The Role of 5% Minoxidil versus Platelet-Rich Plasma in Treatment of Alopecia Areata.

OBJECTIVE: To compare the efficacy of topical minoxidil and platelet-rich plasma (PRP) in the treatment of alopecia areata (AA). STUDY DESIGN: Randomised control trial. Place and Duration of the Study: Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi, Pakistan, from December 2021 to June 2022. METHODOLOGY: The study included all the patients who visited JPMC Karachi during the study period. Permission from the ERB was obtained. The inclusion criteria were any gender and age 10 to 45 years. Topical minoxidil 5% solution was applied twice daily to Group A (six pubs/time), while PRP injections were administered to Group B at baseline and every four weeks for three months. Serial photos and the severity of alopecia tool (SALT) were used to determine the clinical assessment. When comparing the effectiveness between the two groups, a p-value of <0.05 was considered significant. SPSS version 23 was used to analyse the data. RESULTS: Mean age was 23.11 ± 8.9 years in 376 patients. PRP and Minoxidil groups had mean SALT scores at three months that were 1.48 and 1.54, respectively. Both treatments were shown to be efficacious. There was no statistically significant difference in efficacy between the minoxidil solution and PRP (p = 0.483). CONCLUSION: There is no apparent difference between PRP and topical minoxidil 5% solution in the management of AA. To verify the results, additional studies are needed with a larger sample size and a longer duration of follow-up. KEY WORDS: Minoxidil, Platelet-rich plasma, Alopecia areata, Severity of alopecia tool score.

Postnatal cytomegalovirus infection and pulmonary vascular disease in extremely premature infants: A case series.

BACKGROUND: Pulmonary vascular disease (PVD) is a major determinant of both morbidity and mortality in extremely low birth weight infants. It is biologically plausible that postnatal cytomegalovirus (pCMV) infection may lead to PVD in premature infants secondary to pneumonitis or via derangement of pulmonary vascular development directly through endothelial dysfunction. Uncertainty remains, however, regarding thresholds for intervention in premature infants with cardiorespiratory instability and presumed CMV infection likely secondary to the limited understanding of the natural history of the disease. METHODS/RESULTS: We describe four cases of premature infants with clinical and echocardiography features of PVD, in the setting of postnatally acquired CMV. All patients had atypical PVD trajectories, refractory to vasodilator treatment, which improved after initiation of CMV treatment. CONCLUSION: We highlight the need to consider postnatally acquired CMV infection in patients with PVD non-responsive to standard pulmonary vasodilator therapies or disease severity which is out of proportion of the usual clinical trajectory. Treatment of extremely premature infants with CMV-associated PVD may have positive impact on cardiorespiratory health, although duration of therapy remains uncertain.

Assessment of cardiac parameters after the administration of nicorandil before primary percutaneous coronary intervention.

Objective: To assess cardiac troponin I and creatine kinase-myocardial band levels, electrocardiogram changes and major adverse cardiac events after treatment with nicorandil before primary percutaneous coronary intervention. METHODS: The comparative, analytical study was conducted from October to November 2022 at the Pharmacology Department of Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Rawalpindi Institute of Cardiology, Rawalpindi. The sample comprised ST-elevated myocardial infarction patients of either gender aged at least 30 years with an ejection fraction of at least 35% undergoing primary percutaneous coronary intervention. Participants were selected based on the above-mentioned inclusion and informed consent was taken before their enrolment in this research study. The sample was randomised into control group A receiving conventional acute coronary syndrome treatment, and intervention group B receiving nicorandil in addition to the conventional treatment. Cardiac troponin I and creatine kinase-myocardial band levels, electrocardiogram changes, and major adverse cardiac events noted and compared. Data was analysed using SPSS 26. RESULTS: Of the 140 patients, 70(50%) were in each of the 2 groups. In group B, 60(85.7%) patients achieved a completely settled ST segment on electrocardiogram compared to 25(35.7%) in group A (p=0.001). There was a significant inter-group difference with respect to cardiac troponin I value 6 hours after percutaneous coronary intervention and major adverse cardiac events (p<0.05), but creatine kinase-myocardial band level was no significantly different between the groups (p=0.761). Conclusion: Prophylactic use of nicorandil in ST-elevated myocardial infarction patients decreased the incidence of reperfusion injury.

[Acute heart failure (AHF)].

INTRODUCTION: Acute heart failure (AHF) is a frequent cause for emergency consultations, leads to long hospital stays and is characterized by high mortality and rehospitalization rates, with the first months after hospitalization having the highest risk («vulnerable phase¼). The clinical presentation is usually characterized by fluid accumulation. Over the last three decades, few advances have been achieved in the treatment of AHF, as most studies with diuretics or vasodilators failed to show positive effects in terms of mortality and rehospitalization rates. In this context, the treatment of AHF must have an integrative approach, consisting of rapid correction of systemic congestion on the one hand, and specific therapies for the precipitating factors, the underlying cardiac pathology, and non-cardiac comorbidities on the other. Recently, it has been shown that a rapid and intensive up-titration of oral heart failure medical therapy during and immediately after hospitalization can improve the prognosis during the vulnerable phase after AHF. In this article, the principles of optimization and personalization of diuretic therapy and oral heart failure medication during hospitalization and the early outpatient phase after AHF are discussed.

Vasodilators for Acute Heart Failure - A Systematic Review with Meta-Analysis.

BACKGROUND: Acute heart failure is a public health concern. This study systematically reviewed randomized clinical trials (RCTs) to evaluate vasodilators in acute heart failure. METHODS: The search was conducted across the databases of Medline, Embase, Latin American and the Caribbean Literature on Health Sciences, Web of Science, and the Cochrane Central Register of Controlled Trials. Inclusion criteria consisted of RCTs that compared vasodilators versus standard care, placebo, or cointerventions. The primary outcome was all-cause mortality; secondary outcomes were serious adverse events (SAEs), tracheal intubation, and length of hospital stay. Risk of bias was assessed in all trials. RESULTS: The study included 46 RCTs that enrolled 28,374 patients with acute heart failure. Vasodilators did not reduce the risk of all-cause mortality (risk ratio, 0.95; 95% confidence interval [CI], 0.87 to 1.04; I2=9.51%; P=0.26). No evidence of a difference was seen in the risk of SAEs (risk ratio, 1.01; 95% CI, 0.97 to 1.05; I2=0.94%) or length of hospital stay (mean difference, -0.10; 95% CI, -0.28 to 0.08; I2=69.84%). Vasodilator use was associated with a lower risk of tracheal intubation (risk ratio, 0.54; 95% CI, 0.30 to 0.99; I2=51.96%) compared with no receipt of vasodilators. CONCLUSIONS: In this systematic review with meta-analysis of patients with acute heart failure, vasodilators did not reduce all-cause mortality.

Effects of trimetazidine on heart failure with reduced ejection fraction and associated clinical outcomes: a systematic review and meta-analysis.

BACKGROUND: Despite maximal treatment, heart failure (HF) remains a major clinical challenge. Besides neurohormonal overactivation, myocardial energy homoeostasis is also impaired in HF. Trimetazidine has the potential to restore myocardial energy status by inhibiting fatty acid oxidation, concomitantly enhancing glucose oxidation. Trimetazidine is an interesting adjunct treatment, for it is safe, easy to use and comes at a low cost. OBJECTIVE: We conducted a systematic review to evaluate all available clinical evidence on trimetazidine in HF. We searched Medline/PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov to identify relevant studies. METHODS: Out of 213 records, we included 28 studies in the meta-analysis (containing 2552 unique patients), which almost exclusively randomised patients with HF with reduced ejection fraction (HFrEF). The studies were relatively small (median study size: N=58) and of short duration (mean follow-up: 6 months), with the majority (68%) being open label. RESULTS: Trimetazidine in HFrEF was found to significantly reduce cardiovascular mortality (OR 0.33, 95% CI 0.21 to 0.53) and HF hospitalisations (OR 0.42, 95% CI 0.29 to 0.60). In addition, trimetazidine improved (New York Heart Association) functional class (mean difference: -0.44 (95% CI -0.49 to -0.39), 6 min walk distance (mean difference: +109 m (95% CI 105 to 114 m) and quality of life (standardised mean difference: +0.52 (95% CI 0.32 to 0.71). A similar pattern of effects was observed for both ischaemic and non-ischaemic cardiomyopathy. CONCLUSIONS: Current evidence supports the potential role of trimetazidine in HFrEF, but this is based on multiple smaller trials of varying quality in study design. We recommend a large pragmatic randomised clinical trial to establish the definitive role of trimetazidine in the management of HFrEF.

The Great Masquerade: Not All Coronary Artery Stenosis Are Created Equal.

We present the case of a 60-year-old male, with active smoking and cocaine use disorder, who reported progressive chest pain. Various anatomical and functional cardiac imaging, performed to further evaluate chest pain etiology, revealed changing severity and distribution of left main artery (LMA) stenosis, raising suspicion for vasospasm. Intracoronary nitroglycerin relieved the vasospasm, with resolution of the LMA pseudostenosis. A diagnosis of vasospastic angina (VA) led to starting appropriate medical therapy with lifestyle modification counselling. This case highlights VA, a frequently underdiagnosed etiology of angina pectoris. We discuss when to suspect VA, its appropriate work-up, and management.

Emergencies in Pulmonary Hypertension.

Pulmonary hypertension is a challenging disease entity with various underlying etiologies. The management of patients with pulmonary arterial hypertension (WHO Group 1) remains challenging especially in the critical care setting. With risk of high morbidity and mortality, these patients require a multidisciplinary team approach at a speciality care facility for pulmonary hypertension for comprehensive evaluation and rapid initiation of treatment. For acute decompensated right heart failure, management should concentrate on optimizing preload and after load with use of pulmonary vasodilator therapy. A careful evaluation of specialized situations is required for appropriate treatment response.

Influence of trimetazidine on myocardial injury in mice with diabetic cardiomyopathy.

INTRODUCTION: The prevalence of diabetes mellitus is increasing year by year globally, and diabetic cardiomyopathy (DCM), as the most common complication of type 2 diabetes mellitus, seriously affects the prognosis of patients. Trimetazidine (TMZ), as a drug affecting myocardial energy metabolism, mainly reduces the oxidation rate of ß-oxidation by inhibiting 3-ketoacyl-CoA thiolase (3-KAT), a key enzyme in ß-oxidation of free fatty acid (FFA), so that the energy metabolism substrate of cardiomyocytes preferentially selects glucose rather than fatty acids, increases the content of intracellular adenosine triphosphate (ATP), enhances the contractile function of cardiomyocytes, and improves the state of cellular ischemia and hypoxia. Previous studies have shown that TMZ is closely related to the activation and induction of apoptosis of the MAPK pathway and AMPK pathway, and plays a role in the treatment of diabetic cardiomyopathy, but the specific mechanism is still unclear. OBJECTIVE: This study aims to investigate the impact of TMZ on myocardial damage in mice exhibiting diabetic cardiomyopathy (DCM), and to furnish a laboratory foundation for the clinical treatment of diabetic cardiomyopathy. METHOD: Male db/db mice (6 weeks old, n = 21) and male wild-type (wt) (6 weeks old, n = 20) mice were selected for the study. The wt mice were randomly assigned to the wt group (n = 10) and wt + TMZ group (n = 10), while the remaining db/db mice were randomly allocated to the db/db group (n = 11) and db/db + TMZ group (n = 10). Following 8 weeks of feeding, the wt + TMZ group and db/db + TMZ group received TMZ via gavage, whereas the remaining groups were administered physiological saline. Periodic measurements of blood glucose, blood lipids, and myocardial enzymes were conducted in mice, with samples obtained after the 12th week for subsequent biochemical analysis, myocardial pathology assessment, immunohistochemistry, western blot analysis, and TUNEL staining (TdT-mediated dUTP Nick-End Labeling). RESULT: GLU, TC, TG, LDL-C, and CK-MB levels were significantly higher in db/db mice compared to wt mice (GLU: M ± SD wt 5.94 ± 0.37, db/db 17.63 ± 0.89, p < 0.05, ES = 0.991; TC: M ± SD wt 3.01 ± 0.32, db/db 6.97 ± 0.36, p < 0.05, ES = 0.972; TG: M ± SD wt 0.58 ± 0.2, db/db 1.75 ± 0.14, p < 0.05, ES = 0.920; LDL-C: M ± SD wt 1.59 ± 0.12, db/db 3.87 ± 0.14, p < 0.05, ES = 0.989; CK-MB: M ± SD wt 0.12 ± 0.01, db/db 0.31 ± 0.04, p < 0.05, ES = 0.928). HDL-C levels were significantly lower in db/db mice (M ± SD wt 1.89 ± 0.08, db/db 0.64 ± 0.09, p < 0.05, ES = 0.963). Histopathological analysis confirmed myocardial damage in db/db mice. Treatment with TMZ reduced GLU, TC, TG, LDL-C, and CK-MB levels (p < 0.05, ES > 0.9) and increased HDL-C levels compared to untreated db/db mice. Additionally, TMZ treatment significantly decreased myocardial cell apoptosis (p < 0.05, ES = 0.980). These results demonstrate the efficacy of TMZ in reversing myocardial injury in DCM mice. CONCLUSION: TMZ can mitigate myocardial damage in db/db mice by downregulating the expression of caspase-12, a protein associated with the endoplasmic reticulum stress (ERS) cell apoptosis pathway, consequently diminishing cell apoptosis. This underscores the protective efficacy of TMZ against myocardial damage in mice afflicted with DCM.

Nimodipine prophylaxis in aneurysmal subarachnoid hemorrhage, a question of tradition or evidence: A scoping review.

BACKGROUND: The prophylactic use of nimodipine following subarachnoid hemorrhage is a practice established four decades ago when clinical management differed from current and the concept of Delayed Cerebral Ischemia (DCI) was not established. The applicability of the original studies is limited by the fact of not reflecting current practice; by utilising a dichotomised outcome measure such as good neurological outcome versus death and vegetative state; by applying variable dosing regimens and including all causes of poor neurological outcome different than DCI. This study aims to review the available evidence to discuss the ongoing role of nimodipine in contemporaneous clinical practice. METHODS: PRISMA guidelines based review, evaluated the evidence on the prophylactic use of nimodipine. The following search engines: Medline, Embase, Cochrane, Web of Science and PubMed, identified Randomized Control Trials (RCTs) with neurological benefit as outcome measure and the impact of fixed versus weight-based nimodipine dosing regimens. RESULTS: Eight RCT were selected. Three of those trials with a total of 349 patients, showed a reduction on death and vegetative state (pooled RR: 0.62; 95 % confidence interval-CI: 0.45, 0.86) related to DCI. Amongst all studies, all cause death (pooled RR = 0.73, [95 % CI: 0.56, 0.97]) favoured a fixed-dose regimen (pooled RR: 0.60; [95 % CI: 0.43, 0.85]). CONCLUSION: Available evidence demonstrates that nimodipine only reduces the risk for DCI-related death or vegetative state and that fixed-dose regimens favour all cause infarct and death independent of DCI. Contemporaneous studies assessing the benefit of nimodipine beyond death or vegetative states and applying individualized dosing are warranted.

Sildenafil Versus Placebo for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS): protocol for a randomized controlled trial.

BACKGROUND: Pulmonary hypertension (PH) is a leading cause of death in patients with systemic sclerosis (SSc). An important component of SSc patient management is early detection and treatment of PH. Recently the threshold for the diagnosis of PH has been lowered to a mean pulmonary artery pressure (mPAP) threshold of > 20 mmHg on right heart catheterization (RHC). However, it is unknown if PH-specific therapy is beneficial in SSc patients with mildly elevated pressure (SSc-MEP, mPAP 21-24 mmHg). METHODS: The SEPVADIS trial is a randomized, double-blind, placebo-controlled phase 2 trial of sildenafil in SSc-MEP patients with a target enrollment of 30 patients from two academic sites in the United States. The primary outcome is change in six-minute walk distance after 16 weeks of treatment. Secondary endpoints include change in pulmonary arterial compliance by RHC and right ventricular function by cardiac magnetic resonance imaging at 16 weeks. Echocardiography, serum N-terminal probrain natriuretic peptide, and health-related quality of life is being measured at 16 and 52 weeks. DISCUSSION: The SEPVADIS trial will be the first randomized study of sildenafil in SSc-MEP patients. The results of this trial will be used to inform a phase 3 study to investigate the efficacy of treating patients with mild elevations in mPAP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04797286.

The "Preeclampsia and Hypertension Target Treatment" study: a multicenter prospective study to evaluate the effectiveness of the antihypertensive therapy based on maternal hemodynamic findings.

BACKGROUND: Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother besides normalizing the blood pressure values. OBJECTIVE: This study aimed to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy following the baseline hemodynamic findings. STUDY DESIGN: This was a prospective multicenter study that included a population of women with de novo diagnosis of hypertensive disorders of pregnancy. A noninvasive assessment of the following maternal parameters was performed on hospital admission via Ultrasound Cardiac Output Monitor before any antihypertensive therapy was given: cardiac output, heart rate, systemic vascular resistance, and stroke volume. The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and used as first-line treatment a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol) based on his preferences or on the local protocols. The first-line pharmacologic treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: (1) women with a hypodynamic profile (defined as low cardiac output [≤5 L/min] and/or high systemic vascular resistance [≥1300 dynes/second/cm2]) who were administered oral nifedipine or alpha methyldopa and (2) women with a hyperdynamic profile (defined as normal or high cardiac output [>5 L/min] and/or low systemic vascular resistances [<1300 dynes/second/cm2]) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between women treated with a hemodynamically appropriate therapy and women treated with an inappropriate therapy. RESULTS: A total of 152 women with hypertensive disorders of pregnancy were included in the final analysis. Most women displayed a hypodynamic profile (114 [75.0%]) and received a hemodynamically appropriate treatment (116 [76.3%]). The occurrence of severe hypertension before delivery was significantly lower in the group receiving an appropriate therapy than in the group receiving an inappropriately treated (6.0% vs 19.4%, respectively; P=.02). Moreover, the number of women who achieved target values of blood pressure within 48 to 72 hours from the treatment start was higher in the group who received an appropriate treatment than in the group who received an inappropriate treatment (70.7% vs 50.0%, respectively; P=.02). CONCLUSION: In pregnant individuals with de novo hypertensive disorders of pregnancy, a lower occurrence of severe hypertension was observed when the first-line antihypertensive agent was tailored to the correct maternal hemodynamic profile.

Systemic tolerance of intravenous milrinone administration for cerebral vasospasm secondary to non-traumatic subarachnoid hemorrhage.

PURPOSE: Delayed cerebral ischemia (DCI) is a severe subarachnoid hemorrhage (SAH) complication, closely related to cerebral vasospasm (CVS). CVS treatment frequently comprises intravenous milrinone, an inotropic and vasodilatory drug. Our objective is to describe milrinone's hemodynamic, respiratory and renal effects when administrated as treatment for CVS. METHODS: Retrospective single-center observational study of patients receiving intravenous milrinone for CVS with systemic hemodynamics, oxygenation, renal disorders monitoring. We described these parameters' evolution before and after milrinone initiation (day - 1, baseline, day 1 and day 2), studied treatment cessation causes and assessed neurological outcome at 3-6 months. RESULTS: Ninety-one patients were included. Milrinone initiation led to cardiac output increase (4.5 L/min [3.4-5.2] at baseline vs 6.6 L/min [5.2-7.7] at day 2, p < 0.001), Mean Arterial Pressure decrease (101 mmHg [94-110] at baseline vs 95 mmHg [85-102] at day 2, p = 0.001) norepinephrine treatment requirement increase (32% of patients before milrinone start vs 58% at day 1, p = 0.002) and slight PaO2/FiO2 ratio deterioration (401 [333-406] at baseline vs 348 [307-357] at day 2, p = 0.016). Milrinone was interrupted in 8% of patients. 55% had a favorable outcome. CONCLUSION: Intravenous milrinone for CVS treatment seems associated with significant impact on systemic hemodynamics leading sometimes to treatment discontinuation.

Survival and response to pulmonary vasodilator therapies in patients with chronic obstructive pulmonary disease and pulmonary vascular phenotype.

BACKGROUND: The aim of the study was to describe and investigate the effect of pulmonary arterial hypertension (PAH) therapies in a cohort of patients with severe precapillary pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD; PH-COPD), and to assess factors predictive of treatment response and mortality. MATERIAL AND METHODS: We retrospectively included patients with severe incident PH-COPD who received PAH therapy and underwent RHC at diagnosis and on treatment. RESULTS: From 2015 to 2022, 35 severe PH-COPD patients, with clinical features of pulmonary vascular phenotype, were included. Seventeen (48.5%) patients were treated with combined PAH therapy. PAH therapy led to a significant improvement in hemodynamics (PVR -3.5 Wood Units (-39.3%); p < 0.0001), and in the simplified four-strata risk-assessment score, which improved by at least one category in 21 (60%) patients. This effect was more pronounced in patients on dual therapy. Kaplan-Meier estimated survival rates at 1, 3 and 5 years were 94%, 65% and 42% respectively. Univariate analysis showed a significant reduction in survival in patients with a higher simplified risk score at follow-up (Hazard ratio (HR) 2.88 [1.16-7.15]; p = 0.02). Hypoxemia <50 mmHg was correlated to mortality in multivariate analysis (HR 4.33 [1.08-17.42]; p = 0.04). CONCLUSIONS: Our study confirms the poor prognosis of patients with COPD and a pulmonary vascular phenotype and the potential interest of combined PAH therapy in this population, with good tolerability and greater clinical and hemodynamic improvement than monotherapy. Using the simplified risk score during follow-up could be of interest in this population.