Withdrawal of drug therapy in responders to cardiac resynchronization therapy: rationale and design of the REMOVE trial.

INTRODUCTION AND OBJECTIVES: Cardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. METHODS: The REMOVE trial is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF >10% (provided the LVEF is <50%); b) a reduction in LVEF >10% accompanied by an increase >15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. CONCLUSIONS: The results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients. Registred at ClinicalTrials.gov (Identifier: NCT05151861).

The Possible Synergistic Pharmacological Effect of an Oral Berberine (BBR) and Curcumin (CUR) Complementary Therapy Alleviates Symptoms of Irritable Bowel Syndrome (IBS): Results from a Real-Life, Routine Clinical Practice Settings-Based Study.

Irritable bowel syndrome (IBS) is a prevalent chronic functional gastrointestinal disorder, characterised by recurrent abdominal discomfort and altered bowel movements. IBS cause a significantly negative impact on quality of life (QoL). Growing pharmacological evidence suggests that berberine (BBR) and curcumin (CUR) may mitigate IBS symptoms through multiple complementary synergistic mechanisms, resulting in the attenuation of intestinal inflammation and regulation of bowel motility and gut functions. In the present observational study conducted under real-life routine clinical practice settings, 146 patients diagnosed with IBS were enrolled by general practitioner clinics and pharmacies in Belgium. For the first time, this study assessed the potential synergistic pharmacological effect of a combined oral BBR/CUR supplement (Enterofytol® PLUS, containing 200 mg BBR and 49 mg CUR) (two tablets daily for 2 months), serving as complementary therapy in the management of IBS. Following the 2-month supplementation, significant improvements were observed in the patients' IBS severity index (IBSSI) (47.5%) and all the primary IBS symptoms, such as abdominal discomfort (47.2%), distension (48.0%), intestinal transit (46.8%), and QoL (48.1%) (all p < 0.0001). The improvement in the patients' IBSSI was independent of age, sex, and IBS sub-types. The patients' weekly maximum stool passage frequency decreased significantly (p < 0.0001), and the stool status normalized (p < 0.0001). The patients' need for concomitant conventional IBS treatment decreased notably: antispasmodics by 64.0% and antidiarrhoeals by 64.6%. Minor adverse effects were reported by a small proportion (7.1%) of patients, mostly gastrointestinal. The majority (93.1%) experienced symptom improvement or resolution, with a high satisfaction rate (82.6%) and willingness to continue the supplementation (79.0%). These findings support the potential synergistic pharmacological role of BBR and CUR in IBS, and their co-supplementation may alleviate IBS symptoms and improve QoL.

N-terminal pro-B-type natriuretic peptide post-discharge monitoring in the management of patients with heart failure and preserved ejection fraction - a randomized trial: The NICE study.

AIMS: There is a lack of specific studies assessing the impact of natriuretic peptide monitoring in the post-discharge management of patients with heart failure (HF) and preserved ejection fraction (HFpEF), throughout the vulnerable phase following acute HF hospitalization. The NICE study aims to assess the clinical benefit of incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) into the post-discharge management of HFpEF patients. METHODS AND RESULTS: Individuals admitted with HFpEF (left ventricular ejection fraction >50%) were included in a multicentre randomized controlled study employing an open-label design with event blinding (NCT02807168). Upon discharge, 157 patients were randomly allocated to either NT-proBNP monitoring (n = 79) or no access to NT-proBNP (control group, n = 78) during pre-scheduled visits at 2, 4 and 12 weeks. Clinical endpoints were evaluated at 6 months. The primary endpoint of HF rehospitalizations occurred in 12.1% patients, without significant differences observed between the NT-proBNP monitoring group (12.8%) and the control group (11.4%) (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.47-2.81, p = 0.760). Regarding secondary endpoints, the NT-proBNP monitoring group demonstrated a significantly lower risk of death (1.3% vs. 10.1%; HR 0.12, 95% CI 0.02-0.98; p = 0.048), whereas non-HF hospitalizations (12.8% vs. 19.0%, p = 0.171) and any adverse clinical event (26.9% vs. 36.7%, p = 0.17) did not reach statistical significance [Correction added on 29 April 2024, after first online publication: In the preceding sentence, "95% CI 0.02 - 0.09" has been corrected to "95% CI 0.02 - 0.98; p = 0.048" in this version.]. Awareness of NT-proBNP levels were associated with higher doses of diuretics and renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers) in the NT-proBNP monitoring group. CONCLUSIONS: Post-discharge monitoring of NT-proBNP in HFpEF patients did not exhibit an association with reduced rates of HF hospitalization in this study. Nonetheless, it appears to enhance global clinical management by optimizing medical therapies and contributing to improved overall survival.

Age-Related Differences in Testosterone Concentration and Its Relation to Testicular Biometrics, Hemodynamics, and Fertility in Alpacas (Vicugna pacos).

The goal of this study was to investigate the age-related differences in testosterone concentration and its relation to testicular biometrics, testicular blood flow, and fertility in alpacas (Vicugna pacos). Fifteen alpaca males with different ages (young (YM; ~12-14 mo.), n = 5; intermediate (IM; ~24 mo.), n = 5; and old (OM; ≥36 mo.), n = 5) were enrolled in the study. Blood samples were taken from each alpaca male and the circulating plasmatic testosterone concentration (TC; ng/mL) was determined using ELISA analysis. The testicular traits related to bio-morphometric parameters (the length (L), width (W), area (A), and volume (TV)) were assessed using B-mode ultrasonography. Pulse-wave/power Doppler ultrasonography was used to obtain the circulatory dynamic values (testicular hemodynamics) before the beginning of natural service mating. Significant differences were observed in TC among the age groups, increasing as the age of the males increased (2.47 ± 0.31, 8.45 ± 1.53, and 22.66 ± 2.15 for YM, IM, and OM, respectively; p < 0.05); however, no differences were observed regarding the testicular B-mode ultrasonographic parameters (L, W, and A) (p > 0.05). Positive correlations were observed between TV and testicular L, W, and A (r = 0.96, r = 0.95, and r = 0.96, respectively; p ≤ 0.001). Pulse-wave-Doppler-derived parameters such as the pulsatility index (PI) and the resistive index (RI), as well as the total vascularity area (TVA) assessed by power Doppler, were similar in all of the age groups studied (p > 0.05). General linear model (GLM) analysis showed a relationship between TC and TV (OR = 0.95; p = 0.04), as well as between TC and TVA (OR = 0.99; p= 0.02). Finally, no differences were observed regarding the pregnancy rate among the different age groups (p > 0.05). In conclusion, TC increased as the age of the alpaca males increased. Although TC was related to TV and TVA, the pregnancy rates obtained from individuals belonging to the different age groups were similar, indicating that TC, TV, and TVA were not determining factors in assessing the potential age-related fertility differences in alpaca males.

Impact of dapagliflozin on cardiac remodelling in patients with chronic heart failure: The DAPA-MODA study.

AIMS: Dapagliflozin improves the prognosis of patients with heart failure (HF), regardless of left ventricular ejection fraction (LVEF). However, its effect on cardiac remodelling parameters, specifically left atrial (LA) remodelling, is not well established. METHODS AND RESULTS: The DAPA-MODA trial (NCT04707352) is a multicentre, single-arm, open-label, prospective and interventional study that aimed to evaluate the effect of dapagliflozin on cardiac remodelling parameters over 6 months. Patients with stable chronic HF receiving optimized guideline-directed therapy, except for any sodium-glucose cotransporter 2 inhibitor, were included. Echocardiography was performed at baseline, 30 and 180 days, and analysed by a central core-lab in a blinded manner to both patient and time. The primary endpoint was the change in maximal LA volume index (LAVI). A total of 162 patients (64.2% men, 70.5 ± 10.6 years, 52% LVEF >40%) were included in the study. At baseline, LA dilatation was observed (LAVI 48.1 ± 22.6 ml/m2 ) and LA parameters were similar between LVEF-based phenotypes (≤40% vs. >40%). LAVI showed a significant reduction at 180 days (-6.6% [95% confidence interval -11.1, -1.8], p = 0.008), primarily due to a decrease in reservoir volume (-13.8% [95% confidence interval -22.5, -4], p = 0.007). Left ventricular geometry improved with significant reductions in left ventricular mass index (-13.9% [95% confidence interval -18.7, -8.7], p < 0.001), end-diastolic volume (-8.0% [95% confidence interval -11.6, -4.2], p < 0.001) and end-systolic volume (-11.9% [95% confidence interval -16.7, -6.8], p < 0.001) at 180 days. N-terminal pro-B-type natriuretic peptide (NT-proBNP) showed a significant reduction at 180 days (-18.2% [95% confidence interval -27.1, -8.2], p < 0.001), without changes in filling Doppler measures. CONCLUSION: Dapagliflozin administration in stable out-setting patients with chronic HF and optimized therapy results in global reverse remodelling of cardiac structure, including reductions in LA volumes and improvement in left ventricular geometry and NT-proBNP concentrations.

Diatomites from the Iberian Peninsula as Pozzolans.

The object of this work is to study and characterize diatomites from the southeast of the Iberian Peninsula to establish their character and quality as natural pozzolans. This research carried out a morphological and chemical characterization study of the samples using SEM and XRF. Subsequently, the physical properties of the samples were determined, including thermic treatment, Blaine particle finesse, real density and apparent density, porosity, volume stability, and the initial and final setting times. Finally, a detailed study was conducted to establish the technical properties of the samples through chemical analysis of technological quality, chemical analysis of pozzolanicity, mechanical compressive strength tests at 7, 28, and 90 days, and a non-destructive ultrasonic pulse test. The results using SEM and XRF show that the samples are composed entirely of colonies of diatoms whose bodies are formed by silica between 83.8 and 89.99% and CaO between 5.2 and 5.8%. Likewise, this indicates a remarkable reactivity of the SiO2 present in both natural diatomite (~99.4%) and calcined diatomite (~99.2%), respectively. Sulfates and chlorides are absent, while the insoluble residue portion for natural diatomite is 1.54% and 1.92% for calcined diatomite, values comparatively lower than the standardized 3%. On the other hand, the results of the chemical analysis of pozzolanicity show that the samples studied behave efficiently as natural pozzolans, both in a natural and calcined state. The mechanical tests establish that the mechanical strength of the mixed Portland cement and natural diatomite specimens (52.5 MPa) with 10% PC substitution exceeds the reference specimen (51.9 MPa) after 28 days of curing. In the case of the specimens made with Portland cement and calcined diatomite (10%), the compressive strength values increase even more and exceed the reference specimen at both 28 days (54 MPa) and 90 days (64.5 MPa) of curing. The results obtained in this research confirm that the diatomites studied are pozzolanic, which is of vital importance because they could be used to improve cements, mortars, and concrete, which translates to a positive advantage in the care of the environment.

Ignimbrites Related to Neogene Volcanism in the Southeast of the Iberian Peninsula: An Experimental Study to Establish Their Pozzolanic Character.

The speed at which climate change is happening is leading to a demand for new pozzolanic materials that improve the quality of cements and, at the same time, limit the emission of greenhouse gases into the atmosphere. The main objective of this work is the detailed characterization of an ignimbrite sample (IGNS) to demonstrate its effectiveness as a natural pozzolan. To meet this objective, a series of tests were carried out. In the first stage, mineral and chemical analyses were performed, such as petrographic analysis by thin section (TSP), X-ray diffraction (XRD), oriented aggregate (OA), scanning electron microscopy (SEM) and X-ray fluorescence (XRF). In the second stage, the following technical tests were carried out: chemical quality analysis (QCA), pozzolanicity test (PT) and mechanical compressive strength (MS) at 7, 28 and 90 days, using mortar specimens with ignimbrite/cement formulation (IGNS/PC): 10, 25 and 40% to establish the pozzolanic nature of the ignimbrite. The results of the mineral and chemical analyses showed that the sample has a complex mineralogical constitution, consisting of biotite mica, potassium feldspar, plagioclase, smectite (montmorillonite), quartz, volcanic glass, iron, titanium and manganese oxides, chlorite and chlorapatite. On the other hand, the technological tests revealed the pozzolanic nature of the sample, as well as visible increases in the mechanical compressive strengths in the three proportions, the most effective being IGNS/PC:10% and IGNS/PC:25% at 7, 28 and 90 days of setting. The results obtained could be applied in the formulation of new pozzolanic cements with ignimbrite as a natural pozzolanic aggregate.

Impact of ferric carboxymaltose for iron deficiency at discharge after heart failure hospitalization: a European multinational economic evaluation.

AIMS: Iron deficiency (ID) is comorbid in up to 50% patients with heart failure (HF) and exacerbates disease burden. Ferric carboxymaltose (FCM) reduced HF hospitalizations and improved quality of life when used to treat ID at discharge in patients hospitalized for acute HF with left ventricular ejection fraction <50% in the AFFIRM-AHF trial. We quantified the effect of FCM on burden of disease and the wider pharmacoeconomic implications in France, Germany, Poland, Spain and Sweden. METHODS AND RESULTS: The per country eligible population was calculated, aligning with the 2021 European Society of Cardiology (ESC) HF guidelines and the AFFIRM-AHF trial. Changes in burden of disease with FCM versus standard of care (SoC) were represented by disability-adjusted life years (DALYs), hospitalization episodes and bed days, using AFFIRM-AHF data. A Markov model was adapted to each country to estimate cost-effectiveness and combined with epidemiology data to calculate the impact on healthcare budgets. Between 335 (Sweden) and 13 237 (Germany) DALYs were predicted to be avoided with FCM use annually. Fewer hospitalizations and shorter lengths of stay associated with FCM compared to SoC were projected to result in substantial annual savings in bed days, from 5215 in Sweden to 205 630 in Germany. In all countries, FCM was predicted to be dominant (cost saving with gains in quality-adjusted life years), resulting in net savings to healthcare budgets within 1 year. CONCLUSIONS: This comprehensive evaluation of FCM therapy highlights the potential benefits that could be realized through implementation of the ESC HF guideline recommendations regarding ID treatment.

Clonal hematopoiesis is not prevalent in Hutchinson-Gilford progeria syndrome.

Clonal hematopoiesis of indeterminate potential (CHIP), defined as the presence of somatic mutations in cancer-related genes in blood cells in the absence of hematological cancer, has recently emerged as an important risk factor for several age-related conditions, especially cardiovascular disease. CHIP is strongly associated with normal aging, but its role in premature aging syndromes is unknown. Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare genetic condition driven by the accumulation of a truncated form of the lamin A protein called progerin. HGPS patients exhibit several features of accelerated aging and typically die from cardiovascular complications in their early teens. Previous studies have shown normal hematological parameters in HGPS patients, except for elevated platelets, and low levels of lamin A expression in hematopoietic cells relative to other cell types in solid tissues, but the prevalence of CHIP in HGPS remains unexplored. To investigate the potential role of CHIP in HGPS, we performed high-sensitivity targeted sequencing of CHIP-related genes in blood DNA samples from a cohort of 47 HGPS patients. As a control, the same sequencing strategy was applied to blood DNA samples from middle-aged and elderly individuals, expected to exhibit a biological age and cardiovascular risk profile similar to HGPS patients. We found that CHIP is not prevalent in HGPS patients, in marked contrast to our observations in individuals who age normally. Thus, our study unveils a major difference between HGPS and normal aging and provides conclusive evidence that CHIP is not frequent in HGPS and, therefore, is unlikely to contribute to the pathophysiology of this accelerated aging syndrome.

Ovarian Follicular Dynamics and Its Functional Significance in Relation with Follicle Deviation, Vaginal Cytology, and Hormone Profiles in Llamas (Lama glama).

The reproductive physiology in camelid species has its particularities. The present study aimed to characterize the ovarian follicular dynamics and its functional significance in relation to follicular deviation, vaginal cytological characteristics, and sexual hormone profiles in llamas as the first report in South American camelids. Non-pregnant, multiparous llamas (Lama glama; n = 10; age: 48−72 mo.; BCS: 2.5−3.0) were enrolled in the study. The ultrasonographic assessment was carried out transvaginally and follicular ablation was performed (day 0) when follicles were larger than 7 mm. The follicle number and diameter were scored daily throughout the process for a proper evaluation of the deviated follicles and to monitor the presence of new follicle pools (1.5 to 2.5 mm diameter). Vaginal cytological evaluation (parabasal, intermediate, and superficial cells) was performed every other day until day 6. Endocrine profiles (17ß estradiol, anti-Mullerian hormone, testosterone, and progesterone) during pre- and post-follicular deviation were determined by using the ELISA assay. Differential follicular dynamics both in the presence of a single dominant follicle (DF) and in codominance during the follicular deviation process were detected in llamas (p < 0.05). The percentage of superficial cells was the most related to the follicular wave phase. However, the percentage of parabasal, intermediate, and superficial cells was not related to the phases of follicular growth, dominance, and regression (p > 0.05). Differential patterns among the different hormone concentration levels regarding the 17ß estradiol, anti-Mullerian hormone, progesterone, and testosterone during follicular deviation were observed, with the latter being significantly different along the deviation process (p < 0.05). In conclusion, the use of vaginal cytology assessment would not be sufficient to determine the follicular phases in llamas. Therefore, complementary analyses, such as ultrasonography and endocrine assessment, are strongly recommended to determine follicular dynamics during the follicular deviation.

Neuroendocrine Carcinoma of the Gallbladder.

Neuroendocrine carcinoma of the gallbladder (NECGB) is a rare, aggressive tumor with a poor prognosis. There are two main categories, well-differentiated NECGB and poorly differentiated NECGB, the latter with a worse prognosis. The clinical presentation is non-specific, but the occurrence is more frequent in women with cholelithiasis. Histologic and immuno-histochemical confirmation is required to establish the diagnosis. Treatment is primarily surgery with or without adjuvant chemotherapy. We present the case of a 43-year-old woman with pain in the right upper quadrant, diagnosed with NECGB following cholecystectomy. Subsequently, she received cycles of chemotherapy.

Valores extremos del IMC materno: factores determinantes de peores resultados obstétricos y perinatales / Extreme values of maternal BMI: Determinants of worse obstetric and perinatal outcomes

Objetivo: Conocer la influencia del índice de masa corporal (IMC) materno al inicio del embarazo en los resultados obstétricos-perinatales. Material y métodos: Estudio observacional-ambispectivo. Se incluyeron 1.407 pacientes con gestaciones únicas y partos de fetos>24 semanas entre el 01/12/2017 y el 31/07/2019. La muestra fue estratificada según su IMC según la clasificación de la OMS. Se analizaron variables sobre: enfermedad pregestacional, gestacional, asistencia obstétrica y resultados maternos-perinatales y se compararon entre los grupos estudiados. El programa estadístico utilizado ha sido R Core Team 2020, versión 3.6.3. Un valor de p≤0,05 se consideró significativo. Resultados: Las obesas ii-iii (IMC 35-39 e IMC≥40, respectivamente) tienen mayor riesgo de hipertensión arterial crónica (OR 53,54, IC95% 18,21-229,02), diabetes gestacional (OR 5,24, IC95% 2,87-9,51) y preeclampsia (OR 2,38, IC95% 0,95-5,51; p=0,049). Las de bajo peso tuvieron más fetos con crecimiento intrauterino restringido (OR 3,09, IC95% 1,46-6,17). Las inducciones del parto y las cesáreas aumentan conforme lo hace el IMC (p=0,006). Las pacientes con bajo peso también tuvieron mayor riesgo de cesárea (OR 2,46, IC95% 1,06-5,20). Los ingresos neonatales fueron más frecuentes en mujeres obesas y con bajo peso (OR 2,68, IC95% 1,39-5,00, y OR 2,56, IC95% 1,10-5,44, respectivamente). Las obesas tuvieron más riesgo de peso neonatal>4.000g (OR 3,06, IC95% 1,57-5,77) y las gestantes de bajo peso más riesgo de peso neonatal<2.500g (OR 2,94, IC95% 1,54-5,41). Conclusión: Los valores extremos del IMC materno al inicio de la gestación son factores determinantes para un desenlace obstétrico-perinatal adverso.(AU)

Objective: To study the influence of maternal body mass index (BMI) at the beginning of pregnancy on obstetric-perinatal outcomes. Material and methods: Observational-ambispective study. We recruited 1407 patients with singleton gestations and deliveries of foetuses>24 weeks between 01/12/2017 and 31/07/2019. The sample was stratified according to their BMI following the WHO classification. Variables on pre-pregnancy, gestational disease, obstetric care, and maternal-perinatal outcomes were analysed and compared between the studied groups. The statistical program has been R Core Team 2020, version 3.6.3. P≤.05 was considered significant. Results: Class II-III (BMI 35-39 and BMI≥40 respectively) obese women have a higher risk of chronic arterial hypertension (OR 53.54, 95% CI 18.21-229.02), gestational diabetes (OR 5.24, 95% CI 2.87-9.51) and preeclampsia (OR 2.38, 95% CI 0.95-5.51 with P=.049). The underweight women had more intrauterine growth restriction diagnoses (OR 3.09, 95% CI 1.46-6.17). Inductions of labour and caesarean sections increase as BMI increases (P=.006). Low weight patients also had a higher risk of caesarean section (OR 2.46, 95% CI 1.06-5.20). Neonatal admissions were more frequent in obese and underweight women (OR 2.68, 95% CI 1.39-5.00 and OR 2.56, 95% CI 1.10-5.44 respectively). Obese women had a higher risk of neonatal weight>4000g (OR 3.06, 95% CI 1.57-5.77) and low weight pregnant women had a higher risk of neonatal weight<2500g (OR 2.94, 95% CI 1.54-5.41). Conclusion: Extreme values of maternal BMI at the beginning of gestation are determining factors for an adverse obstetric-perinatal outcome.(AU)

Oral Co-Supplementation of Curcumin, Quercetin, and Vitamin D3 as an Adjuvant Therapy for Mild to Moderate Symptoms of COVID-19-Results From a Pilot Open-Label, Randomized Controlled Trial.

Background: Curcumin, quercetin, and vitamin D3 (cholecalciferol) are common natural ingredients of human nutrition and reportedly exhibit promising anti-inflammatory, immunomodulatory, broad-spectrum antiviral, and antioxidant activities. Objective: The present study aimed to investigate the possible therapeutic benefits of a single oral formulation containing supplements curcumin, quercetin, and cholecalciferol (combinedly referred to here as CQC) as an adjuvant therapy for early-stage of symptomatic coronavirus disease 2019 (COVID-19) in a pilot open-label, randomized controlled trial conducted at Mayo Hospital, King Edward Medical University, Lahore, Pakistan. Methods: Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed, mild to moderate symptomatic COVID-19 outpatients were randomized to receive either the standard of care (SOC) (n = 25) (control arm) or a daily oral co-supplementation of 168 mg curcumin, 260 mg quercetin, and 9 µg (360 IU) of cholecalciferol, as two oral soft capsules b.i.d. as an add-on to the SOC (n = 25) (CQC arm) for 14 days. The SOC includes paracetamol with or without antibiotic (azithromycin). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test, acute symptoms, and biochemistry including C-reactive protein (CRP), D-dimer, lactate dehydrogenase, ferritin, and complete blood count were evaluated at baseline and follow-up day seven. Results: Patients who received the CQC adjuvant therapy showed expedited negativization of the SARS-CoV-2 RT-PCR test, i.e., 15 (60.0%) vs. five (20.0%) of the control arm, p = 0.009. COVID-19- associated acute symptoms were rapidly resolved in the CQC arm, i.e., 15 (60.0%) vs. 10 (40.0%) of the control arm, p = 0.154. Patients in the CQC arm experienced a greater fall in serum CRP levels, i.e., from (median (IQR) 34.0 (21.0, 45.0) to 11.0 (5.0, 16.0) mg/dl as compared to the control arm, i.e., from 36.0 (28.0, 47.0) to 22.0 (15.0, 25.0) mg/dl, p = 0.006. The adjuvant therapy of co-supplementation of CQC was safe and well-tolerated by all 25 patients and no treatment-emergent effects, complications, side effects, or serious adverse events were reported. Conclusion: The co-supplementation of CQC may possibly have a therapeutic role in the early stage of COVID-19 infection including speedy negativization of the SARS-CoV-2 RT-PCR test, resolution of acute symptoms, and modulation of the hyperinflammatory response. In combination with routine care, the adjuvant co-supplementation of CQC may possibly help in the speedy recovery from early-stage mild to moderate symptoms of COVID-19. Further research is warranted. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT05130671.

[Retinoblastoma at the Campus-University Teaching Hospital in Lomé, Togo, from 2014 to 2018]. / Le rétinoblastome au Centre Hospitalier Universitaire-Campus de Lomé, Togo, de 2014 à 2018.

INTRODUCTION: Retinoblastoma is a curable cancer when management is early and prompt. OBJECTIVE: To describe the epidemiological, clinical and therapeutic aspects of retinoblastoma. MATERIALS AND METHODS: A retrospective study was carried out from January 2014 to December 2018 (5 years) at the department of ophthalmology in Campus-University Teaching Hospital, Lomé, Togo. It focused on children with retinoblastoma. It included patients with diagnosis supported by ocular ultrasonography, orbito-cerebral computed tomography scan and/or histopathological examination. RESULTS: Among the 75 children with ocular cancer, 26 (34.7%) were diagnosed with retinoblastoma. The mean age at presentation was 31 months. The mean time from symptom onset to diagnosis was 15 months. A predominance of proptosis (65.4%), unilateral involvement (76.9%), extraocular tumor extension (65.4%) and endophytic form (96.15%) was found. Of the 32 eyes with retinoblastoma, 7 (21.9%) were enucleated after a mean time from diagnosis to enucleation of 6 months. Two cases of complete remission, 3 cases of tumor recurrence, and 2 cases lost to follow-up were noted. CONCLUSION: In our setting, retinoblastoma is a frequent childhood ocular cancer. It is important to improve the management of retinoblastoma as well as education of the parents.

Unnecessary Use of Corticosteroids for managing early mild symptoms of COVID-19 may lead to Rhino-ortibal-cerebral mucormycosis in Patients with Diabetes - a case series from Lahore, Pakistan.

Rhino-orbital-cerebral mucormycosis (ROCM), a rare but fatal fungal infection, has recently emerged as a serious complication after corticosteroids therapy in COVID-19 patients, predominantly in diabetic and immunocompromised patients. The World Health Organization (WHO) COVID-19 current guidelines recommend corticosteroids administration in hospitalized COVID-19 patients requiring supplementary oxygen or mechanical ventilation. Herein, we report a case series of seven patients with COVID-19; three mild, three moderate, and one severe, from Lahore, Pakistan; all were using corticosteroids for managing their early mild symptoms of COVID-19 at home for around 2-3 weeks without a physician's advise, presented, and admitted with ROCM to Mayo hospital, Lahore, from March to June 2021. Out of the seven patients, five patients had uncontrolled diabetes mellitus (DM) as comorbidity. Eye pain, facial swelling and pain, nasal blockage, and black coloration around eyes, on palate, and oral mucosa were the presenting complaints at the time of admission. All the patients had radiographic imaging, including computed tomography (CT), paranasal sinuses (PNS), or brain magnetic resonance imaging (MRI) carried out at the hospital, which confirmed mucosal thickening and adjacent sinus bony erosions with intracranial extension. All the patients were treated with local debridement of the infected necrotic tissue along with intravenous liposomal Amphotericin B and Posaconazole or Amphotericin B depending on the case. Due to timely management, in six out of seven patients, prognosis was good due to early diagnosis and treatment, while one patient with severe COVID-19 illness deteriorated and died. The misuse of corticosteroids for managing early mild symptoms of COVID-19 in diabetic and other immunocompromised patients can lead to fatal ROCM, which can further increase their risk of developing severe COVID-19 and mortality. It is stressed that only physician's recommended therapeutic advice should be followed for managing early mild symptoms of COVID-19 in self-isolation and avoid the unnecessary use of corticosteroids. This case series also emphasizes that COVID-19 diabetic patients treated with corticosteroids need more vigilant monitoring and high suspicion of early diagnosis and treatment of invasive fungal infection. Early diagnosis and management can reduce morbidity and mortality.

Sacubitril/valsartan affects pulmonary arterial pressure in heart failure with preserved ejection fraction and pulmonary hypertension.

AIMS: Prior studies have not fully characterized the haemodynamic effects of the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan in heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF-PH). The aim of the Treatment of PH With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in HFpEF Patients With CardioMEMS Device (ARNIMEMS-HFpEF) study is to assess pulmonary artery pressure (PAP) dynamics by means of implanted PAP monitors in patients with HFpEF-PH treated with sacubitril/valsartan. METHODS AND RESULTS: This single-arm, investigator-initiated, interventional study included 14 consecutive ambulatory symptomatic HFpEF-PH patients who underwent CardioMEMS implantation prior to enrolment [mean ejection fraction 60.4 ± 7.2%, baseline mean PAP (mPAP) 33.9 ± 7.6 mmHg]. Daily PAP values were examined during three periods: a 6 week period after CardioMEMS implantation and before sacubitril/valsartan treatment (pre-ARNI), a 6 week period with sacubitril/valsartan treatment (ARNI ON), and a 6 week period of sacubitril/valsartan withdrawal (ARNI OFF). The primary endpoint was change in mPAP with and without sacubitril/valsartan. Secondary endpoints included changes in 6 min walking distance, B-line sum in lung ultrasound, and quality of life (QoL). During the study period, 1717 mPAP measurements were recorded. Between pre-ARNI vs. ARNI ON, mPAP significantly declined by -4.99 mmHg [95% confidence interval (CI) -5.55 to -4.43]. Between ARNI ON vs. ARNI OFF, mPAP significantly increased by +2.84 mmHg [95% CI +2.26 to +3.42]. Between pre-ARNI vs. ARNI ON, we found an improvement in 6 min walking distance, B-lines, and QoL. Mean loop diuretic management did not differ between periods. CONCLUSIONS: Sacubitril/valsartan significantly reduced mPAP in patients with HFpEF-PH, independent of loop diuretic management, together with improvement in functional capacity, lung congestion, and QoL. Sacubitril/valsartan may be a therapeutic alternative in HFpEF-PH.