Treatment adherence and quality of life in colombian patients with lupus nephritis.

BACKGROUND: As with many other chronic diseases, systemic lupus erythematosus (SLE) and lupus nephritis (LN) have significant impacts on the health-related quality of life (HRQoL). Medication non-adherence is a significant challenge in the management of SLE, with consistently up to 75% of patients being non-adherent with their SLE medications. There is a need to assess the patient's perspective using patient-reported outcomes (PROs) to better understand the current impact of LN on HRQoL and treatment adherence in our region. The aim of this study was to explore the relationship between HRQoL and treatment adherence in patients with LN from the Colombian Caribbean. METHODS: A cross-sectional study was conducted from June to December 2022, including patients with biopsy-proven LN. HRQoL and treatment adherence were assessed using the Lupus Quality of Life (LupusQoL) and the Compliance Questionnaire in Rheumatology 19 (CQR19) instruments, respectively. Patients were categorized as adherent or non-adherent based on medication intake (defined as >80% correct dosage). Principal component analysis (PCA) was employed to identify principal components between adherent and non-adherent patients. RESULTS: A total of 42 patients with LN were included. Of these, 38 (90%) were female, and the mean age was 31 ± 10 years. Proliferative class IV was the predominant histopathological profile (90%). Twenty-five (60%) patients were categorized as non-adherent. Across all LupusQoL domains, a comprehensive range of responses was observed. Pain, planning, and intimate relationships domains remained unaffected, while burden to others domain had the lowest score. Poorer planning score correlated with older age (r = -0.72; p < .05) and longer disease duration (r = -0.74; p < .05). SLEDAI-2 K correlated with the pain domain (r = -0.78; p < .05). Non-adherent patients exhibited significantly worse pain domain scores compared to adherent counterparts (p < .05). PCA showed strong interactions between planning and pain, as well as between physical health and body image domains. CONCLUSIONS: LupusQoL pain domain scores were significantly worse in non-adherent patients compared to adherent patients. Effective pain management could be a determinant in HRQoL and treatment adherence rates in our population.

Renal Functional Reserve in Naïve HIV Patients.

Introduction. Renal functional reserve (RFR) is the kidney capability of increasing its basal glomerular filtration rate (GFR) at least 20% after an adequate stimulus. Renal disorders have been reported in seropositive HIV patients, particularly the decrease in glomerular filtration rate (eGFR), nephrotic syndrome, and proximal tubular deficiency associated with the disease itself or the use of some anti-retroviral treatments. Thus, it was decided to carry out a prospective study in order to evaluate if RFR test was preserved in naive HIV patients. Material and Method. GFR was measured by using cimetidine-aided creatinine clearance (CACC), and RFR as described Hellerstein et al. in seropositive naive HIV patients and healthy volunteers. Results. RFR was evaluated in 12 naïve HIV patients who showed positive RFR (24.8±2%), but significantly lower compared to RFR in 9 control individuals (90.3 ± 5%). Conclusion. In this study was found that renal functional reserve was positive in naïve HIV patients, but significantly lower compared to renal functional reserve achieved by seronegative healthy individuals.

Clinical and Immunological Factors Associated with the Progression of Lupus Nephritis in a Population from the Colombian Caribbean.

Lupus nephritis represents a significant immune-mediated glomerulonephritis, constituting the most important organ involvement induced by systemic lupus erythematosus (SLE), with variable epidemiology and clinical presentation among populations. OBJECTIVE: to identify clinical and immunological factors associated with the progression of lupus nephritis in a population from the Colombian Caribbean. METHODS: we evaluated 401 patients diagnosed with SLE and lupus nephritis, treated at a reference center in the Colombian Caribbean, gathering data recorded in medical records. RESULTS: A proportion of 87% were female, with a median age of 42 years. Most patients presented with proliferative classes (90%), with class IV being the most common (70%). A proportion of 52% of patients did not respond to treatment, which is described as the lack of complete or partial response, while 28% had a complete response. A significant decrease in hemoglobin, glomerular filtration rate, and proteinuria was identified by the third follow-up (p < 0.001), along with an increase in creatinine, urea, and hematuria (p < 0.001). Patients with initial proteinuria > 2 g/day were found to be 27 times more likely to be non-responders (p < 0.001). Mortality was associated with the presence of serum creatinine >1.5 mg/dL (p = 0.01) (OR: 1.61 CI 95% 0.75-3.75) and thrombocytopenia (p = 0.01) (OR: 0.36; CI 95% 0.12-0.81). CONCLUSIONS: identifying factors of progression, non-response, and mortality provides an opportunity for more targeted and personalized intervention, thereby improving care and outcomes for patients with lupus nephritis.

Chronic Kidney Disease Stage and Cardiovascular and Mortality Events Among Older Adults: The SPRINT Trial.

Rationale & Objective: The risk implications of the Kidney Disease: Improving Global Outcomes (KDIGO) chronic kidney disease classification in older adults are controversial. We evaluated the risk of adverse outcomes in this population across categories of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). Study Design: Prospective cohort. Settings & Participants: In total, 2,509 participants aged ≥75 years in the Systolic Blood Pressure Intervention Trial (SPRINT). Exposure: KDIGO eGFR and UACR categories. We combined KDIGO categories G1 and G2, G3b and G4, as well as A2 and A3. Outcomes: Primary SPRINT outcome (composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes), and all-cause death. Analytical Approach: Multivariable Cox proportional hazard models. Results: Mean age was 79.8 years, and 37.4% were female. The mean eGFR was 64.0 mL/min/1.73 m2, and the median UACR was 13.1 mg/g. In multivariable Cox proportional hazard analysis, compared with participants with eGFR ≥ 60 mL/min/1.73 m2 and UACR < 30 mg/g, there was no statistically significant difference in the risk of the primary outcome among participants with eGFR 45-59 or 15-44 mL/min/1.73 m2 and UACR < 30 mg/g. However, those with eGFR 45-59 or 15-44 mL/min/1.73 m2 and UACR ≥ 30 mg/g had higher risk of the primary outcome (HR [95% CI], 1.97 [1.27-3.04] and 3.32 [2.23-4.93], respectively). The risk for all-cause death was higher for each category of abnormal eGFR and UACR, with the highest risk observed among those with eGFR 15-44 mL/min/1.73 m2 and UACR ≥ 30 mg/g (3.34 [2.05-5.44]). Limitations: Individuals with diabetes and urine protein >1 g/day were excluded from SPRINT. Conclusion: Among older adults SPRINT participants, low eGFR without albuminuria was associated with higher mortality but not with increased risk of cardiovascular events. Additional studies are needed to evaluate an adapted chronic kidney disease stage-based risk stratification for older adults.

Using data from participants in the SPRINT trial, we evaluated the association of chronic kidney disease stage with adverse clinical outcomes among adults older than 75 years without diabetes. We found that low level of kidney function determined by a low estimated glomerular filtration rate with moderately or severely increased urine albumin excretion was associated with increased risk for cardiovascular events and all-cause mortality. However, low estimated glomerular filtration rate with normal or mildly increased urinary albumin excretion was not consistently associated with these adverse outcomes. This finding supports the need for additional studies to evaluate an age-adapted classification of chronic kidney disease to improve risk stratification among older adults.

Prevalence and target attainment of traditional cardiovascular risk factors in patients with systemic lupus erythematosus: a cross-sectional study including 3401 individuals from 24 countries.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterised by increased cardiovascular morbidity and mortality risk. We aimed to examine the prevalence of traditional cardiovascular risk factors and their control in an international survey of patients with systemic lupus erythematosus. METHODS: In this multicentre, cross-sectional study, cardiovascular risk factor data from medical files of adult patients (aged ≥18) with SLE followed between Jan 1, 2015, and Jan 1, 2020, were collected from 24 countries, across five continents. We assessed the prevalence and target attainment of cardiovascular risk factors and examined potential differences by country income level and antiphospholipid syndrome coexistence. We used the Systemic Coronary Risk Evaluation algorithm for cardiovascular risk estimation, and the European Society of Cardiology guidelines for assessing cardiovascular risk factor target attainment. People with lived experience were not involved in the research or writing process. FINDINGS: 3401 patients with SLE were included in the study. The median age was 43·0 years (IQR 33-54), 3047 (89·7%) of 3396 patients were women, 349 (10.3%) were men, and 1629 (48·1%) of 3390 were White. 556 (20·7%) of 2681 patients had concomitant antiphospholipid syndrome. We found a high cardiovascular risk factor prevalence (hypertension 1210 [35·6%] of 3398 patients, obesity 751 [23·7%] of 3169 patients, and hyperlipidaemia 650 [19·8%] of 3279 patients), and suboptimal control of modifiable cardiovascular risk factors (blood pressure [target of <130/80 mm Hg], BMI, and lipids) in the entire SLE group. Higher prevalence of cardiovascular risk factors but a better blood pressure (target of <130/80 mm Hg; 54·9% [1170 of 2132 patients] vs 46·8% [519 of 1109 patients]; p<0·0001), and lipid control (75·0% [895 of 1194 patients] vs 51·4% [386 of 751 patients], p<0·0001 for high-density lipoprotein [HDL]; 66·4% [769 of 1158 patients] vs 60·8% [453 of 745 patients], p=0·013 for non-HDL; 80·9% [1017 of 1257 patients] vs 61·4% [486 of 792 patients], p<0·0001 for triglycerides]) was observed in patients from high-income versus those from middle-income countries. Patients with SLE with antiphospholipid syndrome had a higher prevalence of modifiable cardiovascular risk factors, and significantly lower attainment of BMI and lipid targets (for low-density lipoprotein and non-HDL) than patients with SLE without antiphospholipid syndrome. INTERPRETATION: High prevalence and inadequate cardiovascular risk factor control were observed in a large multicentre and multiethnic SLE cohort, especially among patients from middle-income compared with high-income countries and among those with coexistent antiphospholipid syndrome. Increased awareness of cardiovascular disease risk in SLE, especially in the above subgroups, is urgently warranted. FUNDING: None.

Urinary metabolomic profiling of a cohort of Colombian patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune and multisystem disease with a high public health impact. Lupus nephritis (LN), commonly known as renal involvement in SLE, is associated with a poorer prognosis and increased rates of morbidity and mortality in patients with SLE. Identifying new urinary biomarkers that can be used for LN prognosis or diagnosis is essential and is part of current active research. In this study, we applied an untargeted metabolomics approach involving liquid and gas chromatography coupled with mass spectrometry to urine samples collected from 17 individuals with SLE and no kidney damage, 23 individuals with LN, and 10 clinically healthy controls (HCs) to identify differential metabolic profiles for SLE and LN. The data analysis revealed a differentially abundant metabolite expression profile for each study group, and those metabolites may act as potential differential biomarkers of SLE and LN. The differential metabolic pathways found between the LN and SLE patients with no kidney involvement included primary bile acid biosynthesis, branched-chain amino acid synthesis and degradation, pantothenate and coenzyme A biosynthesis, lysine degradation, and tryptophan metabolism. Receiver operating characteristic curve analysis revealed that monopalmitin, glycolic acid, and glutamic acid allowed for the differentiation of individuals with SLE and no kidney involvement and individuals with LN considering high confidence levels. While the results offer promise, it is important to recognize the significant influence of medications and other external factors on metabolomics studies. This impact has the potential to obscure differences in metabolic profiles, presenting a considerable challenge in the identification of disease biomarkers. Therefore, experimental validation should be conducted with a larger sample size to explore the diagnostic potential of the metabolites found as well as to examine how treatment and disease activity influence the identified chemical compounds. This will be crucial for refining the accuracy and effectiveness of using urine metabolomics for diagnosing and monitoring lupus and lupus nephritis.

Mortality Rate and Acute Kidney Injury Prevalence Reduction in COVID-19 Critical Patients Treated with Hemoperfusion.

Introduction: Coronavirus disease 2019 (COVID-19) induces organic damage mainly through the patient's immune overreaction. Hemoperfusion (HPF) can remove inflammatory cytokines and can reduce the negative effects of cytokine storm in COVID-19. We compared the mortality rate, inflammatory response, and acute kidney injury (AKI) prevalence among patients suffering from respiratory insufficiency secondary to COVID-19 treated with and without HPF with HA330 cartridge. Methods: Mortality rate, serum creatinine, and ferritin values were compared between patients suffering from respiratory insufficiency secondary to COVID-19 who received conventional treatment and another group of patients who additionally received four sessions of HPF with HA330. Results: Of 116 patients suffering from acute respiratory insufficiency secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), one group (n: 84) received support treatment and the other group (n: 32) additionally received HPF with HA330 cartridge. Both groups had no renal disease and similar age and comorbidities at admission, except for obesity and mechanical ventilation requirement, which were significantly higher in the HPF group. Mortality rate (61% vs. 31%, P: 0.008), serum creatinine (1.4 vs. 0.5 mg/dl, P < 0.001), and post-HPF serum ferritin (2868 vs. 1675, P < 0.001) were significantly lower in the HPF group. Conclusion: Mortality rate, serum ferritin, and AKI were significantly reduced in critical COVID-19 patients who received HPF with HA330 cartridge than in those who did not receive it. These results were obtained despite the HPF group risk factors, such as obesity and mechanical ventilation, worsening its prognosis.

Alactic base excess (ABE): a novel internal milieu parameter-its concept and clinical importance.

Inspired by the Stewart-Figge acid-base approach, Gattinoni et al. recently introduced a new internal milieu parameter known as alactic base excess (ABE). The authors defined ABE as the sum of lactate and standard base excess. In the context of sepsis, ABE has been proposed as a valuable marker to discern between metabolic acidosis resulting from the accumulation of lactate and the retention of fixed acids, which can occur in cases of renal failure. Multiple studies have demonstrated that a negative ABE value (<-3 mmol/L) represents an early marker of renal dysfunction, and significantly correlates with higher mortality rates in septic patients. In conclusion, ABE is a simple and useful parameter that can be used to better interpret a patient's acid-base status, assess renal function, and general prognosis in sepsis. By incorporating ABE into clinical practice, healthcare professionals can enhance their understanding of the complex acid-base imbalances in their patients and tailor more individualized, effective treatment plans.

Pregnancy-Associated Atypical Hemolytic Uremic Syndrome: A Case Report with MCP Gene Mutation and Successful Eculizumab Treatment.

Pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) is a rare condition characterized by microangiopathic hemolytic anemia and kidney injury from thrombotic microangiopathy. P-aHUS occurs in approximately 1 in 25,000 pregnancies and is strongly related to complement dysregulation and pregnancy-related disorders, such as preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelet (HELLP) syndrome, resulting in adverse perinatal and fetal outcomes. Complement dysregulation in P-aHUS is commonly attributed to genetic mutations or autoantibodies affecting complement factors, including CFH , CFI , and MCP. We present a case of a 25-year-old primigravida who experienced severe preeclampsia and HELLP syndrome followed by the development of complicated P-aHUS during the early postpartum period. The patient exhibited severe clinical manifestations, including hypertensive emergency, central nervous system involvement, renal impairment, and microangiopathic hemolytic anemia. Timely initiation of eculizumab therapy resulted in successful disease remission. Further genetic analysis revealed a likely rare pathogenic MCP gene variant.

Atypical Hemolytic Uremic Syndrome: A Nationwide Colombian Pediatric Series.

Objectives. Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated kidney disease with genetic predisposition and represents up to 10% of pediatric hemolytic uremic syndrome (HUS) cases. Few studies have evaluated aHUS in Latin American population. We studied a Colombian pediatric cohort to delineate disease presentation and outcomes. Methods. A multicenter cohort of 27 Colombian children with aHUS were included. Patients were grouped by age at onset. Clinical features were compared using analysis of variance (ANOVA) and Fisher exact tests. Renal biopsy was performed on 6 patients who were suspected of having other renal diseases before aHUS diagnosis. Results. Most patients were male (70%). The onset of aHUS occurred frequently before age 4 years (60%) and followed gastroenteritis as the main triggering event (52%). Age groups showed comparable clinical presentation, disease severity, treatment, and outcomes. Pulmonary involvement (67%) was the main extrarenal manifestation, particularly in the 1 to 7 age group (P = .01). Renal biopsies were as follows: 3 had membranoproliferative glomerulonephritis (MPGN) type I, one MPGN type III, one C3-glomerulonephritis, and one rapidly progressive GN. Genetic screening was available in 6 patients and identified 2xCFHR5, 2xMCP, 1xADAMTS13/THBD, and 1xDGKE mutations. A total of 15 relapses were seen, of which 8 (72%) occurred in the 1 to 7 age group. The renal outcome was not significantly different regardless of age group. Conclusion. In our cohort, we observed a relatively high frequency of extrarenal involvement at first presentation represented by pulmonary manifestations. The renal prognosis at initial presentation was worse than in previous reports.

Surface-enhanced Raman Spectroscopy in urinalysis of hypertension patients with kidney disease.

Arterial hypertension (AH) is a multifactorial and asymptomatic disease that affects vital organs such as the kidneys and heart. Considering its prevalence and the associated severe health repercussions, hypertension has become a disease of great relevance for public health across the globe. Conventionally, the classification of an individual as hypertensive or non-hypertensive is conducted through ambulatory blood pressure monitoring over a 24-h period. Although this method provides a reliable diagnosis, it has notable limitations, such as additional costs, intolerance experienced by some patients, and interferences derived from physical activities. Moreover, some patients with significant renal impairment may not present proteinuria. Accordingly, alternative methodologies are applied for the classification of individuals as hypertensive or non-hypertensive, such as the detection of metabolites in urine samples through liquid chromatography or mass spectrometry. However, the high cost of these techniques limits their applicability for clinical use. Consequently, an alternative methodology was developed for the detection of molecular patterns in urine collected from hypertension patients. This study generated a direct discrimination model for hypertensive and non-hypertensive individuals through the amplification of Raman signals in urine samples based on gold nanoparticles and supported by chemometric techniques such as partial least squares-discriminant analysis (PLS-DA). Specifically, 162 patient urine samples were used to create a PLS-DA model. These samples included 87 urine samples from patients diagnosed with hypertension and 75 samples from non-hypertensive volunteers. In the AH group, 35 patients were diagnosed with kidney damage and were further classified into a subgroup termed (RAH). The PLS-DA model with 4 latent variables (LV) was used to classify the hypertensive patients with external validation prediction (P) sensitivity of 86.4%, P specificity of 77.8%, and P accuracy of 82.5%. This study demonstrates the ability of surface-enhanced Raman spectroscopy to differentiate between hypertensive and non-hypertensive patients through urine samples, representing a significant advance in the detection and management of AH. Additionally, the same model was then used to discriminate only patients diagnosed with renal damage and controls with a P sensitivity of 100%, P specificity of 77.8%, and P accuracy of 82.5%.

Hyponatremia and malnutrition: a comprehensive review.

BACKGROUND: Hyponatremia (serum sodium lower than 135 mmol/L) is the most frequent electrolyte alteration diagnosed in medical practice. It has deleterious clinical effects, being an independent predictor of mortality. Malnutrition encompasses pathological states caused by both nutrients excess and deficiency, being frequently documented in chronic kidney disease patients. In addition, chronic hyponatremia promotes adiposity loss and sarcopenia, while malnutrition can induce hyponatremia. This pathological interaction is mediated by four main mechanisms: altered electrolyte body composition (low sodium, low potassium, low phosphorus, or high-water body content), systemic inflammation (cytokines increase), hormonal mechanisms (renin-angiotensin-aldosterone system activation, vasopressin release), and anorexia (primary or secondary). CONCLUSION: Malnutrition can induce hyponatremia through hydro-electrolytic, hormonal, inflammatory, or nutritional behavior changes; while hyponatremia per se can induce malnutrition, so there is a pathophysiological feedback between both conditions.

Obesity and glomerular filtration rate.

Obesity has received considerable attention in general medicine and nephrology over the last few years. This condition increases the risk of metabolic syndrome, diabetes mellitus, hypertension, and dyslipidemia, which are the main risk factors for developing chronic kidney disease (CKD). Kidney damage caused by obesity can be explained by many mechanisms, such as sympathetic nervous and renin-angiotensin-aldosterone systems activation, mechanical stress, hormonal unbalance, as well as inflammatory cytokines production. Even though creatinine-based glomerular filtration rate (GFR) equations in obese individuals have been validated (Salazar-Corcoran and CKD-MCQ), changes in body weight after bariatric surgery (BS) leads to changes in creatininemia, affecting its reliability. Thus, an average between creatine and cystatin-based GFR equations would be more appropriate in this setting. Bariatric surgery can reverse diabetes mellitus and improve hypertension, which are the main causes of CKD. Conclusion: GFR can be affected by obesity and BS, and its value should be cautiously evaluated in this setting.

Insulin and the kidneys: a contemporary view on the molecular basis.

Insulin is a hormone that is composed of 51 amino acids and structurally organized as a hexamer comprising three heterodimers. Insulin is the central hormone involved in the control of glucose and lipid metabolism, aiding in processes such as body homeostasis and cell growth. Insulin is synthesized as a large preprohormone and has a leader sequence or signal peptide that appears to be responsible for transport to the endoplasmic reticulum membranes. The interaction of insulin with the kidneys is a dynamic and multicenter process, as it acts in multiple sites throughout the nephron. Insulin acts on a range of tissues, from the glomerulus to the renal tubule, by modulating different functions such as glomerular filtration, gluconeogenesis, natriuresis, glucose uptake, regulation of ion transport, and the prevention of apoptosis. On the other hand, there is sufficient evidence showing the insulin receptor's involvement in renal functions and its responsibility for the regulation of glucose homeostasis, which enables us to understand its contribution to the insulin resistance phenomenon and its association with the progression of diabetic kidney disease.

Handgrip Strength Is Associated with Specific Aspects of Vascular Function in Individuals with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a disorder associated with an increased risk for the development of diabetes mellitus and its complications. Lower isometric handgrip strength (HGS) is associated with an increased risk of cardiometabolic diseases. However, the association between HGS and arterial stiffness parameters, which are considered the predictors of morbidity and mortality in individuals with MetS, is not well defined. OBJECTIVE: To determine the association between HGS and HGS asymmetry on components of vascular function in adults with MetS. METHODS: We measured handgrip strength normalized to bodyweight (HGS/kg), HGS asymmetry, body composition, blood glucose, lipid profile, blood pressure, pulse wave velocity (PWV), reflection coefficient (RC), augmentation index @75 bpm (AIx@75) and peripheral vascular resistance (PVR) in 55 adults with a diagnosis of MetS between 25 and 54 years old. RESULTS: Mean age was 43.1 ± 7.0 years, 56.3% were females. HGS/kg was negatively correlated with AIx@75 (r = -0.440), p < 0.05, but these associations were not significant after adjusting for age and sex. However, when interaction effects between sex, HGS/kg and age were examined, we observed an inverse relationship between HGS/kg and AIx@75 in the older adults in the sample, whereas in the younger adults, a weak direct association was found. We also found a significant association between HGS asymmetry and PVR (beta = 30, 95% CI = 7.02; 54.2; p <0.012). CONCLUSIONS: Our findings suggest that in people with MetS, maintaining muscle strength may have an increasingly important role in older age in the attenuation of age-related increases in AIx@75-a marker of vascular stiffness-and that a higher HGS asymmetry could be associated with a greater vascular resistance.

Novel Biomarkers of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a highly prevalent condition worldwide. It represents one of the most common complications arising from diabetes mellitus (DM) and is the leading cause of end-stage kidney disease (ESKD). Its development involves three fundamental components: the hemodynamic, metabolic, and inflammatory axes. Clinically, persistent albuminuria in association with a progressive decline in glomerular filtration rate (GFR) defines this disease. However, as these alterations are not specific to DKD, there is a need to discuss novel biomarkers arising from its pathogenesis which may aid in the diagnosis, follow-up, therapeutic response, and prognosis of the disease.

From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and long COVID.

Reductions in systolic blood pressure achieved by hypertensives with three isometric training sessions per week are maintained with a single session per week.

Isometric handgrip or (wall) squat exercise performed three times per week produces reductions in systolic blood pressure (SBP) in adults with hypertension. We aimed to compare these interventions and the potential to retain benefits with one exercise session per week. We compared blood pressure changes following handgrip and squat isometric training interventions with controls in a randomized controlled multicentre trial in 77 unmedicated hypertensive (SBP ≥ 130 mmHg) adults. Exercise sessions were performed in the workplace and consisted of four repetitions-three sessions per week for the first 12 weeks (phase 1), and one session per week for the subsequent 12 weeks (phase 2). Office blood pressure (BP) was measured at baseline, post-phase 1 and post-phase 2. Post-phase 1, mean reductions in SBP were significantly greater in handgrip (-11.2 mmHg, n = 28) and squat (-12.9 mmHg, n = 27) groups than in controls (-.4 mmHg; n = 22) but changes in DBP were not. There were no significant within-group changes during phase 2 but SBP was 3.8 mmHg lower in the wall squat than the handgrip group-a small magnitude but clinically important difference. While both interventions produced significant SBP reductions, the wall squat appears to be more effective in maintaining benefits with a minimal training dose. The low time investment to achieve and retain clinically significant SBP reductions-42 and 12 min, respectively-and minimal cost, particularly of the wall squat, make it a promising intervention for delivery in public health settings.