Bortezomib-cyclophosphamide-dexamethasone induction/consolidation and bortezomib maintenance for transplant-eligible newly diagnosed multiple myeloma: phase 2 multicenter trial.

OBJECTIVES: We conducted a phase II trial to prospectively evaluate the efficacy and safety of bortezomib-cyclophosphamide-dexamethasone (VCD) induction, autologous stem cell transplantation (ASCT), VCD consolidation, and bortezomib maintenance in transplant-eligible newly diagnosed multiple myeloma (NDMM) patients in Japan (UMIN000010542). METHODS: From 2013 to 2016, 42 patients with a median age of 58 (range 42-65) years with NDMM were enrolled in 15 centers. The primary endpoint was the complete response (CR) /stringent CR (sCR) rate after transplantation, and overall/progression-free survival rates were also evaluated. RESULTS: Following induction therapy, the overall response rate was obtained in 71% of patients, including a CR/sCR of 10% and a very good partial response (VGPR) of 26%. Twenty-six of the 42 patients completed ASCT following the protocol and CR/sCR and VGPR rate 100 days after ASCT was 26% and 17%, respectively. During consolidation therapy, 3 of the 24 patients achieved deeper responses. Eight of the 18 patients completed 2-year bortezomib maintenance without disease progression and grade 3/4 toxicities. Five patients were VGPR or partial response after ASCT but maintained response with 2-year bortezomib maintenance. Two-year overall and progression-free survival rates were 92.5% (95% confidence interval [CI]: 78.5%-97.5%) and 62.6% (95% CI: 45.8%-75.5%), respectively. Grade 3/4 toxicities (≥ 10%) included neutropenia (19%) and anemia (17%) in induction, and thrombocytopenia (29%) in consolidation. CONCLUSION: VCD induction/consolidation and bortezomib maintenance with ASCT for NDMM resulted in a high CR/sCR rate and provided good overall/progression-free survival in Japan.

Sex Difference and Rupture Rate of Intracranial Aneurysms: An Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture. METHODS: We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage. RESULTS: We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89-1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58-0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (≥7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07-1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02-1.90). CONCLUSIONS: Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women.

Difference in Rupture Risk Between Familial and Sporadic Intracranial Aneurysms: An Individual Patient Data Meta-analysis.

BACKGROUND AND OBJECTIVES: We combined individual patient data (IPD) from prospective cohorts of patients with unruptured intracranial aneurysms (UIAs) to assess to what extent patients with familial UIA have a higher rupture risk than those with sporadic UIA. METHODS: For this IPD meta-analysis, we performed an Embase and PubMed search for studies published up to December 1, 2020. We included studies that (1) had a prospective study design; (2) included 50 or more patients with UIA; (3) studied the natural course of UIA and risk factors for aneurysm rupture including family history for aneurysmal subarachnoid haemorrhage and UIA; and (4) had aneurysm rupture as an outcome. Cohorts with available IPD were included. All studies included patients with newly diagnosed UIA visiting one of the study centers. The primary outcome was aneurysmal rupture. Patients with polycystic kidney disease and moyamoya disease were excluded. We compared rupture rates of familial vs sporadic UIA using a Cox proportional hazard regression model adjusted for PHASES score and smoking. We performed 2 analyses: (1) only studies defining first-degree relatives as parents, children, and siblings and (2) all studies, including those in which first-degree relatives are defined as only parents and children, but not siblings. RESULTS: We pooled IPD from 8 cohorts with a low and moderate risk of bias. First-degree relatives were defined as parents, siblings, and children in 6 cohorts (29% Dutch, 55% Finnish, 15% Japanese), totaling 2,297 patients (17% familial, 399 patients) with 3,089 UIAs and 7,301 person-years follow-up. Rupture occurred in 10 familial cases (rupture rate: 0.89%/person-year; 95% confidence interval [CI] 0.45-1.59) and 41 sporadic cases (0.66%/person-year; 95% CI 0.48-0.89); adjusted hazard ratio (HR) for familial cases 2.56 (95% CI 1.18-5.56). After adding the 2 cohorts excluding siblings as first-degree relatives, resulting in 9,511 patients, the adjusted HR was 1.44 (95% CI 0.86-2.40). DISCUSSION: The risk of rupture of UIA is 2.5 times higher, with a range from a 1.2 to 5 times higher risk, in familial than in sporadic UIA. When assessing the risk of rupture in UIA, family history should be taken into account.

Differences Between Subarachnoid Hemorrhage Seen in Daily Practice and Aneurysms That Rupture During Follow-Up.

[Figure: see text].

Predictors of New Dementia Diagnoses in Elderly Individuals: A Retrospective Cohort Study Based on Prefecture-Wide Claims Data in Japan.

Preventing dementia in elderly individuals is an important public health challenge. While early identification and modification of predictors are crucial, predictors of dementia based on routinely collected healthcare data are not fully understood. We aimed to examine potential predictors of dementia diagnosis using routinely collected claims data. In this retrospective cohort study, claims data from fiscal years 2012 (baseline) and 2016 (follow-up), recorded in an administrative claims database of the medical care system for the elderly (75 years or older) in Niigata prefecture, Japan, were used. Data on baseline characteristics including age, sex, diagnosis, and prescriptions were collected, and the relationship between subsequent new diagnoses of dementia and potential predictors was examined using multivariable logistic regression models. A total of 226,738 people without a diagnosis of dementia at baseline were followed. Of these, 26,092 incident dementia cases were detected during the study period. After adjusting for confounding factors, cerebrovascular disease (odds ratio, 1.15; 95% confidence interval, 1.11-1.18), depression (1.38; 1.31-1.44), antipsychotic use (1.40; 1.31-1.49), and hypnotic use (1.17; 1.11-1.24) were significantly associated with subsequent diagnosis of dementia. Analyses of routinely collected claims data revealed neuropsychiatric symptoms including depression, antipsychotic use, hypnotic use, and cerebrovascular disease to be predictors of new dementia diagnoses.

Low back pain precedes the development of new knee pain in the elderly population; a novel predictive score from a longitudinal cohort study.

BACKGROUND: To investigate the association between knee pain and risk factors including low back pain and to develop a score to predict new knee pain in an older population, using population-based longitudinal cohort data. METHODS: We collected a questionnaire on self-reported knee pain and demographic data in a systematic manner from community residents aged ≥ 50 years twice, at baseline, and after 5 years. Multivariate logistic regression analyses were performed to investigate the association between knee pain and risk factors and to build a predictive model that would enable calculation of the risk of the development of knee pain within 5 years. The model is presented in the form of score charts. RESULTS: A total of 5932 residents aged ≥ 50 years from the cohort of 9764 that completed the first questionnaire were enrolled in the second survey. After exclusions, paired data for the two time points an average of 5.4 years apart were analyzed for 4638 participants. Multivariate analyses showed older age, female sex, higher BMI, weight increase, lower mental health score, and higher back pain/disability score were independent risk factors for knee pain. The predictive score comprised six factors: age, sex, BMI, weight increase, mental health, and low back pain/disability. The risk of developing knee pain ranged from 11.0 to 63.2% depending on the total score. CONCLUSION: This study demonstrated a significant association between knee and low back pain/disability along with other risk factors. The score we developed can be used to identify a population without any imaging modality who are at high risk of developing knee pain.

Rupture risk of small unruptured cerebral aneurysms.

OBJECTIVEThe annual rupture rate of small (3-4 mm) unruptured cerebral aneurysms (UCAs) is 0.36% per year, however, the proportion of small ruptured aneurysms < 5 mm is 35%. This discrepancy is explained by the hypothesis that most acute subarachnoid hemorrhage (SAH) is from recently formed, unscreened aneurysms, but this hypothesis is without definitive proof. The authors aimed to clarify the actual number of screened, ruptured small aneurysms and risk factors for rupture.METHODSThe Unruptured Cerebral Aneurysm Study Japan, a project of the Japan Neurosurgical Society, was designed to clarify the natural course of UCAs. From January 2001 through March 2004, 6697 UCAs among 5720 patients were prospectively registered. At registration, 2839 patients (49.6%) had 3132 (46.8%) small UCAs of 3-4 mm. The registered, treated, and rupture numbers of these small aneurysms and the annual rupture rate were investigated. The rate was assessed per aneurysm. The characteristics of patients and aneurysms were compared to those of larger unruptured aneurysms (≥ 5 mm). Cumulative rates of SAH were estimated per aneurysm. Risk factors underwent univariate and multivariate analysis.RESULTSTreatment and rupture numbers of small UCAs were 1132 (37.1% of all treated aneurysms) and 23 (20.7% of all ruptured aneurysms), respectively. The registered, treated, rupture number, and annual rupture rates were 1658 (24.8%), 495 (16.2%), 11 (9.9%), and 0.30%, respectively, among 3-mm aneurysms, and 1474 (22.0%), 637 (20.9%), 12 (10.8%), and 0.45%, respectively, among 4-mm aneurysms. Multivariate risk-factor analysis revealed that a screening brain checkup (hazard ratio [HR] 4.1, 95% confidence interval [CI] 1.2-14.4), history of SAH (HR 10.8, 95% CI 2.3-51.1), uncontrolled hypertension (HR 5.2, 95% CI 1.8-15.3), and location on the anterior communicating artery (ACoA; HR 5.0, 95% CI 1.6-15.5) were independent predictors of rupture.CONCLUSIONSAlthough the annual rupture rate of small aneurysms was low, the actual number of ruptures was not low. Small aneurysms that ruptured during follow-up could be detected, screened, and managed based on each risk factor. Possible selection criteria for treating small UCAs include a history of SAH, uncontrolled hypertension, location on the ACoA, and young patients. Further large prospective and longitudinal trials are needed.Clinical trial registration no.: C000000418 (https://www.umin.ac.jp/ctr).

Size is the Most Important Predictor of Aneurysm Rupture Among Multiple Cerebral Aneurysms: Post Hoc Subgroup Analysis of Unruptured Cerebral Aneurysm Study Japan.

BACKGROUND: Multiple cerebral aneurysms are encountered in approximately 15% to 35% of patients harboring unruptured cerebral aneurysms. It would be of clinical value to determine which of them is most likely to rupture. OBJECTIVE: To characterize features of the ruptured aneurysm relative to other concomitant fellow aneurysms in patients with multiple cerebral aneurysms. METHODS: From a total of 5720 patients who were prospectively registered in the Unruptured Cerebral Aneurysm Study in Japan, a subgroup of patients with multiple cerebral aneurysms who developed subarachnoid hemorrhage was extracted for this post hoc analysis. Intrapatient comparisons of each aneurysm were carried out using aneurysm-specific factors such as size, location, and shape to identify predictors of rupture among the fellow aneurysms in a patient with multiple cerebral aneurysms. RESULTS: Twenty-five patients with 62 aneurysms were identified from the total cohort of 5720 patients. With the distinctiveness in size, which means the aneurysm was the single largest among the multiple aneurysms, the ruptured aneurysm in each case was discriminated from the other coexisting aneurysms with a sensitivity of 0.76 and specificity of 0.86. CONCLUSION: Our results suggest that the largest aneurysm is likely to rupture among coexisting aneurysms in a patient with multiple cerebral aneurysms.

Underuse of Cardiac Rehabilitation in Workers With Coronary Artery Disease　- Claims Database Survey in Japan.

BACKGROUND: Workers with coronary artery disease (CAD) require evidence-based care in order to return to work safely. We assessed the use of cardiac rehabilitation (CR) among workers with CAD, and identified the factors associated with CR use.Methods and Results:A retrospective cohort study based on data from a health insurance claims database was conducted. We identified workers aged ≥18 years who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) between 2006 and 2013, and reviewed the utilization of inpatient or outpatient CR. Logistic regression was used to identify the factors associated with CR use. A total of 1,699 patients were included. The frequency of inpatient and outpatient CR use was 23.7% (n=402) and 4.2% (n=72), respectively. Patients diagnosed with ST-elevated myocardial infarction were most likely to receive inpatient CR, and patients undergoing CABG were more likely to receive inpatient CR than those undergoing PCI. Moreover, inpatient CR use was associated with longer hospitalization duration, catecholamine use, and no history of chronic kidney disease. Furthermore, both unstable and stable angina were negatively correlated with outpatient CR use. CONCLUSIONS: Most of the Japanese workers with CAD in this study did not undergo CR. The type of CAD was strongly associated with inpatient and outpatient CR use. Thus, a strong evidence-practice gap exists in secondary preventative care within this group of patients.

Risk of rupture of unruptured cerebral aneurysms in elderly patients.

OBJECTIVES: The aim of this study was to identify risk factors for rupture of unruptured cerebral aneurysms (UCAs) in elderly Japanese patients aged 70 years or older. METHODS: The participants included all patients 70 years of age or older in 3 prospective studies in Japan (the Unruptured Cerebral Aneurysm Study of Japan [UCAS Japan], UCAS II, and the prospective study at the Jikei University School of Medicine). A total of 1,896 patients aged 70 years or older with 2,227 UCAs were investigated. The median and mean follow-up periods were 990 and 802.7 days, respectively. RESULTS: The mean aneurysm size was 6.2 ± 3.9 mm. Sixty-eight patients (3.6%) experienced subarachnoid hemorrhage during the follow-up period. Multivariable analysis per patient revealed that in patients aged 80 years or older (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.16-3.49, p = 0.012), aneurysms 7 mm or larger (HR, 3.08; 95% CI, 1.35-7.03, p = 0.007 for 7-9 mm; HR, 7.82; 95% CI, 3.60-16.98, p < 0.001 for 10-24 mm; and HR, 43.31; 95% CI, 12.55-149.42, p < 0.001 for ≥25 mm) and internal carotid-posterior communicating artery aneurysms (HR, 2.45; 95% CI, 1.23-4.88, p = 0.011) were independent predictors for UCA rupture in elderly patients. CONCLUSIONS: In our pooled analysis of prospective cohorts in Japan, patient age and aneurysm size and location were significant risk factors for UCA rupture in elderly patients.

Prediction model for 3-year rupture risk of unruptured cerebral aneurysms in Japanese patients.

OBJECTIVE: To build a prediction model that estimates the 3-year rupture risk of unruptured saccular cerebral aneurysms. METHODS: Survival analysis was done using each aneurysm as the unit for analysis. Derivation data were from the Unruptured Cerebral Aneurysm Study (UCAS) in Japan. It consists of patients with unruptured cerebral aneurysms enrolled between 2000 and 2004 at neurosurgical departments at tertiary care hospitals in Japan. The model was presented as a scoring system, and aneurysms were classified into 4 risk grades by predicted 3-year rupture risk: I, < 1%; II, 1 to 3%; III, 3 to 9%, and IV, >9%. The discrimination property and calibration plot of the model were evaluated with external validation data. They were a combination of 3 Japanese cohort studies: UCAS II, the Small Unruptured Intracranial Aneurysm Verification study, and the study at Jikei University School of Medicine. RESULTS: The derivation data include 6,606 unruptured cerebral aneurysms in 5,651 patients. During the 11,482 aneurysm-year follow-up period, 107 ruptures were observed. The predictors chosen for the scoring system were patient age, sex, and hypertension, along with aneurysm size, location, and the presence of a daughter sac. The 3-year risk of rupture ranged from <1% to >15% depending on the individual characteristics of patients and aneurysms. External validation indicated good discrimination and calibration properties. INTERPRETATION: A simple scoring system that only needs easily available patient and aneurysmal information was constructed. This can be used in clinical decision making regarding management of unruptured cerebral aneurysms.

Implementation of mental health service has an impact on retention in HIV care: a nested case-control study in a japanese HIV care facility.

BACKGROUND: Poor retention in the care of patients with human immunodeficiency virus (HIV) is associated with adverse patient outcomes such as antiretroviral therapy failure and death. Therefore, appropriate case management is required for better patient retention; however, which intervention in case management is important has not been fully investigated. Meanwhile, in Japan, each local government is required to organize mental health services for patients with HIV so that a case manager at an HIV care facility can utilize them, but little is known about the association between implementation of the services and loss to follow-up. Therefore, we investigated that by a nested case-control study. METHODS: The target population consisted of all patients with HIV who visited Osaka National Hospital, the largest HIV care facility in western Japan, between 2000 and 2010. Loss to follow-up was defined as not returning for follow-up care more than 1 year after the last visit. Independent variables included patient demographics, characteristics of the disease and treatment, and whether the patients have received mental health services. For each case, three controls were randomly selected and matched. RESULTS: Of the 1620 eligible patients, 88 loss to follow-up cases were identified and 264 controls were matched. Multivariate-adjusted conditional logistic regression revealed that loss to follow-up was less frequent among patients who had received mental health services implemented by their case managers (adjusted odds ratio [95% confidence interval] 0.35 [0.16-0.76]). Loss to follow-up also occurred more frequently in patients who did not receive antiretroviral therapy (adjusted odds ratio [95% confidence interval], 7.51 [3.34-16.9]), who were under 30 years old (2.74 [1.36-5.50]), or who were without jobs (3.38 [1.58-7.23]). CONCLUSION: Mental health service implementation by case managers has a significant impact on patient retention.

Decreased vancomycin clearance in patients with congestive heart failure.

PURPOSE: Congestive heart failure (CHF) alters the pharmacokinetics of various drugs, including cardiovascular agents, due to decreased cardiac output and decreased renal blood flow. The purpose of this study was to evaluate the influence of CHF on the clearance of vancomycin, a glycopeptide antibacterial agent. METHODS: After reviewing more than 1,500 clinical charts of patients who received vancomycin therapy and whose serum vancomycin level was monitored, we identified 101 patients who also had the left ventricular ejection fraction (LVEF) assessed at that time. The fluorescence polarization immunoassay method was used to measure vancomycin serum concentrations in these patients 1 h after the end of vancomycin infusion and just before the next administration. Using these two measurements, we calculated the pharmacokinetic parameters using the Bayesian estimator. RESULTS: Patients with an LVEF of <40 % (16 patients) or those with an LVEF of ≥ 40 % and <60 % (40 % ≤ LVEF < 60 % ; 32 patients) had a significantly lower vancomycin clearance than patients with LVEF of ≥ 60 % (53 patients) (2.29 ± 0.95 or 2.79 ± 0.99 vs. 3.50 ± 1.04 L/h; p < 0.001 or p < 0.01, respectively). Vancomycin clearance was strongly correlated not only with estimated creatinine clearance (CLcr) in patients with an LVEF of <40 % (r = 0.828) and 40 % ≤ LVEF < 60 % (r = 0.773), but also with an LVEF in patients with a CLcr of <60 mL/min (r = 0.646). Consistent with these findings, multiple regression analysis revealed that CLcr, LVEF and body weight were important independent variables for vancomycin clearance (r(2) = 0.649). CONCLUSIONS: Vancomycin clearance decreased with decreasing cardiac function (LVEF) and decreasing CLcr. This finding suggests that vancomycin clearance is affected by cardiac function and would be predicted not only CLcr but also by LVEF.

The natural course of unruptured cerebral aneurysms in a Japanese cohort.

BACKGROUND: The natural history of unruptured cerebral aneurysms has not been clearly defined. METHODS: From January 2001 through April 2004, we enrolled patients with newly identified, unruptured cerebral aneurysms in Japan. Information on the rupture of aneurysms, deaths, and the results of periodic follow-up examinations were recorded. We included 5720 patients 20 years of age or older (mean age, 62.5 years; 68% women) who had saccular aneurysms that were 3 mm or more in the largest dimension and who initially presented with no more than a slight disability. RESULTS: Of the 6697 aneurysms studied, 91% were discovered incidentally. Most aneurysms were in the middle cerebral arteries (36%) and the internal carotid arteries (34%). The mean (±SD) size of the aneurysms was 5.7±3.6 mm. During a follow-up period that included 11,660 aneurysm-years, ruptures were documented in 111 patients, with an annual rate of rupture of 0.95% (95% confidence interval [CI], 0.79 to 1.15). The risk of rupture increased with increasing size of the aneurysm. With aneurysms that were 3 to 4 mm in size as the reference, the hazard ratios for size categories were as follows: 5 to 6 mm, 1.13 (95% CI, 0.58 to 2.22); 7 to 9 mm, 3.35 (95% CI, 1.87 to 6.00); 10 to 24 mm, 9.09 (95% CI, 5.25 to 15.74); and 25 mm or larger, 76.26 (95% CI, 32.76 to 177.54). As compared with aneurysms in the middle cerebral arteries, those in the posterior and anterior communicating arteries were more likely to rupture (hazard ratio, 1.90 [95% CI, 1.12 to 3.21] and 2.02 [95% CI, 1.13 to 3.58], respectively). Aneurysms with a daughter sac (an irregular protrusion of the wall of the aneurysm) were also more likely to rupture (hazard ratio, 1.63; 95% CI, 1.08 to 2.48). CONCLUSIONS: This study showed that the natural course of unruptured cerebral aneurysms varies according to the size, location, and shape of the aneurysm. (Funded by the Ministry of Health, Labor, and Welfare in Japan and others; UCAS Japan UMIN-CTR number, C000000418.).

Increase in serum mitochondrial creatine kinase levels induced by tenofovir administration.

Recently, 2 monoclonal antibodies that specifically inhibit mitochondrial creatine kinase (MtCK) activity have been developed. In this study, we measured the serum MtCK activity in HIV-1-infected individuals (n = 100) by employing a novel method using these antibodies. The mean serum MtCK activity in 44 patients treated with highly active antiretroviral therapy (HAART) including tenofovir disoproxil fumarate (TDF) was 16.0 IU/L. The MtCK activity was significantly higher in patients receiving TDF than in those receiving HAART without TDF (3.4 IU/L) or in naïve patients (6.9 IU/L) (Tukey-Kramer test, p < 0.0001 and p = 0.0029, respectively). The serum MtCK activity reached a plateau at 1 month after the initiation of TDF administration and decreased upon discontinuation. It showed no significant correlation with the trough plasma TDF concentration, serum creatinine level, or red blood cell count. The activity was elevated in 75% of the patients receiving TDF, and this elevation was specific to TDF; it was not observed with other anti-HIV drugs. In addition, our report emphasizes the careful interpretation of creatine kinase-MB (CK-MB) test results in patients receiving TDF because MtCK in serum could cause false-positive results on a conventional CK-MB test, which does not include MtCK-specific inhibitory antibodies.

Immune reconstitution to parvovirus B19 and resolution of anemia in a patient treated with highly active antiretroviral therapy.

Immune reconstitution inflammatory syndrome (IRIS) is an unsolved problem in the treatment of human immunodeficiency virus (HIV)-1 infection. Despite the high seroprevalence of parvovirus B19 (PVB19) among HIV-1-positive patients, reports on PVB19-induced anemia, especially that associated with PVB19-related IRIS, in these patients are limited. We present the case of a man with acquired immunodeficiency syndrome who developed severe transfusion-dependent anemia and was seropositive and borderline positive for immunoglobulin-M and IgG antibodies against PVB19, respectively. PVB19-DNA was also detected in his serum. The patient was diagnosed with pure red cell anemia (PRCA) caused by a primary PVB19 infection and was treated with periodical blood transfusions. However, he subsequently tested negative for IgG antibodies and developed chronic severe anemia with high levels of PVB19 viremia. This indicated a transition from primary to persistent infection. After initiation of highly active antiretroviral therapy, the patient showed an inflammatory reaction with rapid deterioration of anemia and seroconversion of the IgG antibody to PVB19. Subsequently, PRCA was completely resolved, but the patient's serum still contained low levels of PVB19-DNA. Thus, this was a case of IRIS associated with PVB19 infection. Our report highlights the significance of seroconversion to PVB19 in the diagnosis of IRIS and re-emphasizes the finding that persistently high levels of PVB19 viremia after primary infection are probably because of the lack of protective antibodies.

Three cases of fungemia in HIV-infected patients diagnosed through the use of mycobacterial blood culture bottles.

We treated three cases of fungemia in HIV-infected patients. These cases were caused by Candida albicans, Cryptococcus neoformans, and Penicillium marneffei, respectively, and all were diagnosed through the use of mycobacterial blood culture bottles. Although the detection of the etiologic agents of fungal infection is difficult, it has been shown that blood culture media for mycobacteria are more effective for the detection of fungemia than media for aerobes and anaerobes. Some reports have shown that Bactec Myco/F lytic bottles were useful for the diagnosis of fungemia in clinical samples. Here, we report the successful use of BacT MB bottles.

[A diagnosed, cured case of an HIV-infected Japanese subject developing disseminated penicilliosis after Thailand travel].

Disseminated penicilliosis-an AIDS-indicator disease in Southeast Asian countries -but not Japan- is a systemic fungal infection caused by Penicillium marneffei. A 30-year-old HIV-positive Japanese man visiting Southeast Asia three months before admission and reporting fever, general fatigue, and enlarged lymph nodes lasting over one month was admitted for detailed tests. Blood culture and fine-needle aspiration lymph node biopsy a led to a diagnosis of disseminated penicillioisis, later cured by several anti-fungal agents. Caution is thus recommended regarding the possibility of this disease, given the large number of travelers visiting overseas, geographical proximity to Southeast Asia, and increasing numbers of HIV patients in Japan.