Objective The cardiac function, blood distribution, and oxygen extraction in the muscles as well as the pulmonary function determine the oxygen uptake (VO2) kinetics at the onset of exercise. This factor is called the VO2 time constant, and its prolongation is associated with an unfavorable prognosis for heart failure (HF). The mitochondrial function of skeletal muscle is known to reflect exercise tolerance. Morphological changes and dysfunction in cardiac mitochondria are closely related to HF severity and its prognosis. Although mitochondria play an important role in generating energy in cardiomyocytes, the relationship between cardiac mitochondria and the VO2 time constant has not been elucidated.
Methods We calculated the ratio of abnormal cardiac mitochondria in human myocardial biopsy samples using an electron microscope and measured the VO2 time constant during cardiopulmonary exercise testing. The VO2 time constant was normalized by the fat-free mass index (FFMI).
Patients Fifteen patients with non-ischemic cardiomyopathy (NICM) were included. Patients were divided into two groups according to their median VO2 time constant/FFMI value.
Results Patients with a low VO2 time constant/FFMI value had a lower abnormal mitochondria ratio than those with a high VO2 time constant/FFMI value. A multiple linear regression analysis revealed that the ratio of abnormal cardiac mitochondria was independently associated with a high VO2 time constant/FFMI.
Conclusion An increased abnormal cardiac mitochondria ratio might be associated with a high VO2 time constant/FFMI value in patients with NICM.
Objective The relationship between obesity and risk of death in chronic kidney disease (CKD) patients remains controversial. In addition, no clear evidence has been accumulated regarding whether or not exercise improves mortality in CKD patients.
Methods The original cohort was based on a Japanese general population of 685,889 people from 40 to 74 years old who had undergone annual specific health checkups. The number of all-cause deaths during follow-up (mean, 4.7 years) in this study was 1,490. Information on walking and exercise habits was obtained by questionnaires. The study population was divided into 4 categories by the combination of CKD and obesity [body mass index (BMI) ≥25.0 kg/m2]. Changes in the BMI and walking and exercise habits were determined by results for the first year and following year.
Results Obese CKD patients with weight gain (BMI increase by more than +1.0 kg/m2/year) showed a higher crude mortality (1.32%) than those with a stable BMI (within ±1.0 kg/m2/year; 0.69%). In the obese CKD population, mortality was higher with loss of exercise habits (0.96%) than in those continuously maintaining exercise habits (0.52%). The age- and sex-adjusted hazard ratio for all-cause death was 2.23 in the group with weight gain compared to the group with stable weight (p<0.01) and 2.08 in the group with loss of exercise habits compared to those who maintained exercise habits (p<0.01).
Conclusion This observational cohort study suggested that loss of exercise habits as well as weight gain of more than 1 kg/m2/year might worsen all-cause mortality in the obese CKD population.
Objective Compared to prospective trials, the early death rate of newly diagnosed acute promyelocytic leukemia (APL) in the real-world clinical setting is higher. However, the early death rate was heterogeneous according to the reported institutes. Thus, the therapeutic approach at each institute may be important for preventing early death. This study evaluated the management strategy for untreated APL in our institute to avoid early death.
Methods We identified consecutive 21 patients with untreated APL who received induction therapy including all-trans retinoic acid (ATRA) between July 2007 and December 2021 at the University of Tokyo Hospital.
Results As therapeutic approaches, 16 patients (76%) received ATRA administration on the day of admission, and the remaining 5 received ATRA within 4 days from admission. Notably, all patients received conventional chemotherapy added to ATRA at a median of 1 day from admission (range: 0-9 days). As clinical outcomes, no patient died during induction therapy for untreated APL, and all achieved complete molecular remission.
Conclusion Compared to the previous nationwide survey, a higher proportion of patients at our institute received conventional chemotherapy in addition to ATRA, and it was initiated more promptly, which may have helped prevent early death.
Objective Mortality analyses of patients with coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation in Japan are limited. The present study therefore determined the risk factors for mortality in patients with COVID-19 requiring invasive mechanical ventilation.
Methods This retrospective cohort study used the dataset from the Japanese multicenter research of COVID-19 by assembling real-word data (J-RECOVER) study that was conducted between January 1 and September 31, 2020. Independent risk factors associated with in-hospital mortality were evaluated using a multivariate logistic regression analysis. Kaplan-Meier estimates of the survival were calculated for different age groups. A subgroup analysis was performed to assess differences in survival rates according to additional risk factors, including an older age and chronic pulmonary disease.
Patients A total of 561 patients were eligible. The median age was 67 (interquartile range: 56-75) years old, 442 (78.8%) were men, and 151 (26.9%) died in the hospital.
Results Age, chronic pulmonary disease, and renal disease were significantly associated with in-hospital mortality. Compared with patients 18-54 years old, the adjusted odds ratios of patients 55-64, 65-74, and 75-94 years old were 3.34 (95% CI, 1.34-8.31), 7.07 (95% CI, 3.05-16.40), and 18.43 (95% CI, 7.94-42.78), respectively.
Conclusion Age, chronic pulmonary disease, and renal disease were independently associated with mortality in patients with COVID-19 requiring invasive mechanical ventilation, and age was the most decisive indicator of a poor prognosis. Our results may aid in formulating treatment strategies and allocating healthcare resources.
Esophagogastroduodenoscopy in a 58-year-old man revealed a protruding lesion measuring 6 mm in diameter in the fornix. An endoscopic biopsy of the lesion indicated well-differentiated adenocarcinoma. The lesion was resected by polypectomy. According to the Japanese histologic diagnostic criteria, we made a final diagnosis of early gastric cancer (U, Gre, 6×6 mm, Type 0-I, tub1, pT1a (M), pUl0, Ly0, V0, pHM0, pVM0). A retrospective review of the endoscopic images showed that this lesion had already been present in the images taken 16 years ago. The size and morphology of the lesion were the same as those of the first detected lesion.
The therapeutic strategy for sustained ventricular tachycardia (VT) during left ventricular assist device usage remains unclear. We encountered a patient with durable left ventricular assist device who presented sustained VT. Electrophysiological mapping was able to be established appropriately owing to the robust mechanical hemodynamics support despite inter-device interference. The three-dimensional activation map of clinically documented VT demonstrated that the propagation exited from the right ventricular apex through the critical isthmus located at the epicardium or interventricular septum, which was successfully treated by catheter ablation at the exit site. Further experiences like ours should be accumulated to establish a therapeutic strategy.
Adrenal hemorrhaging (AH) is a rare condition characterized by bleeding into the suprarenal glands. A 62-year-old man with untreated obstructive sleep apnea syndrome (OSAS) was admitted to our hospital complaining of abdominal stiffness. He was diagnosed with left-sided AH and underwent adrenalectomy. Pre- and post-surgery, elevated plasma adrenocorticotropic hormone (ACTH) levels were observed. However, Cushing's syndrome and adrenal insufficiency were negative, and nasal continuous positive airway pressure (CPAP) normalized the plasma ACTH levels. Elevated ACTH levels are reportedly present in patients with OSAS. ACTH may be associated with the development of AH through the change in blood supply and other mechanisms.
A 32-year-old man was admitted for the evaluation of proteinuria (5.69 g/day). A light microscopic examination showed markedly dilated glomerular capillary loops with vacuolated areas in many glomeruli, and vacuolated areas were seen on peritubular capillaries in the tubulointerstitium. When electron microscopy specimens prepared by pre-fixation with glutaraldehyde and post-fixation with osmium tetroxide were used for oil red staining, the deposition was confirmed on the affected areas. A genetic analysis of apoE showed that the lipoprotein glomerulopathy was due to apoE-Sendai (Arg145Pro, p.R163P) heterozygosity, which was found in not only the patient but also his mother and twin brother.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), Sjögren's syndrome (SjS), and sarcoidosis are systemic diseases targeting multiple organs. While a careful differential diagnosis of these diseases is often required, their co-occurrence in the same patient has been previously reported. We herein report a 58-year-old Japanese man diagnosed with the co-occurrence of three systemic diseases (AAV, SjS, and sarcoidosis) in addition to monoclonal gammopathy of undetermined significance (MGUS), which emphasizes the importance of considering the possible co-occurrence of these diseases as well as their differentiation.
A 16-year-old Japanese girl developed a fever, thrombocytopenia, and renal dysfunction. Treatment was started with steroids, but cervical lymphadenopathy and ascites developed. A lymph node biopsy indicated TAFRO syndrome. The patient's renal function deteriorated, and dialysis was started. Refractory hypertension and subsequent encephalopathy developed. Treatment was started with an anti-IL-6 receptor antibody and an anti-CD20 monoclonal antibody. A kidney biopsy showed malignant nephrosclerosis-like microangiopathy and glomerular collapse due to narrowing of the small arteries. The majority of TAFRO syndrome cases are adult-onset, with glomerular microangiopathy. To our knowledge, this is the first report of adolescent-onset TAFRO syndrome presenting with malignant nephrosclerosis-like lesions associated with hypertension.
Pulmonary hypertension (PH) often complicates chronic lung disease. However, there are few reports of PH associated with diffuse panbronchiolitis, and there is no effective treatment. We herein report a 64-year-old woman diagnosed with PH due to diffuse panbronchiolitis. She received erythromycin, carbocysteine, and home oxygen therapy (1 L O2/min). After 4 months of therapy, the respiratory function (diffusing capacity of the lungs for carbon monoxide: 23.3% to 76.1%) and PH (mean pulmonary arterial pressure: 50 to 28 mmHg; pulmonary vascular resistance: 680 to 518 dynes・sec・cm-5; pre- vs post-therapy, respectively) had improved markedly.
Autoimmune pulmonary alveolar proteinosis (APAP) is caused by macrophage dysfunction owing to the presence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies. A 77-year-old man with APAP was referred to our hospital for whole-lung lavage (WLL) due to oxygenation exacerbation and pulmonary shadows. The patient had had coronavirus disease 2019 (COVID-19) during the APAP evaluation before WLL. About three months after COVID-19 resolved, his oxygenation and shadow reflecting APAP had obviously improved, thus avoiding the need for WLL. We suspected that the improvement in APAP was due to various immunological reactions induced by COVID-19.
Patients with acute myeloid leukemia (AML) harboring FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication mutation are associated with a poor survival outcome, even those receiving allogeneic stem cell transplantation (Allo-SCT). An additional treatment strategy with allo-SCT is therefore required to reduce relapse in these patients. Gilteritinib is a specific FLT3 inhibitor that has shown clinical benefit for patients with relapsed and refractory (R/R) AML harboring FLT3 mutation. We herein report a 49-year-old woman with R/R AML who was successfully treated with pre- and post-transplant gilteritinib. Post-transplant gilteritnib yielded a durable response with possible exacerbation of graft-versus-host disease.
A 21-year-old woman was diagnosed with acute lymphoblastic leukemia. After the administration of intrathecal methotrexate (MTX), the patient experienced dysarthria and paralysis for one hour. Magnetic resonance imaging (MRI) performed one hour from the onset and just before symptoms disappeared revealed no abnormalities. The next day, the symptoms appeared again, and diffusion-weighed MRI revealed a high-intensity area in the left frontal lobe. The patient was diagnosed with MTX-induced encephalopathy. This case suggested that MRI performed as soon as symptoms appear might show normal findings in MTX-induced encephalopathy.
Two patients, 48- and 50-year-old sisters, presented with a characteristic facial appearance with slowly progressive deafness and cerebellar ataxia starting in their 30s. Genetic testing identified compound heterozygous pathogenic variants in the ERCC6 gene: c.1583G>A (p.G528E) and c.1873T>G (p.Y625D). A diagnosis of Cockayne syndrome (CS) B type III was made. CS is usually diagnosed in childhood with well-defined facial characteristics and photosensitivity. This case report describes rare cases of adulthood CS with a primary presentation of slowly progressing deafness and cerebellar ataxia. CS should be considered in adults with characteristic facial and skin findings, deafness, and cerebellar ataxia.
We herein report a 68-year-old Japanese man with sporadic variant transthyretin (ATTRv) amyloidosis harboring the novel variant A97D (p.A117D) in TTR. He had slow development of asymmetric neuropathy, unintentional weight loss, mild autonomic failure and mild cardiomyopathy. TTR amyloid deposition on the gastric duodenal mucosa was detected. In silico analyses predicted that TTR A97D (p.A117D) altered the structure and function of the TTR protein. ATTRv amyloidosis is often difficult to diagnose in non-endemic regions due to its diverse phenotypes, such as atypical peripheral nerve involvement and a rare family history.
A 55-year-old woman was admitted to our hospital because of gait disturbance and urinary retention that acutely emerged 1 week after severe acute respiratory syndrome coronavirus 2 infection. Acute inflammatory myelopathy was clinically suspected, based on bilateral lower-limb weakness with an extensor plantar response and an elevated immunoglobulin G level in the cerebrospinal fluid. Whole-spine magnetic resonance imaging findings were normal. The central conduction time was extended, based on somatosensory evoked potentials. Her lower-limb weakness was partially ameliorated with immunosuppressive therapy. Postinfectious myelopathy is a rare neurological complication of coronavirus disease 2019 and can develop with normal radiological findings.
Generalized subcutaneous edema is rare in dermatomyositis. We herein report an 82-year-old woman with dermatomyositis who presented with generalized subcutaneous edema. Three weeks before admission, she first noticed facial edema, and the symptoms exacerbated, with limb edema occurring. On admission, muscle weakness in the limbs and skin rash were noted. Her muscle enzyme levels were elevated, and serum anti-transcriptional intermediary factor 1-γ antibody was detected. She was diagnosed with dermatomyositis and treated with corticosteroids and tacrolimus, which improved her muscle weakness, muscle enzymes, and edema. Thus, generalized subcutaneous edema can occur during dermatomyositis, with facial edema as the initial symptom.
A 73-year-old woman with myelodysplastic syndrome and diabetes mellitus, chronic renal failure and paroxysmal atrial fibrillation, received a diagnosis of facial cellulitis and was treated by antibiotics. However, her symptoms deteriorated. Facial magnetic resonance imaging (MRI) showed orbital cellulitis. She had weakness of visual acuity requiring changing the antibiotics. She also underwent steroid pulse treatment. Her symptoms temporarily improved, but she became comatose and died. Results of a molecular analysis of the residual cerebrospinal fluid indicated Rhizopus species infection. For immunocompromised hosts with refractory orbital cellulitis, mucormycosis should be considered as a differential diagnosis, and appropriate treatment should be promptly performed.