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Shuichiro Matsumoto, Manabu Suzuki, Sachi Matsubayashi, Akinari Tsukada, Yusaku Kusaba, Takashi Katsuno, Motoyasu Iikura, Shinyu Izumi, Yuichiro Takeda, Masayuki Hojo, et al.
Internal Medicine, Volume 60, pp 3279-3284;

We herein report a 48-year-old man with a history of chronic atrial fibrillation (AF) and repeated hemoptysis after radiofrequency ablation. Contrast tomography showed soft tissue thickening of the left hilar region and left pulmonary vein stenosis. We performed bronchial artery embolization, but the hemoptysis did not disappear, and AF was not controlled. We performed left lung lobectomy and maze procedures since we considered surgical removal necessary as radical treatment. After the surgery, hemoptysis and atrial fibrillation did not recur. Refractory hemoptysis after catheter ablation is rare, but occasionally occurs in patients with severe pulmonary vein stenosis.
Tatsuya Suwabe, Masahiko Oguro, Yoshifumi Ubara, Daisuke Ikuma, Hiroki Mizuno, Noriko Hayami, Masayuki Yamanouchi, Naoki Sawa
Internal Medicine, Volume 60, pp 3261-3265;

Renal cyst infection is a frequent and serious complication of autosomal dominant polycystic kidney disease (ADPKD) that is often difficult to treat and can be fatal. While nephrectomy is the standard therapy for severe refractory renal cyst infection, it can be associated with severe adverse events. We experienced a case of repetitive renal cyst infection in a 58-year-old Japanese man with ADPKD on dialysis. He underwent renal transcatheter arterial embolization (TAE) four months after the last episodes of renal cyst infection, and his renal cyst infection has not recurred since renal TAE. This case suggested that renal TAE is effective for preventing repetitive renal cyst infection.
Tatsuya Ueno, Norihiro Hanabata, Atsuko Katagai, Rena Okudera, Akira Arai, Masahiko Tomiyama
Internal Medicine, Volume 60, pp 3317-3320;

Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel (LCIG) is an established device-aided therapy for advanced Parkinson's disease (PD). Phytobezoar associated with LCIG is a rare device-related complication and presents with exacerbations of gastrointestinal and PD symptoms. We herein report the case of a phytobezoar that was formed at a knot on the pigtail-shaped J-tube and developed only in association with postprandial abdominal pain, similar to a feeling of a tube being pulled in without an exacerbation of PD symptoms. Such abdominal pain may be a warning sign of phytobezoar in LCIG-treated patients. Despite device-related complications, high-pressure alarms are not always present, and PD symptoms are not always exacerbated.
Tatsuhiro Yamazaki, Takeshi Tomoda, Hironari Kato, Kazuya Miyamoto, Akihiro Matsumi, Eijiro Ueta, Yuki Fujii, Yosuke Saragai, Daisuke Uchida, Kazuyuki Matsumoto, et al.
Internal Medicine, Volume 60, pp 3205-3211;

Objective Strict follow-up is recommended for branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) to avoid missing the development of high-risk stigmata (HRS) at a premalignant stage. This study explored the risk factors associated with the development of HRS during follow-up. Methods We performed a retrospective analysis of 283 patients with BD-IPMN, treated at Okayama University Hospital in Japan between January 2009 and December 2016. Only patients with imaging studies indicative of classical features of BD-IPMN without HRS and followed for over one year were included in the study. We performed radiological follow-up every six months and collected patients' demographic data, cyst characteristics, and clinical outcomes and used univariate logistic regression models to determine the odds of developing HRS. Results Ten patients (3.5%) developed HRS after a median surveillance period of 55.8 months. The main pancreatic duct (MPD) size (5-9 mm) and cyst growth rate (>2.5 mm/year) were both suggested to be possible risk factors for the development of HRS (odds ratio, 14.2; 95% confidence interval [CI], 3.1-65.2, p=0.0006, and odds ratio, 6.1; 95% CI 1.5-25.5, p=0.014). Regarding the number of worrisome features (WFs), the rate of HRS development was 2.0% (4/199) in cases with no WF, 1.6% (1/62) in cases with single WF and 22.7% (5/22) in cases with multiple WFs, respectively. The rate of HRS development was significantly higher in cases with multiple WFs than in the other cases (p<0.0001). Conclusion MPD dilation, rapid cyst growth, and multiple WFs were significant risk factors for the development of HRS. In the presence of such features, it is necessary to closely follow the development of HRS and avoid missing the best opportunity to perform surgical intervention.
Atsushi Hiraoka, Miho Onishi, Satsuki Koyama, Masaya Kato, Kaori Marui, Taisei Murakami, Kei Onishi, Tomoko Adachi, Junko Matsuoka, Hidetaro Ueki, et al.
Internal Medicine, Volume 60, pp 3195-3203;

Objective This study evaluated cases of pruritus, which is known to be associated with sleep disorder, in chronic liver disease (CLD) patients. Methods Questionnaires were given to 339 enrolled CLD outpatients in winter (November 2019 to March 2020) and again in summer (April to October 2020) (median interval: 104 days). Relative changes in symptoms shown by a visual analogue scale (VAS) and Kawashima's pruritus score between winter and summer were evaluated in Study 1 (n=199), while Study 2 examined the clinical features of patients with sleep disorder based on the results of the second questionnaire (n=235, median age 70 years old; 141 men, liver cirrhosis 37%). Results Study 1. There was a significant relationship in VAS between daytime and nighttime for each season, as well as between winter and summer for each time period (p<0.001). A comparison of Kawashima's pruritus scores for the daytime and nighttime showed no significant seasonal differences (p=0.436 and 0.828, respectively). When Kawashima's score increased, so did the average VAS for both daytime (0:1:2:3:4=0.4±0.2:1.4±0.9:3.0±1.8:5.9±2.1:6.2±2.3) and nighttime (0:1:2:3:4=0.3±0.1:1.4±1.5:3.5±2.3:6.7±2.6:6.9±1.8) (p<0.001 for both). Study 2. Twenty subjects (8.5%) complained of sleep disorder. An elevated FIB-4 index (≥3.07) showed a good predictive value for sleep disorder (p<0.01). The cut-off for the daytime and nighttime VAS values for existing sleep disorder were 1.6 [area under the curve (AUC) 0.901] and 3.4 (AUC 0.931). The respective sensitivity, specificity, and positive and negative predictive values for sleep disorder based on Kawashima's score (≥2) were 0.85, 0.28, 0.10, and 0.95 for the daytime and 1.00, 0.29, 0.12, and 1.00 for the nighttime. Conclusion Intervention against pruritus is recommended in CLD patients with a high Kawashima's score (≥2) in any season, especially with an elevated FIB-4 index.
Yuta Kaito, Shunsuke Yui, Kazuki Inai, Daishi Onai, Ryosuke Kinoshita, Satoshi Yamanaka, Muneo Okamoto, Ryuichi Wada, Ryuji Ohashi, Koiti Inokuchi, et al.
Internal Medicine, Volume 60, pp 3299-3304;

Allogeneic hemopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for refractory hematological malignancies. However, there are many treatment-related complications, including organ disorders, graft-versus-host disease (GVHD), and infectious diseases. Furthermore, there are many unclear points regarding central nervous system (CNS) complications, and the prognosis in patients with CNS complications is extremely poor. We herein report a 49-year-old woman who developed CNS-GVHD after a second transplantation for therapy-related myelodysplastic syndrome. CNS-GVHD in this case was refractory to all treatments, including steroids, and progressed. We also present a review of the literature about the symptoms, diagnosis, and treatment of CNS-GVHD.
Shusuke Yagi, Tomoko Takahashi, Keiji Murakami, Momoyo Azuma, Mikio Sugano, Ryosuke Miyamoto, Mariko Niki, Hirotsugu Yamada, Yutaka Kawabata, Akihiro Tani, et al.
Internal Medicine, Volume 60, pp 3251-3255;

Infective endocarditis (IE) may be acquired in the community as community-acquired (CA) IE or in the healthcare setting. In Japan, cases of CA-methicillin-resistant Staphylococcus aureus (MRSA) infection as skin infection have been increasing. CA-MRSA strains, including the USA300 clone, have higher pathogenicity and are more destructive to tissue than healthcare-associated MRSA strains because of the toxins they produce, including arginine-catabolic mobile element (ACME) and Panton-Valentine leukocidin (PVL). However, only a few IE cases induced by USA300 have been reported. We herein report a 64-year-old man who developed CA-IE from a furuncle caused by USA300 MRSA producing PVL and ACME, which resulted in complications of meningitis.
Megumi Koshiishi, Toru Odate, Yukie Nakagawa, Jun Suzuki, Takuya Kumagai, Ichiro Kawashima, Takeo Yamamoto, Kei Nakajima, Masaru Tanaka, Naoki Oishi, et al.
Internal Medicine, Volume 60, pp 3305-3308;

A 71-year-old woman with a four-year history of chronic lymphocytic leukemia (CLL) received ibrutinib as initial treatment due to progressive anemia and thrombocytopenia. Eleven months after the start of the treatments, although her cytopenia had ameliorated, she developed classic Hodgkin lymphoma, a rare form of Richter's transformation. She was successfully treated with two courses of adriamycin, vinblastin, bleomycin and dacarbazine followed by radiotherapy. In general, several clinical, genetic and molecular factors are associated with Richter's transformation. In addition, our present case suggested that ibrutinib could be a potential risk factor for Richter's transformation in CLL patients.
Tokunao Amemiya, Shin-Ichiro Iwakami
Internal Medicine, Volume 60, pp 3081-3086;

Objective This study aimed to elucidate the effects of early macrolide administration on genetically confirmed pertussis-induced cough in adolescents and adults. Methods This single-center, retrospective cohort study examined the effects of the early administration of macrolides and antitussive agents on cough secondary to pertussis. We divided the patients into two groups based on the median duration from the beginning of the cough to the initiation of macrolide administration: early macrolide administration group (EMAG) and non-early macrolide administration group (NEMAG). The clinical improvement of cough was defined as maintaining a cough awareness score of ≤3 points for 3 consecutive days. Patients The medical records of 40 patients diagnosed with pertussis (≥12 years old) who were able to maintain a cough diary and received no other antibiotics aside from macrolides were included in the study. A diagnosis of pertussis was made using the loop-mediated isothermal amplification (LAMP) test. Results The EMAG (24 patients) showed a significantly shorter total cough period than the NEMAG [16 patients; 20.0 (95% confidence interval (CI), 16-28) vs. 30.5 (95% CI, 27-40) days; log-rank test, p=0.002]. There was no significant difference in the post-administration cough periods between the EMAG and NEMAG [11.0 (95% CI, 7-19) vs. 13.0 (95% CI, 5-23) days; log-rank test, p=0.232]. Antitussive agents did not affect the cough. Conclusion The early administration of macrolides, but not antitussive agents, is effective for treating pertussis. Therefore, macrolides should be administered as soon as possible for this disease.
Shiika Watanabe, Tomo Suzuki, Wei Han, Mayumi Nakata, Kenichiro Koitabashi, Daisuke Ichikawa, Atsuko Kamijo-Ikemori, Junki Koike, Yugo Shibagaki
Internal Medicine, Volume 60, pp 3125-3128;

Membranous nephropathy often achieves spontaneous remission. However, there are scarce reports of spontaneous remission of thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous nephropathy. A 64-year-old female presented with nephrotic syndrome and edema of the lower extremities. We diagnosed membranous nephropathy by kidney biopsy and confirmed positive THSD7A on immunofluorescence using frozen sections; serum THSD7A antibodies were also detected. Thirty-four months after the initial diagnosis, she achieved a spontaneous complete remission without immunosuppressive therapy. With the complete remission, no serum THSD7A levels were detected. In this study, we describe serial examinations of kidney biopsies and serum THSD7A antibodies.
Masataka Kudo, Takayuki Uchida, Takahiro Sakano, Takashi Matono
Internal Medicine, Volume 60, pp 3189-3190;

Kyoko Gocho, Tokuhiro Kimura, Shinya Matsushita, Saeko Shinozawa, Nobuyuki Hamanaka, Yoshimasa Inoue, Tamiko Takemura
Internal Medicine, Volume 60, pp 3137-3142;

Good's syndrome is associated with thymoma and acquired immunodeficiency. A 54-year-old man visited our hospital with a complaint of cough. Chest imaging revealed diffuse nodular shadows and anterior mediastinal mass. Hypogammaglobulinemia and a decreased B lymphocyte count were found by a laboratory evaluation. The lung nodules markedly regressed after immunoglobulin therapy. The mediastinal mass and remaining nodule were surgically resected and diagnosed as a type AB thymoma and a necrotizing epithelioid granuloma with T lymphocyte-dominant alveolitis, respectively. The overall appearances of these lesions were mostly in line with the spectrum of granulomatous-lymphocytic interstitial lung disease associated with Good's syndrome.
Takahiro Kanda, Kei Tawarahara, Naoki Nakamura, Yusuke Tokonami, Hiroyuki Aoshima, Gaku Matsukura, Masayoshi Matsunari, Rumi Takabayashi, Mariko Ozeki, Hiroshi Ukigai, et al.
Internal Medicine, Volume 60, pp 3121-3124;

Acute type A aortic dissection is a potentially fatal disease, and emergency surgery should be considered when it is diagnosed. We herein report two cases of retrograde type A aortic dissection with intramural hematoma, followed by re-dissection, rupture, and cardiac tamponade. The diagnoses in these cases had to be made carefully, as the false lumen of the ascending aorta was sometimes unclear on contrast-enhanced computed tomography.
Naoki Arakawa, Kazuo Eguchi, Yuki Nakamura, Yuta Tsukahara, Youhei Koushima, Hidekazu Matsushima
Internal Medicine, Volume 60, pp 3143-3147;

A 94-year-old woman with rheumatoid arthritis who had been treated with low-dose methotrexate was referred to our hospital because of a 3-day history of a fever and pancytopenia. With a diagnosis of febrile neutropenia of unknown origin, empirical antibiotic treatment and folinic acid therapy were initiated. Despite a recovery from pancytopenia, the high fever remained, and dyspnea developed. She was clinically diagnosed with Pneumocystis jirovecii pneumonia (PCP) and successfully treated with trimethoprim/sulfamethoxazole and adjunctive corticosteroid therapy. Folinic acid treatment effectively brought about rapid immune recovery but might have led to a clinical manifestation of PCP resembling immune reconstruction inflammatory syndrome.
Wataru Kitamura, Daisuke Ennishi, Ryoya Yukawa, Ryo Sasaki, Chikamasa Yoshida, Hiroki Takasuka, Hideaki Fujiwara, Noboru Asada, Hisakazu Nishimori, Keiko Fujii, et al.
Internal Medicine, Volume 60, pp 3155-3160;

A 72-year-old man presented with chorea while undergoing treatment for recurrence of nodal peripheral T-cell lymphoma with T follicular helper (TFH) phenotype. An examination by brain N-isopropyl-p-iodoamphetamine (123I-IMP)-single photon emission computed tomography (SPECT) revealed no abnormalities other than a decreased cerebral blood flow (CBF) in the left striatum. After four courses of salvage chemotherapy, his clinical symptoms and asymmetric cerebral perfusion improved, suggesting that the decreased CBF had caused chorea. The significance of brain SPECT has not been fully clarified in patients with chorea-associated malignant lymphoma, warranting further investigations. Brain SPECT is an alternative approach to identify abnormalities in such patients.
Hiroki Tojima, Satoru Kakizaki, Satoshi Takakusagi, Takashi Hoshino, Atsushi Naganuma, Tamon Nagashima, Masashi Namikawa, Takashi Ueno, Yasushi Shimada, Takeshi Hatanaka, et al.
Internal Medicine, Volume 60, pp 3061-3070;

Objective Chronic hepatitis C virus (HCV) infection carries a residual risk of hepatocarcinogenesis even after viral elimination, so appropriate follow-up is necessary. The present study investigated the current hospital visits and hepatocarcinogenesis status of patients who received daclatasvir plus asunaprevir treatment (DCV+ASV) to determine whether or not appropriate follow-up was being performed. Methods We retrospectively analyzed hepatocarcinogenesis, the overall survival, and the length of hospital visits in 442 patients who applied for the medical expense subsidy system for viral hepatitis and received DCV+ASV treatment in Gunma Prefecture between October 2014 and December 2015. This also included 61 patients who had a history of hepatocellular carcinoma (HCC). Results Among 442 patients, 388 achieved a sustained viral response (SVR) by DCV+ASV therapy (87.8%), and 95.9% achieved an SVR if additional treatment was included. HCC was found in 75 cases (17.0%). A history of HCC, the FIB-4 index and the treatment effect SVR were determined to be factors affecting the incidence of HCC. Regarding the follow-up rate, 89.9% of patients continued to regularly visit the hospital after 5 years of treatment. However, patients ≤60 years old had significantly lower persistence rates than older patients. The persistence rate of hospital visits to the same institution was 67.7% over a 5-year period, which was significantly better in small and medium-sized institutions than in large, specialized institutions (71.7% vs. 63.9%, p=0.039). Conclusion Patients with direct-acting antiviral treatment generally received adequate follow-up, but younger patients had a slightly higher rate of follow-up interruption and were considered to need support.
Tsunetaro Morino, Hiroki Kuroyanagi, Taichi Yanagihara, Hiroto Ohto
Internal Medicine, Volume 60, pp 3183-3184;

Yuwa Oka, Akihiro Ueda, Tomokazu Nakagawa, Yujiro Kikuchi, Daiki Inoue, Satoshi Marumo, Sadayuki Matsumoto
Internal Medicine, Volume 60, pp 3167-3170;

We herein report a 49-year-old man with a fever, diagnosed with SARS-CoV-2 infection. After two weeks of hospitalization, he suddenly mentioned visual field impairment. Computed tomography and magnetic resonance imaging revealed white matter damage and vasogenic edema. Cerebrospinal fluid showed increased levels of IL-6. His symptoms and white matter lesion deteriorated. After treatment with intravenous methylprednisolone therapy and plasmapheresis, his symptoms and white matter lesion improved gradually. We suspect that our patient was affected by a secondary hyperinflammatory syndrome related to cytokines, alone or in combination with direct viral injury through endothelial cell damage. The IL-6 levels were elevated only in the cerebrospinal fluid, suggesting focal central nervous system inflammation.
Takumi Tamura, Keisuke Miyajima, Kazuki Watanabe, Kazuki Ito, Fumihiko Kin, Ayako Okazaki, Yasuyo Takashima, Tomoyuki Watanabe, Yoshitaka Kawaguchi, Yasushi Wakabayashi, et al.
Internal Medicine, Volume 60, pp 3113-3119;

A 41-year-old man was admitted with a chief complaint of dyspnea. Echocardiography showed diffuse severe hypokinesis in the left ventricle. Although his heart failure improved, high creatine kinase levels persisted. A muscle biopsy of the biceps brachii showed necrotic and regenerating fibers along with positive findings for major histocompatibility complex class I and membrane attack complex. He was diagnosed with antibody-negative immune-mediated necrotizing myopathy (IMNM). Steroid therapy was started, but he died due to ventricular fibrillation. Autopsy findings revealed CD68- positive macrophages in the myocardium and quadriceps. To our knowledge, this is the first case of antibody-negative IMNM with cardiac involvement.
Asuka Yoshizaki, Tatsuya Nagano, Shintaro Izumi, Yasuhiro Funada, Kyosuke Nakata, Teruaki Nishiuma, Kiyonobu Takatsuki, Hisashi Ohnishi, Nobuko Hazeki, Yuichiro Yasuda, et al.
Internal Medicine, Volume 60, pp 3071-3079;

Objective Nocturnal desaturation is common in patients with chronic respiratory disease and often worsens the prognosis. Therefore, it should be diagnosed accurately and appropriately treated. The aim of this study was to clarify the diversity of nocturnal desaturation. Methods We prospectively enrolled 58 outpatients diagnosed with chronic respiratory disease receiving home oxygen therapy and measured nocturnal SpO2 using a portable oximeter. We classified nocturnal desaturation (3% decrease in SpO2 from baseline) into three patterns: periodic pattern (desaturation duration of <655 seconds), sustained pattern (desaturation duration of ≥655 seconds), and intermittent pattern (desaturation and recovery of SpO2 repeated with a cycle of several minutes). Results Nocturnal hypoxemia (SpO2≤88% for more than 5 minutes) was found in 23.8% of patients. The percentage of patients with chronic obstructive pulmonary disease (COPD) was significantly higher in the nocturnal hypoxemia group than in the non-hypoxemia group (80% vs. 40.6%, p=0.03). Desaturation with a periodic pattern was found in 81% of patients, desaturation with a sustained pattern was found in 40.5% of patients, and desaturation with an intermittent pattern was found in 59.5% of patients. In patients with COPD, desaturation with a periodic pattern was found in 85.7%, desaturation with a sustained pattern was found in 47.6%, and desaturation with an intermittent pattern was found in 57.1%. Conclusion The SpO2 waveform of nocturnal hypoxemia was able to be classified into three patterns. Suitable treatment for each pattern might improve the prognosis of these patients.
Gohei Yamada, Takanari Toyoda, Eiichi Katada, Noriyuki Matsukawa
Internal Medicine, Volume 60, pp 3185-3186;

Hideto Yokoi, Atsushi Sakai, Tomonori Kodama, Shogo Magome, Osamu Itose, Masayuki Tawara, Takahiro Yasaka, Takeru Abe, Ichiro Takeuchi
Internal Medicine, Volume 60, pp 3093-3099;

Objective Tsushima mamushi (Gloydius tsushimaensis) is an endemic species of snake inhabiting only Tsushima Island, a remote Japanese island. We conducted a multicenter, retrospective study of G. tsushimaensis bites for the first time and developed a therapeutic algorithm that unified treatment on the island and is still in use today. Methods This is a multicenter, retrospective study comparing 72 cases from January 2005 to December 2018, before the introduction of the algorithm, and 12 cases from January 2019 to December 2020, after its introduction. Results There was no significant decrease in the maximum grade of symptoms after the introduction of the algorithm, but there was a decreasing trend (p=0.057). Conversely, the median of the maximum creatinine kinase levels was 343.5 IU/L (interquartile range: 115.5-4,745.5) before the algorithm's introduction and significantly lower (142.5; interquartile range: 111.3-163) after the algorithm's introduction (p=0.042). After the algorithm's introduction, the disseminated intravascular coagulation merger rate and the acute kidney injury incidence both dropped to 0%, from 9.7% and 6.9%, respectively, before the algorithm's introduction. There was no significant difference in the length of hospital stay before versus after the algorithm's introduction. Conclusion This study showed that the treatment algorithm can be safely and quickly applied. The algorithm's effectiveness is expected be strengthened by the accumulation of more cases in the future.
Chika Yamada, Yoshimitsu Shimomura, Kimimori Kamijyo, Madoka Kanda-Kato, Satoshi Yoshioka, Daisuke Yamashita, Takayuki Ishikawa
Internal Medicine, Volume 60, pp 3149-3153;

We herein report a rare case of BCR-ABL1-positive B-lymphoblastic lymphoma (B-LBL). An 18-year-old woman had a history of persistent left-sided chest pain. Positron emission tomography showed increased metabolic activity in the fifth rib, duodenum, and pancreas. The pathological findings of the pancreas, duodenum, and bone marrow confirmed the diagnosis of B-LBL. Polymerase chain reaction of duodenum and bone marrow also revealed a minor BCR-ABL1 fusion gene. She was diagnosed with BCR-ABL1-positive B-LBL and administered dasatinib and prednisolone. She achieved complete remission two weeks after the initiation of the treatment. She received stem cell transplantation after consolidation chemotherapy and sustained complete remission.
Satoshi Kurihara, Mikio Nakajima, Richard H. Kaszynski, Yasuhiro Yamamoto, Koichiro Santo, Ryo Takane, Hayato Tokuno, Ayaka Ishihata, Hitoshi Ando, Maki Miwa, et al.
Internal Medicine, Volume 60, pp 3087-3092;

Objective Due to the lack of specific clinical manifestations and symptoms, it is difficult to distinguish COVID-19 from mimics. A common pitfall is to rush to make a diagnosis when encountering a patient with COVID-19-like symptoms. The present study describes a series of COVID-19 mimics using an outpatient database collected from a designated COVID-19 healthcare facility in Tokyo, Japan. Methods We established an emergency room (ER) tailored specifically for patients with suspected or confirmed COVID-19 called the "COVID-ER." In this single-center retrospective cohort study, we enrolled patients who visited the COVID-ER from February 1 to September 5, 2020. The outcomes included the prevalence of COVID-19, admission, potentially fatal diseases and final diagnosis. Results We identified 2,555 eligible patients. The median age was 38 (interquartile range, 26-57) years old. During the study period, the prevalence of COVID-19 was 17.9% (457/2,555). Non-COVID-19 diagnoses accounted for 82.1% of all cases. The common cold had the highest prevalence and accounted for 33.0% of all final diagnoses, followed by gastroenteritis (9.4%), urinary tract infections (3.8%), tonsillitis (2.9%), heat stroke (2.6%) and bacterial pneumonia (2.1%). The prevalence of potentially fatal diseases was 16.2% (298/2,098) among non-COVID-19 patients. Conclusion Several potentially fatal diseases remain masked among the wave of COVID-19 mimics. It is imperative that a thorough differential diagnostic panel be considered prior to the rendering of a COVID-19 diagnosis.
Masaya Iwamuro, Ken-Ichi Matsuoka, Takehiro Tanaka, Hiroyuki Okada
Internal Medicine, Volume 60, pp 3179-3180;

Noboru Hamada, Takafumi Yamano, Yusaku Tada, Yasuhiro Ooue, Junko Itano, Mitsunori Ishiga, Hisaaki Tanaka, Goro Kimura, Yasushi Tanimoto
Internal Medicine, Volume 60, pp 3101-3105;

We herein report the first case of low-dose oxygen therapy for pneumatosis cystoides intestinalis (PCI) using PaO2 as a therapeutic index to prevent acute exacerbation of interstitial pneumonia. An 86-year-old man was admitted to our hospital with abdominal distension. PCI was diagnosed by abdominal computed tomography. Low-dose oxygen therapy was started to avoid acute exacerbation of interstitial pneumonia. The oxygen dose was adjusted so that the PaO2 value was approximately 100 mmHg. After seven days of treatment, the colon gas had disappeared, and no acute exacerbation of interstitial pneumonia was observed. A PaO2 value around 100 mmHg is effective for PCI without inducing acute exacerbation of interstitial pneumonia.
Kazuhide Takata, Takahiro Nagata, Yotaro Uchida, Takanori Kitaguchi, Tomotaka Higashi, Hiromi Fukuda, Ryo Yamauchi, Naoaki Tsuchiya, Takashi Tanaka, Keiji Yokoyama, et al.
Internal Medicine, Volume 60, pp 3107-3112;

We report a case of anorexia nervosa (AN) with gastroesophageal varices (GEV) in a 36-year-old woman. The patient presented to our hospital with progressive bloating due to severe ascites. She had no history of alcohol intake. Esophagogastroduodenoscopy and enhanced computed tomography revealed GEV and multiple hepatic nodules, respectively. The histological examination of a liver biopsy specimen revealed similar features to nonalcoholic fatty liver disease and showed hyperplastic nodules that were suspected to be related to the uneven distribution of portal blood flow in the liver. In conclusion, patients with long-term AN should undergo abdominal imaging to detect signs of portal hypertension.
Yuya Kobayashi, Ryo Itabashi, Takuya Saito, Yuichi Kawabata, Yukako Yazawa
Internal Medicine, Volume 60, pp 3161-3166;

A 68-year-old man was admitted to our department because of left incomplete homonymous hemianopia accompanied by hyperglycemia. Both T2-weighted and diffusion-weighted imaging revealed a low signal intensity along the subcortex and high signal intensity along the cortex on the right parietal and occipital lobes. Furthermore, arterial spin labeling and single-photon emission computed tomography showed hyperperfusion at the right parieto-occipital lobe. However, the electroencephalography result was normal. Hyperperfusion improved after controlling the blood glucose levels; nevertheless, homonymous hemianopia remained. We suspect that the irreversible brain damage was attributable to hyperperfusion associated with long-term hyperglycemia.
Masanori Minato, Taichi Murakami, Naoki Takahashi, Hiroyuki Ono, Kenji Nishimura, Masanori Tamaki, Kojiro Nagai, Hideharu Abe, Masayuki Iwano, Kensuke Joh, et al.
Internal Medicine, Volume 60, pp 3129-3136;

Tubulointerstitial nephritis (TIN) with IgM-positive plasma cells (IgMPC-TIN) is an autoimmune kidney disease characterized by IgM/CD138-double-positive plasma cell infiltration in the tubulointerstitium. A 50-year-old man developed IgMPC-TIN and presented with crystalline inclusions in the rough endoplasmic reticulum. Intracellular crystal formation is a rare finding in paraprotein-related kidney diseases, but this case showed no pathogenic monoclonal immunoglobulin. Prednisolone (PSL, 30 mg) improved the TIN, but PSL tapering resulted in the recurrence of TIN. Combination therapy with 15 mg PSL and 150 mg mizoribine ultimately stabilized TIN. This case offers original evidence concerning the pathophysiology and treatment strategy of IgMPC-TIN.
Takafumi Kubota, Yuichiro Mori, Gen Yamada, Ivor Cammack, Toshiya Shinohara, Suguru Matsuzaka, Tetsuya Hoshi
Internal Medicine, Volume 60, pp 3171-3176;

Localized Listeria infection predominantly occurs in the prosthetic and hip joints. We herein report a case of Listeria monocytogenes ankle osteomyelitis in a 73-year-old man receiving adalimumab who was transferred to our hospital because of suspected rheumatoid arthritis (RA) flare. He reported a four-month history of left ankle swelling. A surgical biopsy revealed L. monocytogenes osteomyelitis in the left tibia and talus bones. The patient was successfully treated with antibiotics and surgical debridement. Thus, infection due to L. monocytogenes can present as ankle osteomyelitis in immunocompromised patients and may mimic an RA flare.
, Nobue K Iwata, Mizuho Kawai, Hideki Nakajima, Katsuhiko Takeda, Hiroyuki Murai, Jun Goto
Internal Medicine, Volume 60, pp 3021-3024;

Anti-leucine-rich glioma-inactivated 1 (LGI1) antibody is associated with limbic encephalitis. We herein report a patient with anti-LGI1 encephalitis who developed severe orthostatic hypotension (OH) responsive to immunoglobulin therapy five years after developing symptoms of encephalitis. A 71-year-old man presented with amnesia caused by limbic encephalitis. The symptoms of encephalitis improved partially without any immunotherapy. Five years later, he developed severe OH, and anti-LGI1 antibody was positive. The catecholamine dynamics indicated that the central autonomic nervous system was the lesion of his OH. Intravenous immunoglobulin therapy improved the OH. This case suggests that anti-LGI1 antibody can be associated with severe OH.
Yuka Fukuo, Tomoyoshi Shibuya, Karin Ashizawa, Kentaro Ito, Michio Saeki, Hirofumi Fukushima, Masahito Takahashi, Kei Nomura, Koki Okahara, Keiichi Haga, et al.
Internal Medicine, Volume 60, pp 2947-2952;

Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoproliferative disorder that is strongly associated with immunodeficiency, most often with human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) infection, and that mainly occurs in the oral cavity. Although some clinical features can lead to a diagnosis, PBL in an extraoral site is difficult to suspect clinically in a patient who is HIV negative. The small intestine as a site of PBL has also been described very rarely. We herein present a rare case of PBL of the small intestine in an 85-year-old HIV- and EBV-negative male.
Manabu Izumi, Kazuo Suzuki
Internal Medicine, Volume 60, pp 2933-2938;

Background and purpose It has been established that stroke occurrence is influenced by seasonality. Stroke is divided into three subtypes: cerebral hemorrhage (CH), cerebral infarction (CI), and subarachnoid hemorrhage (SAH). The purpose of this paper was to analyze stroke events by subtype and month, in order to clarify the biggest factors that affect seasonal differences and thereby gain insight into stroke prevention. Methods Initial stroke events in the Akita Stroke Registry from 1991 to 2010 (58,684 cases; male 30,549, female 28,135) were classified by subtype and the month of onset, and correlations were estimated based on 115 healthy volunteers' monthly mean resting blood pressure (BP) at home and outdoor temperature measured by the Akita Meteorological Observatory in 2001. Results Systolic BP showed monthly variation in both morning and evening measurements. BP and outdoor temperature showed significant correlations with hemorrhagic stroke events by month (CH: r=0.87, r=-0.82; SAH: r=0.68, r=-0.82). Among the stroke subtypes, seasonal differences were the greatest in CH. Systolic BP was the most important factor for monthly and seasonal variation in stroke events. By comparing monthly BP variations with CH incidence throughout the year, we concluded that a decrease in home BP of 5 mmHg can reduce the risk of CH by 35%. Conclusion Our findings suggest that lowering BP would be the best strategy for CH prevention. Simple daily actions may be affected by cold stress. As physicians, we must strive to help patients lower their BP throughout the year not only with medication but with lifestyle guidance, especially in winter.
Tomohiro F. Nishijima, Yasushi Toh, Masahito Tanimizu, Hitoshi Nakagama, On behalf of the Japanese Association of Clinical Cancer Centers
Internal Medicine, Volume 60, pp 2927-2932;

Objective Geriatric screening followed by a more detailed assessment and intervention is recommended for older adults with cancer. However, little is known regarding how the geriatric screening covered by Japanese health insurance is used for hospitalized older cancer patients. We surveyed all hospitals in Japanese Association of Clinical Cancer Centers (JACCC) to explore the current use of this approach. Methods The JACCC member hospitals specialize in cancer care from prevention, through diagnosis and treatment, to palliative care. We mailed paper questionnaires to the presidents of the hospitals in December 2019 and collected them by February 2020. The survey requested general hospital information and asked whether (and how) such geriatric screening for hospitalized older adults with cancer was conducted. Results Twenty-six of 32 hospitals completed the survey (81%). Fourteen hospitals are cancer centers, while the remaining 12 hospitals are general hospitals which care of both cancer and non-cancer patients. Eleven hospitals (42%) performed geriatric screening and the most common use of the results was for "early discharge planning" and for "applying for long-term care insurance". Most clinicians rated the screening "somewhat" or "a little" helpful and found it most helpful for "meeting patient-post discharge needs". The most frequently reported barrier to implementation was a "lack of leadership to improve the care of older adults". Conclusion Geriatric screening was used at less than half of the major cancer centers and hospitals in Japan. One feasible solution to this problem is to establish an interprofessional workgroup at each hospital with the shared goal of providing high-quality care for this population.
Sota Nakamura, Teppei Fujioka, Shoji Kawashima, Takatsune Kawaguchi, Masayuki Mizuno, Masahiro Omura, Kenji Okita, Akio Kimura, Takayoshi Shimohata, Noriyuki Matsukawa
Internal Medicine, Volume 60, pp 3031-3036;

A 29-year-old man presented with a high-grade fever, headache, and urinary retention, in addition to meningeal irritation and myoclonus in his upper extremities. A cerebrospinal fluid (CSF) examination showed pleocytosis and high adenosine deaminase (ADA) levels with no evidence of bacterial infection, including Mycobacterium tuberculosis. T2-weighted brain magnetic resonance imaging showed transient hyper-intensity lesions at the splenium of the corpus callosum (SCC), bilateral putamen, and pons during the course of the disease. The CSF was positive for anti-glial fibrillary acidic protein (GFAP) antibodies. He was diagnosed with autoimmune GFAP astrocytopathy. The present case shows that the combination of an elevated ADA level in the CSF and reversible T2-weighted hyper-intensity on the SCC supports the diagnosis of autoimmune GFAP encephalopathy.
Mia Fujisawa, Masashi Matsushima, Takashi Ueda, Motoki Kaneko, Ryutaro Fujimoto, Masaya Sano, Erika Teramura, Makiko Monma, Hajime Mizukami, Fumio Nakahara, et al.
Internal Medicine, Volume 60, pp 2953-2959;

The risk of carcinogenesis increases after 20 years old in patients with Fanconi anemia (FA). We herein report three rare cases of FA combined with esophageal cancer in women; all patients were diagnosed with FA in early childhood. Patients 1 and 2 were diagnosed with advanced and superficial esophageal cancer, respectively, at 21 and 30 years old, respectively. Patient 3 was diagnosed with superficial esophageal cancer, underwent curative surgery at 26 years old, and survived for over 5 years without recurrence. Therefore, establishing a protocol for the early detection of esophageal cancer in FA patients over 20 years old is important.
Naohiro Oda, Masahiro Tabata, Masatoshi Uno, Yuzo Umeda, Hironari Kato, Toshio Kubo, Satoru Senoo, Takahito Yagi, Toshiyoshi Fujiwara, Yoshinobu Maeda, et al.
Internal Medicine, Volume 60, pp 2967-2971;

Mucinous cystic neoplasm (MCN) of the pancreas is a rare cystic tumor occurring in the pancreatic body and tail in young to middle-aged women that is pathologically characterized by an ovarian-like stroma. Chemotherapy for recurrent/advanced pancreatic MCN has been based on chemotherapy regimens for pancreatic ductal adenocarcinoma, but the prognosis is poor. We herein report a 37-year-old woman with pancreatic mucinous cystadenocarcinoma with liver metastasis that responded dramatically to carboplatin plus paclitaxel therapy (CBDCA + PTX). CBDCA + PTX may be a treatment option for recurrent/advanced pancreatic MCN with an ovarian-like stroma.
Yuji Oe, Eikan Mishima, Takayasu Mori, Koji Okamoto, Yohei Honkura, Tasuku Nagasawa, Mai Yoshida, Hiroshi Sato, Jun Suzuki, Ryoukichi Ikeda, et al.
Internal Medicine, Volume 60, pp 2991-2996;

A 69-year-old woman presented with mild renal dysfunction, proteinuria, and sensorineural hearing loss. A renal biopsy showed focal segmental glomerulosclerosis with thinning of the glomerular basement membrane. There was a positive family history of end-stage kidney disease and hearing loss. Although Alport syndrome was suspected from these features, a genetic test using next-generation sequencer identified a novel missense mutation in LMX1B, c.655C>G: p. (Pro219Ala). In silico analyses predicted the pathogenicity of the mutation. Thus, the present case was diagnosed as LMX1B-associated nephropathy presenting with Alport syndrome-like phenotype, expanding the disease spectrum of LMX1B nephropathy.
Shota Okamoto, Hiroto Tsuboi, Hisashi Noma, Daiki Tabuchi, Toshiki Sugita, Taihei Nishiyama, Toshihiko Terasaki, Masaru Shimizu, Fumika Honda, Mizuki Yagishita, et al.
Internal Medicine, Volume 60, pp 2887-2897;

Objective To identify factors associated with pneumomediastinum during management of connective tissue disease (CTD)-related interstitial lung disease (ILD). Methods Patients diagnosed with pneumomediastinum after the initiation of corticosteroid therapy for their CTD-ILD were enrolled. The baseline characteristics of patients who developed pneumomediastinum after the initiation of corticosteroid therapy (n=13, all occurring within 120 days) were compared to those of patients who did not develop pneumomediastinum (n=49). A multivariate logistic regression analysis was performed to identify factors associated with pneumomediastinum. A receiver operating characteristic (ROC) curve analysis was also performed to assess the predictive performance. Results The body mass index (BMI) [odds ratio (OR) (95% confidence interval (CI)) 0.482 (0.272-0.853)] and serum lactate dehydrogenase (LDH) [OR (95% CI) 1.013 (1-1.025)] levels at baseline were identified as independent factors associated with pneumomediastinum after corticosteroid initiation. The optimal cut-off points of the BMI and LDH levels for predicting pneumomediastinum development, as estimated by the Youden index, were 20.2 kg/m2 and 378 U/L, respectively. LDH showed a sensitivity of 61.5% and the highest specificity of 87.8%. Importantly, combining these markers resulted in the highest sensitivity of 100% and a specificity of 71.4%. Conclusion A low BMI and high serum LDH levels at baseline are useful predictive factors for pneumomediastinum development in CTD-ILD patients.
Wataru Shioyama, Toru Oka, Risa Kamada, Toshinari Yagi, Katsuhiko Nakanishi, Tatsuya Nishikawa, Taku Yasui, Masashi Fujita
Internal Medicine, Volume 60, pp 2973-2977;

Pazopanib, a multi-targeted tyrosine kinase inhibitor, is associated with cardiovascular adverse events, such as hypertension, cardiac dysfunction, and thromboembolism. However, symptomatic pazopanib-related bradycardia is uncommon. We herein report a case of symptomatic bradycardia of 35 beats per minute in a patient with solitary fibrous tumor/hemangiopericytoma (SFT/HPC) treated with pazopanib for 1 month. His heart rate recovered to a normal range soon after pazopanib cessation. He restarted pazopanib at a reduced dose, which was continued without SFT/HPC progression or bradycardia recurrence. This case highlights the possibility of bradycardia induced by pazopanib and the importance of monitoring the patient's heart rate.
Takashi Watari
Internal Medicine, Volume 60, pp 2919-2925;

Objectives Medical litigation resulting from diagnostic errors leads to lawsuits that are time-consuming, expensive, and psychologically burdensome. Few studies have focused on internists, who are more likely to make diagnostic errors than others, with assessments of litigation in terms of system and diagnostic errors. This study explored factors contributing to internists losing lawsuits and examined whether system or diagnostic errors were more important on the outcome. Methods Data regarding 419 lawsuits against internists closed between 1961 and 2017 were extracted from a public Japanese database. Factors affecting litigation outcomes were identified by comparative analysis focusing on system and diagnostic errors, environmental factors, and differences in initial diagnoses. Results Overall, 419 malpractice claims against internists were analyzed. The rate of lawsuits being decided against internists was high (50.1%). The primary cause of litigation was diagnostic errors (213, 54%), followed by system errors (188, 45%). The foremost initial diagnostic error was "no abnormality" (17.2%) followed by ischemic heart disease (9.6%) and malignant neoplasm (8.1%). Following cause-adjustment for loss, system errors were 21.37 times more likely to lead to a loss. Losses were 6.26 times higher for diagnostic error cases, 2.49 times higher for errors occurring at night, and 3.44 times higher when "malignant neoplasm" was the first diagnosis. Conclusions This study found that system errors strongly contributed to internists' losses. Diagnostic errors, night shifts, and initial diagnoses of malignant neoplasms also significantly affected trial outcomes. Administrators must focus on both system errors and diagnostic errors to enhance the safety of patients and reduce internists' risk exposure.
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