Reduced renal function is associated with prolonged hospitalization in frail older patients with non-severe pneumonia.

Objective: Pneumonia is a disease with high morbidity and mortality among older individuals in Japan. In practice, most older patients with pneumonia are not required ventilatory management and are not necessarily in critical respiratory condition. However, prolonged hospitalization itself is considered to be a serious problem even in these patients with non-critical pneumonia and have negative and critical consequences such as disuse syndrome in older patients. Therefore, it is essential to examine the factors involved in redundant hospital stays for older hospitalized patients with non-severe pneumonia, many of whom are discharged alive. Method: We examined hospitalized patients diagnosed with pneumonia who were 65 years and older in our facility between February 2017 and March 2020. A longer length of stay (LOS) was defined in cases in which exceeded the 80th percentile of the hospitalization period for all patients was exceeded, and all other cases with a shorter hospitalization were defined as a shorter LOS. In a multivariate logistic regression model, factors determining longer LOSs were analyzed using significant variables in univariate analysis and clinically relevant variables which could interfere with renal function, including fasting period, time to start rehabilitation, estimated glomerular filtration rate (eGFR), the Quick Sequential Organ Failure Assessment (qSOFA) score of 2 or higher, bed-ridden state. Results: We analyzed 104 eligible participants, and the median age was 86 (interquartile range, 82-91) years. Overall, 31 patients (30.7%) were bed-ridden, and 37 patients (35.6%) were nursing-home residents. Patients with a Clinical Frailty Scale score of 4 or higher, considered clinically frail, accounted for 93.2% of all patients. In multivariate analysis, for a decrease of 5 ml/min/1.73m2 in eGFR, the adjusted odds ratios for longer LOSs were 1.22 (95% confidence interval, 1.04-1.44) after adjusting for confounders. Conclusion: Reduced renal function at admission has a significant impact on prolonged hospital stay among older patients with non-severe pneumonia. Thoughtful consideration should be given to the frail older pneumonia patients with reduced renal function or with chronic kidney disease as a comorbidity at the time of hospitalization to prevent the progression of geriatric syndrome associated with prolonged hospitalization.

Behçet's Disease with Extremely High Levels of Urinary ß2-Microglobulin after Non-Steroidal Anti-Inflammatory Drug Treatment.

Behçet's disease is an inflammatory disease which manifests itself as various symptoms, such as uveitis, oral and genital aphthae, erythema nodosa, gastro-intestinal ulcerations and encephalopathy. Among the manifestations, renal dysfunction is reported in some percentage of the patients with this disorder. We experienced a middle-aged male with Behçet's disease who showed an extremely high level of urinary ß2-microglulin, which is one of the markers of renal dysfunction, despite normal serum creatinine levels. The patient was on non-steroidal anti-inflammatory drug (NSAID) therapy for 7 weeks, and this could have affected his renal dysfunction. The present report suggests that renal injury should not be underestimated in patients with Behçet's disease, especially in patients using NSAIDs.

Evaluation of the FilmArray Blood Culture Identification Panel on Detection of Pathogenic Microorganisms in Positive Blood Cultures: the First Clinical Report in Japan.

FilmArray (FA) is a multiplex PCR-based desktop microbial detection system. The blood culture identification (BCID) panel is an adaptable panel for FA, which diagnoses sepsis and/or systemic infections by detecting 14 bacterial species, 4 bacterial genera, 1 bacterial family, 5 yeast species, and 3 antimicrobial resistance genes (mecA, Klebsiella pneumoniae carbapenemase [KPC], and vanA/B) in positive blood cultures within 1 h. We retrospectively evaluated the FA-BCID panel using 54 positive blood cultures, in which 57 bacterial and 3 yeast strains were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The FA-BCID panel revealed 59 microorganisms in 53 samples; this performance was similar to that of MALDI-TOF MS analysis; however, 1 bacterium in 1 sample was not detected. In addition, mecA genes were detected in 12 Staphylococcus species, which all manifested methicillin resistance in susceptibility testing, whereas genes KPC and vanA/B were not detected, in agreement with the results of antimicrobial susceptibility testing. Although more information on antimicrobial resistance, including activity of IMP-metallo-ß-lactamases, is required in Japan, the FA-BCID panel can detect pathogenic microorganisms in positive blood cultures rapidly, and this method could be beneficial for proper treatment of sepsis and/or systemic infections, especially in small hospitals.

Use of percutaneous image-guided coaxial core-needle biopsy for diagnosis of intraabdominal lymphoma.

Although pathological diagnosis is essential for managing malignant lymphoma, intraabdominal lesions are generally difficult to approach due to the invasiveness of abdominal surgery. Here, we report the use of percutaneous image-guided coaxial core-needle biopsy (CNB) to obtain intraabdominal specimens for diagnosing intraabdominal lymphomas, which typically requires histopathological and immunohistochemical evaluation. We retrospectively reviewed consecutive cases involving computed tomography (CT)- or ultrasonography (US)-guided CNB to obtain pathological specimens for intraabdominal lesions from 1999 to 2011. Liver, spleen, kidney, and inguinal node biopsies were excluded. We compared CNBs with laparotomic biopsies. A total of 66 CNBs were performed for 59 patients (32 males, 27 females; median age, 63.5), including second or third repeat procedures. Overall diagnostic rate was 88.5%. None of the patients required additional surgical biopsies. Notably, the median interval between recognition of an intraabdominal mass and biopsy was only 1 day. Forty-five procedures were performed for hematological malignancies. Adequate specimens were obtained for histopathological diagnosis in 86% of cases. Flow cytometry detected lymphoma cells in 79.5% of cases. Twelve patients (nine males, three females; median age, 60) were eligible for surgical biopsy. While every postoperative course was satisfactory, median duration from lesion recognition to therapy initiation for lymphoma cases was significantly shorter for CNB than for surgical biopsy (14 vs. 35 days). While one-fourth of the patients were not eligible for the procedures, CNB is safe and highly effective for diagnosis of intraabdominal lymphomas. This method significantly improves sampling and potentially helps attain immunohistological distinction, allowing for more timely therapy initiation.

Congenital dysfibrinogenemia coincidentally diagnosed at the onset of chronic myelogenous leukemia.

A 34-year-old man was referred to our hospital for leukocytosis and fundal hemorrhage. Peripheral blood and coagulation tests showed increases in cells at all stages of the neutrophilic series and a low level of fibrinogen (Fbg). Chronic myelogenous leukemia (CML) was diagnosed, and nilotinib was administered. During the clinical course of CML treatment, plasma Fbg levels continued to be low, but the patient showed neither hemorrhagic nor thrombotic complications. Fbg analysis showed normal antigen levels and low activity levels, which indicated dysfibrinogenemia. Genetic analysis revealed a heterozygous gene mutation (γ308AAT→AAG), a mutation which was also found in the patient's mother. Asymptomatic patients with dysfibrinogenemia have a low risk of hemorrhage in daily life and do not require treatment. However, in those undergoing major surgery or in serious accidents, replacement therapy may be required. When the cause of low Fbg levels is unknown, dysfibrinogenemia or fibrinogen deficiency should be considered. Even asymptomatic patients may benefit from more detailed immunologic and genetic analyses.

[Fatal bone marrow necrosis and fat embolism following sepsis in a patient with acute lymphoblastic leukemia after consolidation chemotherapy].

We report a 58-year-old Japanese man with acute lymphoblastic leukemia. On the seventh day of his second course of consolidation therapy, he developed herpes zoster, and on the 17th day, he developed a high fever, dyspnea, and lapsed into a coma. Streptococcus constellatus was isolated from blood culture. Despite intensive therapy, multiple organ failure progressed rapidly, and he died on the 19th day. Pathological examination of autopsy specimens revealed bone marrow necrosis and fat embolism in multiple organs. In this patient, sepsis led to bone marrow necrosis and, subsequently, to fat embolism.

Acute exacerbation of Toxoplasma gondii infection after hematopoietic stem cell transplantation: five case reports among 279 recipients.

Toxoplasmosis is a rare and possibly underestimated complication following hematopoietic stem cell transplantation (HSCT) associated with a high mortality rate, although the incidence of toxoplasmosis after HSCT in Japan has not been established. We retrospectively studied patients with toxoplasmosis after HSCT, and identified five patients who had been diagnosed with an acute exacerbation of toxoplasmosis among 279 HSCT recipients at our institution between 1998 and 2011, representing an incidence of 1.8 %. Among 87 autologous HSCT recipients, one definite case was diagnosed. The serological test for Toxoplasma gondii before HSCT was positive in 18 of 192 allogeneic HSCT recipients. Of the 18 seropositive patients, three had definite infections, and one had possible infection. All four definite cases were diagnosed at autopsy. In the definite cases, three allogeneic HSCT recipients had disseminated or pulmonary toxoplasmosis and one autologous HSCT recipient had toxoplasmic encephalitis, although toxoplasmosis was not suspected at the premortem examination due to non-specific clinical and radiological manifestations. Thus, acute exacerbation of toxoplasmosis should be suspected in recipients after HSCT. Early diagnosis and treatment for toxoplasmosis would certainly contribute to a decrease in mortality after HSCT.

[Long-term remission of Langerhans cell sarcoma by AIM regimen combined with involved-field irradiation].

A 67-year-old woman presented with a right inguinal mass in May 2006. CT scan showed lymph node involvement from the right inguinal to the common iliac and (18)F-FDG-PET revealed uptake in those areas. Biopsy results indicated Langerhans cell sarcoma (LCS). Interestingly, tumor cells expressed a high MIB1 index of 30%. We administered doxorubicin, ifosfamide, and mesna (AIM) chemotherapy, which were reported to effectively treat soft tissue sarcoma. After 5 courses of AIM therapy and involved-field radiation for residual diseases and a relapsed lesion on her right cervical node, she has remained in complete remission for more than 4 years. LCS is an intractable malignant disease and the optimal therapeutic strategy remains unclear. The AIM regimen combined with radiation therapy may be an effective treatment option for this disease.

Severe pulmonary toxoplasmosis mimicking viral pneumonitis after a third allogeneic stem cell transplantation in a man with acute lymphoblastic leukemia.

A 22-year-old man with acute lymphoblastic leukemia underwent allogeneic stem cell transplantation (allo-SCT) twice, then underwent allo-SCT a third time due to relapse. On day 27, he developed acute respiratory distress, and bilateral interstitial infiltrates were noted on CT images. Despite receiving intensive treatment, the patient died on day 32 from progressive respiratory failure. An autopsy revealed evidence of diffuse alveolar damage caused by the genus Toxoplasma. At present, toxoplasmosis is considered to be a rare infectious complication in Japan. However, the actual incidence of toxoplasmosis may be higher than currently believed due to a lack of suspicion of the diagnosis in patients, difficulty in making a diagnosis and low autopsy rates.

Clinical characteristics of human immunodeficiency virus-associated Hodgkin lymphoma patients in Japan.

The incidence of Hodgkin lymphoma (HL) is paradoxically increasing in the combination anti-retroviral therapy (cART) era. However, there has been no nationwide survey of human immunodeficiency virus (HIV)-associated HL (HIV-HL) in Japan. We retrospectively examined the clinical characteristics and outcomes of 19 newly diagnosed HIV-HL patients at 11 HIV/AIDS and hematology regional hospitals in Japan between 1991 and 2010. At the time of HL diagnosis, 79 % of patients were receiving cART. All the patients, but one received HL diagnoses in the cART era. The median CD4+ cell count at HIV-HL diagnosis was 169/µl. Mixed-cellularity classical Hodgkin lymphoma was the most common subtype occurring in 68 % of the patients; 89 % of the patients were positive for Epstein-Barr virus. Of these 19 patients, 84 % were in advanced stages, with bone marrow involvement observed in 47 % of the patients; 58 % had extranodal sites. All the treated patients were given cART concurrent with HL therapy. The complete remission rate of the treated patients was 87 %. The median OS of the entire cohort was 17 months. These results suggest that the characteristics of HIV-HL in Japan are more aggressive than those of non-HIV-associated HL in Japan, but standard chemotherapy is effective and feasible.

[Successful treatment with low-dose etoposide for hemophagocytic syndrome following reduced-intensity conditioning for cord blood transplantation in a patient with acute myelgenous leukemia].

A 56-year-old man was diagnosed with acute myeloid leukemia with myelodysplasia-related changes. Chromosomal analysis showed a complex karyotype. Complete remission could not be achieved even after several induction chemotherapy regimens, and the patient suffered from invasive pulmonary aspergillosis. He was transferred to our hospital and underwent reduced-intensity conditioning cord blood transplantation (RIC-CBT) in a non-remission state. The conditioning regimen involved fludarabine 125 mg/m2 combined with melphalan 140 mg/m2 and total body irradiation (4 Gy). GVHD prophylaxis was tacrolimus alone at relatively low concentrations (app. 5 ng/ml). On days 6 and 9 after CBT, he experienced a pre-engraftment immune reaction and hemophagocytic syndrome (HPS). We started steroid pulse therapy, but this failed to resolve the symptoms. We then administered low-dose etoposide (50 mg/m2). The symptoms gradually resolved after three administrations of etoposide and engraftment was achieved on day 35. Satisfactory hematological recovery was noted on day 300 after CBT and the patient has maintained complete remission to date. HPS is one of the most serious complications following CBT and often results in engraftment failure. This case suggests that repeated administration of etoposide may safely and effectively overcome this serious complication in some cases.