Use Of Blockers Research Articles

Can prolonged P-R interval predict clinical outcomes in non-ST elevation acute coronary syndrome patients?

BackgroundThe present study aimed to respond to clinical question, can prolonged P-R interval predict clinical outcomes in non-ST elevation acute coronary syndrome patients?MethodsThis descriptive-analytical study was conducted on cardiac patients. All of the non-ST elevation acute coronary syndrome (NSTEACS) including non-ST elevation myocardial infarction (NSTEMI) and unstable angina patients included in the study. Then they divided into two groups: prolonged P-R interval and normal P-R interval. The patients who had a history of digoxin and calcium channel blocker use, using antiarrhythmic drugs, known valvular or congenital heart disease and connective tissue, unreadable P-R interval and cardiac block were excluded. Data were collected using the questionnaire consisted demographic data and clinical outcomes and a follow-up part was completed by one of the researchers.ResultsFinally, 248 patients completed the study. The results showed both of the two groups had significant differences in terms of the history of myocardial infarction (MI) (p = 0.018), the level of high-density lipoprotein (HDL) (p = 0.004), heart rate (p = 0.042), inverted T wave (p = 0.017), anterior ST- segment depression (p = 0.008), normal report of coronary angiography (CAG) (p = 0.003), three vessels disease (p = 0.043), left main lesion (p = 0.045) and SYNTAX score (p = 0.032) based on the CAG report. The results of six-month follow-up showed although, the frequency of ischemic stroke, coronary artery disease (CAD) and cardiovascular death were higher in prolonged P-R interval groups. The chi-square test showed this difference was statistically non-significant (p > 0.05). The multivariate logistic regression model revealed non-significant relationships between prolonged P-R interval and SYNTAX score, significant CAD, three-vessel disease, inverted T wave, anterior ST depression, heart rate and HDL.ConclusionsBased on the results of our study the six-month follow-up showed non-significant outcomes. Further studies are recommended to assess the long-term outcomes.

Association between long-term use of calcium channel blockers (CCB) and the risk of breast cancer: a retrospective longitudinal observational study protocol

IntroductionCalcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is...

Evaluation of the <i>GhMAPK</i> gene expression level under salt stress in cotton cultivars

Background: Abiotic environmental stress factors such as salt stress, drought, oxidative stress adversely affect the development and productivity of plants. To combat adverse environmental conditions, plants have developed a number of protective mechanisms. MAP kinases are protein kinases that regulate cellular activity in response to extracellular stimuli. Given the significant role of MAP kinase mechanisms in universal biological processes, elucidation of its role and mechanisms can be used to create stress-resistant genotypes. The use of stimulators and blockers of MAP kinase mechanisms is promising as a new direction in the management of plant stress resistance. The main goal of the conducted research is the comparative analysis of expression patterns of cotton accessions under salt stress conditions, the study of the relation between an increase in salt concentration and the change in the level of transcripts. Thirteen cultivars from Azerbaijan, nine from Turkey, four from Uzbekistan, four from Greece and one from Kyrgyzstan were used in the research, and changes in the expression level of the GhMAPK gene in cotton accessions was studied with the application of the real-time PCR analysis. In the present study, the evaluation of thirty-one cotton cultivars under different salt stress (NaCl) concentrations revealed significant differences in gene expression levels between cultivars of the same species. The ‘Navai-9’ cultivar from Uzbekistan had the highest expression level at both 100 mM and 200 mM salt concentrations compared to all other cultivars. Among local cultivars, cv. ‘Ganja-110’ (at 100 mM salt concentration), and cv. ‘Zafar’ (at 200 mM) differed from others in the level of changes in transcripts. In addition, there was a wide variation in the expression levels of stress-related genes between groups of accessions identified as resistant and sensitive, and within groups. Thus, both the increase and decrease in the expression level were found within these groups. This diversity in gene expression in sensitive and resistant cultivars in response to the salt stress shows that the mechanisms providing salt tolerance in the studied cultivars are different.

Cardiorespiratory fitness in persons with lower limb amputation.

The aim of this study is to gain insight in the cardiorespiratory fitness of persons with lower limb amputation (LLA) during rehabilitation, and in potential factors influencing their cardiorespiratory fitness. We performed a retrospective cohort study using data from cardiopulmonary exercise tests. Included participants were adults with LLA. Main outcome was cardiorespiratory fitness expressed as O 2 peak (ml/min/kg) and was directly determined using breath-by-breath gas analysis. O 2 peak was compared to reference values for able-bodied controls. Multivariate regression analysis was performed to investigate potential factors related to O 2 peak in persons with LLA. Potential factors were age, BMI adjusted, gender, level of amputation, aetiology of amputation, unilateral/bilateral, type of ergometry and use of beta blockers. Data of 74 participants with LLA are presented; 84% male (n = 62), mean age 58.9 (SD 11.6), mean BMI 26.7 (SD 5.6), 44 participants have a LLA above the knee, 30 below the knee. Overall O 2 peak was lower in persons with LLA compared to reference values for able-bodied controls, with mean O 2 peak for the total LLA group of 14.6 ± 4.1 ml/kg/min. In the multivariate regression analysis, only age was a significant predictor for lower O 2 peak (regression coefficient: -0.15, 95% CI [0.23-0.069], r 2 = 0.166). These results indicate that the cardiorespiratory fitness in persons with LLA is low, while they actually need more energy to walk and perform other daily activities. Cardiorespiratory fitness is not closely associated with the analysed demographic or clinical factors and will have to be determined on an individual basis for use in daily practice.

Self-controlled Case Series Study for Acute Kidney Injury after Starting Proton Pump Inhibitors or Potassium-Competitive Acid Blocker in Patients with Cancer Using a Large Claims Database.

To investigate the risk of acute kidney injury (AKI) in patients with cancer following the initiation of proton pump inhibitors (PPIs) and potassium-competitive acid blocker (PCAB), considering sex and anti-cancer drug use. We conducted a self-controlled case-series study using the Japan Medical Data Center claims data from 12422 patients with cancer who were prescribed PPIs or PCAB between January 2017 and December 2019. Considering the timing of PPI or PCAB, control period (days -120 to -1), risk period 1 (days 0 to +30), and risk period 2 (days +31 to +365) were defined. To assess the incidence rate ratio (IRR) and 95% confidence interval (CI) as the risk ratio, we adjusted for anti-cancer drugs to assess the risk of AKI. Additionally, we also examined sex differences to identify the risk of AKI. AKI was observed in risk period 1 [2.05 (1.12-3.72), p = 0.0192], but a slight reduction was noted in risk period 2 [0.60 (0.36-1.00), p = 0.0481]. A sex-specific increase in the risk of AKI was observed only in males during risk period 1 [2.18 (1.10-4.32), p = 0.0260], with a reduction in risk period 2 [0.48 (0.26-0.89), p = 0.0200]. We identified an increased risk of AKI in patients with cancer starting PPIs or PCAB particularly in males within 30 d after PPI or PCAB initiation, emphasizing the need for vigilant monitoring and management of AKI in this patient population.

Statins, ACE/ARBs drug use, and risk of pneumonia in hospitalized older patients: a retrospective cohort study.

The aims of this study is to evaluate the association between angiotensin-converting enzyme inhibitor (ACE-I), angiotensin II receptor blocker (ARBs) and/or statin use with the risk of pneumonia, as well as and with in-hospital and short-term outpatient mortality in hospitalized older patients with pneumonia. Patients aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro Politerapuie SIMI-Società Italiana di Medicina Interna) register from 2010 to 2019 were screened to assess the diagnosis of pneumonia and classified on whether or not they were prescribed with at least one drug among ACE-I, ARBs, and/or statins. Further study outcomes were mortality during hospital stay and at 3 months after hospital discharge. Among 5717 cases included (of whom 18.0% with pneumonia), 2915 (51.0%) were prescribed at least one drug among ACE-I, ARBs, and statins. An inverse association was found between treatment with ACE-I or ARBs and pneumonia (OR = 0.79, 95% CI 0.65-0.95). A higher effect was found among patients treated with ACE-I or ARBs in combination with statins (OR = 0.67, 95% CI 0.52-0.85). This study confirmed in the real-world setting that these largely used medications may reduce the risk of pneumonia in older people, who chronically take them for cardiovascular conditions.

Age at onset of type 1 diabetes between puberty and 30 years old is associated with increased diabetic nephropathy risk

Diabetic nephropathy is a critical complication of patients with type 1 diabetes, while epidemiological studies were scarce among Asian countries. We conducted a cross-sectional study to identify factors associated with diabetic nephropathy by questionnaires, using student’s t-test, chi-square test, and multivariable logistic regression. Among 898 participants, 16.7% had diabetic nephropathy. Compared with non-diabetic nephropathy patients, the patients with diabetic nephropathy had significantly higher percentage with onset age of type 1 diabetes between puberty and under 30 years old (female ≥ 12 or male ≥ 13 years old to 29 years old), longer diabetes duration, having family history of diabetes and diabetic nephropathy, accompanied with hypertension, hyperlipidemia, or coronary artery disease (CAD). Compared with patients with onset age before puberty, the odds of diabetic nephropathy occurrence increased to 1.61 times in patients with onset age between puberty and under 30 years old (p = 0.012) after adjusting diabetes duration. Age of diabetes onset between puberty and under 30 years old, diabetes duration, HbA1c, hospital admission within 3 years, diabetic retinopathy, hypertension, systolic blood pressure (SBP), triglyceride levels, and use of angiotensin converting enzyme inhibitor (ACEI) and/or angiotensin receptor blockers (ARB) were independent factors associated with diabetic nephropathy Screening for proteinuria is important in daily clinical practice and should be part of diabetes self-management education for patients with type 1 diabetes.

Prevalence and factors associated with masked hypertension in chronic kidney disease.

Optimal blood pressure (BP) control is key to prevent cardiovascular complications in patients with chronic kidney disease (CKD). We described the prevalence and factors associated with masked hypertension in CKD. We analyzed 1113 ambulatory 24-h BP monitoring (ABPM) records of 632 patients referred for kidney function evaluation. Masked hypertension was defined as office BP less than 140/90 mmHg but daytime BP at least 135/85 mmHg or nighttime BP at least 120/70 mmHg. Factors associated with masked hypertension were assessed with mixed logistic regression models. At inclusion, 424 patients (67%) had controlled office BP, of whom 56% had masked hypertension. In multivariable analysis conducted in all visits with controlled office BP ( n = 782), masked hypertension was positively associated with male sex [adjusted OR (95% confidence interval) 1.91 (1.16-3.27)], sub-Saharan African origin [2.51 (1.32-4.63)], BMI [1.11 (1.01-1.17) per 1 kg/m 2 ], and albuminuria [1.29 [1.12 - 1.47] per 1 log unit), and was negatively associated with plasma potassium (0.42 [0.29 - 0.71] per 1 mmol/L) and 24-h urinary potassium excretion (0.91 [0.82 - 0.99] per 10 mmol/24 h) as well as the use of renin-angiotensin-aldosterone (RAAS) blockers (0.56 [0.31 - 0.97]) and diuretics (0.41 [0.27 - 0.72]). Our findings support the routine use of ABPM in CKD, as more than half of the patients with controlled office BP had masked hypertension. Weight control, higher potassium intake (with caution in advanced CKD), correction of hypokalemia, and larger use of diuretics and RAAS blockers could be potential levers for better out-of-office BP control.

Clinical Trajectories and Long-Term Outcomes of Alcoholic Versus Other Forms of Dilated Cardiomyopathy

Alcoholic cardiomyopathy (ACM) is a form of dilated cardiomyopathy (DCM) occurring secondary to long-standing heavy alcohol use and is associated with poor outcomes, but the cause-specific risks are insufficiently understood. Between 1997 and 2018, we identified all patients with a first diagnosis of ACM or DCM. The cumulative incidence of different causes of hospitalisation and mortality in the two groups was calculated using the Fine-Gray and Kaplan-Meier methods. A Total of 1,237 patients with ACM (mean age 56.3±10.1 years, 89% men) and 17,211 individuals with DCM (mean age 63.6±13.8 years, 71% men) were identified. Diabetes (10% vs 15%), hypertension (22% vs 31%), and stroke (8% vs 10%) were less common in ACM than DCM, whereas obstructive lung disease (15% vs 12%) and liver disease (17% vs 2%) were more prevalent (p<0.05). Cumulative 5-year mortality was 49% in ACM vs 33% in DCM, p<0.0001, multivariable adjusted hazards ratio 2.11 (95% confidence interval 1.97-2.26). The distribution of causes of death was similar in ACM and DCM, with the predominance of cardiovascular causes in both groups (42% in ACM vs 44% in DCM). 5-year cumulative incidence of heart failure hospitalisations (48% vs 54%) and any somatic cause (59% vs 65%) were also similar in ACM vs DCM. At 1 year, the use of beta blockers (55% vs 80%) and implantable cardioverter defibrillators (3% vs 14%) were significantly less often used in ACM vs DCM. Patients with ACM had similar cardiovascular risks and hospitalisation patterns as other forms of DCM, but lower use of guideline-directed cardiovascular therapies and greater mortality.

Association of Beta-Blocker Use With Exercise Capacity in Participants With Heart Failure With Preserved Ejection Fraction: A Post Hoc Analysis of the RELAX Trial

Patients with heart failure with preserved ejection fraction (HFpEF) often receive β-blocker (BB) therapy for management of co-morbidities. However, the association of BB therapy with exercise capacity and health-related quality of life (HRQL) in HFpEF is not well-studied. In this post hoc analysis of the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF (RELAX) trial, which included patients with chronic stable HFpEF with peak exercise capacity assessment at baseline and at 12 and 24 weeks of follow-up, we evaluated the association of BB use with the measures of exercise capacity (peak exercise oxygen uptake), anaerobic threshold, and HRQL (Minnesota living with heart failure questionnaire). Separate linear mixed-effect models were constructed for each outcome with adjustment for treatment arm, demographics, medical history, left ventricular ejection fraction, and duration of heart failure. Of the 216 study participants (median age 69 years, 48.2% women), 76% reported BB use at baseline. Participants with (vs without) BB therapy were older (70 vs 63.5 years, p = 0.001) and had a higher prevalence of ischemic heart disease (44% vs 23%, p = 0.01). In the adjusted linear mixed model, BB use over time was not associated with peak exercise oxygen uptake (β 95% confidence interval [CI] 0.2 (-0.31 to 0.7), p = 0.5) and 6-minute walk distance (β 95% CI 14.69 [-14.25 to 43.63], p = 0.3). However, BB use was associated with a higher anaerobic threshold (β 95% CI 0.32 (0.02 to 0.62), p = 0.036) and better HRQL (lower quality of life as assessed by Minnesota living with heart failure questionnaire score) (β 95% CI -6.68 [-10.96 to -2.4], p = 0.002). Future trials are needed to better evaluate the effects of BB on exercise capacity in patients with chronic stable HFpEF.

Prescriptions of psychotropic and somatic medications among patients with severe mental disorders and healthy controls in a naturalistic study

Purpose Psychotropic and somatic medications are both used in treating severe mental disorders (SMDs). Realistic estimates of the prevalence of use across medication categories are needed. We obtained this in a clinical cohort of patients with SMD and healthy controls (HCs). Materials and methods Prescriptions filled at Norwegian pharmacies the year before and after admittance to the Thematically Organized Psychosis (TOP) study were examined in 1406 patients with SMD (mean age 32.5 years, 48.2% women) and 920 HC (34.1 years, 46.2% women). Using data from the Norwegian Prescription Database (NorPD), the number of users in different anatomical therapeutic chemical (ATC) categories was compared using logistic regression. Population estimates were used as reference data. Results Use of antipsychotics (N05A), antiepileptics (N03A), antidepressants (N06A), anxiolytics (N05B), hypnotics and sedatives (N05C), anticholinergics (N04A), psychostimulants, attention deficit hyperactivity disorder and nootropic agents (N06B) and drugs for addiction disorders (N07B) was significantly more prevalent in patients with SMD than HC. Use of diabetes treatment (A10), antithrombotic drugs (B01), beta blockers (C07), lipid modifiers (C10), and thyroid and endocrine therapeutics (H03) was also more prevalent in patients with SMD, but with two exceptions somatic medication use was comparable to the general population. Among HC, there was low prevalence of use for most medication categories. Conclusion Patients were using psychiatric medications, but also several types of somatic medications, more often than HC. Still, somatic medication use was mostly not higher than in the general population. The results indicate that HC had low use of most medication types.

Asystole on loop recorder in patients with unexplained syncope and negative tilt testing: age distribution and clinical predictors

BackgroundApproximately 50% of patients with unexplained syncope and negative head-up tilt test (HUTT) who have an electrocardiogram (ECG) documentation of spontaneous syncope during implantable loop recorder (ILR) show an asystolic pause at the time of the event.ObjectiveThe aim of the study was to evaluate the age distribution and clinical predictors of asystolic syncope detected by ILR in patients with unexplained syncope and negative HUTT.MethodsThis research employed a retrospective, single-center study of consecutive patients. The ILR-documented spontaneous syncope was classified according to the International Study on Syncope of Uncertain Etiology (ISSUE) classification.ResultsAmong 113 patients (54.0 ± 19.6 years; 46% male), 49 had an ECG-documented recurrence of syncope during the observation period and 28 of these later (24.8%, corresponding to 57.1% of the patients with a diagnostic event) had a diagnosis of asystolic syncope at ILR: type 1A was present in 24 (85.7%), type 1B in 1 (3.6%), and type 1C in 3 (10.7%) patients. The age distribution of asystolic syncope was bimodal, with a peak at age < 19 years and a second peak at the age of 60–79 years. At Cox multivariable analysis, syncope without prodromes (OR 3.7; p = 0.0008) and use of beta blockers (OR 3.2; p = 0.002) were independently associated to ILR-detected asystole.ConclusionsIn patients with unexplained syncope and negative HUTT, the age distribution of asystolic syncope detected by ILR is bimodal, suggesting a different mechanism responsible for asystole in both younger and older patients. The absence of prodromes and the use of beta blockers are independent predictors of ILR-detected asystole.

Retrospective study assessing the use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers to reduce toxicity from tyrosine kinase inhibitors in metastatic renal cell carcinoma.

411 Background: The main toxicities associated with tyrosine-kinase inhibitors (TKIs) in the treatment of renal cell carcinoma (RCC) are proteinuria and hypertension. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have established reno-protective and anti-hypertensive effects and can help with toxicity in mRCC. We hypothesize that use of ACEIs/ARBs is an effective method to decrease the degree of proteinuria and hypertension in patients treated with TKIs for metastatic/advanced renal cell carcinoma (mRCC). Methods: Single Institution retrospective study; mRCC patients (pts) who received TKI and ACEIs/ARBs and had urine protein measurements available at baseline and at 4-6 wk follow up post ACEs/ARBs were included in the analysis. Primary endpoints included improvement in grade of proteinuria and BP in mRCC pts on TKI treatment at baseline and with addition of ACEIs/ARBs. Secondary endpoints included number of dose interruptions (DI), BUN and creatinine changes. Paired statistical tests were used to compare the selected outcome variables between baseline and post ACE/ARB measures: for example, nonparametric Wilcoxon Signed-rank test for paired quantitative data and McNemar test for paired binary data. Results: Out of 71 screened patients between 2020-2023, N of 22 mRCC (N=22, 72.7% male, 77.3% white; 9% Hispanic; N=14 for TKI+ immunotherapy; N=8 TKI alone) pts were selected. ACEIs/ARBs treatment was associated with significantly reduced levels of proteinuria at 4–6wk follow-up. At baseline vs. follow-up, pts were found to have significantly lower proteinuria overall after ACEI/ARBs (p=0.0147), and 45.4% of pts had clinically insignificant proteinuria vs. 22.7% at baseline. Additionally, DI rates for TKI were significantly lower for pts placed on ACEIs/ARBs, with an 81% chance that pts with prior DI would not experience similar event in the follow-up period (p=0.003). Reductions in BP, creatinine, and TKI dosing were seen but not statistically significant (p&gt;0.05 for all measures). Conclusions: In our small study, degree of proteinuria was notably reduced with administration of ACEIs/ARBs. Further findings show fewer DI of TKIs with ACEIs/ARBs use. Our findings suggest a potential role for ACEIs/ARBs in managing toxicity in patients undergoing TKI based therapy for mRCC. Future studies are needed to evaluate the use of ACE/ARB from the time of initiation of TKI based therapy to reduce the toxicities and improve the adherence to mRCC treatment which may result in better outcomes.

Hypertension Management in Peripheral Artery Disease: A Mini Review.

Lower extremity peripheral artery disease (PAD) affects over 230 million adults globally, with hypertension being one of the major risk factors for the development of PAD. Despite the high prevalence, patients with hypertension who have concomitant PAD are less likely to receive adequate therapy. Through this review, we present the current evidence underlying hypertension management in PAD, guideline-directed therapies, and areas pending further investigation. Multiple studies have shown that both high and relatively lower blood pressure levels are associated with worse health outcomes, including increased morbidity and mortality. Hence, guideline-directed recommendation involves cautious management of hypertensive patients with PAD while ensuring hypotension does not occur. Although any antihypertensive medication can be used to treat these patients, the 2017 American Heart Association/American College of Cardiology (AHA/ACC), 2017 European Society of Cardiology (ESC), and 2022 Canadian guidelines favor the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) as the initial choice. Importantly, data on blood pressure targets and treatment of hypertension in PAD are limited and largely stem from sub-group studies and post-hoc analysis. Large randomized trials in patients with PAD are required in the future to delineate hypertension management in this complex patient population.

Association Between Risk of Clostridium difficile Infection and Duration of Proton Pump Inhibitor or H2-Receptor Antagonist Use in Hospitalized Patients.

Limited studies have evaluated the association between Clostridium difficile infection (CDI) and the duration of proton pump inhibitor (PPI) or histamine H2-receptor blocker (H2RA) use and provided a cutoff duration for PPI or H2RA use to mitigate a substantially increased risk of CDI. We aimed to evaluate these associations in hospitalized patients using a nationwide insurance claims database. We conducted a nested case-control study to identify cases with a first ever record of CDI in a study cohort undergoing PPI or H2RA therapy from the National Health Insurance Database from 2012 to 2018. Each case was matched with one control by age, sex, and calendar year. We used conditional logistic regression to estimate the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC ROC). Youden's Jstatistic was used to identify the optimal cutoff duration in days for PPI or H2RA use. In the main analysis, the AUC ROC was 0.64 (95%CI 0.63-0.66) and optimal cutoff duration was 15days for PPI users. The AUC ROC was 0.63 (95%CI 0.62-0.64) and optimal cutoff duration was 16days for H2RA users. In the sensitivity analyses, the results were similar to those of the main analysis, and the optimal cutoff duration was in the range of 14-15days. The optimal cutoff duration for PPI and H2RA use was about 2weeks. It is necessary to be cautious regarding the risk of CDI in patients taking PPIs or H2RAs for longer than 2weeks.

Residual risk of cardiovascular complications in statin-using patients with type 2 diabetes: the Taiwan Diabetes Registry Study

BackgroundThe residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event.MethodsData on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined.ResultsThe 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log–alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure.ConclusionThis study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

Angiotensin receptor blockers and severe diarrhea and/or enterocolitis induced by CAPOX in patients with colorectal cancer: A multicentric cohort.

88 Background: While patients (pts) with colorectal cancer (CRC) treated with CAPOX (capecitabine and oxaliplatin) may experience severe diarrhea, risk factors for this toxicity remain undetermined. We have previously shown that concurrent use of angiotensin receptors blockers (ARB), a known inhibitor of TGF-B which is important for gut mucosa proliferation, significantly increased the risk of severe diarrhea and/or enterocolitis. Here we conducted a larger and multicenter study to validate this finding, adjusting for other risk factors. Methods: Multicenter retrospective cohort of CRC pts who received ≥ 1 cycle of CAPOX. The primary endpoint was grade (G) ≥ 3 diarrhea and/or enterocolitis as described by Common Terminology Criteria for Adverse Events version 5.0. Clinical data were retrieved from medical charts. Unadjusted logistic regression was used to evaluate risk factors for ≥ G3 diarrhea/enterocolitis (use of ARBs or angiotensin-converting enzyme inhibitors [ACEi], age, ECOG, Age-adjusted Charlson Comorbidity Index [A-CCI], sidedness, presence of ileostomy, treatment intent [curative vs palliative], use of proton pump inhibitors or antiacid, and center). A multivariable analysis was performed with variables with P &lt; 0.05 deemed significant. Results: From April/2010 to December/2023, 348 pts were included: 175 (50.3%) were female, median age was 61 years (28 - 87), 259 (74.4%) had stage III and 76 pts (21.9%), stage IV. 58 pts (16%) had G3 ≥ diarrhea/ enterocolitis, mostly before 3rd cycle. Age ≥ 65 years (Odds ratio [OR] 3.18; P &lt; 0,0001; 95% CI, 1.78 to 5.68 ); right-sided tumors (OR 1.73; P=0.075; 95% CI, 0.95 to 3.17); use of ARBs or ACEi (OR 1.57; P=0.127; 95% CI, 0.88 to 2.79); A-CCI (OR 1.12; P=0.042; 95% CI, 1.004 to 1.23) were associated with ≥ G3 diarrhea/enterocolitis in univariate analyses. In the multivariable analysis, age ≥ 65 years was significant (OR 3.13; P=0.001; 95% CI, 1.58 to 6.20), but use of ARBs or ACEi was not significant (OR 1.16; P=0.635; 95% CI, 0.62 to 2.13). Five out of 9 pts who used Olmesartan had ≥ G3 diarrhea/enterocolitis. Conclusions: Among pts treated with CAPOX, ≥ 65 years, but not use of ARBs or ACEi, was an independent risk factor for ≥ G3 diarrhea/enterocolitis. Concurrent Olmesartan and CAPOX should be used with caution.

Risk factors for the occurrence of laryngopharyngeal reflux disease in the aged and the clinical characteristics of patients complicated with pneumonia

Objective: To investigate the risk factors for the occurrence of laryngopharyngeal reflux disease in the aged, and to analyze the characteristics of patients with pneumonia. Methods: Patients who underwent 24-hour laryngopharyngeal pH monitoring from June 2020 to July 2022 and the positive patients of those who underwent 24-hour esophageal pH monitoring from March 2017 to July 2022 at the Second Medical Center of the PLA General Hospital were enrolled retrospectively. Positive results of 24-hour laryngopharyngeal reflux monitoring were in the laryngopharyngeal reflux group, and the negative results were in the non-laryngopharyngeal reflux group. Patients with pneumonia and simple gastroesophageal reflux disease were in the esophageal reflux pneumonia group, and patients with pneumonia and simple laryngopharyngeal reflux disease were in the laryngopharyngeal reflux pneumonia group. Patients' basic data, co-morbidities, drug use and relevant examination and test results were collected. Multivariate logistic regression analysis was used to analyze the risk factors of laryngopharyngeal reflux disease in the aged and its relationship with pneumonia. Results: A total of 80 patients with 24-hour laryngopharyngeal pH monitoring were enrolled finally, including 34 cases, all male, aged (73±12) years, in the laryngopharyngeal reflux group, and 46 cases [44 males, 2 females, aged (78±11) years] in the non-laryngopharyngeal reflux group. Multivariate logistic regression analysis showed that the risk factors of laryngopharyngeal reflux disease in the aged included age ≤70 years (OR=13.07, 95%CI: 2.53-67.68), body mass index (BMI) (OR=1.37, each additional 1 kg/m2, 95%CI: 1.03-1.83), use of antipsychotic drugs (OR=8.00, 95%CI: 1.40-45.73) and calcium channel blockers (OR=5.27, 95%CI: 1.13-24.53) (all P<0.05). The protective factors of the laryngopharyngeal reflux disease in the aged included antacids (OR=0.19, 95%CI: 0.04-0.90, P=0.035). The incidence of pneumonia was higher in the laryngopharyngeal reflux group compared with the non-laryngopharyngeal reflux group [44.1% (15/34) vs 21.7% (10/46), P=0.033]. The esophageal reflux pneumonia group included 32 cases [31 males and 1 females, aged (84±12) years]. The laryngopharyngeal reflux pneumonia group included 15 cases [ 15 males, aged (79±11) years]. Compared to the patients in the laryngopharyngeal reflux pneumonia group, the patients in the esophageal reflux pneumonia group had a longer course of antibiotics [(27.7±27.0) vs (14.6±13.9) days, P=0.034], a higher frequency of seizure frequency [(4.3±3.0) vs (1.8±1.5) times/year, P<0.001] and a higher maximal body temperature [(38.2±0.9) vs (37.6±1.1) ℃, P=0.037]. Conclusions: The risk factors of laryngopharyngeal reflux disease in the aged included age ≤70 years, higher BMI, use of antipsychotic drugs and calcium channel blockers. The incidence of pneumonia in laryngopharyngeal reflux disease is higher, but the condition of pneumonia is milder.

COL4A2 enhances thyroid cancer cell proliferation through the AKT pathway.

Thyroid cancer (THCA) is the most common malignant tumor in endocrine system and the incidence has been increasing worldwide. And the number of patients dying from THCA has also gradually risen because the incidence continues to increase, so the mechanisms related to effective targets is necessary to improve the survival. This study was to preliminarily investigate the effects of the COL4A2 gene on the regulation of thyroid cancer (THCA) cell proliferation and the associated pathways. Bioinformatics analysis revealed that COL4A2 was closely associated with cancer development. COL4A2 expression in THCA tissues was analyzed using immunohistochemistry, and survival information was determined via Kaplan‒Meier curves. The expression of COL4A2 and AKT pathway-related genes were analyzed using qPCR and western blot analyses. Colony formation as well as CCK-8 assays exhibited the cell proliferation level and cell activity, respectively. Downstream of COL4A2 was identified by Gene set enrichment analysis (GSEA). The effects of the COL4A2 and AKT pathways on THCA tumor growth in vivo were determined using a mouse model. Bioinformatics analysis exhibited that COL4A2 plays a significant role in cancer and that the AKT pathway is downstream of COL4A2. THCA patients with high COL4A2 expression had shorter recurrence-free survival. Upregulation of COL4A2 gene expression in 2 THCA cell lines promoted tumor cell growth and activity. The use of AKT pathway blockers also restrained the growth and activity of the 2 THCA cell lines. The use of AKT pathway blockers reduced tumor volume and mass and prolonged mouse survival. COL4A2 can promote the growth as well as development of THCA through the AKT pathway and COL4A2 could be used as a target for THCA.

Evaluation of the classifications of severity in acute respiratory distress syndrome in childhood by the Berlin Consensus and the Pediatric Acute Lung Injury Consensus Conference.

To compare two methods for defining and classifying the severity of pediatric acute respiratory distress syndrome: the Berlin classification, which uses the relationship between the partial pressure of oxygen and the fraction of inspired oxygen, and the classification of the Pediatric Acute Lung Injury Consensus Conference, which uses the oxygenation index. This was a prospective study of patients aged 0 - 18 years with a diagnosis of acute respiratory distress syndrome who were invasively mechanically ventilated and provided one to three arterial blood gas samples, totaling 140 valid measurements. These measures were evaluated for correlation using the Spearman test and agreement using the kappa coefficient between the two classifications, initially using the general population of the study and then subdividing it into patients with and without bronchospasm and those with and without the use of neuromuscular blockers. The effect of these two factors (bronchospasm and neuromuscular blocking agent) separately and together on both classifications was also assessed using two-way analysis of variance. In the general population, who were 54 patients aged 0 - 18 years a strong negative correlation was found by Spearman's test (ρ -0.91; p < 0.001), and strong agreement was found by the kappa coefficient (0.62; p < 0.001) in the comparison between Berlin and Pediatric Acute Lung Injury Consensus Conference. In the populations with and without bronchospasm and who did and did not use neuromuscular blockers, the correlation coefficients were similar to those of the general population, though among patients not using neuromuscular blockers, there was greater agreement between the classifications than for patients using neuromuscular blockers (kappa 0.67 versus 0.56, p < 0.001 for both). Neuromuscular blockers had a significant effect on the relationship between the partial pressure of oxygen and the fraction of inspired oxygen (analysis of variance; F: 12.9; p < 0.001) and the oxygenation index (analysis of variance; F: 8.3; p = 0.004). There was a strong correlation and agreement between the two classifications in the general population and in the subgroups studied. Use of neuromuscular blockers had a significant effect on the severity of acute respiratory distress syndrome.