Objective We investigated the relationship between the amount and frequency of fish intake, and the white blood cell (WBC) count and aerobic exercise habits.
Methods We conducted a cross-sectional study between April 2019 and March 2020 at the Health Planning Center of Nihon University Hospital on a cohort of 8,981 male subjects.
Results The average amount and frequency of fish intake were 134±85 g/week and 2.14±1.28 days/week, respectively. The WBC count decreased significantly as the amount of fish intake increased (p<0.0001). According to a multivariate regression analysis, a high fish intake amount (β=-0.082, p<0.0001) and regular aerobic exercise (β=-0.083, p<0.0001) were independent determinants of a low WBC count. The proportion of subjects engaged in regular aerobic exercise increased with an increase in the amount of fish intake (p<0.0001). Furthermore, the amount and frequency of fish intake significantly correlated with the amount of n-3 polyunsaturated fatty acid intake determined using the Japan's National Nutrition Survey results (both r=0.962 and 0.958). Therefore, the amount of fish intake could be substituted by the average number of days of fish intake per week.
Conclusion A high fish intake was an independent determinant of a low WBC count and engagement in regular aerobic exercise, regardless of whether the fish intake was defined by the amount or frequency of fish intake. However, since fish intake frequency can be measured more easily, this may be used to measure the fish intake.
Objective The Lewis lead configuration is an alternative bipolar chest lead and it can help detect atrial activity. The utility of the Lewis lead to distinguish orthodromic atrioventricular reentrant tachycardia (AVRT) from typical atrioventricular nodal reentrant tachycardia (AVNRT) by visualizing the apparent retrogradely conducted P waves was investigated.
Methods Forty-four patients with paroxysmal supraventricular tachycardia (PSVT) were included in this study. All patients had PSVT documented by an electrocardiogram (ECG) and underwent an electrophysiological study (EPS). During tachycardia, an ECG recording was performed using a Lewis lead with the electrode on the right aspect of the sternum at the second intercostal space instead of the right arm and the electrode on the fourth intercostal space instead of the left arm. The ECG parameters during tachycardia were compared between AVRT and AVNRT.
Results Fourteen patients were diagnosed with AVRTs and 30 with typical AVNRTs on EPS. The positive P wave could be seen in the Lewis lead configuration in 9 of 14 patients with AVRTs and 21 of 30 patients with AVNRTs. P waves were more often visible in the Lewis lead configuration than in the standard leads (66% vs. 45%). The RP interval was significantly longer for AVRTs than for AVNRTs (88±17 vs. 154±34 ms, p<0.001), which yields 89% sensitivity and 71% specificity for distinguishing these 2 tachyarrhythmias with a cut-off point of 100 ms.
Conclusion A Lewis lead configuration may help to make an accurate diagnosis among the reentrant supraventricular tachycardias prior to procedures, owing to its ability to locate P waves.
Objective Although an association between serum inorganic phosphorus levels and a poor prognosis has been noted in dialysis patients, these associations have been insufficiently reported in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. This study attempted to determine the association between serum inorganic phosphorus levels and adverse outcomes in Japanese NDD-CKD patients.
Methods We investigated the relationships between serum inorganic phosphorus levels and adverse outcomes, such as kidney events, cardiovascular events, and all-cause death, in Japanese NDD-CKD patients using longitudinal data from the Fukushima CKD Cohort Study with a median follow-up period of 2.8 years. The study evaluated 822 patients with NDD-CKD enrolled between June 2012 and July 2014. A kidney event was defined as a combination of doubling of the baseline serum creatinine or end-stage renal disease. Cox regression was performed to analyze the relationships of the quartile of the serum inorganic phosphorus with kidney events, cardiovascular events, and all-cause death.
Results The frequency of kidney events per 1,000 person-years exhibited a U-shaped distribution based on serum inorganic phosphorus levels, with these levels not significantly associated with an increased risk of cardiovascular events and all-cause death. A multivariable Cox regression analysis showed an increased risk of kidney events for the highest quartile of the serum inorganic phosphorus levels (≥3.7 mg/dL) versus the second quartile (2.9-3.2 mg/dL, hazard ratio, 3.30; 95% confidence interval, 1.50-7.28; p=0.003). There were no significant associations between the serum calcium levels and adverse outcomes.
Conclusion Serum inorganic phosphorus levels were associated with an increased risk of CKD progression in Japanese NDD-CKD patients.
Objective Switching from mepolizumab to benralizumab has been reported to significantly improve both asthma control and the lung function. However, the data on its efficacy in elderly patients with severe eosinophilic asthma are limited. This study aimed to assess whether elderly patients with severe eosinophilic asthma could experience an improved asthma control and lung function when switching directly from mepolizumab to benralizumab.
Methods In this single-center, retrospective study conducted between February 2017 and September 2018, we assessed the effect of switching the treatment directly from mepolizumab to benralizumab on eosinophil levels, exacerbation rates, and lung function. We compared the treatment responses between the two groups using either Fisher's exact test or Mann-Whitney U-test, as appropriate.
Patients We enrolled 12 elderly patients (age ≥65 years) with severe eosinophilic asthma treated with mepolizumab at Hiroshima Prefectural Hospital (Hiroshima, Japan) during the study period. Six patients were switched from mepolizumab to benralizumab, and six continued with the mepolizumab treatment.
Results The switch from mepolizumab to benralizumab caused a near-complete reduction in the eosinophil count (p=0.008). The annual rate of clinically relevant exacerbations and hospitalizations diminished as well, albeit with no statistical significance. We found no improvement in the lung function after switching treatment and no difference in the treatment response between the groups.
Conclusion Although this study is based on a small sample of participants, the results indicate that both mepolizumab treatment and switching from mepolizumab to benralizumab treatment without a washout period have clinically relevant asthma control benefits for elderly patients with severe eosinophilic asthma.
Objective Graft failure (GF) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). A standardized conditioning regimen and an appropriate graft source of salvage HSCT for GF have not yet been established. Some case series have shown good hematopoietic recoveries after salvage HSCT using a short-term reduced-intensity preparative regimen consisting of fludarabine (30-90 mg/m2), cyclophosphamide (2 g/m2), and total-body irradiation (2 Gy). However, the dose of fludarabine has varied in these reports based on the clinical condition of the patients, resulting in very limited experiences with each dose of fludarabine.
Methods We retrospectively analyzed 10 patients who developed GF after allogeneic HSCT and underwent salvage cord blood transplantation (CBT) using the above-mentioned conditioning regimen with a fixed dose (90 mg/m2) of fludarabine.
Results Eight patients (80.0%) achieved neutrophil engraftment within 30 days from salvage HSCT with a median of 21 (range, 17-23) days. The 1-year overall survival (OS) rate after the salvage HSCT was 50.0%, and the median OS was 281 (range, 23-1,638) days. Cumulative incidences of non-relapse mortality and relapse at 1 year were 50.0% and 10.0%, respectively.
Conclusion CBT using this short-term reduced-intensity conditioning regimen may be a promising salvage therapy for GF.
Objective Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally. Although the relationship between anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies and COVID-19 severity has been reported, information is lacking regarding the seropositivity of patients with particular types of diseases, including hematological diseases.
Methods In this single-center, retrospective study, we compared SARS-CoV-2 IgG positivity between patients with hematological diseases and those with non-hematological diseases.
Results In total, 77 adult COVID-19 patients were enrolled. Of these, 30 had hematological disorders, and 47 had non-hematological disorders. The IgG antibody against the receptor-binding domain of the spike protein was detected less frequently in patients with hematological diseases (60.0%) than in those with non-hematological diseases (91.5%; p=0.029). Rituximab use was significantly associated with seronegativity (p=0.010).
Conclusion Patients with hematological diseases are less likely to develop anti-SARS-CoV-2 antibodies than those with non-hematological diseases, which may explain the poor outcomes of COVID-19 patients in this high-risk group.
Objective Dementia with Lewy bodies (DLB) is the second-most common form of neurodegenerative dementia after Alzheimer's disease (AD). Falls are a vital prognostic factor in patients with dementia and are a characteristic feature of DLB. This study investigated the screening potential of the fall risk evaluation for DLB and compared it with that of AD to facilitate an accurate diagnosis.
Methods We enrolled patients diagnosed with DLB (n=410) and AD (n=2,683) and categorized the participants into 3 groups depending on their physical ability, age, cognitive function, and fall events. Using the Fall Risk Index-21 (FRI-21) questionnaire, we evaluated and comparatively analyzed the fall risk between DLB and AD patients in three defined groups of participants.
Results The FRI-21 score was significantly higher in DLB patients than in AD patients in every group. Using this score, we were able to distinguish between DLB and AD patients in each group. Among the three groups, the group with a young age, relatively mild cognitive dysfunction, and no fall events exhibited the best specificity for DLB (0.895).
Conclusions The FRI-21 is a useful tool for screening for DLB and differentiating it from AD. This questionnaire can be used at a relatively early stage of the disease in young patients with mild cognitive dysfunction and no history of falling. These preliminary results need to be validated in an interventional study to evaluate the effectiveness of rehabilitative measures and daily environmental changes carried out to prevent falls using this tool.
Objective Smoking is a known risk factor for the development and progression of autoimmune diseases. Previous studies in ocular myasthenia gravis (MG) patients showed that smoking is associated with the severity of symptoms and progression to generalized MG. However, whether smoking affects MG symptoms in patients with a broader clinical spectrum of presentations is unknown. Therefore, in this study, the associations of smoking with the clinical characteristics of MG were analyzed in a cohort of patients including those with generalized, seronegative, and thymoma-associated MG.
Methods The smoking history was investigated in a cross-sectional study of 187 patients with MG followed in a referral hospital for neurology. The association of smoking with MG-activities of daily living score at survey, the presence of generalized manifestations, and the age of onset was assessed using multiple regression models.
Results Neither current nor prior smoking habit was associated with the MG-activities of daily living score at survey. However, smoking exposure after MG onset was significantly associated with the presence of generalized manifestations during the disease course (odds ratio, 3.57; 95% confidence interval, 1.04, 12.3). The smoking history before or at onset of MG was not associated with the age of onset.
Conclusion Smoking exposure after the onset is associated with generalized manifestations of MG in our cohort of patients with a broad clinical spectrum of presentations.
Objective The prognosis differs considerably between patients with psychogenic hyperventilation syndrome (HVS) and those with urinary tract infection (UTI)-associated sepsis; however, the nonspecific symptoms and signs make the diagnosis and management difficult. We herein report the utility of a blood gas analysis for distinguishing HVS from UTI with suspected sepsis.
Methods This single-center retrospective cohort study was conducted in a tertiary-care hospital in Japan. Patients ≥18 years old with a quick Sequential Organ Failure Assessment (qSOFA) score ≥2 and HVS or UTIs were included. The results of an arterial blood gas (ABG) or venous blood gas (VBG) analysis of the two groups were compared using the Mann-Whitney U test. We used a receiver-operating characteristic (ROC) curve analysis of the arterial pH and arterial PCO2 to assess the ability of these analyses to distinguish HVS from UTI with suspected sepsis.
Results A total of 64 patients with HVS (ABG, n=14; VBG, n=50) and 53 with UTI with suspected sepsis (ABG, n=35; VBG, n=18) were included. Patients with HVS had alkalemia and lower PCO2 levels than patients with UTI with suspected sepsis, but the serum lactate levels were similar between the groups. The ROC analysis determined the pH cut-off value to be 7.509 (sensitivity: 0.91; specificity: 0.86) and the PCO2 cut-off value to be 21.6 mmHg (sensitivity: 1.00; specificity: 0.64).
Conclusion Elevated serum lactate levels alone cannot be used to differentiate between patients with HVS and those with UTI with suspected sepsis, but the degree of pH and PCO2 abnormality can help with the differential diagnosis.
We herein report a 73-year-old woman with BRAF V600E-mutated colon cancer treated with encorafenib plus cetuximab with binimetinib as standard salvage therapy for patients with advanced colorectal cancer. She developed bilateral serous retinal detachment the next day, and the regimen was discontinued, resulting in complete resolution by the third day. Doublet therapy without binimetinib was initiated along with a weekly ophthalmologic examination for 10 weeks without recurrence of retinal detachment. Thus, binimetinib was presumed to have been the cause of the retinal detachment. This clinical course suggests the need for close monitoring of patients for vision impairment and close collaboration with ophthalmologists.
Behçet's disease (BD) is a multisystem inflammatory disease of unknown origin. It rarely but occasionally occurs together with myelodysplastic syndrome and primary myelofibrosis. Trisomy 8 is one of the most common cytogenetic abnormalities in myeloid neoplasms; however, the association of BD with polycythemia vera (PV) and trisomy 8 has not been reported. A 70-year-old woman, diagnosed with PV and treated with hydroxyurea, had bloody stool due to multiple ulcers in the ileocecal region. Considering the lack of a response to treatment and other features, we suspected complication with intestinal Behçet's-like disease. Our case suggests relationships among BD, trisomy 8, and PV.
We herein report two cases of potentially life-threatening arrhythmia due to hyperkalemia triggered by the excessive consumption of "Hoshi-Imo" (dried sweet potato). Both patients with chronic renal disease on renin-angiotensin-aldosterone system inhibitors presented at the emergency room with non-specific symptoms. Electrocardiograms revealed potentially life-threatening arrhythmia due to hyperkalemia in both cases: sinus arrest with a ventricular escape rhythm, tall and peaked T waves; and a widened QRS complex in a nearly sine-wave configuration without discernible P wave. Both patients fully recovered after intensive care for hyperkalemia. Physicians should recognize the excessive consumption of "Hoshi-Imo" may lead to the development of life-threatening arrhythmia, especially in patients with risk factors for hyperkalemia.
Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the alpha-galactosidase A (GLA) gene that results in deficiency of the enzyme GLA and leads to the accumulation of globotriaosylceramide (GL-3) in cells. The accumulation of GL-3 may lead to life-threatening complications. Significant advances in genetic sequencing technology have led to a better understanding of genotype-phenotype interactions in Fabry disease. Fabry disease with an R112H mutation is known as the non-classic type. However, the long-term clinical course of the disease remains unknown. We herein report a patient with a 30-year natural history of non-classic Fabry disease with an R112H mutation.
The effect of radiotherapy during immunotherapy on immune-related adverse events (irAEs) is not fully understood. We herein report a 74-year-old woman diagnosed with lung adenocarcinoma with programmed death ligand 1 expression ≥50% and treated with pembrolizumab. She developed fatal immune thrombocytopenia associated with pembrolizumab immediately following radiotherapy. A flow cytometry analysis of peripheral blood detected an increased expression of programmed death-1 (PD-1) and Ki-67 in CD4+ and CD8+ T cells after radiotherapy, compared with pre-irradiation measurements. This case suggests that radiotherapy may evoke irAEs during treatment with anti-PD-1 antibodies, which physicians should consider when using radiotherapy in patients treated with these drugs.
Immune checkpoint inhibitors (ICIs) have demonstrated marked efficacy in some cancer patients, but they may cause various severe immune-related adverse events. Alectinib is a second-generation anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (TKI) approved for ALK-rearranged non-small-cell lung cancer (NSCLC). Alectinib is said to be safer than other TKIs. We conducted an investigator-initiated trial of alectinib, which also has RET kinase-inhibitory activity, against RET-rearranged NSCLC. Two RET-rearranged NSCLC patients experienced severe skin toxicity with alectinib after first undergoing anti-PD-1 antibody treatment with an ICI. These findings suggest that we should carefully follow patients for adverse effects of targeted drugs following ICI treatment.
We herein report a 74-year-old man who developed Lambert-Eaton myasthenic syndrome (LEMS) during atezolizumab treatment for extensive-stage small-cell lung cancer. He was started on maintenance immunotherapy with atezolizumab every three weeks after four cycles of atezolizumab plus carboplatin plus etoposide combination therapy. After 13 cycles of maintenance atezolizumab therapy, he complained of muscular weakness and fatigue. Findings from a nerve conduction study and positive findings for anti-P/Q-type voltage-gated calcium channel antibody resulted in a diagnosis of LEMS. This was a rare case of LEMS as a neurological immune-related adverse event induced by atezolizumab therapy.
Charcot-Marie-Tooth disease (CMT) is a common hereditary peripheral polyneuropathy encompassing distinct monogenetic disorders. Pathogenic mutations in mitofusin 2 (MFN2) are the most frequent cause of its axonal type, CMT type 2A, with diverse phenotypes. We herein report a Japanese patient with a novel heterozygous MFN2 pathogenic variant (c.740 G>C, p.R247P) and severe CMT phenotypes, including progressive muscle weakness, optic atrophy, urinary inconsistency, and restrictive pulmonary dysfunction with eventration of the diaphragm that developed over her 60-year disease course. Our case expands the clinico-genetic features of MFN2-related CMT and highlights the need to evaluate infrequent manifestations during long-term care of CMT patients.
The PRPS1 gene encodes phosphoribosyl pyrophosphate synthetase 1 (PRS-1). The phenotypes associated with PRPS1 mutations include DFN2 (mild PRS-1 deficiency), X-linked Charcot-Marie-Tooth disease type 5 (CMTX5) (moderate PRS-1 deficiency), Arts syndrome (severe PRS-1 deficiency), and PRS-1 superactivity1. CMTX5 is a very rare hereditary neuropathy characterized by deafness, optic atrophy, and polyneuropathy. We herein report a Japanese patient with CMTX5 who had a novel hemizygous mutation c.82 G>C in PRPS1. Despite showing a typical clinical picture, the decrease in enzyme activity measured in the patient's erythrocytes was milder than in previously reported cases.
We herein report a 70-year-old man diagnosed with IgG4-related hypertrophic pachymeningitis with skull base involvement, who presented with isolated glossopharyngeal and vagus nerve palsy. Contrast-enhanced magnetic resonance imaging (MRI) showed enhanced dural thickening of the posterior clivus and skull base involvement. When a patient with hypertrophic pachymeningitis presents with isolated cranial neuropathy without systemic manifestations or definite MRI abnormalities, it is difficult to make a diagnosis, and the patient may be misdiagnosed. This case suggests that a detailed radiological evaluation including contrast enhancement of the skull base is very important in patients with isolated glossopharyngeal and vagus nerve palsy.
Guillain-Barré syndrome (GBS) has occasionally occurred in people who have received coronavirus disease 2019 (COVID-19) vaccines. Dysgeusia is rare symptom of GBS. We herein report a rare case of sensory ataxic GBS with dysgeusia just after the second dose of the Pfizer-BioNTech COVID-19 vaccine. Although autoantibodies against glycolipids were not detected, immunotherapy with intravenous immunoglobulin and methylprednisolone pulse therapy effectively ameliorated the symptoms. Our report suggests that the COVID-19 vaccine may induce various clinical subtypes of GBS, including a rare variant with sensory ataxia and dysgeusia.
Cranial nerve palsy associated with coronavirus disease 2019 (COVID-19) is rare. We herein report the first Asian case of the immediate onset of isolated and unilateral abducens nerve palsy (ANP) accompanied with COVID-19 infection. A 25-year-old man developed diplopia one day after the COVID-19 symptom onset. Neurological examination revealed limitation of left eye abduction without ataxia and hyporeflexia. Negative anti-ganglioside antibody results and mild albuminocytological dissociation were noted. The patient was diagnosed with left ANP accompanied by COVID-19 infection. The ANP spontaneously recovered without treatment. ANP can develop during the early phase of COVID-19 infection and adversely affect patients' quality of life.
The efficacy of early immunosuppressive therapy without invasive therapy, such as endovascular or surgical revascularization, for pulmonary hypertension due to Takayasu arteritis (TAK-PH) remains to be elucidated. We herein report two cases of TAK-PH due to pulmonary arteritis successfully treated with early immunosuppressive therapy. A literature review of 42 cases of TAK-PH with pulmonary artery involvement showed that the cases treated with immunosuppressive therapy early after the onset (within 12 months) had a higher erythrocyte sedimentation rate and better outcome without invasive therapy than those treated later. TAK-PH may be successfully treated with immunosuppressive therapy without invasive therapy when diagnosed early with high disease activity.
We herein report a 71-year-old woman presented with a fever, arthralgia, general malaise and leg muscle stiffness following administration of the COVID-19 mRNA vaccine (Comirnaty, Pfizer-BioNTech). Laboratory findings showed an elevated C-reactive protein level and erythrocyte sedimentation rate. In addition, Gallium-67 scintigraphy demonstrated an increased uptake in multiple joints. Typing of human leukocyte antigen (HLA) revealed the presence of the DRB1*0404/*0803 allele. These findings met the diagnostic criteria for polymyalgia rheumatica (PMR), and when we started steroid treatment, her symptoms improved rapidly. This patient developed PMR after receiving a COVID-19 mRNA vaccine (Comirnaty, Pfizer-BioNTech). This case is considered to be valuable, as the HLA-DRB1 allele was also confirmed.
A 67-year-old man, hospitalized with fever and pancytopenia, experienced cardiogenic shock on the 3rd day of hospitalization. He complained of chest pain and exhibited cardiac dysfunction, upregulated serum troponin levels, and an ST elevation on electrocardiogram. Severe fever with thrombocytopenia syndrome (SFTS) was suspected based on the symptom course after a tick bite and was definitively diagnosed using the serum polymerase chain reaction (PCR) test. An endomyocardial biopsy performed in the convalescent phase revealed a sign of myocardial inflammation with increases in CD3- and CD68-positive cells. We herein report the first case of acute myocarditis complicated with SFTS.
We herein report the case of a 78-year-old woman who was diagnosed as having disseminated herpes zoster (DHZ) complicated with probable varicella-zoster pneumonia during maintenance therapy for microscopic polyangiitis. Because the patient had severe renal dysfunction, amenamevir administration was started to avoid any neurotoxicity of acyclovir, which is suggested to be optimal for treatment. It ameliorated her symptoms without any adverse events. This is the first report suggesting the efficacy of amenamevir in the treatment of severe herpes zoster infection with coexisting DHZ and probable varicella-zoster pneumonia. Amenamevir could thus be a treatment option for severe varicella zoster virus infections.
Secondary cold agglutinin syndrome (CAS) is autoimmune hemolytic anemia secondary to infections and lymphoid disorder. We here report the first Asian case of CAS secondary to novel coronavirus disease 2019 (COVID-19). A 72-year-old Japanese woman presented with a 2-week history of dyspnea and cough, and laboratory data revealed severe hemolytic anemia with a hemoglobin level of 4.7 g/dL. She was diagnosed with COVID-19, CAS, and monoclonal gammopathy of undetermined significance (MGUS). The anemia responded to corticosteroids administered for COVID-19 and required maintenance therapy. Although corticosteroids are not a standard therapy for CAS, they might be effective for CAS secondary to COVID-19 complicated with MGUS.
Scurvy is a rare disease caused by a vitamin C deficiency. Vitamin C is a water-soluble vitamin found in vegetables and fruits, but it is lost after boiling. A 59-year-old man presented with gingival pain after having a tooth extracted five years previously. Following the procedure, his diet comprised boiled vegetables to prevent pain. He then experienced bilateral lower leg pain, and computed tomography revealed intramuscular bleeding. His serum vitamin C level was below the detectable limit. His symptoms immediately improved with vitamin C administration. This case emphasized that consuming only boiled vegetables can lead to the onset of scurvy.