digoxin/metformin/simvastatin (C3) / SUNY Downstate Medical Center, University of Toledo - LARVOL DELTA

Mixed autoimmune hemolytic anemia as a rare initial presentation of systemic lupus erythematosus (ASH 2025) - "The patient was started on immunosuppressive therapy for mixed autoimmune hemolytic anemia with prednisone 1 mg per kilogram divided into twice daily dosing and IVIG 1g/kg for two doses...C4 levels were low at 9, and C3 levels were normal...We preferred IVIG as it is faster acting than rituximab and has fewer side effects... This case highlights that although rare, SLE can present with MAIHA. SLE should be considered as one of the causes of MAIHA, and clinicians should have a high clinical suspicion for it."

Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Influenza • Lupus • Novel Coronavirus Disease • Rare Diseases • Respiratory Diseases • Respiratory Syncytial Virus Infections • Systemic Lupus Erythematosus • HP

Electrode Artifact, Breach Rhythm, or Focal Seizures: Navigating an Electrographic Quandary (AES 2025) - "Careful review of electrographic onset demonstrated that this rhythm, although still first seen in the left anterior temporal region (F7), progressed rapidly to the left frontopolar (Fp1) and central (C3), followed by spread to the left frontal region (F3) (Figure 1 D)...Despite escalation of antiepileptic therapy and use of anesthetic agents, seizures remained refractory (there was reduction in electrographic seizure burden after introducing Ketamine and Phenobarbital)... This case carries an important lesson for the neurophysiologist: Focal electrographic discharges recorded near a skull defect should not be dismissed as artifacts without further investigation. The use of extended EEG arrays, such as the 10–10 montage or additional anterior temporal electrodes, or imaging modalities such as MRI, may help resolve this diagnostic challenge. This is particularly crucial in the context of aggressive treatment of status epilepticus, as delays in treatment may potentially..."

Anesthesia • CNS Disorders • Epilepsy • Vascular Neurology

Melanocortin Therapy Mitigates Glomerular Complement Activation and Podocyte Injury in Membranous Nephropathy via MC5R Signaling (KIDNEY WEEK 2025) - "Mechanistically, glomerular fixation of C5b-9 and C3 was reduced with melanocortin therapy in diseased WT mice but increased by MC5R KO, despite similar glomerular deposition of the nephritogenic antibody and activation of C4, suggesting that MC5R signaling exerts an anti-complement effect primarily through mitigating C3 amplification. In consistency, unbiased transcriptomic analysis of the publicly available renal transcriptome data from ACTH- and vehicle-treated mice indicated a marked suppression of renal expression of CFB and CFD following ACTH treatment. Conclusion MC5R signaling intercepts the complement amplification loop in podocytes, thereby mitigating glomerular injury in experimental MN."

Glomerulonephritis • Renal Disease • CFB

Intercepting the complement amplification loop through podocyte MC5R signaling ameliorates membranous nephropathy. (PubMed, Mol Ther) - "Here, in a heterologous mouse model of THSD7A-associated membranous nephropathy, various melanocortin agents, including repository corticotropin injection, the non-steroidogenic pan-melanocortin receptor agonist NDP-MSH, and the selective melanocortin 5 receptor (MC5R) agonist PG-901, attenuated proteinuria and ameliorated glomerulopathy...Furthermore, glomerular fixation of C5b-9 and C3 was diminished by MC5R agonism but enhanced by MC5R knockout, despite comparable glomerular deposition of the heterologous nephritogenic antibody and activation of C4. Comprehensive complement cascade analysis revealed that this anti-complement effect of MC5R signaling stems from an inhibition of podocyte expression of complement factor B and D, critical regulators of the complement amplification loop, involving a PPARγ-dependent mechanism. Ergo, MC5R-mediated interception of the complement amplification loop in podocytes may serve as a novel therapeutic target for membranous nephropathy."

Journal • Glomerulonephritis • Renal Disease • CFB • PPARG

A Rare Case of Seronegative Lupus Nephritis Presenting as Immune Complex Diffuse Glomerulonephritis. (PubMed, Cureus) - "Renal biopsy demonstrated diffuse proliferative glomerulonephritis with a full house immunofluorescence pattern, including granular capillary wall staining for immunoglobulin G, A, and M (IgG, IgA, and IgM), complement 1q (C1q), and complement 3 (C3)...The patient was initiated on corticosteroids and mycophenolate mofetil, with resolution of edema and stabilization of renal function...In patients presenting with immune complex-mediated glomerulonephritis and absent serologic markers, seronegative lupus nephritis should remain on the differential. Renal biopsy not only establishes diagnosis but also guides timely immunosuppressive therapy critical to preserving renal function."

Journal • Complement-mediated Rare Disorders • Diabetes • Glomerulonephritis • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Metabolic Disorders • Monoclonal Gammopathy • Nephrology • Pulmonary Disease • Renal Disease • Systemic Lupus Erythematosus • Type 1 Diabetes Mellitus

Late Presentation of Galloway-Mowat Syndrome (GAMOS) Associated With Membranous Nephropathy: A Case Report. (PubMed, Cureus) - "His workup revealed worsening proteinuria, which was previously controlled with tacrolimus, low-dose steroid, and enalapril. His laboratory workup showed a serum creatinine level of 1 mg/dL, albumin at 3.5 g/dL, a urine-protein-to-creatinine ratio of 2,800 mg/g, complement 3 (C3) at 127 mg/dL, and complement 4 at 41 mg/dL...Our patient was diagnosed with GAMOS associated with MN, and intensive management of proteinuria was initiated. We present this unique patient with GAMOS and PLA2R-negative MN in an adult."

Journal • Atrial Fibrillation • Cardiomyopathy • Cardiovascular • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Glomerulonephritis • Hematological Disorders • Hypertension • Hypertrophic Cardiomyopathy • Immunology • Inflammatory Bowel Disease • Nephrology • Renal Disease • Thrombosis • Ulcerative Colitis • EGF

Evaluating the Effectiveness of Pegbelfermin in MASH-Associated Hepatic Fibrosis A Meta-Analysis and Systematic Review of Randomized Controlled Trials. (PubMed, JGH Open) - "No significant improvements in liver stiffness, Modified Ishak scores, collagen proportionate area, ALT and AST levels, or treatment-emergent adverse events (TEAEs) were observed in either dosage group. Pegbelfermin, a promising therapy for MASH fibrosis, has demonstrated effectiveness at 10 mg, significantly improving MASH and biomarkers including adiponectin and PRO-C3, while maintaining a generally safe profile."

Journal • Retrospective data • Fibrosis • Gastroenterology • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF

Recurrence of glomerulonephritis in renal transplant- A problem for long-term graft survival, is closer surveillance the answer? (NKF-SCM 2025) - "Upon completion of treatment with steroids and IVIG, the patient was discharged home with plans to initiate Eculizumab as outpatient.Conclusion Recurrence of primary disease is an important cause of graft failure in transplant recipients with glomerulonephritis. This may be important in guiding further treatment and may also influence the decision to pursue an additional transplant due to an increased risk of recurrence in subsequent grafts. The presence of C3 glomerulonephritis should prompt consideration for alternate complement pathway abnormalities"

Acute Kidney Injury • Antibody-mediated Rejection • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Pain • Transplantation

Glomerular Disease Caused by Vinyl Carbamate in A/J Inbred Mice: A Novel Model of Membranoproliferative Glomerulonephritis (MPGN) (KIDNEY WEEK 2024) - "On immunofluorescent staining, abundant granular mesangial C3 staining was noted along with coarse linear capillary staining, whilst immunoglobulin staining was negative... VC, a metabolite of EC, induces complement fixation in glomeruli and MPGN in mice. Complement overactivation due to CFD induction and CFH repression may be an underlying pathomechanism."

Preclinical • Glomerulonephritis • Lupus Nephritis • Nephrology • Oncology • Renal Disease

EFFICACY AND SAFETY OF PEGBELFERMIN IN MASH CIRRHOSIS- A META-ANALYSIS AND SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS (AASLD 2024) - "Pegbelfermin, a promising therapy for MASH cirrhosis, has demonstrated effectiveness at 10 mg, significantly improving MASH and biomarkers such as adiponectin and PRO-C3. Despite mild gastrointestinal side effects, it maintains a generally safe profile. Further research with larger randomized controlled trials and extended follow-up is warranted to explore Pegbelfermin's role in enhancing MASH and liver fibrosis outcomes, particularly in combination with Resmetirom."

Retrospective data • Review • Fibrosis • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

Outcomes Based on Surgical Timing after Neoadjuvant Therapy for Locally Advanced Esophageal Cancer (ASTRO 2024) - "Patients were grouped into one of six cohorts (1-4 weeks (C1), 4-8 weeks (C2), 8-12 weeks (C3), 12 weeks - 6 months (C4), 6 months to 1 year (C5), or >1 year(C6))... Our results indicate an increase in the rate of pCR after 8wks post NAT. The optimal time for surgery may be somewhere between 4-8wks based on complication rate and OS. However, delayed surgery if clinical complete response is a reasonable approach as it relates to complications and OS."

Clinical • Metastases • Esophageal Cancer • Gastrointestinal Cancer • Oncology

Glomerular injury induced by vinyl carbamate in A/J inbred mice: a novel model of membranoproliferative glomerulonephritis. (PubMed, Front Pharmacol) - "Consistently, exposure of primary glomerular endothelial cells to EC or VC resulted in induction of CFD and repression of CFH, accompanied by increased fixation of C3 and C5b9...Indeed, EC or VC-elicited complement activation was associated with activation of Ras signaling, but was abolished by the Ras inhibitor farnesyl thiosalicylic acid. Collectively, our findings suggest that VC, a metabolite of EC, induces glomerular injury in mice akin to human MPGN, possibly via perturbing the expression of complement regulators, resulting in an effect that favors activation of the alternative complement pathway."

Journal • Preclinical • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Oncology • Renal Disease

Shifting trends in the epidemiology of Cervical Spine Injuries: An Analysis of 11,822 patients from the National Electronic Injury Surveillance System (NEISS) over two decades. (PubMed, J Neurotrauma) - "Our study detected a pragmatic demarcation of classifying upper injuries as C1-C3 and lower cervical injuries as C4-C7. Upper injuries were seen more often in older, white females who were treated and admitted, and lower injuries were seen more often in young, black male patients who were released without admission."

Journal • CNS Disorders • Orthopedics

Phase 2A Pilot C3 Trial of Recurrent/Refractory Metastatic Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=25 | Recruiting | Sponsor: State University of New York - Downstate Medical Center | Initiation date: Dec 2023 ➔ Apr 2024

Combination therapy • Metastases • Trial initiation date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Mechanisms by which Factor H protects Trypanosoma cruzi from the alternative pathway of complement. (PubMed, Front Immunol) - "Only trypomastigotes, but not epimastigotes (non-infective, complement susceptible) bound FH directly, independent of C3 deposition, in a dose-dependent manner...FH-related protein-5, whose domains bear significant sequence identity to all known polyanion-binding FH domains (6-7, 10-14, 19-20), fully inhibited FH binding to trypomastigotes and reduced trypomastigote survival to < 24% in the presence of serum. In conclusion, we have elucidated the role of FH in complement resistance of trypomastigotes."

Journal

Phase 2A Pilot C3 Trial of Recurrent/Refractory Metastatic Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=25 | Recruiting | Sponsor: State University of New York - Downstate Medical Center | Phase classification: P2a ➔ P1/2 | Trial completion date: Sep 2024 ➔ Dec 2024 | Trial primary completion date: Sep 2024 ➔ Dec 2024

Combination therapy • Metastases • Phase classification • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

A Rare Presentation of Drug-Induced Pancreatitis After Cyclophosphamide Infusion (ACG 2023) - "Rheumatologic work-up showed normal IGG subclasses, C3 and C4 within normal limits and a normal Erythrocyte Sedimentation Rate. Interestingly, the patient tolerated the first 5 doses with only minor abdominal pain. This demonstrates the need to keep a broad differential and have extensive medication review."

Cardiovascular • Chronic Kidney Disease • Hypertension • Immunology • Inflammatory Arthritis • Lupus • Nephrology • Pain • Pancreatitis • Renal Disease • Rheumatology • Systemic Lupus Erythematosus • CRP

Phase 2A Pilot C3 Trial of Recurrent/Refractory Metastatic Advanced Pancreatic Cancer (clinicaltrials.gov) - P2a | N=25 | Recruiting | Sponsor: State University of New York - Downstate Medical Center | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor