Intrapartum prophylactic efficacy of ampicillin versus clindamycin in preventing vertical transmission of group B Streptococcus.

AIM: To compare the prophylactic efficacy of ampicillin and clindamycin against vertical transmission of group B Streptococcus from mothers to their infants by evaluating the rates of group B Streptococcus colonisation. METHODS: We retrospectively extracted data for mothers who delivered at Showa University Northern Yokohama Hospital between 1 October 2017 and 31 March 2021 and tested positive for antepartum group B Streptococcus, and their infants. The chi-square test was used to compare the rates of group B Streptococcus colonisation, sepsis, and meningitis. We conducted a multivariate logistic regression analysis, including the time interval between membrane rupture and delivery, chorioamnionitis, and maternal intrapartum fever (≥38.0°C). RESULTS: Two hundred fifty-nine mothers and their infants were eligible. Ampicillin and clindamycin were administered to 150 and 109 mothers, respectively. In the ampicillin and clindamycin groups, 12.0% (18/150) and 37.6% (41/109) infants were group B Streptococcus positive, respectively. The rate of group B Streptococcus colonisation among infants was significantly lower in the ampicillin group (p < 0.001). Multivariate regression analysis showed similar results (p < 0.001). No sepsis or meningitis cases were observed in either group. CONCLUSION: Prophylactic efficacy of clindamycin against the vertical transmission of group B Streptococcus is lower than that of ampicillin.

Retained products of conception (RPOC) following delivery without placenta previa: Which patients with RPOC show postpartum hemorrhage?

INTRODUCTION: To clarify the perinatal outcome of retained products of conception (RPOC) after 22 weeks or more. METHODS: The retrospective cohort study reviewed medical records of patients with RPOC without placenta previa at 186 Japanese perinatal centers. RESULTS: Of the 323 patients with RPOC, pregnancies after assisted reproductive technology (ART) accounted for 43%. Transfusion at delivery was required in 33% of the patients. Logistic regression analyses revealed that transfusion was significantly required in the following situations: ART pregnancy (aOR: 6.0, 95%CI: 2.3-16, P < 0.001), and RPOC length ≥4 cm (aOR: 5.3, 95%CI: 2.1-13, P < 0.001). Transarterial embolization (TAE) and/or hysterectomy for subsequent RPOC-related bleeding was performed in 60 patients with RPOC. Logistic regression analysis revealed that additional interventions were significantly required in the following situations: multiparity (aOR: 6.1, 95%CI: 2.1-17.2, P < 0.001), and hypervascular RPOC (aOR: 12.8, 95%CI: 3.2-51.1, P < 0.001). TAE and/or hysterectomy was also frequently employed in ART pregnancy, although this was not significant (aOR: 2.8, 95%CI: 0.9-8.2, P = 0.063). DISCUSSION: Patients with RPOC were significantly more likely to require transfusion at delivery in the presence of large RPOC and ART. They were also more likely to require hemostatic procedures for subsequent bleeding in the presence of hypervascular RPOC and ART.

Infective endocarditis due to Streptococcus agalactiae in the puerperal period.

Streptococcus agalactiae, also known as group B Streptococcus, is a species of bacteria occasionally detected in the vagina and/or rectum of pregnant women. This report describes the case of a 33-year-old woman who developed infective endocarditis on puerperal day 17, owing to group B Streptococcus, and required lifesaving surgery. The patient was rushed to our hospital with chief complaints of fever and fatigue. After hospitalization, antibiotics were administered; however, the symptoms did not improve. Following a detailed examination, vegetation was found in the heart, suggestive of infective endocarditis. Surgical removal of the vegetation improved the patient's condition. The development of group B Streptococcus infection and infective endocarditis in a pregnant woman with no risk factors is rare. This case confirms that this patient's life was saved by a timely diagnosis and appropriate therapeutic intervention.

TAFRO Syndrome Presenting with Retroperitoneal Panniculitis-like Computed Tomography Findings at Disease Onset.

TAFRO syndrome is rare, and its pathophysiology remains unclear. We herein report the case of a 66-year-old man who presented at our emergency department with epigastric pain. Contrast-enhanced computed tomography (CT) showed high-density retroperitoneal panniculus with contrast enhancement. He was treated initially with a protease inhibitor and hydration, to little effect. Anasarca, thrombocytopenia, and renal dysfunction developed gradually, and TAFRO syndrome was diagnosed. He was treated successfully with prednisolone and cyclophosphamide, and subsequent CT findings showed improvement. Abnormal CT findings of the retroperitoneum may indicate the early stages of TAFRO syndrome before the presentation of typical ascites.

Tocilizumab monotherapy for large vessel vasculitis: results of 104-week treatment of a prospective, single-centre, open study.

OBJECTIVE: To evaluate the efficacy and safety of tocilizumab (TCZ) monotherapy for large vessel vasculitides (LVV), including Takayasu arteritis (TAK) and GCA. METHODS: Twelve patients with a newly diagnosed LVV (eight GCA, four TAK) were enrolled. One TAK patient withdrew consent, so 11 (eight GCA, three TAK) were analysed in a prospective, open-label study. TCZ (8 mg/kg) monotherapy, without glucocorticoids or immunosuppressants, was administered every 2 weeks for 2 months and then every 4 weeks for 10 months. Patients were followed for 1 year after the final TCZ dose. Complete and partial responses were defined as disappearance or improvement of all clinical symptoms and normalization of CRP. Relapse was defined as the worsening or recurrence of clinical symptoms, increase in CRP attributable to vasculitis, and/or the need for initiation of glucocorticoids and/or immunosuppressants. Poor clinical response described patients who did not fit the definition of complete response or partial response. RESULTS: Complete and partial responses rates were 75/66% and 25/0% in GCA/TAK patients, respectively, at week 24 and week 52. Five GCA patients and one TAK patient remained disease-free for 1 year after therapy. One GCA patient required TCZ discontinuation due to heart failure at week 24. CONCLUSION: TCZ monotherapy showed a high response rate for newly diagnosed LVV patients, and the majority of patients did not relapse for 1 year after TCZ cessation. Result of this study could help us to understand the crucial role of IL-6 in the pathogenesis of LVV.

Tocilizumab monotherapy for polymyalgia rheumatica: A prospective, single-center, open-label study.

OBJECTIVES: Polymyalgia rheumatica (PMR) is a systemic inflammatory disease in the elderly of unknown etiology. While glucocorticoids are the mainstay of treatment for PMR, various glucocorticoid-related adverse events are common. Recently, several studies have reported the efficacy of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, for PMR treatment in addition to an accompanying reduction, or even tapering-off, of glucocorticoids in some cases. The objective of this study was to elucidate the efficacy of TCZ monotherapy in the absence of glucocorticoids for PMR. METHOD: We conducted a 2-year, prospective, single-center, open-label pilot study of TCZ monotherapy in patients with PMR. TCZ (8 mg/kg) was administered at fortnightly intervals for the first 2 months and monthly over the next 10 months. Subsequently, patients were observed for another year without any treatment. The primary endpoints were the remission rates at weeks 12 and 52, and the secondary endpoints were the relapse rate and safety over the total 104 weeks. RESULTS: Thirteen patients were included in this study. Four of these patients achieved remission at week 12 (remission rate 31%). Four patients withdrew from the study due to adverse events (n = 2) and inefficacy (n = 2). At week 52, all 9 patients who had completed the first year achieved remission. Eight patients completed the drug-free second year, with 7 maintaining remission. CONCLUSIONS: TCZ monotherapy is well tolerated and can lead to remission in most patients with PMR in the absence of glucocorticoids.

Clinicopathologic investigation of methotrexate-induced lymphoproliferative disorders, with a focus on regression.

Although recent accumulative data reveal the clinicopathogenesis of regression in methotrexate-induced lymphoproliferative disorders (MTX-LPDs), the precise understanding including this category remains controversial. In this study, we analyzed 62 patients with MTX-LPD. Forty-three patients showed regression (Reg group), with high rates of Hodgkin lymphoma (HL) and LPD (90 and 88%, respectively). Among the 43 patients of the Reg group, 14 patients (33%) relapsed. The median duration before relapse in the Reg group was 10.6 months. Although the difference of OS between the Reg and Non-Reg groups was not significantly different, relapse-free patients in the Reg group had a superior overall survival (OS). MTX duration had a significant impact on Epstein-Barr virus (EBV) infection (p = .00131). Furthermore, EBV infection was significantly related to clinical manifestations, including spleen invasion, in the regression phenomenon. Some human leukocyte antigens (HLA) alleles might affect MTX-LPD development via EBV infection, although A*2402 and DRB1*0405 might be affected as fundamental factors.

Efficacy and tolerability of six-week extended dosing interval with tocilizumab therapy in a prospective cohort as remission maintenance in patients with rheumatoid arthritis.

OBJECTIVES: To prospectively evaluate the efficacy and tolerability of a six-week extended dosing interval with tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in sustained remission. METHODS: Patients who received over six doses of intravenous TCZ in clinical remission (disease activity score [DAS] 28 - erythrocyte sedimentation rate [ESR] ≤ 2.6) maintained over 3 months between December 2013 and December 2015 were included. Flare was defined as DAS28-ESR >3.2 at two consecutive visits. RESULTS: Twenty-five patients were enrolled; 87.5% achieved clinical remission at week 54 after six-week extension and 95.5% achieved a van der Heijde modified total Sharp score (ΔmTSS) ≤0.5. The Health Assessment Questionnaire Disability Index (HAQ-DI) did not increase during 54 weeks. HAQ-DI at baseline and ΔDAS28-ESR at week six positively correlated with increase in DAS28-ESR at week 54. ΔSwollen joint count at week six positively correlated with ΔmTSS at week 54. A total of 12 adverse events occurring in 10 patients did not lead to cessation of TCZ except for one case of recurrent lymphoproliferative disorder at week five. CONCLUSION: A six-week extended dosing interval of TCZ for patients with RA in sustained remission is proposed as an acceptable treatment option for maintaining efficacy and tolerability.

Current clinical evidence of tocilizumab for the treatment of ANCA-associated vasculitis: a prospective case series for microscopic polyangiitis in a combination with corticosteroids and literature review.

The purpose of this study is to report the efficacy and safety of a combination of tocilizumab (TCZ) and high-dose corticosteroid (CS) in two patients with microscopic polyangiitis (MPA) and review the published current clinical evidence on TCZ in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), except for large vessel vasculitis (LVV) and polymyalgia rheumatica (PMR). Two MPA patients were treated with TCZ at 8 mg/kg every month for 1 year and CS (prednisolone 1 mg/kg/day for 2 weeks, followed by tapering) in a prospective single-arm, single-center, cohort, open-label pilot study (UMIN clinical trials: 000012072). We performed a systematic literature search (PubMed and ICHUSHI [Japan Medical Abstracts Society] until June 30, 2017) to identify published reports on patients with all vasculitis other than LVV/PMR, who were treated with TCZ. We successfully treated the first patient. However, the other patient had serious infection probably associated with the combination of TCZ and high-dose CS. The literature review identified 22 reports with a total of 34 patients who received TCZ for AAV, rheumatoid vasculitis, and other types of vasculitis, in addition to our patients. In 15 of 17 patients (88.2%) with primary and secondary AAV, especially MPA, TCZ induced clinical remission, although TCZ use for rheumatoid vasculitis and vasculitis with mucocutaneous lesions is controversial. This study suggested that TCZ therapy is a potential treatment strategy for patients with AAV. However, TCZ combined with high-dose of CS might not be an appropriate treatment. Future studies are needed to confirm our findings.

The aggressive clinical courses of Hodgkin lymphoma primarily diagnosed as methotrexate-induced non-specific lymphoproliferative disorder in patients with rheumatoid arthritis.

Recently, attention has been focused on methotrexate-induced lymphoproliferative disease (MTX-LPD), and atypical phenotypes are occasionally documented. We encountered two patients with rheumatoid arthritis (RA) who were diagnosed with non-specific LPD (LPD-nos). Biopsy samples were not obtained during the initial examination when the LPD development was discovered, and the patients achieved a complete response after MTX cessation (case 1) or steroid pulse therapy (case 2). However, the tumors flared up 1.5 years later, and LPD-nos was determined following biopsies of the lymph node (LN, case 1) and liver (case 2). Prednisolone was subsequently administered instead of chemotherapy; however, multiple masses, including in the spine (case 1), and severe icterus with liver dysfunction (case 2) were exacerbated within a few months. Although the re-biopsy of LN proved the presence of HL and radiation followed by aggressive chemotherapy rescued the patient (case 1), the superficially accessible biopsy site was not found, and autopsy finally revealed HL (case 2). In both cases, the underlying pathogenesis along with the B symptoms and laboratory abnormalities suggested MTX-LPD, HL in particular. Therefore, even if the pathological diagnosis does not confirm the specific LPD subtype, the administration of aggressive chemotherapy should be considered if the LPD activity flares severely.

Corticosteroid-free treatment of tocilizumab monotherapy for microscopic polyangiitis: a single-arm, single-center, clinical trial.

OBJECTIVES: To assess the efficacy of tocilizumab (TCZ) monotherapy for the remission induction of microscopic polyangiitis (MPA) in a prospective single-arm, single-center, cohort, pilot study. METHODS: Eligible patients were aged between 20 and 80 years and were newly diagnosed with MPA according to Watts' classification algorithm. Seven patients received 8 mg/kg of intravenous TCZ fortnightly for the first 2 months (5 courses), and monthly for the next 10 months (10 courses). One year after TCZ monotherapy, the patients were followed-up without any treatment. The protocol did not permit the use corticosteroids or any other immunosuppressants. Complete remission (CR) was defined as the Birmingham Vasculitis Activity Score of 0 at two consecutive visits made at least a month apart. RESULTS: CR was achieved in two of six patients (33.3%) at 6 months and three patients (50.0%) at 12 months. Two patients were withdrawn: one because of inefficacy at 6 weeks and the other because of flare at 6 months. One patient voluntarily withdrew after CR at 3 months. Four patients (66.7%) could be kept drug-free after 1 year of TCZ without relapse for 6-15 months at the last visit. CONCLUSION: TCZ monotherapy may be an alternative treatment strategy in some patients with MPA.

The efficacy of mizoribine for the treatment of rheumatoid arthritis and its correlation with renal function.

OBJECTIVES: To evaluate the correlation between the efficacy of mizoribine (MZR) and the factors that might effect MZR concentration: renal function and dosage and administration of MZR in patients with rheumatoid arthritis (RA). METHODS: The efficacy of MZR treatment was prospectively evaluated in 97 RA regardless of dosage, at the 14 participated institutions. The Disease Activity Score 28-CRP3 was used to assess RA activity. The renal function was evaluated based on the serum creatinine and serum cystatin-C (Cys-C). The patients were followed up for 24 weeks. RESULTS: The patients with a mean age 66.2 years included 18 male. The renal function assessment showed increased creatinine in 16.4% of patients and increased Cys-C in 54.5%, suggesting the higher sensitivity of Cys-C to detect impaired renal function than creatinine. In patients with good or moderate response according to the European League against Rheumatism classification criteria, the Cys-C was significantly higher compared with those with no response. MZR treatment was significantly more effective in patients with an arithmetic product of the single MZR dose used and Cys-C of 179 or more. CONCLUSIONS: The efficacy of MZR may increase in proportion to its single dose, or increased Cys-C level in patients with impaired renal function.

Successful treatment of class IV+V lupus nephritis with combination therapy of high-dose corticosteroids, tacrolimus and intravenous cyclophosphamide.

A substantial number of patients with lupus nephritis (LN) are refractory to conventional glucocorticoid (GC) treatment. Although many of these patients respond to immunosuppressive drugs such as intravenous cyclophosphamide (IVCY), azathioprine (AZA), mizoribine, tacrolimus, cyclosporine A (CSA) and mycofenolate mofetil (MMF), some remain refractory to such therapies. Recent studies of multi-target therapies have reported effective outcomes for immunosuppression following renal transplantation and refractory LN when therapy consists of two or more immunosuppressive drugs with different mechanisms of action. We herein report a case of LN unresponsive to IVCY that was successfully treated with the addition of tacrolimus and discuss the usefulness of multi-target therapy for LN.

Efficacy of weekly mizoribine pulse therapy in refractory lupus nephritis.

OBJECTIVE: We investigated the efficacy of a high-dose intermittent dosing treatment method (weekly mizoribine pulse therapy) conceived in the hope of achieving better efficacy by increasing the peak blood levels of mizoribine in patients with refractory lupus nephritis. METHODS: Seventeen patients with lupus nephritis who had been resistant to corticosteroid and immunosuppressant therapy received weekly mizoribine pulse therapy. Mizoribine (350 mg) was administered three times at 12 h intervals over 2 consecutive days (700 mg for day 1 and 350 mg for day 2), followed by a washout period from day 3 to day 7. RESULTS: This therapeutic strategy enabled the peak blood levels of mizoribine to be increased to more than 3 µg/mL in most of the patients. Although SLEDAI, anti-ds-DNA antibody titer, CH-50, and serum albumin level did not significantly improve, urinary protein levels decreased, and it was possible to taper the dose of concomitant steroids. Using our definition of clinical response, 10 of the 17 patients were responders and 4 of them were nonresponders. The average peak serum mizoribine concentration of the responders was as high as 3.5 µg/mL. Elevation of serum liver enzymes was seen in 1 patient, and hyperuricemia occurred in 4 cases, but none of these adverse events were serious. CONCLUSION: Intermittent administration of mizoribine can increase blood levels and may be effective for refractory lupus nephritis.

A case of multiple giant coronary aneurysms and abdominal aortic aneurysm coexisting with IgG4-related disease.

IgG4-related disease (IgG4RD) is a unique systemic lymphoproliferative disorder characterized by elevated serum IgG4 levels and IgG4-producing plasma cell expansion in the affected tissues, which are accompanied by fibrotic or sclerotic changes. Vascular lesions may also be a part of IgG4RD as a number of case reports have discussed inflammatory abdominal aortic aneurysms associated with IgG4RD, but coronary artery lesions seem to be rare complications of IgG4RD. A 71-year-old man suffered from multiple giant coronary aneurysms and an abdominal aortic aneurysm with concurrent pancreatic, gall bladder, bile duct, and salivary gland lesions resulting from IgG4RD. The present observations suggest that coronary aneurysms may also develop as a consequence of this disease.

Gestational weight loss has adverse effects on placental development.

OBJECTIVE: To clarify whether mothers with gestational weight loss (GWL) were likely to have adverse effects on the placenta. STUDY DESIGN: Subjects who delivered viable singleton infants after 24 weeks of gestation were enrolled. A retrospective analysis to evaluate cases of GWL in association with the findings of the placenta and amniotic membrane after delivery was conducted. After consideration of confounders, a case-control study with matched pairs (1:2) was performed. RESULTS: Of all subjects (5551 cases), 83 cases (1.5%) with GWL were found. Since the pre-pregnancy maternal body mass index (BMI) was significantly higher in cases, 166 controls with a matched BMI were selected. The neonatal birth weights, placental weights and the umbilical cord length in cases were significantly smaller than in controls (p < 0.05). Preterm delivery and small for gestational age (SGA) infants were more frequently observed in cases compared with controls [odds ratio (OR) 6.3; 95% confidence interval (CI) 3.3, 12.1, OR 4.3; 95% CI 1.9, 9.9]. pPROM were observed in 10.8% of the cases and 1.8% of the control (OR 6.6; 95% CI 1.7, 25.1). However, the frequencies of chorioamnionitis and the cervical length at second trimester were not different between the two groups. CONCLUSION: GWL is associated with SGA, small placenta, short umbilical cord length, preterm delivery and pPROM.

Successful treatment of adult-onset Still's disease with tocilizumab monotherapy: two case reports and literature review.

Adult-onset Still's disease (AOSD) is a systemic inflammatory disease of unknown etiology. Recently, it has been reported that quite a few cases of refractory AOSD were successfully treated with tocilizumab (TCZ) and corticosteroids were withdrawn in some of these patients. We report two AOSD patients who were treated successfully with TCZ monotherapy; thus, avoiding corticosteroid treatment. Because both of the patients refused to take corticosteroids, we planned to treat them with 8 mg/kg of TCZ monotherapy at weeks 0, 2, 6 and subsequently every 4 weeks. The efficacy of TCZ was assessed by patients' clinical symptoms such as fever, arthralgia, skin eruptions, and laboratory markers such as serum levels of CRP, ferritin, and IL-6. We also reviewed 14 previous case reports including 30 cases who had been treated with TCZ for AOSD. Our patients responded rapidly and have been maintained in clinical remission without corticosteroid treatment. In the literature review, concomitant corticosteroid treatment described in 13 cases was successfully tapered in 7 and discontinued in 6 cases. TCZ monotherapy can be a candidate for the first-line therapy for some AOSD patients.

Fcγ receptor IIIb polymorphism and use of glucocorticoids at baseline are associated with infusion reactions to infliximab in patients with rheumatoid arthritis.

OBJECTIVE: Infusion reaction is a major adverse event in patients with rheumatoid arthritis (RA) treated with infliximab. The possible factors including Fcγ receptor (FcγR) polymorphism associated with the development of infusion reactions in patients with RA receiving infliximab were prospectively examined. METHODS: 96 patients with RA were enrolled and scheduled to receive infliximab at a dose of 3 mg/kg at weeks 0, 2 and 6 and every 8 weeks thereafter. Genetic polymorphisms for FcγR were examined in FCGR3A 176F/V and FCGR3B NA1/2 alleles by allele-specific PCR analysis. RESULTS: An infusion reaction was observed in 17 patients (18%) during 52 weeks of treatment with infliximab. The FCGR3B NA1/NA1 genotype was found in 75% of the patients with infusion reactions and in only 37% of those without (p=0.01), whereas the FCGR3A 176F/V genotype was equally distributed in the patients with or without infusion reactions. Glucocorticoids were used in 53% of the patients who developed an infusion reaction and in 80% of those without an infusion reaction (p=0.02). A multivariable logistic regression model showed that the FCGR3B NA1/NA1 genotype and use of glucocorticoids at baseline could be used as independent predictive factors for infusion reactions (OR 6.1 (95% CI 1.9 to 24.3) and OR 0.26 (95% CI 0.08 to 0.84), respectively). The presence of anti-infliximab antibody during infliximab treatment was also associated with infusion reactions. CONCLUSION: FCGR3B NA1/NA1 genotype, use of glucocorticoids and the presence of anti-infliximab antibody accounted for nearly all patients with RA who developed infusion reactions.