Beyond the kidney: extra-renal manifestations of monogenic nephrolithiasis and their significance.

BACKGROUND: The objective of this study was to explore the frequency of occurrence of extra-renal manifestations associated with monogenic nephrolithiasis. METHODS: A literature review was conducted to identify genes that are monogenic causes of nephrolithiasis. The Online Mendelian Inheritance in Man (OMIM) database was used to identify associated diseases and their properties. Disease phenotypes were ascertained using OMIM clinical synopses and sorted into 24 different phenotype categories as classified in OMIM. Disease phenotypes caused by the same gene were merged into a phenotypic profile of a gene (PPG) such that one PPG encompasses all related disease phenotypes for a specific gene. The total number of PPGs involving each phenotype category was measured, and the median phenotype category was determined. Phenotype categories were classified as overrepresented or underrepresented if the number of PPGs involving them was higher or lower than the median, respectively. Chi-square test was conducted to determine whether the number of PPGs affecting a given category significantly deviated from the median. RESULTS: Fifty-five genes were identified as monogenic causes of nephrolithiasis. A total of six significantly overrepresented and three significantly underrepresented phenotype categories were identified (p < 0.05). Four phenotypic categories (growth, neurological, skeletal, and abdomen/gastrointestinal) are significantly overrepresented after Bonferroni correction for multiple comparisons (p < 0.002). Among all phenotypes, impaired growth is the most common manifestation. CONCLUSION: Recognizing the extra-renal manifestations associated with monogenic causes of kidney stones is critical for earlier diagnosis and optimal care in patients.

CD19-targeted chimeric antigen receptor T-cell therapy in patients with concurrent B-cell Non-Hodgkin lymphoma and rheumatic autoimmune diseases: a propensity score matching study.

Rheumatic autoimmune diseases not only involve the production of autoantibodies but also demonstrate T-cell dysfunction. In patients with concurrent B-cell non-Hodgkin lymphoma (NHL) and rheumatic autoimmune diseases, the safety and efficacy of CD19-targeted chimeric antigen receptor (CAR) T-cell therapy are unknown. Using an aggregated electronic health record database, patients with rheumatic autoimmune diseases (auto group) were compared to propensity score-matched patients without rheumatic autoimmune diseases (non-auto group). From 1/2019 to 1/2023, 58 (4.3%) of 1,363 patients who received CD19-targeted CAR T-cell therapy had concurrent rheumatic autoimmune diseases. Both groups had similar incidence, severity, and management of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Moreover, the two groups had similar time-to-next treatment or death (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.60 to 1.59, log-rank p = 0.91) and overall survival (HR 0.90, 95%CI 0.46 to 1.78, p = 0.76). Following CAR T-cell infusion, patients with rheumatic autoimmune diseases achieved decreased inflammatory markers, seronegative conversion of autoantibodies, as well as reduced use of steroids and disease-modifying anti-rheumatic drugs. In conclusion, the safety and efficacy of CAR T-cell therapy were not affected in patients with rheumatic autoimmune diseases. Moreover, they achieved better biochemical control of underlying rheumatic diseases.

Novel compound heterozygote variants: c.4193_4206delinsG (p.Leu1398Argfs*25), c.793C > A (p.Pro265Thr), in the CPS1 gene (NM_001875.4) causing late onset carbamoyl phosphate synthetase 1 deficiency-Lessons learned.

Carbamoyl phosphate synthetase 1 (CPS1) deficiency is an autosomal recessive urea cycle disorder with varying presentations. Patients with a neonatal-onset phenotype are initially healthy but develop severe hyperammonemia days after birth and often have poor or lethal outcomes, while patients who present later in life may exhibit less severe clinical manifestations. CPS1 deficiency is rarely found on newborn screening because most states do not screen for this disease due to the technical difficulties. We report a case of an 11-year-old, previously healthy girl who presented with hyperammonemia and acute psychosis after eating large amounts of meat at summer camp. A diagnosis of carbamoyl phosphate synthetase type 1 deficiency was suspected by biochemical profiles and confirmed by molecular analysis. Subsequent follow up lab results revealed ammonia to be only 25-39 µmol/L shortly after glutamine reached levels as high as 770-1432 µmol/L with concurrent alanine elevations, highlighting the compensating mechanisms of the human body. Her initial hospital course also demonstrated the importance of continuous renal replacement therapy (CRRT) in avoiding rebound hyperammonemia and high glutamine and the benefits of intracranial pressure (ICP) monitoring, providing 3% hypertonic saline and temperature control to avoid fever in treating cerebral edema. Carglumic acid was not considered helpful in this case, with BUN levels ranging between 2 and 4 mg/dL after administration.

Compound heterozygote variants: c.848A > G; p.Glu283Gly and c.890C > T; p.Ala297Val, of Isovaleric acid-CoA dehydrogenase (IVD) gene causing severe Isovaleric acidemia with hyperammonemia.

With the execution of expanded newborn screen (NBS) program nationwide, it is uncommon to see severe hyperammonemia associated with isovaleric acidemia (IVA). We present a seven-day-old boy with severe IVA complicated by hyperammonemia. This child was flagged by NBS at 4 days old, but confirmatory testing was delayed due to COVID19 pandemic and parental skepticism. His parents did not adhere to the leucine-restricted diet as recommended. On day 7, the patient presented to the ER with ammonia of 588 µg/dL. Ammonia subsequently rose to >1000 µg/dL. This child received carnitine, 1 dose of Ammonul (sodium benzoate and sodium phenylacetate), arginine, carglumic acid (Carbaglu) and CRRT. Plasma amino acid assay revealed a glutamine level of 256 µmol/L, which is below the lower limit of normal upon arrival to ER and PICU. The hyperammonemia was corrected in 15 h and with the continued use of carglumic acid for 3 days, there was no rebound of hyperammonemia. However, the patient suffered from bone marrow suppression associated with the organic acidemia and required frequent platelet transfusions, as well as G-CSF for neutropenia. The management of this patient provides supporting evidence of the many theoretic metabolic "facts" including why Ammonul is not helpful in organic acidemias.

Should We Use High-Flow Nasal Cannula in Patients Receiving Gastrointestinal Endoscopies? Critical Appraisals through Updated Meta-Analyses with Multiple Methodologies and Depiction of Certainty of Evidence.

(1) Background: High-flow nasal cannula (HFNC) therapy or conventional oxygen therapy (COT) are typically applied during gastrointestinal (GI) endoscopic sedation. (2) Methods: We conducted a rigorous systematic review enrolling randomized controlled trials (RCTs) from five databases. Risk of bias was assessed using Cochrane's RoB 2.0 tool; certainty of evidence (CoE) was assessed using GRADE framework. Meta-analysis was conducted using inverse-variance heterogeneity model and presented as relative risk (RR) with 95% confidence interval (CI). Trial sequential analysis was performed, and sensitivity analysis was conducted with Bayesian approach. (3) Results: Eight RCTs were included. Compared to COT, HFNC did not reduce the overall incidence of hypoxemia (RR 0.51; 95% CI 0.24-1.09; CoE: very low) but might reduce the incidence of hypoxemia in patients at moderate to high risk for hypoxemia (RR 0.54; 95% CI 0.31-0.96; and CoE: very low). HFNC might reduce the incidence of severe hypoxemia (RR 0.38; 95% CI 0.20-0.74; and CoE: low). HFNC might not affect the need of minor airway interventions (RR 0.31; 95% CI 0.08-1.22; and CoE: very low) and had no effect on procedure duration (CoE: very low); (4) Conclusions: During GI endoscopic sedation, HFNC might reduce the incidence of hypoxemia in patients at moderate to high risk for hypoxemia and prevent severe hypoxemia.

The Early Dynamic Change in Cardiac Enzymes and Renal Function Is Associated with Mortality in Patients with Fulminant Myocarditis on Extracorporeal Membrane Oxygenation: Analysis of a Single Center's Experience.

(1) Background: Fulminant myocarditis (FM) could result in hemodynamic derangement and fatal arrhythmia. Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is used to maintain organ perfusion in FM patients complicating cardiogenic shock. The present study aims to assess the static and dynamic factors in association with mortality in FM patients on V-A ECMO (2) Methods: Twenty-eight patients were enrolled between 2013 to 2019 for analysis (3) Results: In-hospital survival rate was 78.5%. There was no statistical difference in demographics and baseline laboratory data between survivors and non-survivors. However, within 24 h after ECMO support, CK-MB increased by 96.8% among non-survivors, but decreased by 23.7% among survivors (p = 0.022). Troponin I increased by 378% among non-survivors and 1.7% among survivors (p = 0.032). Serum creatinine increased by 108% among non-survivors, but decreased by 8.5% among survivors (p = 0.005). The receiver operating characteristic curve suggested an increase in serum creatinine by 68% within 24 h after ECMO support was associated with increased mortality with an area under the curve of 0.91. (4) Conclusions: V-A ECMO is an excellent tool to support FM patients with cardiogenic shock. The early dynamic change of renal function and cardiac enzymes may be useful for outcome assessment.

Temporary coronary sinus pacing to improve ventricular dyssynchrony with cardiogenic shock: A case report.

BACKGROUND: Temporary transvenous pacing through the coronary sinus is a novel approach rarely used in treating unstable bradycardia. This modality could provide cardiac pacing while achieving better ventricular synchrony. We present a case who received cardiac pacing through the coronary sinus and provide a summary of evidence in the current literature. CASE SUMMARY: A 55-year-old woman with a history of advanced heart failure was admitted to the rehabilitation ward after a recent stroke. During hospitalization, she had paroxysmal atrial fibrillation with rapid ventricular response resulting from fluid overload. While atrial fibrillation was spontaneously reversed to sinus rhythm after diuresis, she developed multiple episodes of polymorphic ventricular tachycardia along with sinus bradycardia and prolonged QTc interval. She became hypotensive despite appropriate medical management. Pacing through her implantable cardioverter-defibrillator was attempted but worsened her hypotension. Ventricular dyssynchrony was suspected. Temporary transvenous atrial pacing through the coronary sinus was performed, which stabilized her blood pressure and improved end-organ perfusion. A permanent biventricular pacemaker was later implanted, and she was safely discharged to a nursing home. CONCLUSION: Temporary transvenous pacing through the coronary sinus, a novel approach to treat unstable bradycardia, may reduce ventricular dyssynchrony.

The Football Sign: An Alarming Feature on Supine Radiograph.

Football sign is a rare radiographic finding on abdominal x-ray that suggests massive pneumoperitoneum. Free air outlines the abdominal cavity and falciform ligament which creates the radiolucent oval contour of a football. Football sign is hardly reported in older children or adults. We present the first clear image of football sign caused by gastric perforation in an adult patient. A 57-year-old male with a history of hepatocellular carcinoma was diagnosed with an undrainable liver abscess and partial gastric outlet obstruction. He developed acute onset of severe abdominal pain afterward and abdominal plain film showed a large oval radiolucency over the central part of the abdomen without interruption by intestine, a classical finding of pneumoperitoneum also known as a "football sign". Emergent laparotomy revealed a 0.5 cm perforation hole at the anterior surface of the gastric antrum. Despite timely intervention, the patient died from progression of multiorgan failure. This case describes an alarming radiographic finding that rarely occurs in the adult population. Air could be identified on x-ray in this patient due to presence of massive ascites in his abdominal cavity. Recognizing radiographic patterns that suggest pneumoperitoneum on supine plain radiographs could expedite the diagnostic process and surgical intervention.