Fluoroquinolones: Neurological Complications and Side Effects in Clinical Practice.

Fluoroquinolones, a popular antibiotic class that inhibits nucleic acid synthesis of bacteria by disrupting the activity of the enzyme's topoisomerase IV and DNA gyrase, are used to treat bacterial infections. However, the widespread use of these drugs has allowed for the development of microbial resistance in recent years. Quinolones also have many clinically relevant side effects, including psychosis, confusion, seizures, headaches, dizziness, and nausea. Common side effects include tendinitis, myopathy, depression, and fatigue. Cardiovascular side effects include increased risk of aortic aneurysm, aortic dissection, and QT interval prolongation. Overall, quinolones can be an effective choice for treating bacterial infections. Still, the side effect profile and decreased efficacy secondary to microbial resistance no longer make the quinolone class an ideal choice for many types of infection. A better understanding of the role of quinolone-mediated or neurological damage, cardiovascular impairment, and musculoskeletal involvement is imperative to determine the risks/benefits for the clinician.

Stevens-Johnson Syndrome From Combined Allopurinol and Angiotensin-Converting Enzyme Inhibitors: A Narrative Review.

Stevens-Johnson syndrome (SJS) is a severe and potentially debilitating skin reaction frequently related to medication use. Allopurinol and angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed medications for prevalent health conditions worldwide, and their interaction associated with SJS warrants further investigation. A comprehensive literature search was performed to investigate cases as studies related to SJS occurring in patients with concomitant use of allopurinol and ACE inhibitors. We identified case reports and studies detailing hypersensitivity reactions, including SJS, attributed to a combination of allopurinol and ACE inhibitors. Despite the drug-drug interactions or lack thereof seen in patient populations, there is no definitive evidence of a pharmacokinetic interaction between allopurinol and ACE inhibitors. We were only able to find one case report specifically detailing SJS in a patient on combined ACE inhibitors and allopurinol. While the exact mechanism of the interaction is unclear, those reported cases of severe hypersensitivity reactions suggest a previous history of impaired renal function as a predisposing factor in the development of SJS. The potential risk of SJS with coadministration of ACE inhibitors and allopurinol is a drug-drug interaction that physicians should be aware of. This topic requires additional attention to determine if this drug combination should be avoided entirely in certain patients.

Association between weight gain following smoking cessation and development of hypertension in the future.

Although quitting smoking lowers the risk of developing chronic conditions, it usually leads to weight gain. Literature on the association between weight gain after quitting smoking and the future development of hypertension is scarce. Among 234 596 individuals who visited our health center, 856 who had quit smoking for whom data were available at least 6 years after smoking cessation were included. We evaluated changes in blood pressure and antihypertensive drug prescription rate at 1 and 6 years after smoking cessation. We also compared weight and blood pressure between the smoking cessation and continued smoking groups after 6 years. Multiple regression analyses were performed to identify predictors of changes in systolic and diastolic blood pressures using covariates affecting blood pressure. Since a median weight gain of 1.8 kg was observed at 1 year after smoking cessation, we divided the participants into high and low-weight gain groups. No significant intergroup difference in the antihypertensive drug prescription rate was observed after 6 years. The high weight gain group showed significant increases in systolic and diastolic blood pressures after 6 years. Multiple regression analyses revealed that systolic blood pressure was affected by age and high weight gain, while diastolic blood pressure was affected by high weight gain. Our findings suggest that weight gain following smoking cessation leads to blood pressure elevation: the smoking cessation group gained more weight and had higher blood pressure than the continued smoking group. Therefore, weight loss guidance may be useful for individuals who want to quit smoking. Participants in the high weight gain group showed significant increases in systolic and diastolic blood pressures at 6 years after smoking cessation that were significantly different from those observed in participants in the low weight gain group and the continued smoking group.

Association between anthropometric indices and 5-year hypertension incidence in the general Japanese population.

No existing reports demonstrate the association between anthropometric indices (body mass index, waist circumference, body roundness index, a body shape index) and hypertension according to sex and age in the general Japanese population. This retrospective analysis involved individuals aged 30-69 years who underwent annual medical checkups at Kagoshima Koseiren Hospital in 2005-2019, and who did not meet hypertension criteria at baseline. The outcome was hypertension incidence after 5 years, and its association with baseline anthropometric indices was evaluated using multivariable logistic regression analysis by sex and age. In 41,902 participants (age 52.3 ± 10.2 years, 47.7% men), 7622 individuals (18.2%) developed hypertension after 5 years. Body mass index, waist circumference, and body roundness index were significantly associated with the development of hypertension in both men and women across all age categories from 30 s to 60 s. In the population with a body mass index <25 kg/m2, waist circumference and body roundness index were significantly associated with hypertension after 5 years. A body shape index was significantly associated with the development of hypertension in men in their 40 s and 50 s but not in women of any age group. The area under the curve values were lower for a body shape index than for body mass index, waist circumference, and body roundness index in both men and women of all age groups. A body shape index was not a stronger indicator for 5-year hypertension incidence than body mass index, waist circumference, or body roundness index in both men and women across age groups from their 30s-60 s. The results of this study will help to more efficiently identify populations at high risk of developing hypertension and provide preventive interventions. A total of 41,902 participants from health checkup programs were stratified by gender and age to investigate the association between baseline anthropometric indices and hypertension incidence over a 5-year period. BMI, WC, and BRI were almost equally effective and showed a better association with risk of developing hypertension in women and young adults compared to men and old adults. Conversely, ABSI showed no greater association than BMI or WC in any age group in both men and women. ABSI, a body shape index; AUC, area under the curve from receiver operating characteristic curve analysis; BMI, body mass index; BRI, body roundness index; WC, waist circumference.

Treatment modalities for infantile spasms: current considerations and evolving strategies in clinical practice.

Infantile spasms, newly classified as infantile epileptic spasm syndrome (IESS), occur in children under 2 years of age and present as an occur as brief, symmetrical, contractions of the musculature of the neck, trunk, and extremities. When infantile spasms occur with a concomitant hypsarrhythmia on electroencephalogram (EEG) and developmental regression, it is known as West Syndrome. There is no universally accepted mainstay of treatment for this condition, but some options include synthetic adrenocorticotropic hormone (ACTH), repository corticotropin injection (RCI/Acthar Gel), corticosteroids, valproic acid, vigabatrin, and surgery. Without effective treatment, infantile spasms can cause an impairment of psychomotor development and/or cognitive and behavioral functions. The first-line treatment in the USA is ACTH related to high efficacy for cessation of infantile spasms long-term and low-cost profile. Acthar Gel is a repository corticotropin intramuscular injection that became FDA-approved for the treatment of IESS in 2010. Though it is believed that ACTH, Acthar Gel, and corticosteroids all work via a negative feedback pathway to decrease corticotropin-releasing hormone (CRH) release, their safety and efficacy profiles all vary. Vigabatrin and valproic acid are both anti-seizure medications that work by increasing GABA concentrations in the CNS and decreasing excitatory activity. Acthar Gel has been shown to have superior efficacy and a diminished side effect profile when compared with other treatment modalities.

Sex-specific associations between serum uric acid levels and risk of hypertension for different diagnostic reference values of high blood pressure.

The association between uric acid (UA) and hyperuricemia with 5-year hypertension incidence using different blood pressure (BP) diagnostic references in men and women without cardiometabolic diseases is unknown. We used the checkup data from Kagoshima Kouseiren Hospital. All participants with hypertension or on BP medication, diabetes, dyslipidemia, obesity, estimated glomerular filtration rate<60 ml/min/1.73m2, metabolic syndrome, history of gout, and UA-lowering medication were excluded. UA was categorized into sex-specific quartiles and hyperuricemia was defined as UA > 7 mg/dl in men and UA > 6 mg/dl in women. We performed multivariate logistic regression to assess the effects of UA on hypertension development. The 5-year hypertension incidence was defined as subsets of BP ≥ 140/90 mmHg in cohort 1 and BP ≥ 130/80 mmHg in cohort 2. The study enrolled 21,443 participants (39.8%, men) in cohort 1 and 15,245 participants (36.5%, men) in cohort 2. The incidence of hypertension in cohorts 1 and 2 over 5 years was 16.3% and 29.7% in men and 10.9% and 21.4% in women, respectively. When comparing the fourth to the first UA quartile, there was an association with hypertension in men in cohort 1, with odds ratio (OR): 1.36 (95% confidence interval [CI], 1.13-1.63, p < 0.01) and cohort 2, OR: 1.31 (95%CI, 1.09-1.57, p < 0.01), respectively, but not in women. Additionally, an association between hyperuricemia and hypertension was observed in men only in cohort 1, with OR: 1.23 (95%CI, 1.07-1.42, p = 0.02), and in women in cohort 2, OR: 1.57 (95%CI, 1.14-2.16, p < 0.01). The effect of UA on the development of hypertension is influenced by sex and incidence differs with the BP reference used. Uric acid effect on the development of hypertension is affected by sex and incidence differs with the BP reference used.

Infigratinib for the Treatment of Metastatic or Locally Advanced Cholangiocarcinoma With Known FGFR2 Gene Fusions or Rearrangements.

Cholangiocarcinoma (CCA) is an aggressive and diverse malignancy with a poor prognosis. Related to a typical indolent course of progression, most cases of CCA are metastatic or locally advanced at the time of presentation. For patients with nonresectable tumors or metastatic disease, the mainstay of treatment is comprehensive with combination chemotherapy. The first-line chemotherapeutic combination for the treatment of CCA are cisplatin and gemcitabine-based chemotherapies. However, many locally advanced and progressive CCA cases are refractory to first-line management. Within the past few years, the increase in the incidence of metastatic CCA and its poor prognosis has brought to light the need for novel therapeutic approaches to treatment. With advancements in next-generation genome sequencing, multiple molecular pathways have been identified in the pathogenesis of CCA and have shown great potential as alternative treatments in cases of CCA refractory to surgical resection. FGFR2 fusions or rearrangements have been identified in 10-16% of all intrahepatic CCA and are thought to serve as a pathway of resistance for a number of nonresectable and refractory cases of cholangiocarcinoma. A novel therapeutic agent that has been discussed is infigratinib, a selective, ATP-competitive inhibitor of fibroblast growth factor receptor 2 (FGFR2). In a phase 1 trial, infigratinib showed a safe profile and showed remarkable clinical efficacy in advanced CCA with FGFR2 fusions or rearrangements in phase II trials. As of May 2021, the Food and Drug Administration (FDA) approved infigratinib for CCA largely based on tumor response and duration of response. As of 2021, infigratinib, futibatinib, and pemigatinib, similar novel selective FGFR inhibitors, have been approved by the FDA for the treatment of locally advanced or metastatic CCA harboring FGFR2 gene mutations. The present investigation reviews the development of infigratinib in particular and its clinical efficacy compared to other available treatment options for cholangiocarcinoma. While the side effect profile of infigratinib is minimal, particularly GI side effects, when compared with futibatinib and pemigatinib, the overall response rate (ORR) and median overall survival (mOS) for infigratinib (ORR=23.1%, mOS=3.8 months) was significantly lower than futibatinib (ORR=35.8%, mOS=21.1 months) and pemigatinib (ORR=35.5%, mOS=21.1 months). While there is ample promise for the use of infigratinib as molecular-directed therapy in the treatment of CCA harboring FGFR2 mutations, there is an appropriate concern for patient-acquired resistance. The heterogeneous nature of FGFR mutations and the emergence of different resistance mechanisms emphasize a need for more agents to inhibit FGFR rearrangements effectively.

Comparative outcomes among inlay grafted incised plate, onlay preputial flap and tubularized incised plate urethroplasty for the repair of distal penile hypospadias with a narrow urethral plate.

PURPOSE: We conducted this study, comparing the outcomes among Transverse Onlay Island Flap, inlay grafted incised plate and our previous records of tubularized incised plate urethroplasty (TIPU) in patients with narrow urethral plates, aiming to determine which method of repair provides a good outcome. METHODS: This hybrid study included two datasets. The first from a prospective randomized study evaluating outcomes of two treatment modalities; Inlay graft and only flap for distal hypospadias with shallow urethral plate with 80 patients (40 patients in each group) included, the second based on our previous records of TIPU in 40 patients with distal primary hypospadias with narrow urethral plate. RESULTS: The success rate in inlay graft urethroplasty group (n = 40) was 87.5%; glandular dehiscence occurred in one case (2.5%), fistulas occurred in 2 cases (5%), and narrow meatus occurred in two cases (5%). Success rate in onlay flap urethroplasty group (n = 40) was 82.5%; glandular dehiscence occurred in two cases (5%), fistulas occurred in two cases (5%), and narrow meatus occurred in three cases (7.5%). TIPU group (n = 40) had success rate of 62.5%; glandular dehiscence occurred in eight cases (20%), fistulas occurred in five cases (12.5%), and narrow meatus occurred in seven cases (17.5%), with five cases exhibiting both narrow meatus with fistula. CONCLUSION: Inlay graft and onlay flap urethroplasty for repair of distal penile hypospadias with narrow urethral plate had higher success rate and fewer complications than traditional TIPU. Moreover, operative time was shorter in TIPU.

J-shaped Association between Serum Uric Acid Levels and the Prevalence of a Reduced Kidney Function: A Cross-Sectional Study Using Japanese Health Examination Data.

Objective While an association between a reduced kidney function and hyperuricemia has been reported, its association with hypouricemia is not well understood. The present study therefore investigated this association. Methods Using a large Japanese health examination dataset, we performed a multivariable logistic regression analysis to assess the association between serum uric acid (SUA) levels and a reduced kidney function. The covariates included the age, body mass index, alcohol intake, and the presence of hypertension, dyslipidemia, or diabetes. Patients This study included 227,672 patients (104,854 men; 46.1%), and the analyses were performed separately for men and women. The patients were classified into 5 groups: hypouricemia (SUA ≤2.0 mg/dL) (1st) and four other (2nd-5th) groups with SUA levels of ≤2.0, 2.1-5.1, 5.2-5.9, 6.0-6.8, ≥6.9 mg/dL in men and ≤2.0, 2.1-3.7, 3.8-4.4, 4.5-5.1, ≥5.2 mg/dL in women, respectively. Results The characteristics of the study population were as follows: men, age 55.9±14.9 years old, SUA 5.9±1.3 mg/dL, estimated glomerular filtration rate (eGFR) 80.0±17.2 mL/min/1.73 m2, and a reduced kidney function (eGFR<60.0 mL/min/1.73 m2) 9.4%; women, age 57.3±15.0 years old, SUA 4.5±1.1 mg/dL, eGFR 81.2±18.0 mL/min/1.73 m2, and a reduced kidney function 9.4%. Compared with the 2nd group, the other 4 groups groups had a significantly higher prevalence of a reduced kidney function [odds ratio (OR), 2.58; 95% confidence interval (CI), 1.64-4.06 in men; OR, 1.66; 95% CI, 1.16-2.39 in women]. Conclusion The prevalence of a reduced kidney function was high in both men and women in the hypouricemia and high-SUA groups. SUA levels and the prevalence of a reduced kidney function showed a J-shaped association.

Predicting left ventricular hypertrophy from the 12-lead electrocardiogram in the UK Biobank imaging study using machine learning.

Aims: Left ventricular hypertrophy (LVH) is an established, independent predictor of cardiovascular disease. Indices derived from the electrocardiogram (ECG) have been used to infer the presence of LVH with limited sensitivity. This study aimed to classify LVH defined by cardiovascular magnetic resonance (CMR) imaging using the 12-lead ECG for cost-effective patient stratification. Methods and results: We extracted ECG biomarkers with a known physiological association with LVH from the 12-lead ECG of 37 534 participants in the UK Biobank imaging study. Classification models integrating ECG biomarkers and clinical variables were built using logistic regression, support vector machine (SVM) and random forest (RF). The dataset was split into 80% training and 20% test sets for performance evaluation. Ten-fold cross validation was applied with further validation testing performed by separating data based on UK Biobank imaging centres. QRS amplitude and blood pressure (P < 0.001) were the features most strongly associated with LVH. Classification with logistic regression had an accuracy of 81% [sensitivity 70%, specificity 81%, Area under the receiver operator curve (AUC) 0.86], SVM 81% accuracy (sensitivity 72%, specificity 81%, AUC 0.85) and RF 72% accuracy (sensitivity 74%, specificity 72%, AUC 0.83). ECG biomarkers enhanced model performance of all classifiers, compared to using clinical variables alone. Validation testing by UK Biobank imaging centres demonstrated robustness of our models. Conclusion: A combination of ECG biomarkers and clinical variables were able to predict LVH defined by CMR. Our findings provide support for the ECG as an inexpensive screening tool to risk stratify patients with LVH as a prelude to advanced imaging.

Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review.

BACKGROUND: Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most common complication of IEIs and children can acquire coronavirus disease 2019 (COVID-19) even when protective measures are taken. OBJECTIVES: To estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with IEIs and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with IEIs with COVID-19 illness. METHODS: For this systematic review, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline for studies on the development of COVID-19 in children with IEIs, published from December 1, 2019 to February 28, 2023, with English language restriction. RESULTS: Of the 1095 papers that were identified, 116 articles were included in the systematic review (73 case report, 38 cohort 4 case-series and 1 case-control studies). Studies involving 710 children with IEIs with confirmed COVID-19 were analyzed. Among all 710 IEIs pediatric cases who acquired SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 119, 16.8%), intubated and placed on mechanical ventilation (n = 87, 12.2%), suffered acute respiratory distress syndrome (n = 98, 13.8%) or died (n = 60, 8.4%). Overall, COVID-19 in children with different IEIs patents resulted in no or low severity of disease in more than 76% of all included cases (COVID-19 severity: asymptomatic = 105, mild = 351, or moderate = 88). The majority of children with IEIs received treatment for COVID-19 (n = 579, 81.5%). Multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 in children with IEIs occurred in 103 (14.5%). Fatality in children with IEIs with COVID-19 was reported in any of the included IEIs categories for cellular and humoral immunodeficiencies (n = 19, 18.6%), immune dysregulatory diseases (n = 17, 17.9%), innate immunodeficiencies (n = 5, 10%), bone marrow failure (n = 1, 14.3%), complement deficiencies (n = 1, 9.1%), combined immunodeficiencies with associated or syndromic features (n = 7, 5.5%), phagocytic diseases (n = 3, 5.5%), autoinflammatory diseases (n = 2, 3%) and predominantly antibody deficiencies (n = 5, 2.5%). Mortality was COVID-19-related in a considerable number of children with IEIs (29/60, 48.3%). The highest ICU admission and fatality rates were observed in cases belonging to cellular and humoral immunodeficiencies (26.5% and 18.6%) and immune dysregulatory diseases (35.8% and 17.9%) groups, especially in children infected with SARS-CoV-2 who suffered severe combined immunodeficiency (28.6% and 23.8%), combined immunodeficiency (25% and 15%), familial hemophagocytic lymphohistiocytosis (40% and 20%), X-linked lymphoproliferative diseases-1 (75% and 75%) and X-linked lymphoproliferative diseases-2 (50% and 50%) compared to the other IEIs cases. CONCLUSION: Children with IEIs infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the immunocompetent pediatric populations. Underlying immune defects does seem to be independent risk factors for severe SARS-CoV-2 infection in children with IEIs, a number of children with SCID and CID were reported to have prolonged infections-though the number of patients is small-but especially immune dysregulation diseases (XLP1 and XLP2) and innate immunodeficiencies impairing type I interferon signalling (IFNAR1, IFNAR2 and TBK1).

Eyes and the heart: what a clinician should know.

The eye is prone to various forms of afflictions, either as a manifestation of primary ocular disease or part of systemic disease, including the cardiovascular system. A thorough cardiovascular examination should include a brief ocular assessment. Hypertension and diabetes, for example, would present with retinopathy and dyslipidaemia would present with corneal arcus. Multisystem autoimmune diseases, such as Graves' disease, rheumatoid arthritis and sarcoidosis, would present with proptosis, episcleritis and scleritis, respectively. Myasthenia gravis, while primarily a neuromuscular disease, presents with fatigable ptosis and is associated with Takotsubo cardiomyopathy and giant cell myocarditis. Connective tissue diseases such as Marfan syndrome, which commonly presents with aortic root dilatation, would be associated with ectopia lentis and myopia. Wilson's disease, which is associated with arrhythmias and cardiomyopathies, would present usually with the characteristic Kayser-Fleischer rings. Rarer diseases, such as Fabry disease, would be accompanied by ocular signs such as cornea verticillata and such cardiac manifestations include cardiac hypertrophy as well as arrhythmias. This review examines the interplay between the eye and the cardiovascular system and emphasises the use of conventional and emerging tools to improve diagnosis, management and prognostication of patients.

Development of predictive equation and score for 5-year metabolic syndrome incidence in Japanese adults.

BACKGROUND: Predicting metabolic syndrome (MetS) is important for identifying high-risk cardiovascular disease individuals and providing preventive interventions. We aimed to develop and validate an equation and a simple MetS score according to the Japanese MetS criteria. METHODS: In total, 54,198 participants (age, 54.5±10.1 years; men, 46.0%), with baseline and 5-year follow-up data were randomly assigned to 'Derivation' and 'Validation' cohorts (ratio: 2:1). Multivariate logistic regression analysis was performed in derivation cohort and scores were assigned to factors corresponding to ß-coefficients. We evaluated predictive ability of the scores using area under the curve (AUC), then applied them to validation cohort to assess reproducibility. RESULTS: The primary model ranged 0-27 points had an AUC of 0.81 (sensitivity: 0.81, specificity: 0.81, cut-off score: 14), and consisted of age, sex, blood pressure (BP), body mass index (BMI), serum lipids, glucose measurements, tobacco smoking, and alcohol consumption. The simplified model (excluding blood tests) ranged 0-17 points with an AUC of 0.78 (sensitivity: 0.83, specificity: 0.77, cut-off score: 15) and included: age, sex, systolic BP, diastolic BP, BMI, tobacco smoking, and alcohol consumption. We classified individuals with a score <15 and ≥15 points as low- and high-risk MetS, respectively. Furthermore, the equation model generated an AUC of 0.85 (sensitivity: 0.86, specificity: 0.55). Analysis of the validation and derivation cohorts yielded similar results. CONCLUSION: We developed a primary score, an equation model, and a simple score. The simple score is convenient, well-validated with acceptable discrimination, and could be used for early detection of MetS in high-risk individuals.

Development of a risk prediction score and equation for chronic kidney disease: a retrospective cohort study.

Chronic kidney disease (CKD) is a risk factor for end-stage renal disease and contributes to increased risk of cardiovascular disease morbidity and mortality. We aimed to develop a risk prediction score and equation for future CKD using health checkup data. This study included 58,423 Japanese participants aged 30-69 years, who were randomly assigned to derivation and validation cohorts at a ratio of 2:1. The predictors were anthropometric indices, life style, and blood sampling data. In derivation cohort, we performed multivariable logistic regression analysis and obtained the standardized beta coefficient of each factor that was significantly associated with new-onset CKD and assigned scores to each factor. We created a score and an equation to predict CKD after 5 years and applied them to validation cohort to assess their reproducibility. The risk score ranged 0-16, consisting of age, sex, hypertension, dyslipidemia, diabetes, hyperuricemia, and estimated glomerular filtration rate (eGFR), with area under the curve (AUC) of 0.78 for the derivation cohort and 0.79 for the validation cohort. The CKD incidence gradually and constantly increased as the score increased from ≤ 6 to ≥ 14. The equation consisted of the seven indices described above, with AUC of 0.88 for the derivation cohort and 0.89 for the validation cohort. We developed a risk score and equation to predict CKD incidence after 5 years in Japanese population under 70 years of age. These models had reasonably high predictivity, and their reproducibility was confirmed through internal validation.

Clinical significance of atherosclerotic risk factors differs in early and advanced stages of plaque formation: A longitudinal study in the general population.

BACKGROUND: Carotid plaque is a well-known prognostic factor for cardiovascular diseases. It is unclear which risk factors are associated with the transformation of carotid plaque over time. In this longitudinal study, we examined the risk factors related to carotid plaque progression. METHODS: We enrolled 738 men without medication (mean age: 55 ± 10 years) who underwent the first and second health examinations. We measured carotid plaque thickness (PT) at three points of the right and left carotid artery. Plaque score (PS) was calculated by summing all the PTs. We divided the PS into three groups: None-group (PS <1.1), Early-group (1.1 ≤ PS <5.1), and Advanced-group (PS ≥5.1). We analyzed the relationship between PS progression and parameters such as age, body mass index, systolic blood pressure (SBP), fasting blood sugar, low-density lipoprotein cholesterol (LDL-C), and smoking and exercise habits. RESULTS: In multivariable logistic regression analysis, age and SBP were independent factors for PS progression from none to early stages (age, OR 1.07, p = 0.002; SBP, 10 mmHg, OR 1.27, p = 0.041). Age, follow-up period and LDL-C were independently associated factors for PS progression from early to advanced stages (age, OR 1.08,p < 0.001; follow-up period OR1.19, p = 0.041; LDL-C, 10 mg/dL, OR 1.10, p = 0.049). CONCLUSIONS: SBP was independently associated with the progress of early atherosclerosis, while LDL-C was independently associated with the progression of advanced atherosclerosis in the general population. Further studies are needed to assess whether early control of SBP and LDL-C levels can reduce the occurrence of future cardiovascular events.

Cutoff Values of Brachial-Ankle Pulse Wave Velocity for Atherosclerotic Risks by Age and Sex in the Japanese General Population.

AIM: In this study, we aim to analyze the correlation between brachial-ankle pulse wave velocity (baPWV) and Suita score or Framingham risk score and obtain the cutoff value of baPWV by sex and age for cardiovascular risk, as assessed by these scores in the large Japanese annual health checkup data. METHODS: In total, 25,602 participants (14,539 men and 11,063 women), who had their annual health checkups, were included in this study. Cutoff values of baPWV for the moderate- and high-risk groups stratified by sex and age were obtained using a receiver operating characteristic (ROC) curve analysis. RESULTS: As per our findings, the Suita score demonstrated better correlations with baPWV than the Framingham risk score in both sexes (men, Suita score R2=0.41 and Framingham risk score R2=0.37; women, Suita score R2=0.54 and Framingham risk score R2=0.33). The ROC curve analysis demonstrated the cutoff values of baPWV for moderate- and high-risk groups estimated using the Suita score, and they are as follows: in men, the baPWV cutoff values were 1,350 cm/s in the 40s, 1,430 cm/s in the 50s, 1,520 cm/s in the 60s, and 1,880 cm/s in the 70s. In women, the baPWV cutoff values were 1,350 cm/s in the 40s, 1,430 cm/s in the 50s, 1,570 cm/s in the 60s, and 1,800 cm/s in the 70s. CONCLUSIONS: We demonstrated that baPWV significantly correlated with the Suita score or Framingham risk score in both men and women, with the former presenting a stronger correlation than the latter. We propose the cutoff values of baPWV for moderate- and high-risk groups estimated using the Suita score.

Insufficient blood pressure control is independently associated with increased arterial stiffness.

Hypertension is a risk factor for atherosclerosis. Achieving the therapeutic target value of blood pressure (BP) prevents the onset of cardiovascular events; however, it is not clear how antihypertensive drug use and BP control status relate to arterial stiffness. The purpose of this study is to investigate the relationship between BP control status with or without antihypertensive drugs and arterial stiffness. Nine hundred eighty individuals (mean age: 68 ± 11 years) who participated in a community-based cohort study were enrolled. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). Higher BP was defined as a systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. Participants were divided into four groups: normal, non higher BP without antihypertensive drugs (n = 421); untreated, higher BP without antihypertensive drugs (n = 174); good control, non higher BP with antihypertensive drugs (n = 209); and poor control, higher BP with antihypertensive drugs (n = 176). In multivariable logistic analysis adjusted for age, sex, dyslipidemia and diabetes mellitus medication use, obesity, smoking, alcohol drinking, and heart rate at the CAVI measurement for a high CAVI-using a borderline cutoff value of 8.0-the other three groups were significantly associated with a high CAVI when compared with the normal group. By contrast, multivariable logistic analysis of a high CAVI using an abnormal cutoff value of 9.0 demonstrated that the poor control and untreated groups were significantly associated with a high CAVI, whereas the good control group was not. In conclusion, even with antihypertensive drugs, poor BP control is independently associated with a high CAVI.

Effects of dietary boron supplementation on the testicular function and thyroid activity in male goats: Involvement of CYP17A1 gene.

The physiological effects of dietary boron (B) supplementation for farm animals specifically goat on male fertility are still scarce and need deep investigation. Thus, the current study was designed to investigate how adding B to the diet of male goats affected their testicular and thyroid activity. For that purpose, twelve male goats were divided randomly into two groups (six animals each); control group that was fed the basal diet and B group that was fed the basal diet containing 70 mg B/kg diet for 6 months. Serum samples were collected at different intervals, while testicular biopsies were obtained at the end of the experiment. The results showed that 6 months of dietary B supplementation resulted in a significant increment in serum B concentration. The results of repeated measure analysis showed that there were significant GROUP and TIME × GROUP interactions effects on blood testosterone levels (F = 119.408, p = .000 and F = 6.794, p = .013, respectively), demonstrating that compared with control, B supplementation caused a significant rise in serum testosterone levels over time. However, the mean animal body weights and the serum levels of triiodothyronine (T3) and thyroxine (T4) were kept comparable with the control ones at the different time points. The most striking finding is that B supplementation increased significantly the mRNA expression of the CYP17A1 which is essential for steroidogenesis (p < .001). In addition, a histological examination of testicular tissue corroborated our findings and demonstrated that B supplementation had a positive effect. As a result, B might be considered an excellent food supplement that could be safely added to the male goats' diet at the current dose to improve their reproductive capacity.

Assessment of Future Hypertension Risk by Sex Using Combined Body Mass Index and Waist-to-Height Ratio.

Background: Body mass index (BMI) and the waist-to-height ratio (WHtR) are widely used anthropometric indices of obesity to predict cardiovascular risks. However, the usefulness of combining WHtR and BMI values to predict hypertension risk by sex has not been well elucidated. Methods and Results: This cohort study enrolled 45,921 participants (mean [±SD] age 53.8±10.5 years; 47.0% men) without hypertension from among those undergoing annual health checkups. Participants were divided into 4 categories based on median BMI and WHtR values, and the 5-year incidence of hypertension was assessed for both sexes using logistic regression analysis. Mean (±SD) BMI and WHtR values were 23.5±3.1 kg/m2 and 0.50±0.05, respectively, in men and 22.4±3.3 kg/m2 and 0.53±0.06, respectively, in women. Among the women, those with high BMI and low WHtR had an increased risk of hypertension compared with those with low BMI and low WHtR (odds ratio [OR] 1.37, P<0.001); however, the same result was not found in men (OR 1.14, P=0.080). In both sexes, the incidence of hypertension was higher among participants with low BMI and high WHtR than among those with low BMI and low WHtR (men: OR 1.26, P<0.001; women: OR 1.15, P=0.048). Conclusions: Using WHtR and BMI together provides a better hypertension risk assessment. Among men, those with a high BMI had no increased hypertension risk when WHtR was low.

Experience with modified two stage inner preputial flap for repair of proximal hypospadias with chordee: A single institution study with intermediate follow up.

PURPOSE: We present our modified technique of using the inner preputial flap to cover the penile shaft, while removing the subcutaneous tissue of the distal part of the flap to act similar to graft. Herein, we present our experience with modified two stage inner preputial flap for repair of proximal hypospadias with chordee. PATIENTS AND METHODS: The current study was a single-institution retrospective study between January 2016 and December 2020. Thirty-one patients with proximal hypospadias with chordee were included and underwent our modified technique. We excluded re-operative hypospadias and incomplete follow-up cases (<6 month of follow up). Patient demographics, outcomes and complications in the form of fistula formation, diverticulum, metal stenosis, stricture formation and glans dehiscence were reviewed. RESULTS: A total of 31 patients were included in the study and underwent our modified technique. The median age was 18 months (9-60) & IQR 15-25). The median follow up was 40 months. Overall, success was achieved in 24 cases (77.4%). Complications occurred in seven cases (22.6%) and included urethrocutanous fistula in three patients (9.7%), diverticulum in two patients (6.5.%), metal stenosis in one patient (3.2%) and glans dehiscence in one patient (3.2%). CONCLUSION: Our technique provides a favourable outcome with a low complication rate for repair of proximal severe hypospadias. LEVEL OF EVIDENCE: Case Series Study (Level IV).