Association Between Clonal Hematopoiesis and Left Ventricular Reverse Remodeling in Nonischemic Dilated Cardiomyopathy.

Although clonal hematopoiesis of indeterminate potential (CHIP) is an adverse prognostic factor for atherosclerotic disease, its impact on nonischemic dilated cardiomyopathy (DCM) is elusive. The authors performed whole-exome sequencing and deep target sequencing among 198 patients with DCM and detected germline mutations in cardiomyopathy-related genes and somatic mutations in CHIP driver genes. Twenty-five CHIP driver mutations were detected in 22 patients with DCM. Ninety-two patients had cardiomyopathy-related pathogenic mutations. Multivariable analysis revealed that CHIP was an independent risk factor of left ventricular reverse remodeling, irrespective of known prognostic factors. CHIP exacerbated cardiac systolic dysfunction and fibrosis in a DCM murine model. The identification of germline and somatic mutations in patients with DCM predicts clinical prognosis.

Utilizing environmental DNA and imaging to study the deep-sea fish community of Takuyo-Daigo Seamount.

The increase in interest of mining at seamounts means there is a critical need to establish baseline inventories through environmental survey, with the aim of promoting the conservation and stewardship of these remote habitats. To efficiently evaluate fish biodiversity around a seamount, we compared environmental DNA (eDNA) methods using seawater and sponge samples against methods using imagery obtained with a remotely operated vehicle (ROV) and a free-fall deep-sea camera lander called the Edokko Mark I on the Takuyo-Daigo Seamount (153.0°E, 23.5°N) in the northwestern Pacific Ocean. We detected a total of 18 fish families by these methods. The fish fauna detected on the seamount included many families commonly found in deep-sea areas and were similar to the fish fauna of other seamounts located at similar latitudes in the northwestern Pacific. Significant differences in the patterns of detection of fish families between the eDNA and imaging methods is attributed to the differing powers of detection of some fish groups between methods (related to primer compatibility and fish size). For deep-sea fish, the difference in fish composition at the family level between seawater and sponge eDNA methods was not significant, but the difference between Edokko Mark I and ROV methods was significant; the latter difference is likely due to whether or not bait is used to attract fish. Although the eDNA workflow implemented here requires improvements, the use of eDNA and imaging methods in combination provided better insight into the biodiversity of deep-sea fishes in the deep-sea around a seamount, where our knowledge of the fish fauna has been extremely limited. Our recovery of eDNA from seawater and sponge samples around the seamount demonstrates the potential of these methods for facilitating environmental baseline surveys and impact assessments of mining activities to obtain results not previously possible with the use of visual methods only.

Prolonged extracellular low sodium concentrations and subsequent their rapid correction modulate nitric oxide production dependent on NFAT5 in microglia.

Hyponatremia is the most common clinical electrolyte disorder. Chronic hyponatremia has been recently reported to be associated with falls, fracture, osteoporosis, neurocognitive impairment, and mental manifestations. In the treatment of chronic hyponatremia, overly rapid correction of hyponatremia can cause osmotic demyelination syndrome (ODS), a central demyelinating disease that is also associated with neurological morbidity and mortality. Using a rat model, we have previously shown that microglia play a critical role in the pathogenesis of ODS. However, the direct effect of rapid correction of hyponatremia on microglia is unknown. Furthermore, the effect of chronic hyponatremia on microglia remains elusive. Using microglial cell lines BV-2 and 6-3, we show here that low extracellular sodium concentrations (36 mmol/L decrease; LS) suppress Nos2 mRNA expression and nitric oxide (NO) production of microglia. On rapid correction of low sodium concentrations, NO production was significantly increased in both cells, suggesting that acute correction of hyponatremia partly directly contributes to increased Nos2 mRNA expression and NO release in ODS pathophysiology. LS also suppressed expression and nuclear translocation of nuclear factor of activated T cells-5 (NFAT5), a transcription factor that regulates the expression of genes involved in osmotic stress. Furthermore, overexpression of NFAT5 significantly increased Nos2 mRNA expression and NO production in BV-2 cells. Expressions of Nos2 and Nfat5 mRNA were also modulated in microglia isolated from cerebral cortex in chronic hyponatremia model mice. These data indicate that LS modulates microglial NO production dependent on NFAT5 and suggest that microglia contribute to hyponatremia-induced neuronal dysfunctions.

Metabolome analysis in patients with heart failure and implantable cardioverter defibrillators.

Heart failure (HF) is a complex, heterogeneous syndrome with several comorbidities, often life-threatening and requires urgent therapy. In HF, metabolic alterations that can be assessed using comprehensive plasma, and tissue profiling will help establish new biomarkers and therapeutic targets. Metabolomic analysis of sudden death in HF cases remains unresolved. We prospectively evaluated 19 patients who underwent implantable cardioverter defibrillator (ICD) placement for the primary prevention of sudden cardiac death (SCD). Metabolomic analysis was performed using plasma samples before ICD implantation. Ventricular arrhythmia (VA)/SCD was defined as VA with an appropriate ICD therapy or SCD. During a median follow-up of 29 months (range, 13-35 months), four patients developed VA and one patient developed SCD. Using metabolomic analysis, arginine, lysine, and valine were significantly reduced in patients with VA/SCD (n = 5) compared with those without VA/SCD (n = 14). The molecules involved in energy metabolism might be associated with VA/SCD, thus requiring further investigation as a predictive value of metabolomic analysis of VA/SCD.

Aspiration of acidified milk induces milk allergy by activating alveolar macrophages in mice.

BACKGROUND: Epidemiological studies have identified associations between gastroesophageal reflux (GER) and cow's milk allergy (CMA) in infants. However, the role of GER in the development of CMA remains poorly understood. Our primary objectives were to develop a mouse model that suggests GER as a potential pathogenic mechanism for CMA and to elucidate the immunological mechanisms that connect lung innate immunity with CMA. METHODS: Mice were exposed to cow's milk (CM) treated with hydrochloric acid through repeated aspiration into their airways. Subsequently, they were challenged by intraperitoneal injection of CM extract. The immunological mechanisms were investigated using comprehensive single-cell RNA sequencing (scRNA-seq) analysis of the lungs, combined with the use of genetically modified mice. RESULTS: Mice exposed to CM mixed with hydrochloric acid via airway sensitization developed CMA, as evidenced by the production of antigen-specific IgE and IgG antibodies, and the induction of anaphylaxis upon systemic antigen administration. In contrast, aspiration of CM alone did not induce CMA. scRNA-seq analysis revealed potential roles of alveolar macrophages in response to hydrochloric acid. Mice lacking the TLR4 pathway were protected from developing CMA. CONCLUSIONS: We have developed a novel mouse model for CMA that utilizes the natural antigen and follows the physiological airway sensitization pathway, thus potentially resembling clinical scenarios. This model, named the acidified milk aspiration-induced allergy model, has the potential to shed light on the role of early innate immunity by analyzing a more physiological model.

Validation of a diagnostic flowchart for tuberculous pleurisy in pleural fluid with high levels of adenosine deaminase.

INTRODUCTION: Adenosine deaminase (ADA) in pleural fluid is a useful marker for diagnosing tuberculous pleurisy. However, recent studies have reported a lower specificity of pleural fluid ADA levels. We previously developed a diagnostic flowchart for patients with pleural fluid ADA ≥40 U/L, incorporating variables such as pleural fluid lactate dehydrogenase <825 U/L, predominant pleural fluid neutrophils or cell degeneration, and a pleural fluid ADA/total protein ratio <14. This flowchart was effective in distinguishing between tuberculous pleurisy and other diseases. Here, we conducted a validation analysis of this flowchart. MATERIALS AND METHODS: We retrospectively collected data from 458 patients with pleural fluid ADA concentrations ≥40 U/L across eight institutions from January 2019 to December 2023. The diagnostic accuracy rate, sensitivity, and specificity of the diagnostic flowchart were analysed and compared to those in the original study. RESULTS: Eighty-seven patients were diagnosed with tuberculous pleurisy, and 371 patients were diagnosed with other diseases. The diagnostic accuracy, sensitivity, and specificity for diagnosing tuberculous pleurisy were 77.7%, 86.2%, and 75.7%, respectively. Compared with that in the original study, the rate of tuberculous pleurisy was lower (19.0% vs. 44.5%, p < 0.001), but the diagnostic accuracy rates were not significantly different (p = 0.253). On the basis of the findings from this validation study, we have revised the flowchart to enhance its utility. CONCLUSION: The diagnostic flowchart exhibited high diagnostic accuracy in this validation study, comparable to that in the original study. This validation confirms the effectiveness of the flowchart, even in settings with a low incidence of tuberculosis.

Acute procedural safety of the latest radiofrequency ablation catheters in atrial fibrillation ablation: Data from a large prospective ablation registry.

BACKGROUND: Safety data of the latest radiofrequency (RF) technologies during atrial fibrillation (AF) ablation in real-world clinical practice are limited. OBJECTIVES: We sought to evaluate the acute procedural safety of the four latest ablation catheters commonly used for AF ablation. METHODS: A total of 3957 AF ablation procedures performed between January 2022 and December 2023 at 20 centers with either the THERMOCOOL SMARTTOUCH SF (STSF), TactiCath (TC), QDOT Micro (QDM), or TactiFlex (TF) were retrospectively analyzed. RESULTS: In total, QDM, STSF, TF, and TC were used in 343 (8.7%), 1793 (45.3%), 1121 (28.4%), and 700(17.7%) procedures. Among 2406 index procedures, electrical pulmonary vein isolations were successfully achieved in 99.5%. Despite similar total procedure times in the four groups, the total fluoroscopic time was significantly shorter for QDM/STSF with CARTO than TF/TC with EnSite (18.7 ± 14 vs. 27.6 ± 20.6 min, p < .001) and longest in the TF group. The incidence of cardiac tamponade was 0.7% (0.5% and 0.9% during index and redo procedures, 0.8% and 0.3% for paroxysmal and non-paroxysmal AF) and was significantly lower for QDM/STSF than TF/TC (0.2% vs. 1.1%, p = .008) and highest in the TF group. The incidence of cardiac tamponade was higher for TF than TC and STSF than QDM. In the multivariate analysis, TF/TC with EnSite was a significant independent predictor of cardiac tamponade during both the index (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.3-17.5, p = .02) and all procedures (OR = 3.0, 95% CI = 1.3-7.2, p = .01). CONCLUSIONS: The incidence of cardiac tamponade and the fluoroscopic time during AF ablation significantly differed among the latest RF catheters and mapping systems in real-world clinical practice.

A case of central diabetes insipidus after COVID-19 as a probable diagnosis of lymphocytic infundibulo-neurohypophysitis with positive anti-rabphilin-3A antibodies with review of literature.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2, and various complications have been reported. Furthermore, there have been increasing reports of endocrinopathy related to COVID-19 following the pandemic. We report a 49-year-old healthy woman who developed rapid onset of polydipsia and polyuria three weeks after COVID-19. Laboratory tests indicated low urine osmolarity and increased serum osmolarity, and antidiuretic hormone (ADH) was undetectable. Urine osmolality remained low with water deprivation. Similarly, plasma ADH responses to hypertonic-saline infusion were blunted and urine osmolality increased in response to desmopressin. There was no clear evidence of anterior pituitary dysfunction. T1-weighted magnetic resonance imaging (MRI) showed pituitary stalk thickening and absence of posterior pituitary bright signal spots, suggesting the presence of hypophysitis. Based on these results, we made a probable diagnosis of lymphocytic infundibulo-neurohypophysitis (LINH) which have caused central diabetes insipidus. Positive findings for serum anti-rabphilin-3A antibodies, reported as a potential diagnostic marker for LINH, were also noted. Following oral desmopressin administration, polydipsia and polyuria were quickly improved, though treatment with desmopressin was still required over four months. This is the first report of a patient with a probable diagnosis of LINH after COVID-19 who tested positive for anti-rabphilin-3A antibodies. Positive findings for those antibodies suggest that pituitary dysfunction associated with COVID-19 is hypophysitis involving an abnormal immune mechanism. The presence of anti-rabphilin-3A antibodies may be useful as a non-invasive diagnostic marker of LINH and potentially serve as a valuable diagnostic aid in cases of LINH associated with COVID-19.

Safety and effectiveness of tofogliflozin in Japanese people with type 2 diabetes: A multicenter prospective observational study in routine clinical practice.

AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors effectively and safely reduce fasting and postprandial hyperglycemia while promoting weight loss. However, their unique mechanism of action contributes to concerns regarding their safety. We therefore carried out a large-scale, non-commercial, investigator-initiated study on the safety and effectiveness of the SGLT2 inhibitor tofogliflozin. MATERIALS AND METHODS: This multicenter, open-label, uncontrolled, prospective observational study was carried out at hospitals and clinics across Japan in participants aged ≥20 years who were SGLT2 inhibitor-naïve and had an established diagnosis of type 2 diabetes. The primary endpoint was adverse drug reactions (ADRs) of special interest. Secondary endpoints included all other ADRs and adverse events, glycated hemoglobin (HbA1c), and weight loss. RESULTS: The study, carried out from June 2014 through February 2020, enrolled 11,480 participants from 1,103 medical institutions; 6,967 participants completed the 104-week follow up. The most common ADRs of special interest were urinary and genital tract infections (1.53%), followed by volume depletion (1.25%). Hypoglycemia occurred in 27 participants (0.24%), adverse events in 1,054 (9.18%) and ADRs in 645 (5.62%). HbA1c decreased by 0.85% (95% confidence interval 0.82%-0.88%) and bodyweight decreased by 3.05 kg (95% confidence interval 2.94-3.17 kg). The HbA1c target was achieved by 51.70% of participants for target HbA1c <7.0%, 85.3% for <8.0% and 5.4% for <6.0% at week 104. CONCLUSIONS: Tofogliflozin was associated with only mild or moderate ADRs characteristic of SGLT2 inhibitors, with no unpredictable, new, serious, or high-incidence adverse events or ADRs. This independent study confirmed the safety and effectiveness of tofogliflozin in adult type 2 diabetes patients.

Arginine vasopressin deficiency onset after COVID-19 vaccination with positive anti-rabphilin-3A antibodies: a case report and literature review.

BACKGROUND: Arginine vasopressin deficiency (AVP-D) can occur due to various conditions, so clarifying its cause is important for deciding treatment strategy. Although several cases of AVP-D following coronavirus disease 2019(COVID-19) infection or COVID-19 vaccination have been reported, the diagnosis of the underlying disease has not been reported in most cases. CASE PRESENTATION: A 75-year-old woman who presented with polydipsia and polyuria 9 weeks after contracting COVID-19 and 5 weeks after receiving the SARS-CoV-2 vaccination, leading to the final diagnosis of AVP-D 8 months after the first appearance of symptoms. Interestingly, pituitary magnetic resonance imaging (MRI) still revealed stalk enlargement frequently observed in patients with SARS-CoV-2 vaccination-induced AVP-D. Although this finding could not rule out any malignancies, we additionally measured anti-rabphilin-3A antibodies, a known marker for lymphocytic infundibulo-neurohypophysitis (LINH), and found that the results were positive, strongly suggesting LINH as the cause of this disease. Thus, we avoided pituitary biopsy. At the follow-up MRI conducted 12 months after the initial consultation, enlargement of the pituitary stalk was still observed. CONCLUSION: We experienced a case with LINH probably induced by SARS-CoV-2 vaccination. In SARS-CoV-2 vaccination-related LINH, unlike typical LINH, there is a possibility of persistent pituitary stalk enlargement on MRI images for an extended period, posing challenges in differential diagnosis from other conditions. Pituitary stalk enlargement and positive anti-rabphilin-3A antibodies may help in the diagnosis of AVP-D induced by SARS-CoV-2 vaccination.

Impaired Fat Absorption from Intestinal Tract in High-Fat Diet Fed Male Mice Deficient in Proglucagon-Derived Peptides.

(1) Background: Proglucagon-derived peptides (PDGPs) including glucagon (Gcg), GLP-1, and GLP-2 regulate lipid metabolism in the liver, adipocytes, and intestine. However, the mechanism by which PGDPs participate in alterations in lipid metabolism induced by high-fat diet (HFD) feeding has not been elucidated. (2) Methods: Mice deficient in PGDP (GCGKO) and control mice were fed HFD for 7 days and analyzed, and differences in lipid metabolism in the liver, adipose tissue, and duodenum were investigated. (3) Results: GCGKO mice under HFD showed lower expression levels of the genes involved in free fatty acid (FFA) oxidation such as Hsl, Atgl, Cpt1a, Acox1 (p < 0.05), and Pparα (p = 0.05) mRNA in the liver than in control mice, and both FFA and triglycerides content in liver and adipose tissue weight were lower in the GCGKO mice. On the other hand, phosphorylation of hormone-sensitive lipase (HSL) in white adipose tissue did not differ between the two groups. GCGKO mice under HFD exhibited lower expression levels of Pparα and Cd36 mRNA in the duodenum as well as increased fecal cholesterol contents compared to HFD-controls. (4) Conclusions: GCGKO mice fed HFD exhibit a lesser increase in hepatic FFA and triglyceride contents and adipose tissue weight, despite reduced ß-oxidation in the liver, than in control mice. Thus, the absence of PGDP prevents dietary-induced fatty liver development due to decreased lipid uptake in the intestinal tract.

Effects of hypernatremia on the microglia.

Signs and symptoms of hypernatremia largely indicate central nervous system dysfunction. Acute hypernatremia can cause demyelinating lesions similar to that observed in osmotic demyelination syndrome (ODS). We have previously demonstrated that microglia accumulate in ODS lesions and minocycline protects against ODS by inhibiting microglial activation. However, the direct effect of rapid rise in the sodium concentrations on microglia is largely unknown. In addition, the effect of chronic hypernatremia on microglia also remains elusive. Here, we investigated the effects of acute (6 or 24 h) and chronic (the extracellular sodium concentration was increased gradually for at least 7 days) high sodium concentrations on microglia using the microglial cell line, BV-2. We found that both acute and chronic high sodium concentrations increase NOS2 expression and nitric oxide (NO) production. We also demonstrated that the expression of nuclear factor of activated T-cells-5 (NFAT5) is increased by high sodium concentrations. Furthermore, NFAT5 knockdown suppressed NOS2 expression and NO production. We also demonstrated that high sodium concentrations decreased intracellular Ca2+ concentration and an inhibitor of Na+/Ca2+ exchanger, NCX, suppressed a decrease in intracellular Ca2+ concentrations and NOS2 expression and NO production induced by high sodium concentrations. Furthermore, minocycline inhibited NOS2 expression and NO production induced by high sodium concentrations. These in vitro data suggest that microglial activity in response to high sodium concentrations is regulated by NFAT5 and Ca2+ efflux through NCX and is suppressed by minocycline.

Potential microemboli formation risk and its management during the heated saline-enhanced radiofrequency needle-tip catheter ablation.

BACKGROUND: The potential risk of embolic events during ablation in the left ventricle (LV) with a heated saline-enhanced radiofrequency (SERF) needle-tip ablation catheter has not been characterized. OBJECTIVE: This study aimed to investigate the formation of microemboli or other untoward events during SERF ablation. METHODS: Ninety-three radiofrequency (RF) ablation procedures were performed in the LV of 14 pigs by using a SERF catheter (35 W, 70 seconds, and 60°C; normal or degassed saline [NS or DS] irrigation with a flow rate of 10 mL/min) vs a standard irrigated-tip radiofrequency (S-RF) catheter (30 or 50 W, 30 seconds, and 17 mL/min). Microbubble formation was graded on the basis of intracardiac echocardiography. Microbubbles, microembolic signals, and microparticles were monitored using our established model. RESULTS: There was no significant difference in microbubble volume among SERF-NS, SERF-DS, and S-RF 30 W with "grade 1" intracardiac echocardiography microbubbles (median and 25th-75th percentiles 0.201 [0.011-3.13], 0.455 [0.06-2.66], and 0.004 µL [0.00-0.16 µL], respectively). There was no significant difference in microembolic signals among SERF-NS, SERF-DS, and S-RF 30 W with grade 1 bubbles (n = 8.0 ± 5.8, n = 7.6 ± 4.2, and n = 6.1 ± 6.1, respectively). Both SERF-NS and SERF-DS created larger lesions than did both S-RF 30 W and S-RF 50 W deliveries (mean 1241.5 ± 658.6, 1497.7 ± 893.4, 75.0 ± 24.8, and 184.0 ± 93.8 mm3; P < .001). There was no significant difference in microparticle incidence among groups (P = .675). No evidence of embolic events was found in the brain and other organs at the histology assessment. CONCLUSION: In the setting of SERF ablation, significantly large LV lesions can be created without any increment in embolic microbubble or particle events. Grade 1 microbubble is related to the efficacy and safety.

A Study on the Compatibility of a Food-Recording Application with Questionnaire-Based Methods in Healthy Japanese Individuals.

In Japan, nutritional guidance based on food-recording apps and food frequency questionnaires (FFQs) is becoming popular. However, it is not always recognized that different dietary assessment methods have different nutritional values. Here, we compared the compatibility of dietary intake data obtained from an app with those obtained from FFQs in 59 healthy individuals who recorded information regarding their diet for at least 7 days per month using an app developed by Asken (Tokyo, Japan). The diurnal coefficient of variation in total energy and protein intake was 20%, but those for vitamins B12 and D were >80%, reflecting the importance of 7 days of recording rather than a single day of recording for dietary intake analyses. Then, we compared the results of two FFQs-one based on food groups and one based on a brief self-administered diet history questionnaire-for 7 days, as recorded by the app. There was a correlation coefficient of >0.4 for all the items except salt. Regarding the compatibility between the app and FFQs, the percentage errors for total energy and nutrients were >40-50%, suggesting no agreement between the app and the two FFQs. In conclusion, careful attention should be paid to the impact of different dietary assessment methods on nutrient assessment.

Soluble SLAMF7 is generated by alternative splicing in multiple myeloma cells.

Not available.

Sildenafil amplifies calcium influx and insulin secretion in pancreatic ß cells.

Sildenafil, a phosphodiesterase-5 (PDE5) inhibitor, has been shown to improve insulin sensitivity in animal models and prediabetic patients. However, its other metabolic effects remain poorly investigated. This study examines the impact of sildenafil on insulin secretion in MIN6-K8 mouse clonal ß cells. Sildenafil amplified insulin secretion by enhancing Ca2+ influx. These effects required other depolarizing stimuli in MIN6-K8 cells but not in KATP channel-deficient ß cells, which were already depolarized, indicating that sildenafil-amplified insulin secretion is depolarization-dependent and KATP channel-independent. Interestingly, sildenafil-amplified insulin secretion was inhibited by pharmacological inhibition of R-type channels, but not of other types of voltage-dependent Ca2+ channels (VDCCs). Furthermore, sildenafil-amplified insulin secretion was barely affected when its effect on cyclic GMP was inhibited by PDE5 knockdown. Thus, sildenafil stimulates insulin secretion and Ca2+ influx through R-type VDCCs independently of the PDE5/cGMP pathway, a mechanism that differs from the known pharmacology of sildenafil and conventional insulin secretory pathways. Our results reposition sildenafil as an insulinotropic agent that can be used as a potential antidiabetic medicine and a tool to elucidate the novel mechanism of insulin secretion.

Hepatocytes differentiate into intestinal epithelial cells through a hybrid epithelial/mesenchymal cell state in culture.

Hepatocytes play important roles in the liver, but in culture, they immediately lose function and dedifferentiate into progenitor-like cells. Although this unique feature is well-known, the dynamics and mechanisms of hepatocyte dedifferentiation and the differentiation potential of dedifferentiated hepatocytes (dediHeps) require further investigation. Here, we employ a culture system specifically established for hepatic progenitor cells to study hepatocyte dedifferentiation. We found that hepatocytes dedifferentiate with a hybrid epithelial/mesenchymal phenotype, which is required for the induction and maintenance of dediHeps, and exhibit Vimentin-dependent propagation, upon inhibition of the Hippo signaling pathway. The dediHeps re-differentiate into mature hepatocytes by forming aggregates, enabling reconstitution of hepatic tissues in vivo. Moreover, dediHeps have an unexpected differentiation potential into intestinal epithelial cells that can form organoids in three-dimensional culture and reconstitute colonic epithelia after transplantation. This remarkable plasticity will be useful in the study and treatment of intestinal metaplasia and related diseases in the liver.

IgG4-Related Membranous Nephropathy After COVID-19 Vaccination: A Case Report.

Although immunoglobulin G4 (IgG4)-related kidney diseases are typically characterized by tubulointerstitial nephritis with abundant infiltration of IgG4-positive plasma cells and fibrosis, there have been relatively rare cases of IgG4-related glomerulonephritis. Several cases of IgG4-related disease (IgG4-RD) following coronavirus disease 2019 (COVID-19) mRNA vaccination have been reported. However, there are no reports of IgG4-related glomerulonephritis following COVID-19 vaccination. Herein, we present a case of IgG4-related membranous nephropathy (MN) occurring after COVID-19 vaccination. A 69-year-old Japanese male presented to our hospital with edema that started the day after his second COVID-19 vaccination. The patient exhibited nephrotic syndrome and was diagnosed with MN based on the results of a kidney biopsy. Although serum IgG4 levels were elevated to 946 mg/dL, no evidence of organ involvement suggestive of IgG4-RD was observed. Treatment with prednisolone and cyclosporine resulted in complete remission, and immunosuppressive agents were tapered. However, one month after discontinuing the immunosuppressive agents, the patient was readmitted with swelling around the submandibular glands and exertional dyspnea. Serum IgG4 level was markedly elevated at 2,320 mg/dL, and computed tomography revealed submandibular gland swelling and thickening of the interlobular septum and bronchovascular bundles in both lungs. The patient was diagnosed with IgG4-RD based on elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in the submandibular gland biopsy. Upon resuming treatment with prednisolone, the symptoms attributed to IgG4-RD improved within a few days. In cases of nephrotic syndrome following COVID-19 vaccination, it may be advisable to conduct detailed examinations to assess the possibility of the development of IgG4-RDs.

A Pregnant Woman with Excess Vasopressinase-Induced Diabetes Insipidus Complicated by Central Diabetes Insipidus like Lymphocytic Infundibulo-Neurohypophysitis.

Background: Gestational diabetes insipidus (DI) is a very rare complication of pregnancy. We present a case of gestational DI combining two different types of DI. Case Presentation. A 39-year-old pregnant woman suddenly presented with thirst, polydipsia, and polyuria after 31 gestation weeks (GWs). Based on laboratory findings of hypotonic urine (78 mOsm/kgH2O) with higher plasma osmolality (298 mOsm/kgH2O) and higher serum sodium levels (149 mEq/L), gestational DI was suspected, and the clinical course was monitored without therapy until the results of a measurement of plasma arginine vasopressin (AVP) levels were available. However, she subsequently developed acute prerenal failure and underwent an emergency cesarean section at 34 GWs. Her resected placenta weighed 920 g, nearly twice the normal weight. Immediately following delivery, intranasal 1-desamino-8-D-arginine vasopressin was administered, and her symptoms promptly disappeared. Afterward, her predelivery plasma AVP level was found to have been inappropriately low (0.7 pg/mL) given her serum sodium level. The patient's serum vasopressinase level just before delivery was 2,855 ng/mL, more than 1,000 times the upper limit of the normal range, suggesting excess vasopressinase-induced DI. The presence of anti-rabphilin-3A antibodies in the patient's blood, a hypertonic saline infusion test result, and loss of the high-intensity signal of the posterior pituitary on fat-suppressed T1-weighted magnetic resonance images without thickening of the stalk and enlargement of the neurohypophysis suggested concurrent central DI-like lymphocytic infundibulo-neurohypophysitis (LINH). Conclusion: In addition to the degradation of AVP by excess placental vasopressinase due to the enlarged placenta, an insufficient compensatory increase in AVP secretion from the posterior pituitary gland due to LINH-like pathogenesis might have led to DI symptoms.