The length of the sanitary napkins can be used as a handier index than pictorial blood loss assessment chart to predict the heavy menstrual bleeding.

AIM: Many women with inherited bleeding disorders are not diagnosed because of a lack of appropriate indicators. This study aimed to assess the predictability of the pictorial blood loss assessment chart (PBAC) as an indicator of menorrhagia and identify an easy indicator of menorrhagia resulting from bleeding disorders. METHODS: A multicenter study enrolled 9 patients with von Willebrand disease (VWD), 23 hemophilia carriers, and 71 controls aged 20-45 years who completed PBACs for two menstrual cycles as well as questionnaires. RESULTS: The PBAC scores of the VWD were significantly higher than those of other groups, even in multivariate analysis with age and sanitary item factors (p = 0.014). A PBAC score of 100 was not an appropriate cutoff because of its low specificity (VWD: sensitivity, 100; specificity, 29.5; hemophilia carriers: 74 and 29.5, respectively). In the ROC analysis, the cutoff of optimal PBAC for VWD was 171 (sensitivity, 66.7; specificity, 72.3; AUC, 0.7296). As the pad length increased, the total length of the pads used during one menstrual period could be a new and easy indicator. However, the cutoff for VWD was 735 cm (sensitivity, 42.9; specificity, 94.3; AUC 0.6837). A threshold could not be established for the hemophilia carrier. Therefore, we multiplied the coefficient by the length of thick pads, which caused a lower PBAC. For the VWD, the sensitivity increased to 85.7 (specificity, 77.1). For the hemophilia carrier, sensitivity (66.7) and specificity (88.6) could be separated from the control. CONCLUSIONS: The total length of the pads with a thick-pad adjustment can be a simple method to identify bleeding disorders.

Changes in Leptin to Adiponectin Ratio After Antiretroviral Therapy: A Pilot Observational Study.

AIM: Weight gain with the use of dolutegravir, bictegravir, and tenofovir alafenamide for antiretroviral therapy has been reported. However, studies on changes in body composition and the leptin/adiponectin ratio after antiretroviral therapy initiation are limited. These factors are important because they can be used as indicators of metabolic syndrome and cardiovascular disease risk. INTRODUCTION: This study aimed to investigate the changes in waist circumference, body composition, and adipokine levels after the initiation of antiretroviral therapy consisting of dolutegravir, bictegravir, and tenofovir alafenamide and evaluate the relationships between these parameters in Japanese patients living with human immunodeficiency virus. METHODS: This is a single-center, prospective, observational study. Waist circumference, body composition, and adipokine levels were measured at baseline and 12 months after antiretroviral therapy initiation in antiretroviral therapy-naive Japanese patients living with human immunodeficiency virus. Body composition was determined by bioelectrical impedance analysis. RESULTS: We included 11 patients (10 bictegravir/TAF/emtricitabine, 1 dolutegravir/lamivudine) in this study. The results showed no significant changes in waist circumference and body composition among the patients. The leptin/adiponectin ratio and serum leptin levels significantly increased after antiretroviral therapy initiation. Changes in waist circumference, fat mass, and visceral fat area showed a strong positive correlation. CONCLUSION: The leptin/adiponectin ratio increased following antiretroviral therapy initiation. The waist circumference measurement can be a simple, inexpensive, and useful method to identify changes in fat mass and visceral fat area after initiation of antiretroviral therapy.

Comparison between the impact of tenofovir alafenamide and that of abacavir on rapid kidney function decline: A retrospective observational study.

OBJECTIVES: To compare the impact of tenofovir alafenamide (TAF) on the slope of the estimated glomerular filtration rate (eGFR) with that of abacavir in Japanese patients living with HIV infection. METHODS: The participants in this single-centre, retrospective, observational study were Japanese patients with HIV infection who started antiretroviral therapy with TAF/emtricitabine or abacavir/lamivudine or were switched from tenofovir disoproxil fumarate/emtricitabine to TAF/emtricitabine or abacavir/lamivudine (anchor drugs remained constant) between January 2012 and December 2020. The eGFR slope was defined as the regression coefficient between eGFR and time. The study outcome was rapid kidney function decline (RKFD; eGFR slope < -5 mL/min/1.73 m2 /year). The adjusted effect of TAF on the eGFR slope was compared with that of abacavir using multivariate logistic regression analysis. RESULTS: The study included 184 patients (with 2835 eGFR data points). The median duration of exposure to TAF or abacavir was 2.6 years [interquartile range (IQR): 1.7-3.3], and the median eGFR slope was -4.1 mL/min/1.73 m2 /year (IQR: -6.4 to -1.2). In all, 72 patients (39%) experienced RKFD. Patients receiving TAF were more likely to experience RKFD (adjusted odds ratio = 3.74) than those receiving abacavir. There was a significant independent association between baseline eGFR and RKFD. CONCLUSIONS: These findings suggest that renal function should be monitored carefully after the initiation of TAF in Japanese patients with HIV infection.

[Hemostatic management of hemophilia].

Replacement therapy is the basic treatment for hemophilia by infusing deficient clotting factors, including replacement therapy for prophylaxis (i.e., prevention of breakthrough bleeding for physical activity), episodic replacement therapy, replacement therapy during and after procedures and surgery, and replacement therapy for physical activity, each administered at doses and intervals appropriate for the purpose and the product used. Although emicizumab is increasingly used for prophylaxis in severe hemophilia A, the combination of replacement therapy is necessary, especially during severe bleeding, highly invasive procedures, and major surgery. Furthermore, the usual APTT measurements cannot be used for monitoring the replacement therapy and detecting the presence of inhibitors while patients are receiving emicizumab. Hemostatic management of patients with inhibitors should be implemented based on the purpose of the therapy, the latest inhibitor titer, and the clinical response to the product, with the choice of inhibitor neutralization or bypass agent therapy. When bypassing agents are used in patients with hemophilia A with emicizumab inhibitor during and after bleeding, procedures, and surgery, the choice of agent and dose adjustment should be made with attention to thrombotic complications.

Effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide on estimated glomerular filtration rate slope in patients with HIV: A retrospective observational study.

INTRODUCTION: There is limited data on the effects of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on estimated glomerular filtration rates (eGFR) slope in patients with human immunodeficiency virus (HIV) infection. This study aimed to compare the eGFR slope when administering TDF and TAF and to investigate the predictors of improvement in eGFR slope after switching from TDF to TAF. METHODS: We conducted a single-center, retrospective, observational study in Japanese patients with HIV infection who switched the antiretroviral drug from TDF to TAF. eGFR was calculated using serum cystatin C. The eGFR slope was defined as the regression coefficient between eGFR and time. Differences between eGFR slope during TDF and TAF administration were compared using Wilcoxon signed rank test. A stepwise logistic regression model was used to examine the associations between improvement of eGFR slope after switching from TDF to TAF and various parameters. RESULTS: Overall, 63 patients (656 eGFR) were included in the analysis. The median analyzed durations of TDF and TAF exposures were 1.6 and 1.5 years, respectively. There were no significant differences between eGFR slope during TDF and TAF periods (median: 0.6 vs. 4.0 mL/min/1.73 m2/year, p = 0.165). The eGFR slopes during the TDF period and while switching from TDF to TAF were independent predictors of improvement in eGFR slope after switching from TDF to TAF. CONCLUSIONS: The results suggest that patients with poor renal function and those with progressive worsening during TDF administration would benefit from switching to TAF.

[Diagnosis and management of hemophilia].

Hemophilia A and B are hereditary coagulation disorders caused by functional and quantitative abnormalities of coagulation factor VIII (FVIII) in hemophilia A and coagulation factor IX (FIX) in hemophilia B. A definitive diagnosis is made through the measurement of FVIII or FIX activity and ruling out other pathological conditions or diseases with decreased FVIII or FIX activity. Severity is classified as severe, moderate, and mild according to factor activity level. Moreover, as frequency of hemorrhage and severity are usually correlated, severe patients have a high risk of intracranial hemorrhage during infancy as well as joint damage due to recurrent hemarthrosis. However, there are some non-severe patients who have symptoms like bleeding and joint damage. Therefore, it is necessary to determine the treatment strategy not only based on severity but also on bleeding symptoms. The treatment for hemophilia is mainly replacement therapy using clotting factor concentrates (standard or extended half-life), such as prophylaxis or on-demand therapy for bleeding. However, there are also clinical problems, such as venous access and development of inhibitors. Recently, a non-factor agent has emerged as a new treatment option. Thus, the management of hemophilia is on a turning point.

[Acquired hemophilia A].

Acquired hemophilia A (AHA) is a bleeding disorder due to the autoantibody (inhibitor) production targeting blood coagulation factor VIII. It is characterized by a sudden onset, and it often causes extensive and severe bleeding in soft tissue. The incidence of AHA is 1.48 cases per 1 million individuals per year and is common among postpartum women and elderly with underlying diseases. The risk factors include autoimmune diseases, malignancy, and aging. The diagnosis requires exclusion of other diseases with activated partial thromboplastin time (APTT) prolongation and an APTT cross-mixing test during early differential diagnosis. The treatment of AHA is immunosuppressive therapy to reduce the inhibitors. In case of bleeding that requires hemostasis, hemostatic therapy with bypass agents should be administered. The first-line immunosuppressive therapy is prednisolone (1 mg/kg/day) alone or in combination with cyclophosphamide (1-2 mg/kg/day). Recently, the effect of a rituximab-based-regimen has also been utilized.

Predictive value of interim FDG-PET/CT findings in patients with diffuse large B-cell lymphoma treated with R-CHOP.

Objectives: To examine the prognostic value of interim 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings after 2-4 cycles of rituximab, plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with diffuse large B-cell lymphoma (DLBCL) receiving standardized treatment. Results: After a median 3.36 years (range 0.33 to 9.14 years), 24 of the 80 patients had documented relapse. In Interim-PET findings, 2-year PFS was significantly shorter for PET-positive as compared with PET-negative patients (50.0% vs. 86.4%; p = 0.0012). In End-PET findings, 2-year PFS was significantly shorter for PET-positive as compared with PET-negative patients (25.0% vs. 84.7%; p < 0.0001). The positive predictive value (PPV) and negative predictive value (NPV) of Interim-PET for predicting relapse or disease progression were 57.1% and 75.8%, respectively, while those for End-PET were 75.0% and 75.0%, respectively. Methods: Eighty DLBCL patients treated with first-line 6-8 R-CHOP courses regardless of interim imaging findings were enrolled. Each underwent FDG-PET/CT scanning at staging, and again during (Interim-PET) and at the end of (End-PET) therapy. PET positivity or negativity at Interim-PET and End-PET as related to progression-free survival (PFS) was examined using Kaplan-Meier analysis. Conclusion: Mid-treatment FDG-PET/CT findings may be useful for determining disease status in patients with DLBCL undergoing induction R-CHOP chemotherapy, though are not recommended for treatment decisions as part of routine clinical practice.

Utility of urinary liver-type fatty acid-binding protein as a predictor of renal dysfunction in Japanese patients with HIV receiving tenofovir disoproxil fumarate with low urinary ß2 microglobulin levels: a retrospective observational study.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is known to reduce estimated glomerular filtration rate (eGFR). It is clinically important to identify patients at high risk for renal dysfunction as early as possible. Among the tubular markers, urinary ß2 microglobulin (Uß2MG) is a well-known biomarker of TDF-related tubulopathy. However, renal dysfunction has often been occurred in patients receiving TDF with low Uß2MG levels. Recently, urinary liver-type fatty acid-binding protein (UL-FABP) was suggested to be predictor of the progression of renal dysfunction. Thus, we focused on UL-FABP in patients receiving TDF with low Uß2MG levels. METHODS: A retrospective, observational, single-center study, between January 2013 and December 2016, was conducted. Two renal end points (> 25% decrement in eGFR and > 20 mL/min/1.73 m2 decrement relative to the baseline) were assessed. To estimate the effect of UL-FABP on time to the first event, log-rank test was performed. RESULTS: A total of 24 Japanese outpatients with human immunodeficiency virus receiving TDF were enrolled. The outcome each occurred in two patients during the follow-up period. UL-FABP levels ≥4.0 µg/g creatinine was significantly associated with > 25% decrement and > 20 mL/min/1.73 m2 decrement (p = 0.006 and 0.001, respectively). CONCLUSION: Based on our preliminary analysis, UL-FABP levels ≥4.0 µg/g creatinine predict renal dysfunction in patients receiving TDF with low Uß2MG levels.

Early evaluation of tumor response to 90Y-ibritumomab radioimmunotherapy in relapsed/refractory B cell non-Hodgkin lymphoma: what is the optimal timing for FDG-PET/CT?

PURPOSE: To determine the earliest optimal timing for assessment of early response following radioimmunotherapy in non-Hodgkin lymphoma patients using FDG-PET/CT. METHODS: FDG-PET/CT was performed prior to treatment (PET1), at 2 (PET2) weeks, and at 6 (PET3) weeks after 90Y-ibritumomab radioimmunotherapy in 55 patients. Response was evaluated based on the Deauville 5-point scale and Lugano criteria as well as semiquantitative analysis and compared with progression-free survival (PFS). RESULTS: PET 2 showed complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD) in 33, 13, 6, and 3 patients, respectively, while PET 3 in 41, 8, 3, and 3 patients, respectively. Mean SUVmax of 168 target lesions decreased over time (PET1, 2, 3; 5.58 ± 2.58, 1.87 ± 1.78, 1.75 ± 2.25, respectively). Progression or recurrence after a median of 12.6 months (range 2.6-72.0 months) was seen in 44 patients. Patients with CMR or metabolic response (CMR + PMR) on PET2 showed significantly longer PFS as compared to those who did not (p = 0.00028 and p = 0.029, respectively). A similar significant difference was observed based on PET3 (p = 0.00013 and p = 0.017, respectively). The same trend was observed when analyzing only the subgroup of patients with follicular lymphoma (N = 43/55) (p < 0.0001). CONCLUSION: Use of FDG-PET/CT findings with Lugano criteria for assessing early response to radioimmunotherapy after 6 weeks allowed for accurate evaluation and prognostic stratification, though scanning after 2 weeks was too soon to precisely evaluate response. KEY POINTS: • The optimal timing of FDG-PET/CT to obtain a suitable tool for assessment of response after 90 Y-ibritumomab radioimmunotherapy of lymphoma has not yet been defined. • Assessment after 6 weeks by FDG-PET/CT using the Lugano criteria accurately evaluates treatment response and prognosis. • FDG-PET/CT performed 2 weeks after radioimmunotherapy is too early as it significantly misses objective responses.

[Diagnosis and management of von Willebrand disease].

von Willebrand disease (VWD) is an inherited bleeding disorder resulting from either a quantitative or a qualitative deficiency in the plasma glycoprotein von Willebrand factor (VWF). A diagnosis of VWD can be made when a patient presents with appropriate bleeding and VWF <30 IU/dl. However, persons with VWF levels of 30-50 IU/dl cannot be precluded from the diagnosis of VWD. Desmopressin acetate (DDAVP) or VWF-containing factor VIII (pdVWF/FVIII) concentrate is used for treating VWD. The effect of DDAVP varies among individuals; a trial should be performed while in a nonbleeding state. For patients in whom DDAVP is invalid or those that require long-term management of hemostasis, pdVWF/FVIII is administered. The treatment of the hype rmenorrhea is the hope of every pregnant patient with VWD. When a patient with VWD becomes pregnant, VWF and FVIII should be regularly monitored throughout pregnancy. During childbirth, pdVWF/FVIII concentrate should be administered to achieve VWF and FVIII levels of ≥50 IU/dl before delivery.

Urinary liver-type fatty acid-binding protein levels as a potential risk factor for renal dysfunction in male HIV-infected Japanese patients receiving antiretroviral therapy: a pilot study.

Renal dysfunction is recognized with increasing frequency among the non-infectious co-morbidities associated with human immunodeficiency virus (HIV) infection. Recently, urinary liver-type fatty acid-binding protein (L-FABP) was suggested to be a predictor of the progression of renal dysfunction in patients without HIV. However, little is known regarding the utility of urinary L-FABP as a predictor of renal dysfunction in patients with HIV. A retrospective, observational, single-centre study was conducted between July 2014 and December 2016. The primary outcome was renal dysfunction defined as decrease in estimated glomerular filtration rate to less than 60 ml/min/1.73 m2. To estimate the effect of urinary L-FABP, proteinuria category, and urinary ß2 microglobulin (ß2MG) on the time to the first event, a log-rank test was performed. Accuracy, determined by area under the curve and calculated from receiver operating characteristic curves, was also assessed. Thirty Japanese outpatients with HIV receiving antiretroviral therapy (ART) were enrolled. The primary outcome occurred in five patients during the follow-up period. Urinary L-FABP level and proteinuria category were significantly associated with renal dysfunction (p = 0.045 and p = 0.037, respectively). In contrast, urinary ß2MG level was not significantly associated with renal dysfunction (p = 0.141). Urinary L-FABP was the most accurate predictor of renal dysfunction among the three urinary parameters. In conclusion, urinary L-FABP levels in HIV patients receiving ART were more accurate for predicting renal dysfunction than proteinuria and urinary ß2MG. In addition, urinary L-FABP helped to discriminate those patients with a higher risk for renal dysfunction.

A potential drug interaction between phenobarbital and dolutegravir: A case report.

In this report, we describe a human immunodeficiency virus (HIV)-infected patient in whom changes in phenobarbital (PB) dosage resulted in associated changes in plasma concentrations of dolutegravir (DTG). His plasma concentrations of DTG were 0.934, 0.584, 1.003 and 3.25 µg/mL, respectively, with concomitant daily PB doses of 40, 70, 30 and 0 mg, respectively. This case suggests that PB can lead to a remarkable reduction in the plasma concentration of DTG in a dose-dependent manner.

Quality of life of people living with HIV compared with that of the general population in Japan.

OBJECTIVE: To evaluate the health-related quality of life (HRQOL) of people living with HIV (PLWH) in Japan. METHODS: A cross-sectional comparative study was conducted between June and December 2016 on PLWH. HRQOL was assessed using the Japanese version of the Short Form-36 Health Survey questionnaire (SF-36), and the three-component model of SF-36 scores was used. The values from the present study were compared with the published general Japanese values. Multivariate analysis was performed to identify the independent factors associated with the HRQOL of PLWH. RESULTS: A total of 151 PLWH were enrolled in the present study. Six out of the eight subscales were significantly lower than the normative data. With respect to the summary scores, compared with those in the general population, the physical component summary score (PCS) was significantly higher in PLWH, although the mental and social/role component summary scores (MCS and RCS, respectively) were lower. Older Age was independently related to lower PCS; formal employment and higher CD4 counts were independently related to higher PCS. The factor associated with lower MCS was taking psychoactive drug(s). Formal employment was independently associated with higher RCS; taking psychoactive drug(s) was independently associated with lower RCS. CONCLUSIONS: The physical HRQOL of PLWH was slightly higher; however, the mental and social/role HRQOL were slightly lower than in the general population in Japan.

The association between urinary liver-type fatty acid-binding protein and chronic kidney disease classification in HIV-infected Japanese patients.

BACKGROUND: Renal dysfunction is recognized with increasing frequency among the noninfectious comorbidities associated with human immunodeficiency virus (HIV) infection. Urinary liver-type fatty acid-binding protein (L-FABP) has been shown to be a new biomarker to screen for not only tubulointerstitial damage but also kidney dysfunction. METHODS: We performed a cross-sectional study to determine the association between the urinary L-FABP and chronic kidney disease (CKD) among 77 HIV-infected Japanese patients by backward-stepwise multivariable logistic regression. RESULTS: The prevalence of individuals in the low risk was 80 %. Urinary L-FABP level was not associated with antiretroviral therapy and tenofovir disoproxil fumarate. On the other hand, urinary L-FABP level was independently associated with the CKD classification. CONCLUSION: Urinary L-FABP may be used as an adjunct to diagnose the CKD stage.

[Recurrence of chronic active Epstein-Barr virus infection presenting with myelopathy after umbilical cord blood transplantation].

A 38-year-old man was admitted to our hospital with neck pain, dysesthesia of both hands, and weakness of the left upper limb. He had been diagnosed with a chronic active Epstein-Barr virus infection (CAEBV) at the age of 34 and had undergone umbilical cord blood transplantation at the age of 37. MRI of the spinal cord revealed an intramedullary hyperintense lesion on T2-weighted images with gadolinium enhancement. Because his laboratory tests revealed proliferation of CD19(+) lymphocytes in the peripheral blood, and EBV DNA was detected in both peripheral blood and CSF, he was diagnosed as having post-transplant EBV associated lymphoproliferative disease. However, chemotherapy did not alleviate his symptoms. At a later time, quantitative chimerism analysis of his CSF showed a higher proportion of lymphocytes that had originated from the recipient. Finally, he was diagnosed as having a recurrence of CAEBV in the central nervous system, and his symptoms were restored by intrathecal chemotherapy (methotrexate, cytosine arabinoside, and prednisolone). Quantitative chimerism analysis of CSF was useful for diagnosing the recurrence of CAEBV in the central nervous system.

Primary follicular lymphoma of the spleen incidentally found in a patient with alcohol- and hepatitis C-related liver cirrhosis.

Primary splenic lymphoma is rare as non-Hodgkin lymphomas. Splenic infiltration of lymphoma cells may cause splenomegaly in many cases. However, splenomegaly is caused not only by tumor involvement but also by non-tumorous disorders. One of the most prevalent non-neoplastic causes is portal hypertension mostly due to liver cirrhosis. On the other hand, liver cirrhosis may underlie various extrahepatic manifestations including development of B-cell non-Hodgkin lymphomas. Here, we report a case of primary follicular lymphoma of the spleen in a patient with liver cirrhosis related to hepatitis C and alcohol. The lymphoma was incidentally found in an enlarged spleen resected palliatively to alleviate symptomatic pancytopenia of the patient. The main characteristic of our case is an incidental finding of a rare situation brought by careful pathological examination. Our case illustrates the importance to recognize a possibility of co-occurrence of chronic liver disease and extrahepatic lymphoma.

Strategy for bone marrow transplantation in eculizumab-treated paroxysmal nocturnal hemoglobinuria.

Although the recent introduction of eculizumab has had a significant impact on the management of paroxysmal nocturnal hemoglobinuria (PNH), bone marrow transplantation (BMT) remains the only therapeutic option for patients who develop severe aplasia in the clinical course of PNH. However, information regarding BMT for eculizumab-treated PNH patients is scarce, and two major points-the optimal duration of eculizumab therapy, and the optimal BMT conditioning regimen-remain unclear. Here, we describe the clinical course of a PNH patient who was successfully treated with unrelated reduced-intensity BMT. Eculizumab was discontinued 2 weeks prior to the initiation of the conditioning regimen, which consisted of fludarabine 180 mg/m(2), cyclophosphamide 100 mg/kg, rabbit anti-thymocyte globulin 2 mg/kg, and TBI 3 Gy. Complete donor chimerism was rapidly achieved in association with a rapid decrease in the proportion of PNH erythrocytes. The patient became transfusion-free immediately after BMT, and had no recurrence of hemolysis. The present case suggests that discontinuation of eculizumab before BMT and the use of a highly lymphoablative conditioning regimen may act as a successful treatment strategy in BMT for PNH. Further studies are warranted to evaluate the efficacy and safety of this treatment strategy.