Associations of disease duration and anti-citrullinated peptide antibody status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis: Post hoc analysis of a multicentre, real-world observational study in Japan (ORIGAMI).

OBJECTIVES: The aim of the article is to investigate the associations of disease duration and anti-cyclic citrullinated peptide antibody (ACPA) status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis (RA). METHODS: We performed post hoc analyses of the Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study of biologic-naïve RA patients aged ≥20 years with moderate disease activity who were prescribed abatacept. Changes in the Simplified Disease Activity Index (SDAI) and Japanese Health Assessment Questionnaire (J-HAQ) at 4, 24, and 52 weeks of treatment were analysed in patients divided according to ACPA serostatus (positive/negative), disease duration (<1/≥1 year), or both. RESULTS: SDAI scores decreased from baseline in all groups. SDAI scores tended to decrease more in the ACPA-positive group and disease duration <1-year group than in the ACPA-negative group and disease duration ≥1-year group, respectively. In the disease duration <1-year group, SDAI tended to decrease more in the ACPA-positive group than in the ACPA-negative group. Disease duration was independently associated with the change in SDAI and SDAI remission at Week 52 in multivariable regression models. CONCLUSIONS: These results suggest that starting abatacept within 1 year of diagnosis was associated with greater effectiveness of abatacept in biologic-naïve patients with RA and moderate disease activity.

Predictive factors for mortality in elderly Japanese patients with severe microscopic polyangiitis: A retrospective single-center study.

PURPOSE: To determine mortality and its predictive factors in elderly Japanese patients with severe microscopic polyangiitis (MPA). METHOD: This retrospective single-center study determined the mortality of 52 patients with MPA who were admitted to our geriatric medical center from 2002 to 2014. The variables at baseline, including patient demographics, clinical characteristics, and treatment, were analyzed for their association with mortality. RESULT: Mean age at onset of MPA was 73.2 years, and the one-year survival rate was 65.9%. Relapse was observed in 32.7%. Among variables at diagnosis, age, cardiomyopathy, central nervous system (CNS) involvement, alveolar hemorrhage, disease severity, the 1996 Five-Factor Score (FFS), and the 2009 FFS were associated with mortality in univariate analysis. Cardiomyopathy, CNS involvement, age >65 years, disease severity, Birmingham Vasculitis Activity Score, the 1996 FFS, and the 2009 FFS were associated with relapse-free survival in univariate analysis. CONCLUSION: We investigated mortality and relapse-free survival and their predictive factors in elderly Japanese patients with severe MPA. Age, disease severity, the 1996 FFS, and the 2009 FFS at diagnosis were prognostic factors for both mortality and relapse-free survival.

[Blood culture results in elderly febrile patients].

AIM: We retrospectively evaluated blood culture results in elderly patients (≥65 years) with a fever due to infection. METHODS: We examined the bacteria isolated from blood cultures and compared them to bacteria detected in infected lesions that caused bacteremia. We compared the types of bacteria isolated in the two groups (the community-acquired group and the hospital-acquired group). RESULTS: Blood cultures were obtained from 638 patients. Bacteria were detected in 182 patients (28.5%), including 66 (36.3%) patients in the community-acquired group and 116 (63.7%) patients in the hospital-acquired group. There were 259 positive samples (25.1%). In arterial blood specimens, 153 (30.9%) samples were positive, while in venous blood specimens, there were 106 (19.8%) positive samples (P<0.001). In the community-acquired group, the most common bacteria identified were E. coli compared to S. epidermidis in the hospital-acquired group. More than 50% of the bacteria identified in the blood cultures were of the same species identified in the respective urine samples and central venous catheter tips. CONCLUSIONS: The bacteria detection rate in this study was 28.5% for blood cultures, which is higher than the 17.5% reported by the Japan Nosocomial Infections Surveillance Program conducted by the Japanese Ministry of Health, Labour and Welfare. These results suggest that in elderly patients from whom an insufficient volume of blood can be drawn from a vein, an arterial sample may increase the detection rate. A high percentage of bacterial species isolated from the blood cultures was also detected in urinary tract infections and central venous catheter-related infections, indicating that a blood culture is useful for detecting various infectious diseases, even in elderly febrile patients.

Dental Care to Reduce Aspiration Pneumonia Recurrence: A Prospective Cohort Study.

BACKGROUND: Aspiration pneumonia has a high recurrence rate, and oral care by dentists has been found effective in preventing its onset; however, this has not been evaluated using prospective studies. Therefore, we conducted a prospective study to evaluate the effectiveness of professional oral care by dentists in reducing aspiration pneumonia recurrence in older adult patients. METHODS: In this prospective cohort study, we evaluated a dental oral care intervention, using a historical control group (control group). It was conducted at a single-centre regional core hospital in Japan that serves a large number of patients aged older than 80 years. Patients who were hospitalised for aspiration pneumonia were included in this study. During the study period (1 April 2021 to 31 March 2022), the clinical group received weekly professional cleaning by a dentist and the control group received standard oral care by a nurse as usual from 1 April 2020 to 31 March 2021. The dentist oral care group received weekly professional oral care from a dentist and was followed prospectively for 1 year. A Kaplan-Meier analysis was used to evaluate the timing of recurrent aspiration pneumonia or death. A Cox proportional hazards model was used to obtain a hazard ratio and determine the 95% confidence intervals. RESULTS: There were 91 participants in the clinical group and 94 in the control group. The mean age of participants was 85 years, and 75 (40.5%) were female. The recurrence rate was 27.5% in the clinical group and 44.7% in the control group (P = .005). Professional cleaning by a dentist reduced the risk of recurrence of aspiration pneumonia by approximately 50% (adjusted hazard ratio, 0.465; 95% confidence interval, 0.278-0.78). CONCLUSIONS: Professional cleaning by a dentist was associated with a lower rate of aspiration pneumonia recurrence than nurse-provided conventional oral care.

Dietary Intake in Older Patients with Dementia Prior to and After the Onset of Coronavirus Disease 2019.

This was an observational study of hospitalized patients with dementia who developed COVID-19. The disease course, dietary intake, and disease severity (mild/severe) were evaluated. Twenty-nine patients with a median age of 84 years, with both mild (18) and severe conditions, (11) were evaluated. Mild group had decreased food intake from the day of symptom onset. In the severe group, the decline began the day before symptom onset. On day 30 of the disease, the median food intake of the mild group returned to levels observed prior to symptom onset, in contrast to those in the severe group.

[A case of intravascular large B-cell lymphoma with rapidly progressive cognitive impairment after cerebral infarction].

A 67-year-old man started to show symptoms of dementia and developed convulsions accompanied by presyncope. Since an old cerebral infarction was found, he was given a diagnosis of symptomatic epilepsy, treated with antiepileptics. Dementia progressed rapidly, resulting in admission to a dementia ward. There were no physical abnormalities, and only slight elevations of LDH and CRP were noted. He suddenly developed a fever between 38°C and 39°C. Only the serum concentration of soluble IL-2 receptor was elevated at 6,430 U/L. Although a malignant tumor of the lymphatic system was suspected, there was no swelling noted in the superficial lymph nodes. The patient suddenly developed hypoxemia, thrombocytopenia, and an increase in fibrin degradation products. Pulmonary thromboembolism was suspected, but contrast-enhanced chest CT did not reveal any abnormalities. Bone marrow aspiration did not detect any infiltrations of lymphoid cells but was suggestive of hemophagocytic syndrome. After that, a new cerebral infarction occurred. Based on the course, intravascular lymphoma, which causes microvascular occlusions in various organs, was considered probable. Prednisolone was administered at a dose of 60 mg daily and skin biopsy was scheduled. However, the patient experienced a sudden deterioration and died. In autopsy, immunostain with CD20 showed that the arteriolae, capillaries, and venulae of thoracic and abdominal organs were filled with cells of large B-cell lymphoma. The presence of similar cerebrovascular lesions was not confirmed, but can reasonably be speculated. Thus, the present case suggests that it is necessary to consider intravascular lymphoma when dementia rapidly progresses for unknown reasons.

[Death in geriatric pneumonia patients].

AIM: Pneumonia-associated deaths are the 4th leading cause of death in elderly people, and fatality tends to increase with age, especially after the age of 65. We aimed to further define convalescence in this patient population by examining the clinical characteristics of elderly pneumonia patients. METHODS: We retrospectively examined the data of 292 patients aged 65 years or older who had died of pneumonia. Analysis was performed according to the guidelines for the management of pneumonia of the Japanese Respiratory Society (JRSGMP), which retrospectively classifies pneumonia into a community-acquired type (c type) and hospital-acquired type (h type). In the present study, there were 110 cases of c type and 182 cases of h type. RESULTS: Among the factors that accurately predicted disease severity in the c type group, age was associated with the highest frequency (104; 94.5%). Furthermore, age was most frequently associated with a convalescence prediction factor in the h type group (150; 82.4%). The remaining factors collectively comprised approximately 50%. Except in mild cases in the c type group, deaths occurred in each of the disease severity groups for both pneumonia types. Dysphagia occurred in many cases in both groups, and in both pneumonia types the most common complication was dementia. In the h type group, cerebrovascular diseases were the second most common complication. CONCLUSION: When assessing disease severity in elderly pneumonia patients, the JRSGMP may not allow accurate judgment of convalescence. It is very likely that dementia and cerebrovascular diseases cause dysphagia. Furthermore, very elderly patients are frequently at risk of developing aspiration pneumonia during treatment. For these reasons, it may be necessary to add the condition of a patient with these complications to the disease severity rating or convalescence prediction factor when considering the outcome of pneumonia in very elderly patients. It is necessary to consider all these factors when treating such episodes.

Polymyalgia Rheumatica in a Patient with Pseudogout and Dementia.

BACKGROUND The differential diagnosis of generalized pain includes reactivity associated with bacterial and viral infections, autoimmune rheumatic disease, and orthopedic diseases. Obtaining a detailed medical history and establishing an accurate diagnosis are difficult in elderly patients with dementia. In addition, the differential diagnosis between polymyalgia rheumatica and pseudogout is often difficult. Thus, in our work, we examined the importance of interviewing the family of an elderly patient with dementia. CASE REPORT We report the case of an 88-year-old woman with dementia and a history of recurrent pseudogout who presented with a 12-day history of fever and generalized pain. Physical examination findings revealed warmth and swelling in the shoulder joints and right knee. Blood tests indicated increased inflammatory marker levels. The primary working impression was oligo-articular pseudogout. Based on family interview, the patient was seen to manifest atypical symptoms, including movement difficulty. Joint ultrasound findings showed inflammation of the left long head of the biceps attachment. Further, right knee arthrocentesis detected no calcium pyrophosphate crystals. After obtaining a detailed medical history from the patient's family and conducting other diagnostic tests, the patient was finally diagnosed with polymyalgia rheumatica, rather than oligo-articular pseudogout, with rapid improvement after undergoing low-dose prednisolone treatment. CONCLUSIONS Family interviews can be helpful for obtaining correct diagnosis in elderly patients with dementia.

Delayed treatment of bacteremia during the COVID-19 pandemic.

OBJECTIVES: Coronavirus disease (COVID-19) blindness, that is, the excessive consideration of the disease in diagnosis, has reportedly led to delayed diagnosis of some diseases. We compared several clinical measures between patients admitted for bacteremia during the two months of the COVID-19 pandemic and those admitted during the same period in 2019. We hypothesized that the pandemic has led to delayed treatment of bacteremia. METHODS: This retrospective observational study compared several measures undertaken for patients who visited the emergency unit in two hospitals between March 1 and May 31, 2020, during the COVID-19 pandemic and whose blood cultures tested positive for bacteremia with those for corresponding patients treated during the same period in 2019. The primary measure was time from consultation to blood culture/antimicrobials. RESULTS: We included 29 eligible patients from 2020 and 26 from 2019. In 2020, the time from consultation to antimicrobial administration was significantly longer than in 2019 (mean [range], 222 [145-309] min vs. 139 [102-179] min, p=0.002). The frequency of chest computed tomography (CT) was significantly higher in 2020 (96.6 vs. 73.1%, p=0.021). Significant differences were not observed in the time to blood culture or chest CT preceding the blood culture between the two periods. CONCLUSIONS: Our findings suggested that due to the COVID-19 epidemic/pandemic, focusing on the exclusion of its infection using CT scans leads to an overall delay in the diagnosis and treatment of bacteremia. Medical providers must be aware of COVID-19 blindness and evaluate patients objectively based on rational criteria and take appropriate action.

Investigation of pathological and clinical features of lupus nephritis in 73 autopsied cases with systemic lupus erythematosus.

The aims of this study were to analyze the clinical and pathological features of lupus nephritis (LN) and examine the association between these features and pathological condition, treatment, and prognosis. Of the 177 systemic lupus erythematosus patients who died while receiving inpatient care at Juntendo University Hospital between 1960 and 2001, we investigated the clinical features, treatment, and pathological features of 73 of these who underwent pathological autopsy and had a clear medical history. We divided these cases into two groups, i.e., those up to 1979 (Group A) and those during and after 1980 (Group B) in order to investigate changes in tendencies by age. We also divided the cases into three groups by time interval between diagnosis and death to investigate long-term prognosis. Uremia was the direct cause of death in 38.9% of cases in Group A and only 10.8% of cases in Group B. Pathological features showed a tendency to change to a sclerotic lesion as the duration of the disorder became longer. Uremia attributable to LN was the direct cause of death in relatively fewer cases, although it is still found in the majority of LN cases and remains a problem requiring stringent management. The treatment of sclerotic lesions may be an issue that needs further attention.

Plasma Exchange Therapy to Reduce Mortality in Japanese Patients With Diffuse Alveolar Hemorrhage and Microscopic Polyangiitis.

Diffuse alveolar hemorrhage (DAH) is well known as a serious complication of microscopic polyangiitis (MPA). We examined the effectiveness of plasma exchange (PLEX) therapy to reduce mortality in Japanese DAH patients with MPA. This retrospective, double-center, observational cohort study included 20 DAH patients with MPA who were admitted to Juntendo University Hospital or Juntendo Koto Geriatric Medical Center between April 1998 and March 2018. The primary outcome was non-disease-specific mortality. The 1-year survival rate of patients with PLEX therapy (N = 4) was higher than that of patients with conventional therapy (N = 16, 75% and 13%, respectively, P = 0.037). Higher values of the 1996 Five-Factor Score (FFS) and 2009 FFS were associated with increased mortality, with hazard ratios of 2.29 (P = 0.040) and 2.41 (P = 0.043), respectively, by Cox univariate analysis. We investigated PLEX therapy for reducing mortality in DAH patients with MPA, and the 1996 FFS and 2009 FFS were both independent prognostic factors.

Immunoadsorption plasmapheresis using a phenylalanine column as an effective treatment for lupus nephritis.

Immunoadsorption plasmapheresis (IAPP) is effective for eliminating pathogenic molecules such as anti-DNA antibody (anti-DNA Ab) and immune complexes from the serum of patients with systemic autoimmune diseases. The purpose of this study was to assess patients with lupus nephritis (LN) treated by IAPP using a phenylalanine column and determine its efficacy with respect to conventional therapies. Six patients (M = 1, F = 5) with histologically proven LN associated with proteinuria and abnormal sedimentation on urinalysis were the subjects for this study. All were treated with oral corticosteroid (prednisolone 1 mg/kg/day) and IAPP (Immusorba PH - 350; 2 L of plasma twice weekly for 2 weeks). Serum anti-DNA Ab and complement, urinary protein, and creatinine clearance were measured over 6 weeks (pretreatment, before and after each of 2 IAPP sessions, and 1 and 4 weeks after the second IAPP session). Clinical efficacy of IAPP was compared with conventional pharmacotherapy regimes by conducting a retrospective review of 23 LN patients treated at our hospital using corticosteroid pulse therapy (CSPT, N = 7, intravenous methylprednisolone 500 mg/day for 3 days), intravenous cyclophosphamide pulse therapy (IVCY, N = 7), or corticosteroid monotherapy (CSMT, N = 9, oral prednisone 1 mg/kg body weight daily, for 4 weeks). Immunosuppressants and anticoagulants were not used. With IAPP, mean urinary protein excretion decreased from 2.2 +/- 1.7 g/day pretreatment to 0.4 +/- 0.6 g/day post-treatment (P < 0.001). Mean serum anti-DNA Ab also decreased from 84.0 +/- 88.1 U/mL pretreatment to 5.8 +/- 5.5 U/mL post-treatment (P < 0.05). In combination with corticosteroid therapy, IAPP would appear to be an effective and safe treatment for LN.

A case of very-late-onset systemic lupus erythematosus.

A 93-year-old woman was admitted to our hospital because of fever. Radiographic findings revealed accumulation of pleural fluid. Moreover, blood tests revealed inflammation, lymphopenia, hypocomplementemia, positive for anti-nuclear antibody, and elevated anti-DNA antibody level. Therefore, the patient was diagnosed with pleuritis associated with systemic lupus erythematosus (SLE). Administration of prednisolone 20 mg/day resulted in a marked improvement in fever, pleuritis, and laboratory findings. We report a case of very-late-onset SLE that occurred at the age of 93.

Plasma adsorption in critical care.

Plasmapheresis therapies such as plasma exchange (PE), double filtration plasmapheresis (DFPP), or immunoadsorption plasmapheresis (IAPP) have become therapeutic tools in critical care. PE or DFPP are limited by their non- or semiselective removal of all plasma components. Replacement fluids such as fresh frozen plasma and albumin are necessary during PE or DFPP. There is the risk of infection and allergic reactions whenever such fluids are used. On the other hand, IAPP is superior to PE and DFPP because it does not require any replacement fluid. There has been development of many adsorbent columns used for removing specific pathogenic substances, and patients with various kinds of critical illness have been treated with IAPP. However, IAPP can be applied only for certain diseases because of the limitations of the commercially available columns. It is concluded that the development of new adsorption therapy may improve the high mortality and morbidity rate in critically ill patients.

CD154 expression and mRNA stability of activated CD4-positive T cells in patients with systemic lupus erythematosus.

Abstract The expression of CD154 (CD40 ligand) on activated CD4+ T cells is known to be transient and tightly regulated for antigen-specific immune responses, and is increased and prolonged among patients with systemic lupus erythematosus (SLE). We investigated the regulation of CD154 expression by determining the protein and mRNA expression with PMA and ionomycin stimulation in CD4+ T cells, and confirmed their increase and prolongation in SLE T cells. Treatment with actinomycin D, a transcription inhibitor, after PMA and ionomycin stimulation was performed, and the findings revealed that the stability of CD154 mRNA increased significantly in activated SLE T cells compared with that of controls. However, alternations or abnormal sequences were not identified in the 3″ untranslated region, including AU-rich elements and CU-rich sequences, while their partial involvement in the posttranscriptional regulation of CD154 mRNA stability has been reported. With 96 h culture in vitro, the destabilization of CD154 mRNA was demonstrated, resulting in a corresponding decrease and normalization of surface expression on activated SLE T cells. We speculate that the CD154 expression on T cells from SLE patients may be increased and prolonged, with mRNA stabilization being related to a continuous stimulation in vivo.