Objective The survival advantage of females over males is lost in dialysis patients in many countries. Japanese female hemodialysis patients, however, have a survival advantage over their male counterparts. This study explored causes of death that contribute to sex differences in all-cause mortality in Japanese dialysis patients.
Methods Data from the Japanese Society for Dialysis Therapy registry and National Vital Statistics from 2017 and 2018 were used. Standardized mortality ratios, male-to-female mortality rate ratios, and age-adjusted differences between sexes were calculated for all-cause, cardiovascular, and non-cardiovascular mortality, as well as cause-specific mortality, in dialysis patients and the general population.
Results During the 2-year study period, 41,006 and 21,254 deaths occurred in 417,740 and 225,292 patient-years in male and female dialysis patients, respectively. The age-standardized all-cause mortality ratio was 1.21 (95% confidence interval, 1.20-1.23) for male patients compared to female patients. The male-to-female mortality rate ratio for cardiovascular disease was about 1.4 in younger age categories but closer to 1.0 in older age categories. Conversely, the ratio for non-cardiovascular disease was about 1.3 in older age categories but closer to 1.0 in younger age categories. Death from infectious disease, malignancy, and heart failure contributed to 38.4%, 22.7%, and 12.1%, respectively, of the male-to-female difference in all-cause mortality of dialysis patients.
Conclusion Low cardiovascular mortality in younger age categories and low non-cardiovascular mortality in older age categories contributed to the survival advantage of female Japanese dialysis patients. Infectious disease was the greatest contributor to sex differences in all-cause mortality.
Objective Whether or not combined lifestyle factors are associated with similar decreases in risks of incident hypertension and diabetes among individuals with and without chronic kidney disease (CKD) remains unclear.
Methods This population-based prospective cohort study included participants 40-74 years old who were free from heart disease, stroke, renal failure, hypertension, diabetes, and hypercholesterolemia at baseline (n =60,234). Healthy lifestyle scores (HLSs) were calculated by adding the total number of 5 healthy lifestyle factors (non-smoking, body mass index <25 kg/m2, regular exercise, healthy eating habits, and moderate or less alcohol consumption). Cox proportional hazards models were used to examine associations between the HLS and incident hypertension or type 2 diabetes and whether or not CKD modified these associations.
Results During a median of 4 years, there were 2,773 incident hypertension cases (30.1 cases per 1,000 person-years) and 263 incident diabetes cases (2.4 cases per 1,000 person-years). The risk of developing hypertension and diabetes decreased linearly as participants adhered to more HLS components. Compared with adhering to 0, 1, or 2 components, adherence to all 5 HLS components was associated with a nearly one-half reduction in the risk of hypertension [hazard ratio (HR) =0.52; 95% confidence interval (CI), 0.45-0.60] and diabetes (HR=0.51; 95% CI, 0.32-0.81) in fully adjusted models. CKD did not have a modifying effect on associations between the HLS and incident hypertension (Pinteraction=0.6) or diabetes (Pinteraction=0.3).
Conclusion Adherence to HLS components was associated with reduced risks of incident hypertension and diabetes, regardless of CKD status.
Objective High-dose melphalan and autologous stem cell transplantation (ASCT) therapy for AL amyloidosis are now associated with reduced mortality based on the application of strict criteria. However, there is no long-term evidence concerning the performance of induction therapy with newer agents, such as bortezomib or daratumumab. Concerns regarding long-term relapse despite treatment with ASCT exist, and missing the opportunity to perform ASCT might occur if induction proves to not be efficacious and cardiac amyloidosis progression deprives the patients of a chance to receive ASCT. We herein report good amyloid control by vincristine, doxorubicin, and dexamethasone (VAD) induction therapy and argue the importance of induction therapy before ASCT.
Methods We compared patients who underwent VAD induction and ASCT (VAD+ASCT) with patients who underwent frontline ASCT in our hospital.
Patients A total of 26 patients with histologically proven AL amyloidosis were included (18 in the VAD+ASCT group and 8 in the frontline ASCT).
Results In the VAD+ASCT group, the 10-year overall survival and renal response rates were 82% and 43%, respectively. The renal response rate at two years in the VAD+ASCT group was significantly better than that in the frontline ASCT group. Although there was no significant difference in the survival rates between the two groups, the time to next treatment or death was significantly better in the VAD+ASCT group than in the the frontline ASCT group. Acute kidney injury was the most frequent reason for failure to receive two courses of VAD, and early mortality was mainly due to gastrointestinal complications.
Conclusion Considering that only those who underwent 2 courses of VAD experienced a 10-year renal response, induction therapy was deemed to be directly related to the long-term control of AL amyloidosis.
Objective The incidence and clinical importance of delirium in coronavirus disease 2019 (COVID-19) have not yet been fully investigated. The present study reported the prevalence of delirium in patients with COVID-19 and identified the factors associated with delirium and mortality.
Methods We performed an observational, retrospective study of patients diagnosed with COVID-19 at the Kinki-Chuo Chest Medical Center. Univariate and multivariate logistic regression analyses were used to explore delirium risk factors.
Patients All consecutive patients diagnosed with COVID-19 at the Kinki-Chuo Chest Medical Center.
Results We identified 600 patients [median age: 61.0 (interquartile range: 49.0-77.0) years old], of whom 61 (10.2%) developed delirium during their stay. Compared with patients without delirium, these patients were older (median age 84.0 vs. 56.0 years old, p<0.01) and had more comorbidities. Based on a multivariate analysis, age, dementia, severe disease, and lactate dehydrogenase (LDH) levels were independent risk factors for developing delirium. For every 1-year increase in age and 10-IU/L increase in LDH, the delirium risk increased by 10.8-12.0% and 4.6-5.7%, respectively. There were 15 (24.6%) in-hospital deaths in the group with delirium and 8 (1.6%) in the group without delirium (p<0.01). Delirium was associated with an increased mortality.
Conclusion Delirium in patients with COVID-19 is prevalent and associated with poor clinical outcomes in Japan. Despite difficulties with COVID-19 patient care during the pandemic, physicians should be aware of the risk of delirium and be trained in its optimal management.
Nivolumab is an immune-checkpoint inhibitor (ICI) that can induce unique treatment-related toxicities, such as immune-related adverse events (irAEs). Myocarditis is a serious irAE with an incidence between 0.06% and 1.14%. Although the peak onset of irAE is generally within three months from the start of treatment, we experienced an autopsy case of late-onset fulminant myocarditis caused by nivolumab in Epstein Barr virus-associated gastric cancer. Pathological complete remission of the primary lesion was confirmed by the autopsy. We should consider possible complications of cardiac irAEs, especially fulminant myocarditis, even beyond three months after starting ICI therapy.
An 80-year-old man presented to our hospital with general fatigue on exertion that had gradually worsened over 6 months. His blood test revealed severe anemia, and gastroscopy revealed findings consistent with gastric antral vascular ectasia (GAVE) and autoimmune gastritis. We diagnosed the patient with severe anemia caused by GAVE and autoimmune gastritis. The present case suggested that GAVE is triggered by autoimmune gastritis, and the mechanism is likely related to hypergastrinemia. The reporting of this rare case may help elucidate the cause of GAVE, which is currently unknown.
Amyloidosis causes various symptoms in many organs of the body, but amyloidosis that presents with liver damage alone has never been reported. We treated an 83-year-old man with amyloidosis who presented with liver damage alone. The liver damage in this patient was histologically proven to be liver amyloidosis. The administration of bortezomib and dexamethasone was not effective, so he rapidly died of liver failure. An aggressive liver biopsy should be considered when unexplained jaundice is observed.
Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder, and a genetic analysis is important to make a definitive diagnosis. A comprehensive genetic analysis using next generation sequencing (NGS) and whole exome sequencing (WES) is feasible. However, the application of NGS in the assessment of genomic structural variations is generally limited, and a substantial number of control samples are needed for such assessments. Thus, NGS alone is unlikely to detect genomic structural variations in a "singleton." We present the case of a patient with compound HeFH (heterozygous FH), whose causative mutations in the LDLR gene could not be identified by WES, necessitating the application of the multiplex ligation-dependent probe amplification (MLPA) technique.
The patient was a 34-year-old woman who suddenly collapsed. On arrival, she was in cardiac arrest. Cardiac ultrasound revealed cardiac tamponade; thus, urgent thoracotomy with pericardiotomy was performed. Spontaneous circulation was temporarily obtained; however, her circulation was not stabilized, and she ultimately died. An autopsy revealed a pericardial inflammatory myofibroblastic tumor (IMT) causing bloody cardiac tamponade. There were no signs of cardiac rupture, myocardial infarction or aortic dissection. We reported the first case of fatal bloody cardiac tamponade due to pericardial IMT in an adult. An autopsy is important for clarifying the etiology in cases of fatal cardiac tamponade of unknown cause.
A 60-year-old woman with a history of hypothyroidism was referred to our hospital for shortness of breath and a left ventricular ejection fraction (LVEF) of 13%, which required continuous dobutamine injection with intra-aortic balloon pump support. An endomyocardial biopsy obtained from the right ventricle revealed an infiltration of giant cells and eosinophils, indicating giant cell myocarditis. In addition to heart failure treatment, combined immunotherapy with steroids, tacrolimus, and intravenous immunoglobulin was administered. Transthoracic echocardiography demonstrated a dramatic improvement in the LVEF after this therapy, and the patient was discharged home without symptoms on day 72.
A 54-year-old man had been drinking approximately 1.2 L of soy milk (equivalent to approximately 310 mg of isoflavones) per day for the previous 3 years. He then developed erectile dysfunction and gynecomastia. On an examination in our department in May, blood tests showed low gonadotropin and testosterone levels, indicative of secondary hypogonadism. He stopped drinking soy milk on his own in June of that year. When he was admitted in August, blood tests showed an improved gonadal function. Secondary hypogonadism caused by the excessive intake of isoflavones in soy milk was diagnosed. In men, an excessive intake of isoflavones may cause feminization and secondary hypogonadism.
Biguanide is an ideal drug for the treatment of type 2 diabetes mellitus. When used appropriately, the incidence of lactic acidosis is reported to be very low. Risk factors associated with biguanide-related lactic acidosis include chronic kidney disease, congestive heart failure, alcohol use, severe dehydration, shock, hypoxic states, sepsis, and advanced age. We herein report a case of cardiac dysfunction due to thiamine deficiency after hemodialysis in a patient with suspected biguanide-related lactic acidosis. Patients who develop severe lactic acidosis while taking biguanides should be given a large dose of thiamine without delay, given the possibility of thiamine deficiency as a complication.
A 59-year-old man undergoing hemodialysis was administered levetiracetam, after which he developed a systemic rash, high fever, severe liver dysfunction, and leukocytopenia with reactivation of human herpes virus 6. Atypical drug-induced hypersensitivity (DIHS) was diagnosed, and prednisolone was administered at 60 mg/day. However, liver failure rapidly progressed, and the patient died 12 days following treatment. Despite the rarity of DIHS with concomitant fulminant liver failure from levetiracetam and sufficient clearance thereof by hemodialysis, our case suggests that this syndrome may still ensue, resulting in mortality, even in hemodialysis patients. Although no treatment has yet been established, strict monitoring and aggressive treatment may be required.
A 44-year-old woman was admitted due to gross hematuria and progressive renal dysfunction. Poststreptococcal acute glomerulonephritis (PSAGN) was suspected due to her elevated anti-streptolysin O and anti-streptokinase titers and hypocomplementemia. A renal biopsy showed crescent formation and endocapillary hypercellularity with neutrophil infiltrate. An immunofluorescence analysis showed granular immunoglobulin G and C3 deposition, suggesting immune-complex-type glomerulonephritis. However, myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA) was positive, and peritubular capillaritis was observed. Furthermore, citrullinated histone H3-positive neutrophils were detected as markers for neutrophil extracellular trap formation. Therefore, she was diagnosed with ANCA-associated vasculitis superimposed on PSAGN that was the main contributor to her progressive renal injury.
The extent of rare side effects of mRNA vaccines for coronavirus disease 2019 (COVID-19) remains unclear. Several cases of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) following COVID-19 vaccination have been reported. We herein report a 72-year-old man who presented with a fever after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine. He was diagnosed with acute kidney injury due to myeloperoxidase-ANCA-associated vasculitis and was treated with intermittent hemodialysis, high-dose prednisolone, and intravenous rituximab. His general symptoms and renal impairment subsequently improved. When systemic symptoms are prolonged or renal abnormalities appear after COVID-19 vaccination, the possibility of AAV should be considered.
A 38-year-old man with renal cell carcinoma was referred to our hospital because of a productive cough. He had received radiotherapy for lung metastasis and been treated with axitinib. Bronchoscopy revealed necrosis in the bronchi of the right middle and lower lobes. Culture of the necrotic bronchial specimen revealed methicillin-resistant Staphylococcus aureus (MRSA). Although radiotherapy in combination with axitinib carries a risk of causing airway toxicity, MRSA necrotizing bronchitis has not been reported. Physicians should consider the possibility of infectious necrotizing bronchitis if irradiated patients show prolonged respiratory symptoms.
Both 1,3-beta-D-glucan (BDG) and galactomannan (GM) are polysaccharide components of the fungal cell wall. Although elevated levels of serum BDG and Aspergillus GM suggest invasive fungal infection or Pneumocystis pneumonia and aspergillosis, respectively, it is also necessary to consider the possibility of false-positives. We herein report a 68-year-old man with marked elevation in serum BDG and GM levels accompanied by Mendelson's syndrome after rice aspiration. With the improvement of Mendelson's syndrome, his serum BDG and GM levels decreased. The false-positive serum BDG and GM findings may have been due to his aspiration of food containing them. It is important to take a detailed history of aspiration in addition to making a conventional differential diagnosis in patients with pneumonia with elevated serum BDG and GM levels.
A 59-year-old woman with a diabetes history experienced mild neck pain. A neurological examination revealed only mild neck stiffness. Magnetic resonance imaging showed extensive T2-weighted high-intensity lesions with patchy gadolinium enhancement mainly involving the white matter in the right parietal lobe. A cerebrospinal fluid analysis revealed increased protein levels and pleocytosis. While QuantiFERON-TB Gold was positive, computed tomography (CT) and fluorodeoxyglucose on positron emission tomography-CT of the whole body showed no abnormal accumulation, suggesting tuberculosis. A brain biopsy revealed cerebral tuberculoma. As cerebral tuberculoma can show minimal neurological symptoms despite extensive lesions, a cautious examination and early treatment are required to prevent a devastating prognosis.
We herein report a 47-year-old man with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) revealed by periventricular radial linear enhancement on repeated brain magnetic resonance imaging (MRI). He presented with a history of headache and a fever followed by somnolence and worsening of consciousness. On admission (16 days from the onset), although lymphocytic pleocytosis and hypoglycorrhachia in the cerebrospinal fluid (CSF) were noted, initial brain MRI demonstrated non-specific findings. At 30 days from the onset, repeated brain MRI revealed characteristic findings of GFAP-A, and we detected anti-GFAP antibodies in the CSF. Thus, repeated brain MRI provides clues for the diagnosis of GFAP-A.
A 57-year-old man presented with difficulty speaking and walking along with increased daytime somnolence. His symptoms fluctuated throughout the day but never completely disappeared. A neurological examination revealed mild dysarthria, limb weakness, and staggering gait. Polysomnography showed rapid eye movement (REM) sleep excess (55.0%). Multiple sleep latency tests revealed a mean sleep latency of zero minutes with sleep-onset REM periods in all naps. The Orexin-A concentration in the cerebrospinal fluid was low (50.8 pg/mL). Human leukocyte antigen testing demonstrated DQB1*0602 positivity. His neurological symptoms were relieved by clomipramine. Thus, he was diagnosed with late-onset narcolepsy type 1 with status cataplecticus.
Loss of taste is a relatively common symptom of coronavirus disease 2019 (COVID-19) and has also been considered a rare Guillain-Barré syndrome (GBS) symptom. We herein report a case of a facial diplegia and paresthesia (FDP) variant of GBS that initially presented as a loss of taste occurring two weeks after COVID-19 mRNA vaccination. The patient recovered completely after intravenous immunoglobulin therapy. Clinicians should consider the possibility of post-vaccination FDP manifesting as facial palsy and should be aware that GBS, including the FDP variant, can initially present as an isolated loss of taste.
A 72-year-old woman with rheumatoid arthritis was treated with methotrexate (MTX) and iguratimod. Upon examination of a liver tumor, blisters due to varicella-zoster virus (VZV) infection were observed. Despite oral administration of valacyclovir, she developed varicella pneumonia and meningoencephalitis. A VZV antibody test revealed reinfection. The liver tumor shrank after discontinuance of MTX, and polymerase chain reaction revealed the reactivation of the Epstein-Barr virus (EBV). Therefore, we were unable to deny MTX-associated lymphoproliferative disorder (MTX-LPD). This is the first case of a complication of pneumonia and meningoencephalitis due to VZV reinfection and EBV reactivation.
Thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome is a systemic inflammatory disorder characterized by the above-mentioned symptoms. Because of the similarity in phenotypes between TAFRO syndrome and decompensated liver cirrhosis, an accurate diagnosis is often difficult. We herein report a 62-year-old Japanese patient with TAFRO syndrome who was misdiagnosed with intractable ascites associated with liver cirrhosis. Improvement of symptoms after treatment with prednisolone was associated with interleukin-6 rather than C-reactive protein. The pathogenesis of TAFRO syndrome, which has similar clinical manifestations to liver cirrhosis, remains unclear, and our findings may help elucidate the concept of this condition.
Immune checkpoint inhibitors (ICIs) are complicated by immune-related adverse events (irAEs), such as myositis, myocarditis, and myasthenia gravis (MG). Anti-titin antibody and anti-voltage-gated potassium channel Kv1.4 antibody are anti-striated antibodies that are frequently detected in MG patients with myositis and/or myocarditis. However, the clinical relationship between positive anti-striated antibodies and irAEs of ICIs remains unknown. We herein report a case of nivolumab-induced myositis and myocarditis with positive anti-titin antibody and anti-voltage-gated potassium channel Kv1.4 antibody in a patient with non-small-cell lung cancer. We also review reported cases of positive anti-striated antibodies related to irAEs of ICIs.