Treatment of Severe Lupus Nephritis
Treatment of Lupus nephritis is a race against nephron loss. Current sequential therapy for LN allows for 20-30% complete clinical renal response. A treat-to-target approach might be implemented to avoid nephron loss. Per-protocol repeat renal biopsy may be a part of this strategy. A switch from sequential therapy to combination therapy is warranted compared to current therapy.
Secondary Immunodeficiency in Patients with Autoimmune Diseases
The most common secondary immunodeficiencies are antibody or cellular deficiencies. Secondary antibody deficiency is 30 times more common than primary antibody deficiency. Secondary immunodeficiencies are overlooked and undertreated and may be reversible but many are not. Assessment and decision on treatment require clinical context and functional Ab testing.
Autoimmunity and Primary Immunodeficiency
In the future with increasing use of functional genetics, many ill-defined syndromes of immunodeficiency or inflammatory diseases will be dissolved into genetic categories. Leniolisib is a potent and selective oral PI3Kδ inhibitor and also led to significant improvement in the immunological status and clinical presentation of patients with APDS/PASLI. Most common are antibody deficiencies.
Treatment of ILD in Patients with Primary Sjogren's Syndrome: A Single-center Retrospective Analysis
The study determined whether adding cyclophosphamide or rituximab to steroid and oral DMARD therapy improves pulmonary function test results in individuals with primary Sjogren's syndrome-interstitial lung disease (pSS-ILD) who have poor baseline pulmonary function. The study found that FVC improved significantly in patients who received add-on CYC and/or RTX.
Is There an Added Value of Imaging to Composite Index Measurement of Disease Activity in RA Patient?
The study determined whether there is an added value of imaging to the composite index measurement of disease activity in patients with RA. Clinical evaluation of remission alone may be inadequate to capture a persistent lack of inflammation at different joint sites. Imaging can complement the assessment of patients in clinical remission, offering additional data.
How to Assess Heart Function in Rheumatic Diseases?
A study analyses the heart function in rheumatic diseases, particularly how to assess it either in systemic sclerosis & rheumatic arthritis as a prototype disease. Myocardial damage modifies electric conduction and functionality. The ischemic microcirculatory component is always present in SSc patients. The disturbance of electric potentials is fundamental to suspect primary heart involvement.
Lupus Low Disease Activity State (LLDAS)
LLDAS has better performance than other definitions of low disease activity and is associated with low mortality. It was found to be almost same as that of remissions when SLE was treated with belimumab while comparing real world evidence. Post hoc clinical trial data for drugs like Anifrolumab, Azathioprin etc, concluded that LLDAS is discriminatory in clinical trials.
Dapagliflozin Improves Renal Function in Obese Indian Diabetics with Microalbuminuria
Mahapatra H briefed about the Renoprotective effect of Dapagliflozin (DAPA) compared with the RAAS blockers in obese Indian type 2 diabetics (T2D) with microalbuminuria. Dapagliflozin showed substantial and analytically superior decrease in UACR than RAAS blocking agents in obese patients with microalbuminuric diabetes. Dapagliflozin utilization also showed substantial HbA1c reduction.
Insulin Driving Obesity-Related Cancers
Obesity and diabetes are associated with risk of cancers. IR/IGF-IR ratio in breast cancer is associated with BMI, NPI & race. Studies are going on to find therapeutics to treat cancer and improve metabolism. Hyperinsulinemia and insulin receptor signaling are important mechanisms contributing to cancer growth and progression, may explain part of the radical disparity in cancer outcome.
Heart Failure with Preserved Ejection Fraction: Can we Navigate the Black Hole of Heart failure?
SGLT2i reduced the composite of total cardiovascular deaths and hospitalizations for heart failure. These are first randomized data from prespecified analysis of clinical trials to show effect of a therapy on heart failure with preserved ejection fraction. The main goal is to manage co-morbidities. Potential drugs for HPpEF are MRA, ARNi, SGLT2i & Finerenone.
Heart Failure with Reduced Ejection Fraction: How to Prioritise among an Array of Therapy?
The four pillars of survival-enhancing medical therapy for HErEF are angiotensin receptor-neprilysin inhibitors, β-blocker, mineralocorticoid receptor antagonists & SGLT2i. Some ways to combat the situation with combination therapy include ensuring the patient can tolerate the medication and frequent use of telehealth services.
Finerenone in Patients with CKD and T2D by SGLT2i Treatment: FIDELIO-DKD Study Analysis
Finerenone was investigated in patients with CKD & T2D. Finerenone reduced the primary (kidney failure, reduction in eGFR ≥40%, or renal death) and secondary CV outcomes (CV death, nonfatal MI, nonfatal stroke, or hospitalization for HF). Benefits were consistent in the absence or presence of SGLT2i, with UACR improvement observed in patients receiving SGLT-2i at baseline.
Update on SCORED Trial - Main Results
Sotagliflozin is a dual inhibitor of SGLT2 and SGLT1 that is yet to be approved by the FDA. Clinical trials show that early use of this drug provides benefits across full range of albuminuria, a sign of kidney disease that involves excess of protein in the urine. It decreases the chance of heart attack by 32% & stroke by 34%.
Update on SOLOIST Trial - Main Results
Clinical trials were conducted to study the safety & efficacy of Sotagliflozin. Sotagliflozin was proved to be beneficial in patients hospitalized with acute heart failure. Early in-hospital initiation of Sotagliflozin reduced the risk of death from CVD and hospitalization or urgent visits for heart failure by 33%. The drugs were well tolerated among participants.
GIPR Signalling in Alpha Cells Completes the Incretin Axis
Incretin stimulates insulin secretion in a glucose-dependent manner as glucose is required to activate beta cells. GIP infusion elevates glucagon, this effect is glucose-dependent & only observed at hypoglycemia and euglycemia. GIP produced incretin requires activation by amino acid stimulation. Alpha cell GPCR is necessary for glucose homeostasis in response to mixed nutrient feeding.
Inflammatory Cytokines Rewire the Proinsulin Interaction Network in Islets
Cytokines induce proinsulin binding to KIF family microtubule-associated factors. Inflammatory cytokines rewire the proinsulin interaction network in human islets. The peroxidation of PRDX4 promotes proinsulin folding and is selectively disabled in islets from patients with T2D. Cytokines sensitize human beta cells. Proinsulin folding is maintained despite moderate ER stress induced by cytokines.
High Glucose Level Increases Expression of SARS-CoV-2 Receptor
A low incidence of SARS-CoV-2 receptors was observed on CD14 macrophage cells, pinpointing a poor recognition of the virus particle by CD14 cells. But a higher expression of the SARS-CoV-2 receptors was noted when HUVEC cells were cultured in HG for 7 days. Thus, a longer exposure of human endothelial cells to a high glucose condition increases the SARS-CoV-2 receptor expression.
Efficacy and Safety of Dapagliflozin by Glycemic Status in the DAPA-CKD Trial
The safety profile of dapagliflozin was similar over glycemic groups, with no incidents of major hypoglycemia or ketoacidosis in participants with normoglycemia or prediabetes, and no ketoacidosis in any participant managed with dapagliflozin. Dapagliflozin showed significant reduction in the risk of kidney and cardiovascular incidents independent of baseline glycemic status.
Soliqua: Sustained Cost Efficacy and Safety When Used in Combination with Metformin and Glimepiride
Soliqua trials evaluated Soilqua with Glimepiride and Metformin in patients with type 2 diabetes. Daily dose of Soliqua with metformin 1000-2000 mg were started pre-breakfast based on previous basal insulin dose. Soliqua is cost efficacious and safe in all patients irrespective of BMI, when administered in combination with glimepiride and metformin in the long term.
Combination Therapies for Kidney Protection in Diabetes: Is One Plus One More than Two?
Combination therapies reduce the risks of kidney failure and heart failure. Current treatment of ACEi and ARBs are insufficient to slow CKD progression. SGLT2 inhibitors, ERA, MAR, and GLP-1 RA slow down the progression of kidney disease. When used in combination, SGLT2 inhibitors may abrogate fluid retaining effects of ERA and hyperkalemic effects of MRA.
