiving anti-PD-(L)1 monotherapies. METHODS: We conducted a single-site retrospective cohort study of aNSCLC patients who initiated PD-(L)1 inhibitor monotherapy as the first-line treatment from October 24, 2016, to August 25, 2021, and had a PD-L1 + e ≥ 50%. The primary outcome was overall survival, measured from the start of the first-line PD-(L)1 inhibitor monotherapy (index date) to date of death or last confirmed activity prior to the cohort exit date. Propensity score-based inverse probability weighting (IPW) was used to control for confounding in Kaplan-Meier curves and Cox proportional hazard regression analysis. RESULTS: One hundred sixty-six patients with aNSCLC receiving PD-(L)1 inhibitor monotherapy met inclusion criteria. 54% were female, 90% received pembrolizumab, median age was 68 years, 70% had non-squamous cell carcinoma, 94% had a history of smoking, 29% had a KRAS mutation, and 37% had very high PD-L1 + e. Unweighted covariates at cohort entry were similar between groups (absolute standardized mean differences [SMDs] <0.1) except for race (SMD = 0.2); age at therapy initiation (SMD = 0.13); smoking status (SMD = 0.13), and BRAF mutation status (SMD = 0.11). After weighting, baseline covariates were well balanced (all absolute SMDs <0.1). In the weighted analysis, having a very high PD-L1 + e was associated with lower mortality (weighted hazard ratio 0.57, 95% CI 0.36-0.90) and longer median survival: 3.85 versus 1.49 years. CONCLUSIONS: Very high PD-L1 + e (≥90%) was associated with an overall survival benefit over high PD-L1 + e (50%-89%) in patients receiving the first-line PD-(L)1 inhibitor monotherapy in a model controlling for potential confounders. These findings should be confirmed in a larger real-world data set.

Outcome of angiotensin receptor-neprilysin inhibitor on anxiety and depression in heart failure with reduced ejection fraction vs. heart failure with preserved ejection fraction.

Objective: In patients with heart failure (HF), anxiety and depression are commonly observed and confer an adverse outcome. The first-in-class member of angiotensin receptor-neprilysin inhibitor (ARNI), sacubitril/valsartan has been demonstrated to improve functional class and decrease mortality in patients with heart failure with reduced ejection fraction (HFrEF) and reduce the readmission of heart failure with preserved ejection fraction (HFpEF). However, its effects on anxiety and depression levels remain unknown.Methods: Sacubitril/valsartan was started on 764 symptomatic patients with HFrEF and HFpEF who were receiving guideline-directed medical therapy (GDMT) with an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). Patients were evaluated using Hamilton's depression rating scale (HDRS) and the hospital anxiety and depression scale (HADS) for their levels of depression and anxiety before and after treatment at a six-month follow-up.Results: A significant reduction in HADS and HDRS scores was observed in patients with HFrEF (9.7 ± 1.3 to 6.4 ± 0.7, p = 0.032 and 19.2 ± 2.2 to 8.9 ± 1.6, p < 0.001, respectively) compared with HFpEF (p = 0.161 and 0.273, respectively). The six-minute walk test (6-MWT) significantly increased HFrEF from 195 ± 68 to 321 ± 97 (p < 0.001). There was an overall improvement in the functional class of all patients.Conclusion: Patients with HFrEF have the additional advantage of using sacubitril/valsartan in the form of decreased anxiety and depression symptoms in addition to an improvement in functional class. However, patients with HFpEF did not exhibit significant improvement in their psychological scores.