Internal Medicine
Online ISSN : 1349-7235
Print ISSN : 0918-2918
ISSN-L : 0918-2918
63 巻, 2 号
選択された号の論文の33件中1~33を表示しています
ORIGINAL ARTICLES
  • Kei Moriya, Keigo Saeki, Norihisa Nishimura, Shinya Sato, Yasuhiko Saw ...
    2024 年 63 巻 2 号 p. 145-152
    発行日: 2024/01/15
    公開日: 2024/01/15
    [早期公開] 公開日: 2023/05/17
    ジャーナル オープンアクセス
    電子付録

    Objecive 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.

    Materials 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.

    Conclusion Zinc supplementation safely and efficiently improved mental impairment, possibly caused by continuous treatment with corticosteroids, in patients with AIH.

  • Noriyuki Imazu, Takehiro Torisu, Yutaro Ihara, Junji Umeno, Keisuke Ka ...
    2024 年 63 巻 2 号 p. 153-158
    発行日: 2024/01/15
    公開日: 2024/01/15
    [早期公開] 公開日: 2023/05/17
    ジャーナル オープンアクセス

    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.

  • Yuki Ito, Kentaro Yoshioka, Kazuhiko Hayashi, Yuko Shimizu, Ryo Fujimo ...
    2024 年 63 巻 2 号 p. 159-167
    発行日: 2024/01/15
    公開日: 2024/01/15
    [早期公開] 公開日: 2023/05/24
    ジャーナル オープンアクセス

    Objective 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.

  • Masaaki Nakase, Kai Ninomiya, Yu Horiuchi, Masahiro Sekiguchi, Yusuke ...
    2024 年 63 巻 2 号 p. 169-177
    発行日: 2024/01/15
    公開日: 2024/01/15
    [早期公開] 公開日: 2023/05/31
    ジャーナル オープンアクセス
    電子付録

    Objective Whether or not the initial dip in the glomerular filtration rate (GFR) after the initiation of sodium-glucose co-transporter 2 inhibitors (SGLT2is) is associated with renal tubular injury in patients with heart failure with a reduced ejection fraction (HFrEF) is unclear. We therefore investigated the relationship between changes in the estimated GFR (eGFR) and urine N-acetyl-β-D-glucosaminidase (uNAG) after the initiation of dapagliflozin in patients with HFrEF.

    Methods We prospectively investigated 89 patients with HFrEF who were newly started on dapagliflozin 10 mg/day. Changes in the eGFR and uNAG-to-creatinine ratio (uNAG/Cre) were evaluated at 2 weeks and 2 months after the initiation of dapagliflozin.

    Results The eGFR was decreased at 2 weeks but had not declined further by 2 months. The uNAG/Cre was increased at 2 weeks but had not increased further by 2 months. There was no correlation between the changes in the eGFR and uNAG/Cre (r=-0.022, p=0.853 at 2 weeks and r=0.078, p=0.538 at 2 months). The relative change in the systolic blood pressure, hematocrit, plasma volume, and N-terminal pro-brain natriuretic peptide (NT-proBNP) were correlated with the relative change in the eGFR. In a multiple linear regression analysis, the relative change in the eGFR at 2 weeks was significantly associated with NT-proBNP, and the relative change in the uNAG/Cre was significantly associated with the use of loop diuretics and the relative change in urine osmolality at 2 weeks.

    Conclusion A transient decrease in the eGFR after the initiation of dapagliflozin in patients with HFrEF was not generally associated with renal tubular injury and might have been the result of hemodynamic alteration.

  • Shizuka Watanabe, Maho Suzukawa, Hiroyuki Tashimo, Nobuharu Ohshima, I ...
    2024 年 63 巻 2 号 p. 179-187
    発行日: 2024/01/15
    公開日: 2024/01/15
    [早期公開] 公開日: 2023/05/24
    ジャーナル オープンアクセス

    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.

    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 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).

    Conclusion A low baseline serum IL-18 level may be a useful predictor of an unfavorable response to dupilumab in terms of the ACQ-6.

  • Naoto Imoto, Yuka Kondo, Kazuho Uchida, Shingo Kurahashi
    2024 年 63 巻 2 号 p. 189-195
    発行日: 2024/01/15
    公開日: 2024/01/15
    [早期公開] 公開日: 2023/05/24
    ジャーナル オープンアクセス

    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.

    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.

  • Masahiro Ogasawara, Rintaro Nozu, Kosuke Miki, Shunnsuke Sugimura, Kei ...
    2024 年 63 巻 2 号 p. 197-205
    発行日: 2024/01/15
    公開日: 2024/01/15
    [早期公開] 公開日: 2023/05/24
    ジャーナル オープンアクセス

    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 (Aza) 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.

  • Motohisa Yamamoto, Tomonao Tanaka, Satsuki Aochi, Masaaki Uehara
    2024 年 63 巻 2 号 p. 207-211
    発行日: 2024/01/15
    公開日: 2024/01/15
    [早期公開] 公開日: 2023/05/24
    ジャーナル オープンアクセス

    Objective 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.

  • Noriko Sasaki, Yoko Nakagome, Azusa Kojima, Keigo Shimura, Akira Ishii ...
    2024 年 63 巻 2 号 p. 213-219
    発行日: 2024/01/15
    公開日: 2024/01/15
    [早期公開] 公開日: 2023/05/24
    ジャーナル オープンアクセス

    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 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).

    Conclusion The early initiation of ePE therapy plus intensive immunosuppressive therapy was effective for patients with DM and refractory RP-ILD.

  • Takashi Watari, Ashwin Gupta, Yu Amano, Yasuharu Tokuda
    2024 年 63 巻 2 号 p. 221-229
    発行日: 2024/01/15
    公開日: 2024/01/15
    [早期公開] 公開日: 2023/06/07
    ジャーナル オープンアクセス
    電子付録

    Objective The etiologies of diagnostic errors among internal medicine physicians are unclear. To understand the causes and characteristics of diagnostic errors through reflection by those involved in them.

    Methods We conducted a cross-sectional study using a web-based questionnaire in Japan in January 2019. Over a 10-day period, a total of 2,220 participants agreed to participate in the study, of whom 687 internists were included in the final analysis. Participants were asked about their most memorable diagnostic error cases, in which the time course, situational factors, and psychosocial context could be most vividly recalled and where the participant provided care. We categorized diagnostic errors and identified contributing factors (i.e., situational factors, data collection/interpretation factors, and cognitive biases).

    Results Two-thirds of the identified diagnostic errors occurred in the clinic or emergency department. Errors were most frequently categorized as wrong diagnoses, followed by delayed and missed diagnoses. Errors most often involved diagnoses related to malignancy, circulatory system disorders, or infectious diseases. Situational factors were the most cited error cause, followed by data collection factors and cognitive bias. Common situational factors included limited consultation during office hours and weekends and barriers that prevented consultation with a supervisor or another department.

    Conclusion Internists reported situational factors as a significant cause of diagnostic errors. Other factors, such as cognitive biases, were also evident, although the difference in clinical settings may have influenced the proportions of the etiologies of the errors that were observed. Furthermore, wrong, delayed, and missed diagnoses may have distinctive associated cognitive biases.

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