End-organ Damage Research Articles

A Case Report of Kidney After Heart Transplant in Patient With Fabry Disease

Fabry disease is an X-linked inherited lysosomal storage disorder caused by a mutation in the gene encoding the enzyme α-galactosidase A. It is characterized by the accumulation of globotriaosylceramide in different tissues, resulting in a wide range of clinical presentations. Fabry cardiomyopathy and Fabry nephropathy are the disease's 2 most important life-threatening manifestations and can contribute to higher morbidity and mortality. Heart and kidney transplants can play a major role in patients with Fabry disease who develop end organ damage. We report a case of a successful heart transplant in a male patient with Fabry disease at the age of 62, followed by a kidney transplant later at the age of 69. He has had an uneventful post-transplant course and has been tolerating maintenance immunosuppression and enzyme replacement therapy with recombinant human α-galactosidase A.

SPIROMETRY EVALUATION OF PULMONARY FUNCTIONS IN TYPE 2 DIABETES MELLITUS PATIENTS: A CROSS-SECTIONAL STUDY

Background and Aims: Type 2 diabetes mellitus (T2DM) during the chronic stage elicits significant micro and macrovascular complication and imposes mortality and morbidity among the individuals. However, the effect of T2DM on the lung as a target end organ damage was not widely studied. Hence, the present study was done for the spirometry analysis of pulmonary functions in T2DM patients. Methods: This was a cross-sectional study conducted on 50 T2DM patients and they were subjected to spirometry evaluation. The restrictive pattern of lung functions was analyzed by evaluating the following parameters forced vital capacity (FVC) in liters, forced expiratory volume in 1 second (FEV1), and FEV1/FVC were evaluated. The association between lung function parameters and duration of diabetes, glycated hemoglobin (HbA1c) were also analyzed. Results: In this study among the diabetic patients, the mean FVC was 2.45±0.36 L, the mean FEVI was 1.82±0.12 (L/s) and the mean FEV1/FVC was 87.42±7.54, respectively. Regarding lung complication, out of 50 diabetic patients, 25 (50%) had normal lung functions, 16 (32%) had mild restriction and 9 (18%) had moderate restriction. The FVC, FEVI, and FEV1/FVC were significantly reduced in diabetic patients with moderate lung restriction as compared to normal and mild restriction patterns. Diabetes duration displayed no significant association with a decline in pulmonary function and FEV1/FVC showed weak significant negative correlation (r=−0.412; p=0.02) with HbA1c levels. Conclusion: The study shows that in diabetics patients there was a marked decline in pulmonary function and it might be due to uncontrolled diabetes-related complications.

Does cooled dialysate still have a role in reducing intradialytic stress? Implications of the MyTEMP trial.

There is an excess of cardiovascular morbidity and mortality in the maintenance haemodialysis population. Targeting traditional risk factors (e.g. hypercholesterolaemia) do not improve cardiovascular outcomes. Repeated myocardial stunning during haemodialysis is an important nontraditional risk, resulting in pathological cardiac remodelling and fibrosis. This review explores dialysate cooling as a management strategy to promote haemodynamic stability, reduce myocardial injury, and improve cardiovascular disease outcomes for individuals receiving maintenance haemodialysis. Observational data and small interventional studies demonstrate dialysate cooling has the potential to reduce end-organ damage and provide cardioprotection, renal protection and neuroprotection compared with standard care. These data are limited by the small sample sizes, short follow-up times and lack of long-term patient important outcomes. The MyTEMP study, a multicentre pragmatic randomized controlled trial, demonstrated cooled dialysate (0.5°C below body temperature) vs. standard care did not improve cardiovascular outcomes for prevalent haemodialysis patients. Dialysate cooling has been widely adopted into routine clinical practice; the MyTEMP study challenges the unit-level approach to implementing dialysate cooling. Due to methodological limitations, the absence of other important patient outcome measures, and lack of granularity of patient-level data, dialysate cooling should not be hastily removed from all dialysis care and warrants further research.

Management of Hypertension With Non-pharmacological Interventions: A Narrative Review.

Hypertension (HTN) is a condition that affects nearly half of the adult population in the United States. HTN is the elevation of blood pressure (BP) 130/80 mm Hg or higher. Untreated high blood pressure may increase the risk of myocardial infarction, stroke, and other serious complications. BP over 180/120 mm Hg with end-organ damage is called a hypertensive emergency. Despite advancements in medicine and treatment options, the global burden of HTN has been increasing due to the advancing age of the population and an increasing prevalence of obesity. Non-pharmacological management of HTN has gained prominence worldwide due to its additional benefits and positive impact on the overall health of individuals, having almost no side effects and reducing the financial burden of medication expenses. This article has compiled studies like systematic reviews, meta-analyses, and randomized controlled trials and reviewed the role of non-pharmacological management of HTN, including lifestyle modifications like exercise, weight loss, dietary interventions like dietary approaches to stop hypertension (DASH) diet, low sodium diet, limiting alcohol consumption, smoking cessation and stress management to help control blood pressure. However, non-pharmacological interventions should be initiated in an early phase, and for proper management of HTN, we may need to include both pharmacological and non-pharmacological interventions. This article explored andintegrated various studies to highlight the role of non-pharmacological interventions to manage HTN. We also examined the need for more research studies for strategies to alleviate morbidity and mortality associated with HTN.

Elevated Aortic Stiffness after Pediatric Heart Transplantation.

In adults, arterial stiffness has been linked to the development of target end-organ damage, thought to be related to abnormal transmission of pulse pressure. Increased arterial stiffness and endothelial dysfunction have been hypothesized to contribute to the development of microvascular dysfunction and coronary allograft vasculopathy (CAV), an important comorbidity after heart transplantation. However, little data exists regarding arterial stiffness in pediatric heart transplantation and its influence on development of coronary allograft vasculopathy is not well understood. We sought to assess aortic stiffness and distensibility in pediatric post-heart transplant patients. A prospective, observational study analyzing the ascending (donor tissue) and descending aorta (recipient tissue) using transthoracic echocardiographic M-mode measurements in patients aged < 21 years was conducted. Descending and ascending aorta M-modes were obtained from the subcostal long axis view, and the parasternal long axis view 3-5mm above the sinotubular junction, respectively. Two independent reviewers averaged measurements over 2-3 cardiac cycles, and Aortic Distensibility (AD) and Aortic Stiffness Index (ASI) were calculated using previously validated methods. We recruited 39 heart transplant (HT) patients and 47 healthy controls. Median end diastolic dimension of the ascending aorta (donor tissue) was significantly larger in the transplant group than the control group (1.92cm vs. 1.74cm, p = 0.01). Ascending aortic distensibility in post-transplant patients was significantly lower than in the control group (4.87 vs. 10.53, p < 0.001). Ascending aortic stiffness index was higher in the transplant patients compared to the controls (4.63 vs. 2.21, p < 0.001). There is evidence of altered ascending aortic distensibility and stiffness parameters in post-heart transplant patients. Further studies are required to assess its influence on complications like development of coronary artery vasculopathy.

United States rural residence is associated with increased acute maternal end-organ injury or mortality after birth: a retrospective multi-state analysis, 2007–2018

BackgroundGeographic-based healthcare determinants and choice of anesthesia have been shown to be associated with maternal morbidity and mortality. We explored whether differences in maternal outcomes based on maternal residence, and anesthesia type for cesarean and vaginal birth, exist. MethodsThis study was a retrospective multi-state analysis; patient residence was the predictor variable of interest and a composite binary measure of maternal end-organ injury or inpatient mortality was the primary outcome. Our secondary outcomes included a binary measure of anesthesia type for cesarean birth (general vs. neuraxial [NA]) and NA analgesia for vaginal birth (no NA vs. NA). Our predictor variable of interest was patient residency (reference category central metropolitan areas of >1 million population), fringe large metropolitan county, medium metropolitan, small metropolitan, micropolitan, and non-metropolitan or micropolitan county. ResultsWomen residing in micropolitan (OR 1.17; 95% CI 1.09 to 1.27) and non-metropolitan or micropolitan counties (OR 1.14; 95% CI 1.04 to 1.24) had the highest adjusted increased odds of adverse maternal outcomes. Those residing in suburban, medium, and small metropolitan areas underwent general anesthesia less often during cesarean births than those residing in urban areas. Patients residing in micropolitan rural (OR 2.07; 95% CI 2.02 to 2.12) and non-metropolitan or micropolitan (2.25; 95% CI 2.16 to 2.34) counties underwent vaginal births without NA analgesia more than twice as often as those residing in urban areas. ConclusionsRural-urban disparities in maternal end-organ damage and mortality exist and anesthesia choice may play an important role in these disparate outcomes.

Treatment Modalities in Calcium Channel Blocker Overdose: A Systematic Review.

Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified approach for treating these patients in the existing literature. This study aimed to assess the effects of different treatment modalities used in calcium channel blocker poisoning, as reported by previous studies. The primary outcomes studied were mortality and hemodynamic parameters after treatment. The secondary outcomes were the length of hospital stay, length of intensive care unit stay, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. A thorough literature search was performed through Ovid, PubMed, Cochrane Library, and Google Scholar from January 2014 to December 31, 2022, to identify all studies analyzing the effects of the treatment of calcium channel blocker poisoning on the desired outcomes. Two reviewers reviewed 607 published articles from January 2014 to December 2022 to identify studies analyzing the effects of the treatment of calcium channel blocker poisoning on desired outcomes. In this review, 18 case reports, one case series, and one cohort study were included. Most patients were treated with an injection of calcium gluconate or calcium chloride. The use of calcium along with dopamine and norepinephrine was found to have lower mortality rates. A few patients were also treated with injection atropine for bradycardia. High-dose insulin therapy was used in 14 patients, of whom two did not survive. In the cohort study, 66 calcium channel blocker toxicity patients were included. These patients were treated with high-dose insulin therapy. A total of 11 patients with calcium channel blocker toxicity succumbed. Although it was found to be associated with improved hemodynamic parameters and lower mortality, side effects such as hypokalemia and hypoglycemia were noted. Intravenous lipid emulsion therapy (administered to eight patients), extracorporeal life support (used in three patients with refractory shock or cardiac arrest), injection glucagon, methylene blue, albumin infusion, and terlipressin were associated with a lower mortality rate as well as improvement in hemodynamic parameters. None of the case reports provided any information on end-organ damage on long-term follow-up.

STING/ACSL4 axis-dependent ferroptosis and inflammation promote hypertension-associated chronic kidney disease

Hypertension is a primary modifiable risk factor for cardiovascular diseases, which often induces renal end-organ damage and complicates chronic kidney disease (CKD). In the present study, histological analysis of human kidney samples revealed that hypertension induced mtDNA leakage and promoted the expression of stimulator of interferon genes (STING) in renal epithelial cells. We used angiotensin II (AngII)- and 2K1C-treated mouse kidneys to elucidate the underlying mechanisms. Abnormal renal mtDNA packing caused by AngII promoted STING-dependent production of inflammatory cytokines, macrophage infiltration, and a fibrogenic response. STING knockout significantly decreased nuclear factor-κB activation and immune cell infiltration, attenuating tubule atrophy andextracellular matrix accumulation invivo and invitro. These effects delayed CKD progression. Immunoprecipitationassays and liquid chromatography-tandem mass spectrometry showed that STING and ACSL4 were directly combined at the D53 and K412 amino acids of ACSL4. Furthermore, STING induced renal inflammatory response and fibrosis through ACSL4-dependent ferroptosis. Last, inhibition of ACSL4 using small interfering RNA, rosiglitazone, or Fer-1 downregulated AngII-induced mtDNA-STING-dependent renal inflammation. These results suggest that targeting the STING/ACSL4 axis might represent a potential strategy for treating hypertension-associated CKD.

Aspirin Discontinuation at 24 to 28 Weeks’ Gestation in Pregnancies at High Risk of Preterm Preeclampsia: A Randomized Clinical Trial

ABSTRACT Preeclampsia affects up to 4% of pregnancies and is marked by the development of hypertension and proteinuria after 20 weeks of gestation. Complications associated with the disorder include preterm birth, fetal growth restriction, placental abruption, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, seizures, and other end organ damage. Aspirin has been shown to reduce the incidence of preterm preeclampsia by 62%. However, it can also lead to peripartum bleeding. Screening for preeclampsia in the first trimester (11 to 13 weeks' gestation) can help identify up to 60% of pregnant individuals who will develop preterm preeclampsia. If preeclampsia screening is conducted during this first trimester, aspirin can be initiated earlier and discontinued earlier to mitigate the risk of peripartum bleeding. In addition, increased soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1:PlGF) ratio is associated with preeclampsia weeks before its clinical onset. An sFlt-1:PlGF of ≤38 has been shown to accurately exclude preeclampsia in pregnant individuals with suspected disease. The aim of this study was to compare the effect of discontinuing aspirin in pregnant individuals at 24 and 28 weeks' gestation with a normal sFlt-1:PlGF ratio of ≤38 against those who continued aspirin treatment until 36 weeks of gestation. This was an open-label, randomized, noninferiority trial conducted at 9 maternity hospitals in Spain. Included were adult individuals with singleton pregnancies who had live births, were found to be at high risk of preeclampsia at the first-trimester screening, and a normal sFlt-1:PlGF between 24 and 28 weeks of gestation. Participants were randomly assigned 1:1 to discontinue aspirin (intervention group) or continue aspirin treatment (control group). The primary outcome was delivery due to preterm preeclampsia (before 37 weeks' gestation). Noninferiority was met if the higher 95% confidence interval (CI) for the difference in the incidences of preterm preeclampsia between the 2 groups was &lt;1.9%. A total of 964 pregnant individuals, who were identified as high-risk for preterm preeclampsia and prescribed 150 mg of aspirin daily at bedtime, were eligible for the analysis. The rates of preterm preeclampsia in the intervention and control groups were 1.48% and 1.73%, respectively (absolute difference, −0.25% [95% CI, −1.86% to 1.36%]). In conclusion, the threshold for noninferiority was not met. In pregnant individuals at high risk of preeclampsia and a normal sFlt-1:PlGF ratio of ≤38, discontinuing aspirin at 24 to 28 weeks' gestation was noninferior to continuing aspirin until 36 weeks to prevent preterm preeclampsia.

Prevention of Intradialytic Hypotension in Hemodialysis Patients: Current Challenges and Future Prospects.

Intradialytic hypotension, defined as rapid decrease in systolic blood pressure of greater than or equal to 20 mmHg or in mean arterial pressure of greater than or equal to 10 mmHg that results in end-organ ischemia and requires countermeasures such as ultrafiltration reduction or saline infusion to increase blood pressure to improve patient's symptoms, is a known complication of hemodialysis and is associated with several potential adverse outcomes. Its pathogenesis is complex and involves both patient-related factors such as age and comorbidities, as well as factors related to the dialysis prescription itself. Key factors include the need for volume removal during hemodialysis and a suboptimal vascular response which compromises the ability to compensate for acute intravascular volume loss. Inadequate vascular refill, incorrect assessment or unaccounted changes of target weight, acute illnesses and medication interference are further potential contributors. Intradialytic hypotension can lead to compromised tissue perfusion and end-organ damage, both acutely and over time, resulting in repetitive injuries. To address these problems, a careful assessment of subjective symptoms, minimizing interdialytic weight gains, individualizing dialysis prescription and adjusting the dialysis procedure based on patients' risk factors can mitigate negative outcomes.

Association between HIV and treatment-resistant hypertension in Malawian adults: a protocol for a case–control study

IntroductionTreatment-resistant hypertension (RH), defined as uncontrolled blood pressure (≥140/90 mm Hg) despite treatment with ≥3 medications of different classes (including diuretics) at optimal doses, is associated with poor prognosis and...

Ocular manifestations in renal diseases.

The eyes and kidneys are the targets for end-organ damage in multiple pathologies. Both these organs develop during the same embryonic stage around the fourth to sixth week of gestation, thus sharing a strong correlation between both eye and kidney diseases. Both the eyes and kidneys can be the target of the systemic disease process; however, the eyes can also be affected as a consequence of renal disease or its treatment. Risk factors such as diabetes, hypertension, and smoking are commonly shared between kidney and eye diseases. Ocular manifestations can be predictive of renal disease, and/or patients with renal disease are at higher risk for developing ocular manifestations. Various congenital anomalies of the eyes and kidneys can also present as an oculorenal syndrome. This article summarizes the ocular pathology, which can be seen in renal diseases.

Effects of Nondipping Blood Pressure Changes: A Nephrologist Prospect.

Blood pressure (BP) variations depend on various internal, environmental, and behavioral factors. BP fluctuations occur both in normotensive and hypertensive people. Although it fluctuates over the 24-hr day and night, the morning BP increases after waking up and declines throughout sleep.It is typical for BP to decrease by 10% to 20%, while sleeping, known as dipping BP. However, if there is no decrease in nighttime mean systolic BP or a drop of less than 10 mmHg, it is called nondipping BP. Conversely, reverse dipping BP means an increase in mean systolic BP instead of a drop during the night. Reverse dipping is observed in hypertension (HTN), diabetes mellitus (DM), chronic kidney disease (CKD), and obstructive sleep apnea (OSA) syndrome. The introduction of ambulatory BP monitoring (ABPM) led to the emergence of identifying normal and elevated BP patterns. Non-dipping BP increases the risk of cardiovascular system (CVS) complications such as left ventricular hypertrophy, proteinuria, glomerular filtration rate (GFR) reduction, and CKD progression.A loss or blunting of the normal BP profile is recognized as a deleterious variant, and restoring abnormal BP patterns has been reported to significantly impact end-organ damage, morbidity, and mortality. In this non-systematic clinically-oriented, comprehensive review, we aim to update the BP variables and the pathophysiology of nondipping BP and point out the areas which need more investigation from a nephrology perspective because the nondipping BP increases the risk of proteinuria, GFR reduction, and CKD progression. A literature search of PubMed, Google, EMBASE, and Google Scholar was conducted. Checks of selected papers and relevant reviews complemented the electronic search. With improved BP measurement methods, the physiology of BP profile variations is readily detectable during the day and night. A nondipping BP profile is a distinct BP pattern that may have significant end-organ damage effects and therapeutic importance for nephrologists. The pathophysiology of the nondipping BP variant must be clarified to prevent complications, and further investigations are required. Furthermore, there is debate about the best BP index to utilize: systolic BP, diastolic BP, mean arterial pressure, or a mixture of all. All these areas are important and need new research projects.

Preeclampsia and Long-term Kidney Outcomes: An Observational Cohort Study

Preeclampsia is a pregnancy-related complication characterized by acute hypertension and end-organ dysfunction. We evaluated the long-term association between preeclampsia and the risk of developing chronic hypertension and kidney disease. Observational cohort study. 27,800 adults with deliveries in the Geisinger Health System between 1996 and2019. Preeclampsia. Hypertension, reduced estimated glomerular filtration rate (eGFR)<60mL/min/1.73m2), and albuminuria>300mg/g. Propensity-score matching and Cox proportional hazards models to evaluate the association between preeclampsia and incident hypertension, reduced eGFR, and albuminuria. Of 27,800 adults with pregnancies during the study period (mean age, 28 years; 3% Black race), 2,977 (10.7%) had at least 1 pregnancy complicated by preeclampsia. After matching for multiple characteristics, individuals with preeclampsia had a higher risk of developing chronic hypertension (HR, 1.77 [95% CI, 1.45-2.16]), eGFR<60mL/min/1.73m2 (HR, 3.23 [95% CI, 1.64-6.36]), albuminuria (HR, 3.60 [95% CI, 2.38-5.44]), and a subsequent episode of preeclampsia (HR, 24.76 [95% CI, 12.47-48.36]), compared with matched controls without preeclampsia. Overall, postpartum follow-up testing was low. In the first 6 months after delivery, 31% versus 14% of individuals with and without preeclampsia had serum creatinine tests, respectively, and testing for urine protein was the same in both groups, with only 26% having follow-up testing. Primarily White study population, observational study, reliance on ICD codes for medical diagnosis. Individuals with a pregnancy complicated by preeclampsia had a higher risk of hypertension, reduced eGFR, and albuminuria compared with individuals without preeclampsia. Preeclampsia is a significant contributor to perinatal and maternal morbidity and is marked by new-onset hypertension and end-organ damage, including acute kidney injury or proteinuria. To gain insight into the long-term kidney effects of the disease, we compared adults with deliveries complicated by preeclampsia with those without preeclampsia in the Geisinger Health System, while also assessing postpartum testing rates. Our results demonstrate that pregnant individuals with preeclampsia are at a heightened risk for future hypertension, reduced eGFR, and albuminuria, with overall low rates of postpartum testing among both individuals with and without preeclampsia. These findings underscore the need to consider preeclampsia as an important risk factor for the development of chronic kidney disease. Further studies are required to determine optimal postpreeclampsia monitoring strategies.

Biallelic truncating variants in children with titinopathy represent a recognizable condition with distinctive muscular and cardiac characteristics: a report on five patients.

Monoallelic and biallelic TTN truncating variants (TTNtv) may be responsible for a wide spectrum of musculoskeletal and cardiac disorders with different age at onset. Although the prevalence of heterozygous TTNtv is relatively high in the general population, cardiac phenotyping (mainly cardiomyopathies, CMPs) in biallelic titinopathy has rarely been described in children. We reviewed the medical records of pediatric patients with biallelic TTNtv and cardiac involvement. Clinical exome sequencing excluded pathogenic/likely pathogenic variants in major CMP genes. Five pediatric patients (four male) with biallelic TTNtv were included. Major arthrogryposis multiplex was observed in four patients; no patient showed intellectual disability. At a cardiac level, congenital heart defects (atrial and ventricular septal defects, n = 3) and left ventricular non-compaction (n = 1) were reported. All patients had dilated cardiomyopathy (DCM) diagnosed at birth in one patient and at the age of 10, 13, 14, and 17 years in the other four patients. Heart rhythm monitoring showed tachyarrhythmias (premature ventricular contractions, n = 2; non-sustained ventricular tachycardia, n = 2) and nocturnal first-degree atrio-ventricular block (n = 2). Cardiac magnetic resonance (CMR) imaging was performed in all patients and revealed a peculiar late gadolinium enhancement distribution in three patients. HyperCKemia was present in two patients and end-stage heart failure in four. End-organ damage requiring heart transplantation (HT) was indicated in two patients, who were operated on successfully. Biallelic TTNtv should be considered when evaluating children with severe and early-onset DCM, particularly if skeletal and muscular abnormalities are present, e.g., arthrogryposis multiplex and congenital progressive myopathy. End-stage heart failure is common and may require HT.

Whole blood hydroxychloroquine: Does genetic polymorphism of cytochrome P450 enzymes have a role?

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations and multifactorial etiologies ranging from environmental to genetic. SLE is associated with dysregulated immunological reactions, with increased immune complex formation leading to end-organ damages such as lupus nephritis, cutaneous lupus, and musculoskeletal disorders. Lupus treatment aims to reduce disease activity, prevent organ damage, and improve long-term patient survival and quality of life. Antimalarial, hydroxychloroquine (HCQ) is used as a first-line systemic treatment for lupus. It has shown profound efficacy in lupus and its associated conditions. However, wide variation in terms of clinical response to this drug has been observed among this group of patients. This variability has limited the potential of HCQ to achieve absolute clinical benefits. Several factors, including genetic polymorphisms of cytochrome P450 enzymes, have been stipulated as key entities leading to this inter-individual variation. Thus, there is a need for more studies to understand the role of genetic polymorphisms in CYP450 enzymes in the clinical response to HCQ. Focusing on the role of genetic polymorphism on whole blood HCQ in lupus disorder, this review aims to highlight up-to-date pathophysiology of SLE, the mechanism of action of HCQ, and finally the role of genetic polymorphism of CYP450 enzymes on whole blood HCQ level as well as clinical response in lupus.

Cyclosporine in the Treatment of Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome: Retrospective Cohort Study.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, life-threatening reaction to a culprit drug that frequently involves end-organ damage. Corticosteroids are the first-line treatment for DRESS syndrome; however, corticosteroids may be contraindicated in certain patient populations. There are currently only 54 cases detailing the use of cyclosporine for the treatment of DRESS syndrome reported in the literature. The aim of this case series was to examine the treatment of DRESS syndrome with cyclosporine in a large patient cohort by aggregating time to symptom resolution, recurrence rate, and treatment dose and duration. This study was a retrospective cohort study. Patients diagnosed with DRESS syndrome by a board-certified dermatologist and treated at the University of Colorado Hospital from 2015 to 2019 were included. Our inclusion criterion was met by 19 occurrences of DRESS syndrome. With a short course of cyclosporine, 17 of 19 patients in our cohort (89%) had resolution of symptoms (mean treatment length of 5.26 days). DRESS syndrome's relapse after treatment with cyclosporine occurred in 3 of 19 (16%) occurrences of the cohort. Our study supports the use of cyclosporine in the treatment of DRESS syndrome, particularly in patients who are unable to sustain prolonged immunosuppression. Further research is necessary to compare the efficacy of cyclosporine to the current standard of care in a larger study population and investigate long-term outcomes.

Elevated blood pressure among adolescents in sub-Saharan Africa: a systematic review and meta-analysis

More people from sub-Saharan Africa aged between 20 years and 60 years are affected by end-organ damage due to underlying hypertension than people in high-income countries. However, there is a paucity of data on the pattern of elevated blood pressure among adolescents aged 10-19 years in sub-Saharan Africa. We aimed to provide pooled estimates of high blood pressure prevalence and mean levels in adolescents aged 10-19 years across sub-Saharan Africa. In this systematic review and meta-analysis, we searched PubMed, Google Scholar, African Index Medicus, and Embase to identify studies published from Jan 1, 2010, to Dec 31, 2021. To be included, primary studies had to be observational studies of adolescents aged 10-19 years residing in sub-Saharan African countries reporting the pooled prevalence of elevated blood pressure or with enough data to compute these estimates. We excluded studies on non-systemic hypertension, in African people not living in sub-Saharan Africa, with participant selection based on the presence of hypertension, and with adult cohorts in which we could not disaggregate data for adolescents. We independently extracted relevant data from individual studies using a standard data extraction form. We used a random-effects model to estimate the pooled prevalence of elevated blood pressure and mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels overall and on a sex-specific basis. This study is registered with PROSPERO (CRD42022297948). We identified 2559 studies, and assessed 81 full-text studies for eligibility, of which 36 studies comprising 37 926 participants aged 10-19 years from ten (20%) of 49 sub-Saharan African countries were eligible. A pooled sample of 29 696 adolescents informed meta-analyses of elevated blood pressure and 27 155 adolescents informed meta-analyses of mean blood pressure. Sex data were available from 26 818 adolescents (14 369 [53·6%] were female and 12 449 [46·4%] were male) for the prevalence of elevated blood pressure and 23 777 adolescents (12 864 [54·1%] were female and 10 913 [45·9%] were male) for mean blood pressure. Study quality was high, with no low-quality studies. The reported prevalence of elevated blood pressure ranged from 4 (0·2%) of 1727 to 1755 (25·1%) of 6980 (pooled prevalence 9·9%, 95% CI 7·3-12·5; I?=99·2%, pheterogeneity<0·0001). Mean SBP was 111 mm Hg (95% CI 108-114) and mean DBP was 68 mm Hg (66-70). 13·4% (95% CI 12·9-13·9; pheterogeneity<0·0001) of male participants had elevated blood pressure compared with 11·9% (11·3-12·4; pheterogeneity<0·0001) of female participants (odds ratio 1·04, 95% CI 0·81-1·34; pheterogeneity<0·0001). To our knowledge, this systematic review and meta-analysis is the first systematic synthesis of blood pressure data specifically derived from adolescents in sub-Saharan Africa. Although many low-income countries were not represented in our study, our findings suggest that approximately one in ten adolescents have elevated blood pressure across sub-Saharan Africa. Accordingly, there is an urgent need to improve preventive heart-health programmes in the region. None.

Association of uncontrolled blood pressure in apparent treatment-resistant hypertension with increased risk of major adverse cardiovascular events plus.

Patients with apparent treatment-resistant hypertension (aTRH) are at increased risk of end-organ damage and cardiovascular events. Little is known about the effects of blood pressure (BP) control in this population. Using a national claims database integrated with electronic medical records, the authors evaluated the relationships between uncontrolled BP (UBP; ≥130/80mmHg) or controlled BP (CBP; <130/80mmHg) and risk of major adverse cardiovascular events plus (MACE+; stroke, myocardial infarction, heart failure requiring hospitalization) and end-stage renal disease (ESRD) in adult patients with aTRH (taking ≥3 antihypertensive medication classes concurrently within 30 days between January 1, 2015 and June 30, 2021). MACE+ components were also evaluated separately. Multivariable regression models were used to adjust for baseline differences in demographic and clinical characteristics, and sensitivity analyses using CBP<140/90mmHg were conducted. Patients with UBP (n=22333) were younger and had fewer comorbidities at baseline than those with CBP (n=11427). In the primary analysis, which adjusted for these baseline differences, UBP versus CBP patients were at an 8% increased risk of MACE+ (driven by a 31% increased risk of stroke) and a 53% increased risk of ESRD after 2.7 years of follow-up. Greater MACE+ (22%) and ESRD (98%) risk increases with UBP versus CBP were seen in the sensitivity analysis. These real-world data showed an association between suboptimal BP control in patients with aTRH and higher incidence of MACE+ and ESRD linked with UBP despite the use of multidrug regimens. Thus, there remains a need for improved aTRH management.

Parenchymal volume analysis to assess longitudinal functional decline following partial nephrectomy.

To identify factors associated with longitudinal ipsilateral functional decline after partial nephrectomy (PN). Of 1140 patients managed with PN (2012-2014), 349 (31%) had imaging/serum creatinine levels pre-PN, 1-12 months post-PN (new baseline), and >3 years later necessary for inclusion. Parenchymal-volume analysis was used to determine split renal function. Patients were grouped as having significant renal comorbidity (CohortSRC : diabetes mellitus with insulin-dependence or end-organ damage, refractory hypertension, or severe pre-existing chronic kidney disease) vs not having significant renal comorbidity (CohortNoSRC ) preoperatively. Multivariable regression was used to identify predictors of annual ipsilateral parenchymal atrophy and functional decline relative to new baseline values post-PN, after the kidney had healed. The median follow-up was 6.3 years with 87/226/36 patients having cold/warm/zero ischaemia. The median cold/warm ischaemia times were 32/22 min. Overall, the median tumour size was 3.0 cm. The preoperative glomerular filtration rate (GFR) and new baseline GFR (NBGFR) were 81 and 71 mL/min/1.73 m2 , respectively. After establishment of the NBGFR, the median loss of global and ipsilateral function was 0.7 and 0.4 mL/min/1.73 m2 /year, respectively, consistent with the natural ageing process. Overall, the median ipsilateral parenchymal atrophy was 1.2 cm3 /year and accounted for a median of 53% of the annual functional decline. Significant renal comorbidity, age, and warm ischaemia were independently associated with ipsilateral parenchymal atrophy (all P < 0.01). Significant renal comorbidity and ipsilateral parenchymal atrophy were independently associated with annual ipsilateral functional decline (both P < 0.01). Annual median ipsilateral parenchymal atrophy and functional decline were both significantly increased for CohortSRC compared to CohortNoSRC (2.8 vs 0.9 cm3 , P < 0.01 and 0.90 vs 0.30 mL/min/1.73 m2 /year, P < 0.01, respectively). Longitudinal renal function following PN generally follows the normal ageing process. Significant renal comorbidities, age, warm ischaemia, and ipsilateral parenchymal atrophy were the most important predictors of ipsilateral functional decline following establishment of NBGFR.