Underlying Mechanisms and Treatment of Hypertension in Glomerular Diseases.

PURPOSE OF REVIEW: This review aims to explore the underlying mechanisms that lead to hypertension in glomerular diseases and the advancements in treatment strategies and to provide clinicians with valuable insights into the pathophysiological mechanisms and evidence-based therapeutic approaches for managing hypertension in patients with glomerular diseases. RECENT FINDINGS: In recent years, there have been remarkable advancements in our understanding of the immune and non-immune mechanisms that are involved in the pathogenesis of hypertension in glomerular diseases. Furthermore, this review will encompass the latest data on management strategies, including RAAS inhibition, endothelin receptor blockers, SGLT2 inhibitors, and immune-based therapies. Hypertension (HTN) and cardiovascular diseases are leading causes of mortality in glomerular diseases. The latter are intricately related with hypertension and share common pathophysiological mechanisms. Hypertension in glomerular disease represents a complex and multifaceted interplay between kidney dysfunction, immune-mediated, and non-immune-mediated pathology. Understanding the complex mechanisms involved in this relationship has evolved significantly over the years, shedding light on the pathophysiological processes underlying the development and progression of glomerular disease-associated HTN, and is crucial for developing effective therapeutic strategies and improving patients' outcomes.

Consensus recommendations on fasting during Ramadan for patients with kidney disease: review of available evidence and a call for action (RaK Initiative).

Ramadan fasting (RF) involves abstaining from food and drink during daylight hours; it is obligatory for all healthy Muslims from the age of puberty. Although sick individuals are exempt from fasting, many will fast anyway. This article explores the impact of RF on individuals with kidney diseases through a comprehensive review of existing literature and consensus recommendations. This study was conducted by a multidisciplinary panel of experts.The recommendations aim to provide a structured approach to assess and manage fasting during Ramadan for patients with kidney diseases, empowering both healthcare providers and patients to make informed decisions while considering their unique circumstances.

Anterior Distal Femoral Hemiepiphysiodesis Using Coronally Oriented 8-plates for the Correction of Fixed Knee Flexion Deformities in Children-Preliminary Results.

INTRODUCTION: The original technique for guided growth of the distal femur for correction of pediatric fixed knee flexion deformities (FKFDs) involves the utilization of two 8-plates inserted on either side of the trochlear groove, a technique that has been frequently linked to the development of persistent postoperative knee pain and crepitus. The present study aimed to assess the preliminary results of a novel technique where the two 8-plates are fixed in the coronal plane, one on each of the medial and lateral surfaces, so that they occupy the anterior part of the distal femur. METHODS: Our study was a prospective case series that included cases with FKFD of >10 degrees in children with at least 12 months of predicted growth remaining. The preoperative knee flexion contracture angle was documented. The surgical procedure entailed the insertion of 2 coronally oriented 8-plates on the medial and lateral surfaces of the distal femur as anterior as possible to the axis of the femur without encroachment on the trochlear groove. The duration of time required to attain full knee extension and any complications encountered were recorded. Wilcoxon signed-rank was used to compare the preoperative and final contracture angles. The level of statistical significance was set at P<0.05. RESULTS: Thirteen knees in 8 patients (6 boys and 2 girls) were included. The median age was 11 years (6 to 14). There was a significant improvement in the FKFD for the whole cohort from 25 degrees (14 to 42) to 0 degrees (-9 to 8), P<0.05. The median rate of correction was 2.0 degrees/month (0.9 to 5.8). The time till full correction was 14 months (4 to 25). Postoperative knee pain and metalware-related complications were not reported by any patient during follow-up. CONCLUSIONS: Guided growth of the distal femur using coronally oriented 8-plates is an effective procedure for the treatment of FKFDs in children. This modified technique may achieve faster correction while minimizing the risk of postoperative knee pain compared with the conventional technique. LEVEL OF EVIDENCE: Level IV-case series.

Human Monoclonal Antibody Cocktail for the Treatment or Prophylaxis of Middle East Respiratory Syndrome Coronavirus.

BACKGROUND: REGN3048 and REGN3051 are human monoclonal antibodies (mAb) targeting the spike glycoprotein on the Middle East respiratory syndrome coronavirus (MERS-CoV), which binds to the receptor dipeptidyl peptidase-4 (DPP4) and is necessary for infection of susceptible cells. METHODS: Preclinical study: REGN3048, REGN3051 and isotype immunoglobulin G (IgG) were administered to humanized DPP4 (huDPP4) mice 1 day prior to and 1 day after infection with MERS-CoV (Jordan strain). Virus titers and lung pathology were assessed. Phase 1 study: healthy adults received the combined mAb (n = 36) or placebo (n = 12) and followed for 121 days. Six dose levels were studied. Strict safety criteria were met prior to dose escalation. RESULTS: Preclinical study: REGN3048 plus REGN3051, prophylactically or therapeutically, was substantially more effective for reducing viral titer, lung inflammation, and pathology in huDPP4 mice compared with control antibodies and to each antibody monotherapy. Phase 1 study: REGN3048 plus REGN3051 was well tolerated with no dose-limiting adverse events, deaths, serious adverse events, or infusion reactions. Each mAb displayed pharmacokinetics expected of human IgG1 antibodies; it was not immunogenic. CONCLUSIONS: REGN3048 and REGN3051 in combination were well tolerated. The clinical and preclinical data support further development for the treatment or prophylaxis of MERS-CoV infection.

Assessment of glycemia in chronic kidney disease.

Reliable assessment of glycemia is central to the management of diabetes. The kidneys play a vital role in maintaining glucose homeostasis through glucose filtration, reabsorption, consumption, and generation. This review article highlights the role of the kidneys in glucose metabolism and discusses the benefits, pitfalls, and evidence behind the glycemic markers in patients with chronic kidney disease. We specifically highlight the role of continuous glucose monitoring as an emerging minimally invasive technique for glycemic assessment.

Diabetes and COVID-19: Short- and Long-Term Consequences.

When the corona pandemic commenced more than two years ago, it was quickly recognized that people with metabolic diseases show an augmented risk of severe COVID-19 and an increased mortality compared to people without these comorbidities. Furthermore, an infection with SARS-CoV-2 has been shown to lead to an aggravation of metabolic diseases and in single cases to new-onset metabolic disorders. In addition to the increased risk for people with diabetes in the acute phase of COVID-19, this patient group also seems to be more often affected by long-COVID and to experience more long-term consequences than people without diabetes. The mechanisms behind these discrepancies between people with and without diabetes in relation to COVID-19 are not completely understood yet and will require further research and follow-up studies during the following years. In the current review, we discuss why patients with diabetes have this higher risk of developing severe COVID-19 symptoms not only in the acute phase of the disease but also in relation to long-COVID, vaccine breakthrough infections and re-infections. Furthermore, we discuss the effects of lockdown on glycemic control.

Obesity and COVID-19: What are the Consequences?

Obesity is an increasing health problem all over the world. In combination with the current COVID-19 pandemic, this has turned into a massive challenge as individuals with overweight and obesity at all ages show a significant increase in their risk of getting severe COVID-19. Around 20% of all patients that were hospitalized for COVID-19 suffered from obesity alone, whereas obesity in combination with other metabolic comorbidities, such as type 2 diabetes and hypertension, account for up to 60% of all hospitalizations in relation to COVID-19. Therefore, it is of immense importance to put the spotlight on the high incidence of obesity present already in childhood both by changing the individual minds and by encouraging politicians and the whole society to commence preventive interventions for achieving a better nutrition for all social classes all over the world. In the current review, we aim to explain the different pathways and mechanisms that are responsible for the increased risk of severe COVID-19 in people with overweight and obesity. Furthermore, we discuss how the pandemic has led to weight gains in many people during lockdown. At the end, we discuss the importance of preventing such an interface between a non-communicable disease like obesity and a communicable disease like COVID-19 in the future.

Prevalence and associated risk factors of hypertension and pre-hypertension among the adult population: findings from the Dubai Household Survey, 2019.

BACKGROUND: Minimal data is available on the prevalence and correlates of hypertension and prehypertension in Dubai. The study aims to measure the prevalence of hypertension and pre-hypertension and the associated socio-demographic characteristics, behavioral risk factors and comorbidities among the adult population of Dubai. METHODS: This study used data from the Dubai Household Health Survey, 2019. A cross-sectional population survey based on a complex stratified cluster random design. The total eligible sample included 2530 adults (18+). Sociodemographic and behavioral factors were considered as independent covariates. The main study outcome variables, pre-hypertension and hypertension, were ordinal, with normotension as the reference group. RESULTS: The overall prevalence of hypertension in adults was 32.5% (38.37% in males and 16.66% in females). Prehypertension was prevalent in 29.8% of adults in Dubai (28.85% in males and 32.31% in females). The multivariate logistic regression analysis revealed that age groups, gender, occupation, and high Body Mass Index were significantly associated with a higher risk of hypertension at the level of P < 0.05. No clear trend toward a higher correlation of hypertension was noted with the increase in age, except after the age of 50 years. Males were five- times more likely to be hypertensive than females. Participants enrolled in skilled and service works had a five times higher risk of hypertension, compared with the reference group (professionals). Obese subjects had a 5.47-times greater correlation of hypertension compared with normal-weight subjects. Physically active individuals were less likely to develop hypertension. For the correlates with prehypertension in the present analysis, skilled and service workers and those working in elementary jobs had a higher risk of prehypertension, compared with the reference group (professionals) Individuals with a status of overweight were associated with a higher prevalence of prehypertension compared with people of normal weight. CONCLUSIONS: This study showed a high prevalence of prehypertension and hypertension among adults in Dubai. Some socio-demographic and behavioral risk factors were correlated with prehypertension and hypertension among the studied population. Interventions aiming at increasing public awareness about such risk factors are essential.

Mini-open Anterior Pelvic Osteotomy and Spica Casting for Primary Closure of the Pelvis in Infants With Classic Bladder Exstrophy.

BACKGROUND: The objective of this study was to investigate the efficacy and safety of mini-open Salter-like anterior pelvic osteotomy followed by spica casting as an adjunct to urological reconstruction in infants with classic bladder exstrophy (CBE). METHODS: Twenty-eight infants with CBE were operated upon according to the following protocol: initial bilateral mini-open Salter-like osteotomies followed by urological reconstruction and subsequent spica casting for 3 to 4 weeks. Postoperative clinical and radiologic assessments of wound complications and union were done, respectively. During subsequent follow-ups, the foot progression angle (FPA), the interpubic (IP) distance, interischial (IS) distance, and the IS/IP ratio were measured. The Pearson correlation was used to correlate between age at the time of last follow-up, the FPA, the IP and IS distances, and the IS/IP ratio. RESULTS: The mean age at the time of operation was 5.89±0.89 months. The operative procedure took 10 to 15 minutes (mean of 12.5±1.5 min) for each side and the blood loss was negligible. Tension-free complete approximation of the symphysis was achieved in all cases. No wound complications were reported in any case. The total duration of the cast was 3.07±0.14 weeks. The mean duration of follow-up was 4.78±3.09 years. Strong positive correlation was found between the IP and IS distances ( r =0.833, P <0.0001) as well as the IS distance and age (r=0.455, P =0.015). CONCLUSION: Mini-open anterior pelvic osteotomy and spica casting may provide a minimally invasive and effective option for closure of the pelvis in infants with CBE. LEVEL OF EVIDENCE: Level IV-case series.

Mechanics of guided growth of the distal femur for correction of fixed knee flexion deformities: an extra-articular technique.

INTRODUCTION: Anterior distal femoral hemiepiphysiodesis using intra-articular plates for correction of pediatric fixed knee flexion deformities (FKFD) has two documented complications: postoperative knee pain and implant loosening. The aim of this study is to investigate the mechanical properties of a novel extra-articular technique for anterior distal femoral hemiepiphysiodesis in patients with FKFD and to compare them to the conventional technique. MATERIALS AND METHODS: Sixteen femoral sawbones were osteotomized at the level of the distal femoral physis and fixed by rail frames to allow linear distraction simulating longitudinal growth. Each sawbone was tested twice: first using the conventional technique with eight plates placed anteriorly just medial and lateral to the femoral sulcus (group A) and then with plates inserted in the proposed novel location at the most anterior part of the medial and lateral surfaces of the femoral condyles with screws in the coronal plane (group B). Gradual linear distraction was performed, and the resulting angular correction was measured. Strain gauges were attached to the plates, and the amount of strain (and equivalent stress) over the plates in response to linear distraction was recorded. The two groups were compared using the Wilcoxon signed-rank test. RESULTS: The amount of angular correction was statistically higher in group B (extra-articular plates) at 5, 10-, and 15-mm of distraction (p < 0.001). As regards stress over the plates, the maximum stress and the area under the curve (sum of all stresses measured throughout the distraction process) were significantly higher when the plates were inserted at the conventional position (group A) (p < 0.001). CONCLUSIONS: During anterior distal femoral hemiepiphysiodesis, the fixation of the eight plates in the coronal plane at the anterior part of the femoral condyles may produce a greater amount of correction and a lower degree of stress over the implants as compared to the conventional technique.

Ramadan Intermittent Fasting Is Associated with Changes in Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Metabolically Healthy Obese Subjects.

Background and Objectives: Dietary modification is the principal approach to the management of hyperlipidemia in adults. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of plasma cholesterol and a target for novel lipid-lowering pharmacotherapies. This study aimed to explore how circulating levels of PCSK9 changed during Ramadan intermittent fasting in metabolically healthy obese subjects. Materials and Methods: This cross-sectional study used convenience sampling to recruit 55 overweight and obese participants (22 females and 33 males) who observed Ramadan fasting. Body weight and composition, glucoregulatory factors, serum PCSK9 concentration, dietary intake, and physical activity were assessed 1 week before and at the end of Ramadan fasting. Results: The median (interquartile range) age was 35 (22) years, and body mass index was 30.2 (5.4). We found significant (p < 0.05) increases in serum levels of PCSK9, serum insulin, insulin resistance, and leptin at the end of Ramadan compared with pre-fasting levels. Significant (p < 0.05) reductions in body weight, waist circumference, systolic and diastolic blood pressure, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and adiponectin were also observed at the end of Ramadan. Conclusions: Observing Ramadan fasting was associated with increased PCSK9 levels in metabolically healthy obese subjects. The complex relationships between PCSK9 and insulin resistance and dysregulation of adipokine secretion in relation to dietary and lifestyle modifications during Ramadan warrant further research.

Comprehensive care for patients with diabetes in Ramadan: A module for pharmacy students and pharmacists.

Introduction: Prior studies show that many patients with diabetes whose health maybe impacted by fasting, choose to fast during Ramadan. This study describes the implementation and evaluation of an online module targeting bachelor of pharmacy (BPharm) and doctor of pharmacy (PharmD) students that aims to improve participants' knowledge, communication, and self-efficacy concerning proper care for patients with diabetes in Ramadan. Methods: An online module consisting of two phases targeting both BPharm and PharmD students was implemented over two semesters in fall 2020 and spring 2021. Participants were directed to fill pre-module and post-module assessments to evaluate the change in their knowledge and self-efficacy using two scales. Pre- and post-survey data for participants' knowledge and self-efficacy were analyzed for significance using paired sample t-tests. Qualitative data analysis was performed to assess participants' responses to the open-ended question concerning what they liked and disliked about the module. Results: All BPharm and PharmD students taking the lesson responded to both the baseline survey and the follow-up one resulting in 92 responses (participation rate of 100%). The average score for participants in the pre-module self-efficacy section was 1.5 (SD = 1) and increased post-module to 3.5 (SD = 0.7), t (91) = 20.2, p < 0.001. Further, the average score for participants in the pre-module knowledge section was 14 (SD = 3), which similarly increased to 22 (SD = 3) post-module t (91) = 19.7, p < 0.001. Qualitative analysis provided insights on how participants perceived the module design, content, and its impact on practice. Participants described the module as an informative one that addresses a much-needed issue they haven't been exposed to before. They emphasized how the module addresses the cultural needs of patients in their communities. They particularly appreciated seeing instructor videos depicting real-life scenarios and the focus on their communication skills, but some preferred learning about this topic through live sessions. Conclusion: An online module positively impacted both self-efficacy and knowledge in relation to caring for patients with diabetes considering fasting in Ramadan. Future studies should explore how different versions of this module can be integrated into educational activities for pharmacy students, pharmacists in different settings, and for other health care professionals.

Association of acute kidney injury with outcomes in patients undergoing percutaneous left atrial appendage closure.

OBJECTIVES: Using a large nationally representative database, we aimed to examine risk factors for acute kidney injury (AKI) and its association with outcomes in patients undergoing percutaneous left atrial appendage closure (LAAC). BACKGROUND: Previous small-scale studies have reported poor outcomes with AKI following percutaneous LAAC. METHODS: We queried the Nationwide Readmission Database to identify LAAC procedures performed from 2016 to 2017. Multivariable logistic and linear regression models were used to identify risk factors for AKI and determine the association between AKI and clinical outcomes. The primary outcome of interest was in-hospital mortality. RESULTS: Of 20,703 patients who underwent LAAC during the study period, 1,097 (5.3%) had a diagnosis of AKI. Chronic kidney disease, non-elective admission, coagulopathy, weight loss, prior coronary artery disease, heart failure, diabetes mellitus, and anemia were independently associated with an increased risk of AKI after LACC. In patients undergoing LAAC, AKI was associated with an increased risk of in-hospital mortality (adjusted odds ratio [aOR], 16.01; 95% CI, 8.48-30.21), stroke/transient ischemic attack (aOR, 2.50; 95% CI, 1.69-3.70), systemic embolization (aOR, 3.78; 95% CI, 1.64-8.70), bleeding/transfusion (aOR, 1.96; 95% CI, 1.50-2.56), vascular complications (aOR, 3.53; 95% CI, 1.94-6.42), pericardial tamponade requiring intervention (aOR, 6.83; 95% CI, 4.37-10.66), index length of stay (adjusted parameter estimate, 7.46; 95% CI, 7.02-7.92), and 180-day all-cause readmissions (aOR, 1.43; 95% CI, 1.09-1.88). CONCLUSION: AKI in the setting of LAAC is uncommon but is associated with poor clinical outcomes. Further studies are needed to determine if a similar association exists for long-term outcomes.

Association of baseline kidney disease with outcomes of transcatheter mitral valve repair by MitraClip.

OBJECTIVES: This study sought to determine the impact of baseline chronic kidney disease (CKD) on in-hospital outcomes of transcatheter mitral valve repair with MitraClip (MC). BACKGROUND: MC is now an established treatment in high surgical risk patients. However, limited data are available on outcomes of MC in patients with baseline renal dysfunction. METHODS: The authors used data from January 2014 to December 2017 National Readmission Database to identify all patients ≥18 years of age who underwent MC. International classification of diseases (ICD)-9 and ICD-10 codes were used to identify patients with no-CKD, CKD (without chronic dialysis), or end-stage renal disease (ESRD) on dialysis. Multivariable logistic regression models were constructed using generalized estimating equations to examine in-hospital outcomes. RESULTS: Of 13,563 patients undergoing MC, 8,935 (65.8%) had no-CKD, 4,152 (30.6%) had CKD, and 476 (3.5%) had ESRD. ESRD patients compared to CKD and no-CKD had significantly higher mortality (7.2% vs. 2.5% vs. 2.0%; p < .001), higher incidence of bleeding, blood transfusions, and 30 day all cause readmission. CKD patients compared to no-CKD had significantly higher mortality (odds ratio-1.29; CI 1.01-1.65; p = .04), acute kidney injury (odds ratio-3.0; CI 2.69-3.34; p < .001), new in-hospital hemodialysis (odds ratio- 2.70; CI 1.57-4.62; p < .001), blood transfusions, 30 day all cause and congestive heart failure (CHF) readmissions. In-hospital stroke and cardiac tamponade did not differ between the three groups. Patients with baseline kidney disease undergoing MC had higher mortality at high volume centers compared to low volume centers. CHF was the most common cause of readmission postMC in patients with or without preprocedural kidney disease. CONCLUSION: Patients with baseline kidney disease have worse outcomes after MC with higher readmission rates requiring careful patient selection and follow up in this population.

Early post-transplant cutaneous bacillary angiomatosis in a kidney recipient: Case report and review of the literature.

Bacillary angiomatosis (BA) is an uncommon systemic disease caused by Bartonella henselae (BH) or Bartonella quintana (BQ) that occurs primarily in immunocompromised hosts. Few cases of BA recipients have been reported in adult solid transplant recipients over the years, with most cases presenting years after transplant. We describe a case of a kidney transplant recipient who developed cutaneous BA very early in the post-transplant period despite not having any exposures. Retrospective testing of donor and recipient's serum was performed and raised the concern for possible donor-derived infection. A literature review encompassing 1990 to present was also performed in order to better understand the clinical presentation, diagnostics and therapeutic approach of this unusual disease. Combined serology, histopathology and molecular testing (polymerase chain reaction [PCR]) were useful in diagnosing BA in our patient as serology alone might be unreliable. Macrolides or doxycycline for at least 3 months is the recommended therapeutic strategy; however, the optimal duration of treatment is not well established in transplant recipients. In our patient, we decided to use doxycycline for 1 year due to gradual resolution of lesions and ongoing immunosuppression. Patient responded successfully without any documented relapse.

Impact of Ramadan-focused diabetes education on hypoglycemia risk and metabolic control for patients with type 2 diabetes mellitus: A systematic review.

BACKGROUND: Ramadan fasting is regarded as a form of worship amongst Muslims. However, patients with a high risk of diabetic complications are advised to avoid fasting, as the practice is associated with significant impacts on several health factors for type 2 diabetic patients, including glycaemic control. Thus, a lack of focused education before Ramadan may result in negative health outcomes. AIM: To evaluate the impact of a Ramadan-focused diabetes education programme on hypoglycaemic risk and other clinical and metabolic parameters. METHODS: A systematic literature search was performed using Scopus, PubMed, Embase, and Google Scholar to identify relevant studies meeting the inclusion criteria from inception. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and guidelines were followed when performing the search and identification of appropriate studies. RESULTS: Seventeen studies were included in this systemic review; five of them met the criteria to compile for a meta-analysis. The included studies were with various study designs, including randomised controlled trials, quasi-experimental and non-randomised studies. Overall, the results revealed a significant reduction of hypoglycemia risk (81% reduction) for fasting patients in intervention groups who received Ramadan-focused education compared with patients receiving conventional care (OR 0.19, 95% CI: 0.08-0.46). Moreover, HbA1c significantly improved amongst patients who received a Ramadan-focused diabetes education intervention, compared with those receiving conventional care. CONCLUSION: Ramadan-focused diabetes education had a significant impact on hypoglycemia and glycaemic control, with no significant effect on body weight, blood lipids or blood pressure.

Lateral Column Lengthening Revisited: A Simple Intraoperative Approach to Ensure a True Extra-Articular Osteotomy.

Lateral column lengthening is a common method for treatment of patients with symptomatic flat feet. Although variations of the technique have been described by many authors, there is a lack of agreement about the exact location of the osteotomy. Most authors tried to find the interval between the anterior and middle talocalcaneal facets but did not offer a reproducible method to achieve this purpose. The use of a plantarflexion anteroposterior view of the foot provides better visualization of the anatomic landmarks and helps to precisely perform the osteotomy anterior to the sustentaculum tali, with protection of the anterior and middle talocalcaneal facets.

The RNA binding protein FXR1 is a new driver in the 3q26-29 amplicon and predicts poor prognosis in human cancers.

Aberrant expression of RNA-binding proteins has profound implications for cellular physiology and the pathogenesis of human diseases such as cancer. We previously identified the Fragile X-Related 1 gene (FXR1) as one amplified candidate driver gene at 3q26-29 in lung squamous cell carcinoma (SCC). FXR1 is an autosomal paralog of Fragile X mental retardation 1 and has not been directly linked to human cancers. Here we demonstrate that FXR1 is a key regulator of tumor progression and its overexpression is critical for nonsmall cell lung cancer (NSCLC) cell growth in vitro and in vivo. We identified the mechanisms by which FXR1 executes its regulatory function by forming a novel complex with two other oncogenes, protein kinase C, iota and epithelial cell transforming 2, located in the same amplicon via distinct binding mechanisms. FXR1 expression is a candidate biomarker predictive of poor survival in multiple solid tumors including NSCLCs. Because FXR1 is overexpressed and associated with poor clinical outcomes in multiple cancers, these results have implications for other solid malignancies.