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Masayuki Endo, Taisuke Jo, Takaaki Konishi, Ryosuke Kumazawa, Hiroki M ...
Article ID: 1115-22
Published: 2023
Advance online publication: May 24, 2023
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Objective Recommendations on the timing of Legionella urinary antigen tests for community-acquired pneumonia patients differ among guidelines in Japan, the United States, and European nations. We therefore evaluated the association between the timing of urinary antigen tests and in-hospital mortality in patients with Legionella pneumonia.
Methods We conducted a retrospective cohort study using the Diagnosis Procedure Combination database, a nationwide database of acute care inpatients in Japan. Patients who underwent Legionella urinary antigen tests on the day of admission formed the tested group. Patients who were tested on day 2 of admission or later or were unexamined formed the control group. We performed a propensity score matching analysis to compare in-hospital mortality, length of hospital stay and duration of antibiotics use between the two groups.
Results Of the 9,254 eligible patients, 6,933 were included in the tested group. One-to-one propensity score matching generated 1,945 pairs. The tested group had a significantly lower 30-day in-hospital mortality than the control group (5.7 vs. 7.7%; odds ratio, 0.72; 95% confidence intervals, 0.55-0.95; p=0.020). The tested group also showed a significantly shorter length of stay and duration of antibiotics use than the control group.
Conclusions Urine antigen testing upon admission was associated with better outcomes in patients with Legionella pneumonia. Urine antigen tests upon admission may be recommended for all patients with severe community-acquired pneumonia.
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Yasunori Inaba, Kenichi Goda, Masayuki Kondo, Keiichiro Abe, Akira Kan ...
Article ID: 1257-22
Published: 2023
Advance online publication: May 24, 2023
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We herein report a rare case of hereditary diffuse gastric cancer in a Japanese man. A 41-year-old man underwent esophagogastroduodenoscopy which revealed a small gastric erosion. Biopsy specimens showed signet ring cell carcinoma, and endoscopic submucosal dissection was performed. The patient's elder sister had died of gastric cancer at 38 years old. Considering the family history, a genetic test was conducted and revealed a CDH1 germline mutation. Although no carcinomatous lesion was detected endoscopically, prophylactic total gastrectomy was performed. The resection specimen showed seven microlesions of signet ring cell carcinoma confined to the lamina propria mucosae.
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Ryutaro Hirama, Kenichiro Takeda, Seiichiro Sakao, Hajime Kasai, Shizu ...
Article ID: 1399-22
Published: 2023
Advance online publication: May 24, 2023
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Objective We evaluated the clinical differences in coronavirus disease 2019 (COVID-19) patients between the sixth wave with the Omicron BA.1/BA.2 dominant variant (from January to April 2022) and seventh wave with the Omicron BA.5 dominant variant (from July to August 2022).
Methods This retrospective, single-center, observational study included COVID-19 patients admitted to our institution in the sixth wave (sixth-wave group) and the seventh wave (seventh-wave group). Inter-group comparisons of clinical presentations, the prognosis, and proportion of nosocomial infections were performed.
Results A total of 190 patients were included (93 and 97 patients in the sixth- and seventh-wave groups, respectively). While there were no significant differences in severity, significantly more patients developed pneumonia caused by COVID-19 in the sixth-wave group than in the seventh-wave group. Although there was no marked difference in in-hospital deaths, more patients died from COVID-19 in the sixth-wave group than in the seventh-wave group. There were significantly more COVID-19 inpatients with nosocomial infections in the seventh-wave group than in the sixth-wave group. Pneumonia from COVID-19 was significantly more severe in the sixth-wave group than in the seventh-wave group.
Conclusions COVID-19 patients in the seventh wave are at a lower risk of pneumonia than those in the sixth wave. However, even in the seventh wave, patients with underlying diseases have a risk of death because of the exacerbation of underlying diseases triggered by COVID-19.
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Noriko Sasaki, Yoko Nakagome, Azusa Kojima, Keigo Shimura, Akira Ishii ...
Article ID: 1410-22
Published: 2023
Advance online publication: May 24, 2023
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Objectives Dermatomyositis (DM) is often associated with fatal anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive rapidly progressive interstitial lung disease (RP-ILD). RP-ILD often fails to respond to intensive treatment and has a poor prognosis. We examined the effectiveness of early plasma exchange therapy plus intensive treatment with high-dose corticosteroids and multiple immunosuppressants.
Methods Autoantibodies were identified by an immunoprecipitation assay and enzyme-linked immunosorbent assay. All clinical and immunological data were collected retrospectively from medical charts. We divided patients into two groups based on treatment regimen: intensive immunosuppressive therapy alone as initial treatment (IS group) and early initiation of plasma exchange (PE) plus intensive immunosuppressive therapy (ePE group). Early PE therapy was designated if PE therapy was initiated within two weeks of starting treatment. Comparisons of the treatment response and prognosis between groups were performed.
Patients or Materials Anti-MDA5-positive DM with RP-ILD was screened.
Results Forty-four RP-ILD and DM patients had anti-MDA5 antibodies. Four patients were excluded because they died before receiving sufficient combined immunosuppressive therapy or before the evaluation of the immunosuppressive treatment effectiveness (IS, n=31; ePE, n=9). All 9 patients in the ePE group had improved respiratory symptoms and were alive, whereas 12 of 31 patients in the IS group died (100 vs. 61%, p=0.037). Of the 8 patients who had 2 values for a poor prognosis, indicating the highest risk for death using the MCK model, 3 of 3 patients in the ePE group and 2 of 5 in the IS group were alive (100 vs. 40%, p=0.20).
Conclusions The early initiation of ePE therapy plus intensive immunosuppressive therapy was effective for patients with DM and refractory RP-ILD.
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Mitsuyoshi Takahara, Toshihiko Shiraiwa, Naoto Katakami, Yoshifumi Mae ...
Article ID: 1441-22
Published: 2023
Advance online publication: May 24, 2023
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Objective This prospective observational study explored the changes in the daily glycemic profile after switching from injectable to oral semaglutide in patients with type 2 diabetes mellitus.
Methods Patients with type 2 diabetes mellitus who were treated with once-weekly 0.5 mg injectable semaglutide and wished to switch to once-daily oral semaglutide participated in this study. Oral semaglutide was initiated at 3 mg and increased to 7 mg a month later, according to the package insert. Before and two months after the switch, participants wore a sensor for continuous glucose monitoring for up to 14 days. We also evaluated the questionnaire-based treatment satisfaction and the preference between the two formulations.
Patients Twenty-three patients participated.
Results Mean glucose levels significantly increased by 9 mg/dL on average, from 132±20 to 141±27 mg/dL (p=0.047), which was equivalent to a change of 0.2% in the estimated hemoglobin A1c (6.5±0.5% to 6.7±0.7%). The inter-individual variability assessed with standard deviation also significantly increased (p=0.004). The change in treatment satisfaction varied considerably among patients, with no specific trend in the overall population. After trying oral semaglutide, 48% of patients responded that they preferred the oral formulation, while 35% preferred the injectable formulation, and 17% had no preference.
Conclusion The mean glucose levels increased by 9 mg/dL on average after switching from once-weekly 0.5 mg injectable semaglutide to once-daily 7 mg oral semaglutide, with an increased inter-individual variability. The change in treatment satisfaction considerably varied among patients.
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Ryuta Shigefuku, Motoh Iwasa, Akiko Eguchi, Mina Tempaku, Yasuyuki Tam ...
Article ID: 1475-22
Published: 2023
Advance online publication: May 24, 2023
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Background Zinc-α2-glycoprotein (ZAG) is secreted by various organs, such as liver, kidney and adipose tissue; is involved in lipolysis; and may contribute to the pathogenesis of chronic liver disease (CLD). We therefore assessed whether or not ZAG is a surrogate marker for the hepatorenal function, body composition and all causes of mortality, as well as complications, including ascites, hepatic encephalopathy (HE) and portosystemic shunts (PSS) in CLD.
Methods Serum ZAG levels were measured in 180 CLD patients upon hospital admission. The associations of ZAG levels with the liver functional reserve and clinical parameters were investigated using a multiple regression analysis. Kaplan-Meier analyses were performed to evaluate the associations of the ZAG/creatinine ratio (ZAG/Cr) and prognostic factors with mortality.
Results High serum ZAG levels were associated with preserving the liver function and renal insufficiency. A multiple regression analysis showed that the estimated glomerular filtration rate (p<0.0001), albumin-bilirubin (ALBI) score (p=0.0018) and subcutaneous fat area (p=0.0023) had a significant independent correlation with serum ZAG levels. Serum ZAG levels were elevated in the absence of HE (p=0.0023) and PSS (p=0.0003). In all patients and those without hepatocellular carcinoma (HCC), the cumulative mortality rate was significantly decreased in patients with a high ZAG/Cr compared with those with a low ZAG/Cr (p=0.0018 and p=0.0002, respectively). The ZAG/Cr, presence of HCC, ALBI score and psoas muscle index were independent predictors of the prognosis in CLD patients.
Conclusion Serum ZAG levels are associated with the hepatorenal function and can be used to predict the survival in CLD patients.
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Noriyuki Kounoue, Hideyo Oguchi, Tetuo Mikami, Yutaka Yamaguchi, Akino ...
Article ID: 1515-22
Published: 2023
Advance online publication: May 24, 2023
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A man who was an inactive HBV carrier with positive HBs antigen and undetectable HBV-DNA under anti-viral treatment developed nephrotic syndrome at 52 years old, and a renal biopsy revealed advanced membranous nephropathy (MN) with focal cellular crescents, interstitial hemorrhaging, and peritubular capillaritis. Immunofluorescence studies demonstrated granular IgG deposition and hepatitis B surface antigen-positivity along the capillaries. Glomeruli were negative for phospholipase A2 receptor 1. There were no clinical findings of systemic vasculitis. We considered MN combined with small-vessel vasculitis due to HBV infection. These results suggest that HBV-related kidney disease should be considered even in patients with an inactive HBV carrier status under treatment.
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Masaya Toyoshima, Naoki Suzuki, Shio Mitsuzawa, Temma Soga, Rumiko Izu ...
Article ID: 1574-23
Published: 2023
Advance online publication: May 24, 2023
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The patient was 57 years old when he was diagnosed with amyotrophic lateral sclerosis (ALS) at 1 year after developing bulbar symptoms. At 58 years old, he stated that he was considering donating his kidney to his son suffering from diabetic nephropathy. We confirmed the patient's intentions through repeated interviews before his death at 61 years old. Nephrectomy was performed 30 min after his cardiac death. Organ donation spontaneously proposed by an ALS patient should be considered in order to meet the requests of patients who want their families and other patients to live longer, thereby imparting a beneficial legacy through their deaths.
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Kyoko Gocho, Aya Yamashita, Noboru Iizuka, Kenya Sato, Keisuke Imasaka ...
Article ID: 1638-23
Published: 2023
Advance online publication: May 24, 2023
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Cytomegalovirus infection is typically asymptomatic in immunocompetent individuals. A 26-year-old woman was admitted to our hospital with a fever and breathlessness. Chest computed tomography (CT) revealed bilateral diffuse reticulation and nodules. Laboratory investigations showed atypical lymphocytosis and increased transaminases. She was treated with corticosteroid pulse therapy because of acute lung injury, and her clinical condition improved. Based on the presence of Cytomegalovirus antibodies, antigen, and polymerase chain reaction findings, she was diagnosed with primary Cytomegalovirus pneumonia and treated with valganciclovir. Primary Cytomegalovirus pneumonia is very rare in immunocompetent individuals. The efficacy of corticosteroid and valganciclovir against Cytomegalovirus pneumonia in this patient is noteworthy.
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Masato Kono, Yuiko Oshima, Megumi Katsumata, Ryutaro Hirama, Kenichiro ...
Article ID: 1663-23
Published: 2023
Advance online publication: May 24, 2023
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A 48-year-old woman was admitted to our hospital with acute respiratory failure. Chest computed tomography showed ground-glass opacity and patchy emphysematous lesions in both lungs. Corticosteroid therapy was effective; however, the disease worsened with the tapering of corticosteroids. Bronchoalveolar lavage revealed hemosiderin-laden macrophages, and video-assisted thoracic surgery showed diffuse interstitial fibrosis with diffuse alveolar hemorrhage (DAH). There was no evidence of vasculitis nor autoimmune diseases. This patient was diagnosed with idiopathic pulmonary hemosiderosis (IPH) that progressed to end-stage pulmonary fibrosis despite treatment. Autopsy demonstrated DAH with pulmonary fibrosis and emphysematous change, suggesting IPH-related pulmonary lesions.
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Naoto Imoto, Yuka Kondo, Kazuho Uchida, Shingo Kurahashi
Article ID: 1697-23
Published: 2023
Advance online publication: May 24, 2023
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Objective Several institutions outsource CD34+ cell counting of leukapheresis products, limiting rapid measurements, as results are obtained the next day. This problem is compounded with plerixafor use, a stem cell-mobilizing drug that increases leukapheresis efficiency but requires administration the day before leukapheresis. Use of this drug for a second leukapheresis procedure before the first-day leukapheresis CD34+ count results are confirmed causes unnecessary leukapheresis and expensive plerixafor administration. We investigated whether or not measuring hematopoietic progenitor cells in leukapheresis products (AP-HPCs) using a Sysmex XN-series analyzer could resolve this problem.
Patients and methods We retrospectively compared the absolute AP-HPC value per body weight with the CD34+ (AP-CD34+) count in 96 first-day leukapheresis product samples obtained between September 2013 and January 2021. Comparisons were also conducted according to regimen: granulocyte colony-stimulating factor (G-CSF) monotherapy, chemotherapy plus G-CSF, or plerixafor mobilization.
Results AP-CD34+ and AP-HPC counts correlated strongly (rs =0.846) overall and, in particular, under chemotherapy plus G-CSF (rs =0.92) but correlated mildly under G-CSF monotherapy (rs =0.655). AP-HPCs could not completely be dichotomized based on an AP-CD34+ threshold of 2×106/kg for any stimulation procedure. In most cases with AP-HPCs >6×106/kg, the AP-CD34+ count exceeded 2.0×106/kg, but in 5.7% of these cases, the AP-CD34+ count was <2.0×106/kg. A cut-off of AP-HPCs >4.843×106/kg yielded a sensitivity of 71% and specificity of 96% for predicting AP-CD34+≥2×106/kg.
Conclusion AP-HPCs can identify cases in which sufficient stem cells have been collected.
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Masahiro Ogasawara, Rintaro Nozu, Kosuke Miki, Shunnsuke Sugimura, Kei ...
Article ID: 1714-23
Published: 2023
Advance online publication: May 24, 2023
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Objective The prognosis of the patients who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poor, and therapeutic options are limited. In the present study, we investigated the efficacy and factors associated with the survival in patients with acute leukemia or myelodysplastic syndrome (MDS) who relapsed following allo-HSCT and were treated with donor lymphocyte infusion (DLI) in real-world practice.
Patients Twenty-nine patients with acute myeloid leukemia21, acute lymphoid leukemia4 or MDS4 were enrolled. Eleven patients were diagnosed with hematological relapse, and 18 were diagnosed with molecular or cytogenetic relapse.
Results The median injection number and median total number of infused CD3+ T cells were 2 and 5.0×107/kg, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) of grade ≥II at 4 months after the initiation of DLI was 31.0%. Extensive chronic graft-versus-host disease (cGVHD) occurred in 3 (10.3%) patients. The overall response rate was 51.7%, including 3 cases of hematological complete remission (CR) and 12 cases of molecular/cytogenetic CR. Cumulative relapse rates at 24 and 60 months following DLI in patients who achieved CR were 21.4% and 30.0%, respectively. The overall survival rates at 1, 2 and 3 years after DLI were 41.4%, 37.9% and 30.3%, respectively. Molecular/cytogenetic relapse, a longer interval from HSCT to relapse, and concomitant chemotherapy with 5-azacytidine were significantly associated with a relatively long survival following DLI.
Conclusion These results indicated that DLI was beneficial for patients with acute leukemia or MDS who relapsed after allo-HSCT and suggested that DLI in combination with Aza for molecular or cytogenetic relapse might result in favorable outcomes.
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Shizuka Watanabe, Maho Suzukawa, Hiroyuki Tashimo, Nobuharu Ohshima, I ...
Article ID: 1808-23
Published: 2023
Advance online publication: May 24, 2023
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Objective Dupilumab, a monoclonal antibody specific for the human interleukin (IL)-4 receptor α, is used to treat severe asthma, especially in patients with elevated blood eosinophil counts and fractional exhaled nitric oxide (FeNO). The therapeutic response to dupilumab is highly variable. In this study, we explored new serum biomarkers to accurately predict the effect of dupilumab and examine the effect of dupilumab based on changes in the clinical parameters and cytokine levels.
Patients and Methods Seventeen patients with severe asthma treated with dupilumab were enrolled. Responders, defined as those with a >0.5-point decrease in the Asthma Control Questionnaire (ACQ) score after 6 months of treatment, were included.
Results There were 10 responders and 7 non-responders. Serum type 2 cytokines were equivalent between responders and non-responders; the baseline serum interleukin (IL)-18 level was significantly lower in responders than in non-responders (responders, 194.9±51.0 pg/mL; non-responders, 323.4±122.7 pg/mL, p =0.013). The cut-off value of IL-18 at 230.5 pg/mL could be used to distinguish non-responders from responders (sensitivity 71.4, specificity 80.0, p =0.032).
Conclusions A low baseline serum IL-18 level may be a useful predictor of an unfavorable response to dupilumab in terms of the ACQ6.
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Motohisa Yamamoto, Tomonao Tanaka, Satsuki Aochi, Masaaki Uehara
Article ID: 1847-23
Published: 2023
Advance online publication: May 24, 2023
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Objectives Glucocorticoids are key drugs used in remission induction therapy for IgG4-related disease (IgG4-RD). However, the therapeutic outcomes vary widely, with some patients requiring long-term maintenance therapy and others relapsing repeatedly, whereas still others can tolerate withdrawal. These variations underscore the need for personalized treatment strategies for IgG4-RD. We examined the relationship between human leukocyte antigen (HLA) genotypes and the response to glucocorticoid treatment in patients with IgG4-RD.
Methods Eighteen IgG4-RD patients visiting our hospital were included in the study. Peripheral blood samples were collected, HLA genotypes were determined, and the response to glucocorticoid treatment (maintenance dose at the time of last observation, glucocorticoid dose when the serum IgG4 level was the lowest after remission induction therapy, and occurrence of relapse) was examined retrospectively.
Results The DQB1*12:01 genotypes were associated with a prednisolone maintenance dose of <7 mg/day. A prednisolone dose ≥10 mg with a minimum serum IgG4 level was significantly more common in B*40:01 and DRB1-GB-7-Val (DRB1*04:01, *04:03, *04:05, *04:06, and *04:10) patients than other alleles. Relapse also tended to be more common in DRB1-GB-7-Val carriers than other alleles.
Conclusion These data suggest that HLA-DRB1 is associated with glucocorticoid treatment responsiveness and is important for follow-up monitoring of serum IgG4 levels during glucocorticoid tapering. We believe that these data will contribute to the future development of personalized medicine for IgG4-RD.
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Yuki Ito, Kentaro Yoshioka, Kazuhiko Hayashi, Yuko Shimizu, Ryo Fujimo ...
Article ID: 1861-23
Published: 2023
Advance online publication: May 24, 2023
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Aim To assess the prevalence and clinical correlates of non-alcoholic fatty liver disease (NAFLD) identified by computed tomography (CT) in the general population compared with ultrasonography (US).
Methods Four hundred and fifty-eight subjects who received health checkups at Meijo Hospital in 2021 and underwent CT within a year of US in the past decade were analyzed. The mean age was 52.3±10.1 years old, and 304 were men.
Results NAFLD was diagnosed in 20.3% by CT and in 40.4% by the US. The NAFLD prevalence in men was considerably greater in subjects 40-59 years old than in those ≤39 years old and in those ≥60 years old by both CT and US. The NAFLD prevalence in women was substantially higher in the subjects 50-59 years old than in those ≤49 years old or those ≥60 years old on US, while no significant differences were observed on CT. The abdominal circumference, hemoglobin value, high-density lipoprotein cholesterol level, albumin level, and diabetes mellitus were independent predictors of NAFLD diagnosed by CT. The body mass index, abdominal circumference, and triglyceride level were independent predictors of NAFLD diagnosed by the US.
Conclusion NAFLD was found in 20.3% of CT cases and 40.4% of US cases among recipients of health checkups. An "inverted U curve" in which the NAFLD prevalence rose with age and dropped in late adulthood was reported. NAFLD was associated with obesity, the lipid profile, diabetes mellitus, hemoglobin values, and albumin levels. Our research is the first in the world to compare the NAFLD prevalence in the general population simultaneously by CT and US.
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Takahito Ota, Hiroki Suzuki, Yoshinori Kawabata, Toshihiko Hino, Naoki ...
Article ID: 1875-23
Published: 2023
Advance online publication: May 24, 2023
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We herein report a case of polyclonal hyperglobulinemia with multiple pulmonary cysts and nodules. The histopathological findings allowed us to speculate about the mechanism underlying cyst formation in these pathological conditions, which has not yet been thoroughly elucidated. The patient was a 49-year-old woman who presented with multiple pulmonary multilocular cysts and nodules. A lung biopsy revealed features of nodular lymphoid hyperplasia. Notably, lung structure fragmentation was evident, suggesting that structural destruction may have accompanied the disease during its course. The cysts were considered to have formed due to destruction of the lung structures.
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Naoki Takegami, Masashi Hamada, Nanaka Yamaguchi-Takegami, Kaori Sakui ...
Article ID: 1883-23
Published: 2023
Advance online publication: May 24, 2023
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Charcot-Marie-Tooth (CMT) disease is a heterogeneous hereditary motor and sensory neuropathy of the peripheral nervous system, with CMT1A in particular being the most common form. We encountered a 76-year-old woman with CMT1A who had a history of pain attacks and hearing loss from a young age, with motor symptoms manifesting late in life. Her pain and hearing loss may have been related to CMT. Our case also raises the possibility that neuropathic pain and hearing loss may precede the classic motor symptoms of CMT1A.
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Hideo Kihara, Shingo Konno, Takahumi Uchi, Jun Isonishi, Hideki Sugimo ...
Article ID: 1942-23
Published: 2023
Advance online publication: May 24, 2023
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Encephalitis caused by antibodies targeting the leucine-rich glioma-inactivated 1 protein receptor, which belongs to the anti-voltage-gated potassium channel receptor complex, is characterized by hyponatremia, progressive cognitive impairment, seizures, and psychiatric disorders. The patient initially presented with faciobrachial dystonic seizures and subsequently developed encephalopathy. Brain MRI revealed atypical unilateral hyperintense signals in the cerebral cortex and white matter. Intravenous corticosteroid pulse therapy effectively improved faciobrachial dystonic seizures and brain lesions.
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Yoshikazu Motomura, Kei Nakashima, Shunsuke Harada, Kentaro Tochigi, H ...
Article ID: 1240-22
Published: 2023
Advance online publication: May 17, 2023
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An 83-year-old man presented with chronic dyspnea, and chest X-ray showed bilateral pleural effusion. Right thoracentesis revealed lymphocyte-predominant exudate with no malignancy; bacterial and mycobacterial cultures were negative. Thoracoscopy via the right chest and a biopsy of the same site were performed; these showed lymphoplasmacytic infiltration and fibrosis, ruling out malignancy or tuberculosis. We decided to start corticosteroid therapy for the diagnosis of idiopathic lymphocytic pleuritis (ILP). The patient was discharged after clinical improvement, and steroids were tapered off. An early diagnosis by thoracoscopy and the exclusion of other diseases are important for initiating steroid therapy in patients with ILP.
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Masanari Asai, Masayoshi Kiyokuni, Kazuho Ishii, Yuuna Kine, Yu Yamada ...
Article ID: 1491-22
Published: 2023
Advance online publication: May 17, 2023
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A 62-year-old male was transferred to our hospital complaining of palpitations. His heart rate was 185/min. Electrocardiogram showed a narrow QRS regular tachycardia and the tachycardia changed spontaneously to another narrow QRS tachycardia with two alternating cycle lengths. The arrhythmia was stopped by the administration of adenosine triphosphate. Findings from electrophysiological study suggested that there was an accessory pathway (AP) and dual atrioventricular (AV) nodal pathways. After AP ablation, any other tachyarrythmias were not induced. We supposed that the tachycardia was paroxysmal supraventricular tachycardia involving AP and anterograde conduction alternating between slow and fast AV nodal pathways.
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Yusuke Saishoji, Keisuke Mori, Yasumori Izumi
Article ID: 1563-23
Published: 2023
Advance online publication: May 17, 2023
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Sternoclavicular septic arthritis is a rare form of septic arthritis that can lead to fatal complications, such as abscess formation and mediastinitis, in the absence of prompt diagnosis and appropriate treatment. A man in his 40s presented with pain in the right sternoclavicular joint area, and after a joint injection of steroids was administered, he was diagnosed with septic sternoclavicular arthritis caused by Parvimonas micra and Fusobacterium nucleatum. Gram staining of a specimen obtained from the abscess formation area led to early suspicion of anaerobic infection, and appropriate antibiotics were administered.
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Kenshiro Kojo, Toru Morikawa, Tomoko Kikawa, Kantaro Sasaki, Yasuhiro ...
Article ID: 1569-23
Published: 2023
Advance online publication: May 17, 2023
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We herein report a complicated case of recurrent syncope accompanying bundle branch block and hiatal hernia of the esophagus. An 83-year-old woman presented with syncope. Echocardiography visualized the left atrium compressed by an esophageal hiatal hernia, which had potential to decrease the cardiac output. Although she underwent esophageal repair surgery, two months after the surgery, she presented to the emergency department again with complaints of syncope. At the return visit, her face was pale and her pulse rate was 30 beats per minute. Electrocardiography showed complete atrioventricular block. On reviewing the patient's previous electrocardiography findings, we found a record of trifascicular block. This case illustrates the importance of predicting atrioventricular blocks in patients with high-risk bundle-branch blocks. Keeping in mind high-risk bundle-branch blocks will help clinicians avoid anchoring bias due to a striking image masquerading as the true diagnosis.
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Eiko Kawakami, Tomohisa Uchida, Naoki Iwamoto, Kazusato Hara, Kazuhiro ...
Article ID: 1621-23
Published: 2023
Advance online publication: May 17, 2023
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We herein report a case of melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis that developed in a patient with refractory gingivitis. The diagnosis of anti-MDA5 antibody-positive dermatomyositis was made based on a characteristic skin rash, weakness of proximal muscles, interstitial pneumonia, and positivity for anti-MDA5 antibody. The patient was started on triple therapy with high-dose prednisolone, tacrolimus, and intravenous cyclophosphamide. After treatment, the refractory gingivitis disappeared, and the other skin rash and interstitial lung disease also improved. In the diagnosis and treatment of anti-MDA5 antibody-positive dermatomyositis, it is necessary to pay attention to the intraoral findings, including the gingiva.
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Takashi Aikawa, Takuro Yamada, Tomohiro Iida
Article ID: 1674-23
Published: 2023
Advance online publication: May 17, 2023
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A 78-year-old man was admitted to our hospital with obstructive shock caused by a large hiatal hernia that occupied the posterior mediastinum. Tension gastro-duodenothorax was detected in his stomach and duodenum, and we performed urgent endoscopy to relieve shock. Large hiatal hernia occasionally leads to cardiac failure. This is the first reported use of urgent endoscopy to treat a large hiatal hernia.
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Noriyuki Imazu, Takehiro Torisu, Yutaro Ihara, Junji Umeno, Keisuke Ka ...
Article ID: 1724-23
Published: 2023
Advance online publication: May 17, 2023
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Objective T helper (Th) cells play a central role in the pathogenesis of ulcerative colitis (UC). The present study analyzed the changes in circulating T cells by administration of ustekinumab (UST), an interleukin-12/23p40 antibody.
Methods CD4 T cells were isolated from peripheral blood at 0 and 8 weeks after UST treatment, and we analyzed the proportion of CD4 T cells by flow cytometry. Clinical information and laboratory data were obtained at 0, 8, and 16 weeks.
Patients We evaluated 13 patients with UC who received UST for the induction of remission between July 2020 and August 2021.
Results The median partial Mayo score improved from 4 (1-7) to 0 (0-6) (p<0.001) with UST. Among serological parameters, albumin concentrations, C-reactive protein concentrations, the sedimentation rate, and leucine-rich alpha 2 glycoprotein concentrations showed significant improvement with UST. A flow cytometric analysis of circulating CD4 T cells showed that the percentage of Th17 cells was significantly decreased by UST treatment in all patients (1.85% to 0.98%, p<0.0001). Th1 cells were significantly increased by UST treatment (9.52% to 10.4%, p<0.05), but Th2 and regulatory T cells were not significantly different. The high-Th17 subgroup had a significantly better partial Mayo score than the low-Th17 subgroup at 16 weeks after UST treatment (0 vs. 1, p=0.028).
Conclusion Treatment with UST decreases circulating Th17 cells, suggesting that this change may be related to the anti-inflammatory effect of UC.
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Nobuo Sanjo, Motohiro Suzuki, Rei Yoshihama, Yasuko Toyoshima, Ikuko M ...
Article ID: 1726-23
Published: 2023
Advance online publication: May 17, 2023
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A 57-year-old man whose mother had been pathologically diagnosed with Alexander disease (ALXDRD), presented with cerebellar ataxia, pyramidal signs, and mild dysarthria. Brain magnetic resonance imaging revealed typical ALXDRD alterations, such as atrophy of the medulla oblongata (MO) and cervical spinal cord, a reduced sagittal diameter of the MO, and garland-like hyperintensity signals along the lateral ventricular walls. A genetic analysis of GFAP by Sanger sequencing revealed a single heterozygous mutation of Glu to Lys at codon 332 (c.994G>A) in the GFAP gene. Our results newly confirmed that p.E332K alone is the pathogenic causative mutation for adult-onset ALXDRD.
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Yuki Doi, Naoya Kataoka, Teruhiko Imamura
Article ID: 1791-23
Published: 2023
Advance online publication: May 17, 2023
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Akito Setoguchi, Hiroaki Kawano, Shinji Okano, Tomohiro Honda, Takehar ...
Article ID: 1809-23
Published: 2023
Advance online publication: May 17, 2023
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A 24-year-old man was admitted to our hospital because of severe heart failure. Although he was treated with diuretics and positive inotropic agents, his heart failure progressed. An endomyocardial biopsy revealed iron deposition in his myocytes. Finally, he was diagnosed with hereditary hemochromatosis. After starting administration of an iron-chelating agent in addition to conventional treatment for heart failure, his condition improved. We should consider hemochromatosis in heart failure patients with severe right ventricular dysfunction in addition to left ventricular dysfunction.
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Kei Moriya, Keigo Saeki, Norihisa Nishimura, Shinya Sato, Yasuhiko Saw ...
Article ID: 1817-23
Published: 2023
Advance online publication: May 17, 2023
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Background and Aims Patients with autoimmune hepatitis (AIH) reportedly have an impaired quality of life (QOL), mainly due to depression, even during remission. In addition, hypozincaemia has been demonstrated in patients with chronic liver disease, including AIH, and is known to be related to depression. Corticosteroids are known to cause mental instability. We therefore investigated the longitudinal association between zinc supplementation and changes in the mental status among AIH patients treated with corticosteroids.
Patients and Methods This study enrolled 26 patients with serological remission of AIH routinely treated at our facility after excluding 15 patients who either discontinued polaprezinc (150 mg/day) within 24 months or interrupted treatment. Two questionnaires, the Chronic Liver Disease Questionnaire (CLDQ) and SF-36, were adopted to evaluate the QOL before and after zinc supplementation.
Results Serum zinc levels were significantly elevated after zinc supplementation (P <0.0001). The CLDQ worry subscale significantly improved after zinc supplementation (P = 0.017), but none of the SF-36 subscales was affected. Multivariate analyses demonstrated that daily prednisolone dosing was inversely related to both the CLDQ worry domain score (P = 0.036) and the SF-36 mental health component (P = 0.031). There was a significant negative correlation between the changes in the daily steroid dose and the CLDQ worry domain scores before and after zinc supplementation (P = 0.006). No serious adverse events occurred during the observation period.
Conclusions Zinc supplementation safely and efficiently improved mental impairment, possibly caused by continuous treatment with corticosteroids, in patients with AIH.
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Ryo Yano, Masashi Hirooka, Makoto Morita, Yuki Okazaki, Yoshiko Nakamu ...
Article ID: 1844-23
Published: 2023
Advance online publication: May 17, 2023
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We herein report a 63-year-old man who presented with left lower jaw pain and was diagnosed with hepatocellular carcinoma with bone metastases post-examination. All tumors grew after immunotherapy with atezolizumab and bevacizumab, and his jaw pain worsened. After palliative radiation therapy, however, the tumors shrank markedly, with no recurrence seen after stopping immunotherapy. To our knowledge, this is the first case in which a radiotherapy- and immunotherapy-mediated abscopal effect facilitated tumor shrinkage and immunotherapy discontinuation.
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Seongdae Kim, Sanghee Lee, Dongsun Han, Ilgyu Jeong, Hee-Hyuk Lee, Yun ...
Article ID: 1957-23
Published: 2023
Advance online publication: May 17, 2023
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Takahide Okamoto, Akemi Ito
Article ID: 0451-22
Published: 2023
Advance online publication: May 10, 2023
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Objective Gastroesophageal reflux disease (GERD), including reflux esophagitis (RE), is recognized as a common gastrointestinal disease, and its prevalence is reported to be increasing. While current cigarette smoking has been established as a risk factor for RE in several cross-sectional studies, most of these studies did not include details concerning the smoking status in their analyses. Smoking-related conditions, such as chronic lung disease and cough, are reportedly also related to GERD.
Methods To investigate the association between RE and detailed smoking habits, we performed a cross-sectional analysis of healthy men enrolled in a comprehensive health checkup program conducted in 2015 that included esophago-gastro-duodenoscopy. Smoking status was assessed using a self-reported questionnaire. Other smoking-related parameters, including the lung function, cough symptoms and presence of chronic lung disease, were also assessed. Unconditional logistic regression was applied to calculate the odds ratio (OR) with 95% confidence intervals (CIs) after adjusting for confounding factors.
Results The study included 151 subjects with RE (RE group) and 814 without RE (control group). Compared with never-smokers, former smokers (OR, 1.5; 95% CI, 0.9-2.9) and current smokers (OR, 2.4; 95% CI, 1.5-3.9) showed an increased risk of RE. An increased risk of RE was also observed among subjects with current smoking for 10-20 PYs and more than 20 PYs (OR, 2.8; 95% CI, 1.4-5.8, OR, 3.1; 95% CI, 1.6-5.7 respectively). An elevated risk was observed in former smokers who reported more than 20 PYs (OR, 2.5; 95% CI, 1.3-4.8). When former smokers were stratified according to time since smoking cessation, a significant RE risk was observed in participants who had stopped smoking less than 10 years earlier compared with never smokers (OR, 1.9; 95% CI, 1.1-3.3). No significant associations were observed between chronic cough, FEV1.0%, and RE.
Conclusion Cumulative lifetime exposure to smoking plays an important role in the risk of RE.
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Taito Miyake, Hajime Sanada, Takahiro Yamano, Kaori Yamaguchi
Article ID: 1040-22
Published: 2023
Advance online publication: May 10, 2023
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Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) predominantly affects small vessels. Almost all AAV patients are positive for myeloperoxidase- or proteinase 3-ANCA, and ANCA plays a crucial role in the pathogenesis of AAV. We herein report an ANCA-negative AAV patient with pauci-immune necrotizing glomerulonephritis and plasma cell-rich tubulointerstitial nephritis who was complicated with pleuritis and digital ischemia. ANCA-negative AAV is a rare clinical entity that is difficult to diagnose, and pleuritis and digital ischemia are rare manifestations of AAV. An early diagnosis and appropriate treatment are important, as any delay in the diagnosis may worsen the prognosis.
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Yasuhiro Oda, Kunihiro Ishioka, Takayasu Ohtake, Rikako Oki, Shinya Ta ...
Article ID: 1095-22
Published: 2023
Advance online publication: May 10, 2023
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A 74-year-old woman with a 34-year history of hemodialysis presented with an intermittent fever, which later coincided with recurrent bilateral shoulder and hip joint pain. Imaging studies suggested amyloid arthropathy, which was histologically confirmed by a synovial biopsy. Increasing β2-microglobulin clearance during dialysis alone attenuated the intermittent fever and joint pain, but the symptoms did not disappear until the administration of prednisolone 10 mg/day. Reported cases of dialysis-related amyloidosis with a fever imply that changing to blood purification methods with high β2-microglobulin clearance is crucial for controlling the condition long-term, whereas concurrent use of anti-inflammatory agents promptly alleviates the symptoms.
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Kaori Nagao, Masato Kadoya, Yukie Shimizu, Nami Murahara, Hiroko Fujii ...
Article ID: 1344-22
Published: 2023
Advance online publication: May 10, 2023
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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.
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Yuki Sakurai, Yoshitaka Furuto, Takahiro Saito, Akio Namikawa, Hiroko ...
Article ID: 1413-22
Published: 2023
Advance online publication: May 10, 2023
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A 79-year-old man experienced a fever and immobility after receiving 6 doses of Bacillus Calmette-Guerin (BCG) intravesical instillation therapy for bladder tumor. Rhabdomyolysis and acute kidney injury occurred; therefore, hemodialysis was performed. His kidney function was restored. However, he exhibited an inflammatory reaction that was resistant to broad-spectrum antibiotics and eventually developed interstitial pneumonia. Corticosteroid treatment partially relieved the symptoms of interstitial pneumonia, although disuse syndrome persisted. He was diagnosed with disseminated BCG infection through sputum culture. BCG infection shows various symptoms and is difficult to diagnose microbiologically. It should be suspected when systemic symptoms occur after BCG intravesical instillation therapy.
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Atsushi Yanagisawa, Yuhei Kinehara, Masaki Tanaka, Ryusuke Ninomiya, M ...
Article ID: 1520-22
Published: 2023
Advance online publication: May 10, 2023
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A 39-year-old vegan man was admitted with diabetic ketoacidosis. He had also developed pneumonia that was unresponsive to antibiotics. Based on bronchoscopy findings, the diagnosis of Candida pneumonia was made, and the pulmonary shadow disappeared rapidly after antifungal therapy. Candida pneumonia has been mostly reported in severely immunocompromised patients. This is a rare case of Candida pneumonia that was found in a young vegan man with diabetes mellitus (DM). Although malnutrition caused by DM or an unbalanced diet is often underestimated as a cause of immunodeficiency, these conditions can be risk factors for serious opportunistic infections, including Candida pneumonia.
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Mariko Yamauchi, Sahoko Kamejima, Risa Ueda, Akio Nakashima, Fumihiko ...
Article ID: 1523-22
Published: 2023
Advance online publication: May 10, 2023
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A 58-year-old woman was admitted to our hospital. At 10 years old, she had undergone bilateral uretero-sigmoid anastomosis for congenital epispadias, and at 57 years old, she had received transverse colostomy. Biochemical tests showed marked metabolic acidosis. Computed tomography showed urine stagnation in the sigmoid colon, leading to a diagnosis of metabolic acidosis associated with transverse stoma after bilateral uretero-sigmoid anastomosis. Her bone mineral density was below normal, and the bone metabolic marker levels were high, indicating high-turnover osteoporosis. Both metabolic acidosis and bone metabolism were stabilized by treatment with a transanal urinary catheter, sodium bicarbonate, and vitamin D.
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Atsushi Yanagisawa, Takayuki Takimoto, Ryota Shintani, Takehiko Kobaya ...
Article ID: 1592-23
Published: 2023
Advance online publication: May 10, 2023
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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.
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Yoshiki Morihisa, Shunji Urai, Hiroyoshi Iwagami, Masayuki Shimoyama, ...
Article ID: 1593-23
Published: 2023
Advance online publication: May 10, 2023
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We herein report a rare case of primary retroperitoneal mucinous cystadenocarcinoma (PRMC) in a 60-year-old man. The patient, who had been treated with infliximab for Crohn's disease of the colon for 13 years, was referred to our hospital for lower back pain. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging revealed multiple cystic lesions in the right retroperitoneum, the calcification of the cyst, and bone lesions. Bone and CT-assisted biopsies of the retroperitoneal lesions revealed poorly differentiated adenocarcinoma. The patient was diagnosed with PRMC with bone metastases using immunohistochemical staining and positron emission tomography/CT.
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Yusuke Shimada, Rie Ohtomo, Hiroaki Hayashi, Yasuhiro Suyama
Article ID: 1608-23
Published: 2023
Advance online publication: May 10, 2023
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Hiroki Teragawa, Ayaka Shirai, Chikage Oshita, Yuko Uchimura
Article ID: 1616-23
Published: 2023
Advance online publication: May 10, 2023
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A 46-year-old man presented to our hospital with chest pain followed by coughing and dyspnea. His myocardial enzyme levels were almost normal, and electrocardiography and echocardiography showed no obvious abnormalities. Chest radiography revealed congestion. He was diagnosed with heart failure with a preserved ejection fraction (HFpEF). Although subjective symptoms improved with intravenous diuretics, the patient was admitted to the hospital for a close examination. Coronary angiography showed no obvious stenosis, and a subsequent spasm provocation test demonstrated the presence of multi-vessel and diffuse spasms. Coronary spasm should be considered as a differential cause of heart failure, even in patients with HFpEF.
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Moeko Omiya, Takaaki Murata, Akira Sawaki, Shinichi Teshima, Jun Kawac ...
Article ID: 1629-23
Published: 2023
Advance online publication: May 10, 2023
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A 79-year-old woman was diagnosed with transverse colon cancer, moderately differentiated adenocarcinoma. She underwent surgery and postoperative adjuvant chemotherapy. At 80 years old, the patient exhibited changes in skin tone at the chest and abdomen with CK7+/CK20-/CDX2- immunostaining that was later identified as poorly differentiated adenocarcinoma. The diagnosis was cancer of unknown primary origin. The patient passed away three months after the detection of the skin lesion. Autopsy revealed recurrence at the transverse colon, multiple organ metastases, a similar postmortem immunostaining pattern, and high-frequency microsatellite instability (MSI-high). We herein report this case of CK7+/CK20-/CDX2- and MSI-high transverse colon cancer showing cutaneous metastasis.
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Tatsuya Ueno, Kensuke Murakami, Akira Arai, Masahiko Tomiyama
Article ID: 1655-23
Published: 2023
Advance online publication: May 10, 2023
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Hideaki Yamakawa, Akiko Adachi, Masako Amano, Hidekazu Matsushima
Article ID: 1708-23
Published: 2023
Advance online publication: May 10, 2023
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Yosuke Ohashi, Keisuke Iwata, Tsuyoshi Mukai, Yuhei Iwasa, Mitsuru Oku ...
Article ID: 1783-23
Published: 2023
Advance online publication: May 10, 2023
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A 59-year-old man receiving sunitinib chemotherapy for postoperative recurrence of renal cell carcinoma (RCC) metastases was found to have multiple metastases on contrast-enhanced computed tomography (CECT). CECT revealed a typical hyperdense enhanced nodule in the arterial phase of the stomach and head and tail of the pancreas. However, in the uncinate process of the pancreas, CECT revealed an atypical image and a hypodense enhanced nodule in each phase. Both lesions were finally pathologically diagnosed as clear cell carcinoma. Treatment-modified pancreatic metastases from RCC may present with nonspecific images; therefore, caution is required when deciding on treatment strategies.
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Takuhide Utsunomiya, Yoshiaki Kinoshita, Masayo Yoshimura, Yohei Koide ...
Article ID: 1802-23
Published: 2023
Advance online publication: May 10, 2023
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A 70-year-old man who smoked was referred to our hospital because of progressive cough and dyspnea. Radiologic images showed ground-glass attenuation predominantly in the lower lung lobes. A surgical lung biopsy was performed, and a diagnosis of desquamative interstitial pneumonia (DIP) was made. The patient's symptoms improved with smoking cessation and steroid treatment, but the ground-glass attenuation did not completely resolve. At 10 years after the diagnosis, the fibrotic lesions deteriorated and treatment with nintedanib was subsequently initiated. Careful observation is needed in patients with DIP whose lung involvement does not completely improve with initial treatment.
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Kiyoshi Takemoto, Kazuaki Atagi
Article ID: 1816-23
Published: 2023
Advance online publication: May 10, 2023
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Fumitaka Mizuno, Norihiro Imai, Kazushi Yasuda, Shinya Yokoyama, Kenta ...
Article ID: 1826-23
Published: 2023
Advance online publication: May 10, 2023
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Vanishing bile duct syndrome (VBDS) is a rare but potentially serious cholestatic liver disease caused by various etiologies, including drugs. We herein report a complicated case of VBDS with acute tubular necrosis (ATN) that improved significantly with steroid treatment. An Asian man in his 30s was admitted with the acute onset of severe jaundice and a decline in the renal function. Although initial treatment with ursodeoxycholic acid did not reduce jaundice or renal dysfunction, steroid treatment remarkably improved the VBDS and ATN to within the respective normal ranges. Steroid treatment can be considered in cases of VBDS that appear to have an immune-mediated cause.
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Hideaki Miyamoto, Fumi Kawakami, Sakiko Abe, Hiroki Sugita, Hirotaka M ...
Article ID: 1845-23
Published: 2023
Advance online publication: May 10, 2023
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Comprehensive genomic profiling (CGP) of a metastatic liver tumor biopsy specimen suggested that the patient, who was initially diagnosed with cholangiocarcinoma, had colorectal cancer. The identification of both FBXW7 and APC mutations is deemed characteristic of colorectal cancer. Indeed, subsequent colonoscopy revealed sigmoid colon carcinoma that led to tumor resection followed by systemic chemotherapy. CGP is principally used to identify agents that might potentially benefit the patient. However, results must be interpreted carefully to ensure consistency with the initial diagnosis.
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