Surgical antimicrobial prophylaxis in Japanese hospitals: Real status and challenges.

BACKGROUND: Information regarding the status of surgical antimicrobial prophylaxis (SAP) in Japanese hospitals is lacking. This study aimed to explore the status of SAP prescriptions for surgeries and adherence to Japanese SAP guidelines. METHODS: From February to July 2020, a 1-day multicentre point prevalent survey was conducted at 27 hospitals in Aichi Prefecture, Japan. Patients prescribed SAP were included in this study. The appropriateness of the SAP was evaluated based on the guidelines for selection of antimicrobials and their duration. Surgery was defined as appropriate when all the items were appropriate. RESULTS: A total of 728 patients (7.1 %; 728/10,199) received antimicrobials for SAP. Among them, 557 patients (76.5 %, 557/728) underwent the surgeries described in the guidelines. The overall appropriateness of all surgeries was 33.9 % (189/557). The appropriate selection of antimicrobial before/during and after surgery and their durations were 67.5 % (376/557), 67.5 % (376/557), and 43.3 % (241/557), respectively. The overall appropriateness ranged from 0 % (0/37, oral and maxillofacial surgery) to 58.7 % (88/150, orthopaedic surgery) and 27.7 % (36/130, community hospitals with 400-599 beds) to 47.2 % (17/36, specific hospitals). Cefazolin was the most prevalent antimicrobial prescribed before/during (55.5 %, 299/539), and after (45.1 %, 249/552) surgery. In total, 101 oral antimicrobials were prescribed postoperatively. CONCLUSIONS: SAP adherence by specific surgical fields and hospitals was shown in this study. Intensive intervention and repeated surveillance are necessary to improve SAP prescriptions in Japanese hospitals.

Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis-Associated Lymphoproliferative Disorders.

OBJECTIVE: In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA). METHODS: In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models. RESULTS: Overall, 752 patients with RA-associated LPD (RA-LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA-LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD-associated immunosuppressive conditions. Furthermore, patients with RA-LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX-only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein-Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)-only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens. CONCLUSION: Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA-LPD, with patterns changing over time. Furthermore, TCZ-only regimens are recommended after LPD onset.

Association of a Single Nucleotide Variant in TERT with Airway Disease in Japanese Rheumatoid Arthritis Patients.

Interstitial lung disease and airway disease (AD) are often complicated with rheumatoid arthritis (RA) and have a poor prognosis. Several studies reported genetic associations with interstitial lung disease in RA. However, few genetic studies have examined the susceptibility to AD in RA patients. Here, we investigated whether single nucleotide variants susceptible to idiopathic pulmonary fibrosis might be associated with interstitial lung disease or AD in Japanese RA patients. Genotyping of rs2736100 [C/A] in TERT and rs1278769 [G/A] in ATP11A was conducted in 98 RA patients with usual interstitial pneumonia, 120 with nonspecific interstitial pneumonia (NSIP), 227 with AD, and 422 without chronic lung disease using TaqMan assays. An association with AD in RA was found for rs2736100 (p = 0.0043, Pc = 0.0129, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.11-1.77). ATP11A rs1278769 was significantly associated with NSIP in older RA patients (>65 years, p = 0.0010, OR 2.15, 95% CI 1.35-3.40). This study first reported an association of rs2736100 with AD in RA patients and ATP11A rs1278769 with NSIP in older RA patients.

Antibodies against Serum Anti-Melanoma Differentiation-Associated Gene 5 in Rheumatoid Arthritis Patients with Chronic Lung Diseases.

Chronic lung diseases (CLD), including interstitial lung disease (ILD) and airway diseases (ADs), are common complications of rheumatoid arthritis (RA). Rheumatoid factor (RF) and anti-citrullinated peptide antibodies are reported to be associated with CLD in RA patients. The presence of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies (Abs) is associated with clinically amyopathic dermatomyositis developing into rapidly progressive ILD. However, few studies on anti-MDA5 Abs in RA have been published. Here, we analyzed the association of anti-MDA5 Abs with CLD complications in RA. Anti-MDA5 Abs were quantified in sera from RA patients with or without CLD. Anti-MDA5 Ab levels were higher in RA patients with ADs than without (mean ± SDM, 4.4 ± 2.4 vs. 4.0 ± 4.2, p = 0.0001). AUC values of anti-MDA5 Ab and RF ROC curves were similar in RA patients with or without CLD (0.578, 95%CI 0.530-0.627 and 0.579, 95%CI 0.530-0.627, respectively, p = 0.9411). Multiple logistic regression analysis of anti-MDA5 Abs and clinical characteristics yielded an MDA5-index with a higher AUC value than anti-MDA5 Ab alone (0.694, 95%CI 0.648-0.740, p = 5.08 × 10-5). Anti-MDA5 Abs were associated with ADs in RA patients and could represent a biomarker for CLD, similar to RF. The involvement of anti-MDA5 Abs in the pathogenesis of ADs in RA is proposed.

Association of functional (GA)n microsatellite polymorphism in the FLI1 gene with susceptibility to human systemic sclerosis.

OBJECTIVE: Susceptibility genes that can account for characteristic features of SSc such as fibrosis, vasculopathy and autoimmunity remain to be determined. In mice, deficiency of Friend leukaemia integration 1 transcription factor (Fli1) causes SSc-like disease with these features. The human FLI1 gene contains (GA)n microsatellite, which has been shown to be associated with expression level. Because microsatellite polymorphisms are difficult to capture by genome-wide association studies, we directly genotyped FLI1 (GA)n microsatellite and examined its association with SSc. METHODS: Genomic DNA from 639 Japanese SSc patients and 851 healthy controls was genotyped for (GA)n microsatellite using the fragment assay. The cut-off repeat number for susceptibility to SSc was determined by receiver operating characteristics (ROC) analysis. Association with susceptibility and clinical characteristics was examined using logistic regression analysis. FLI1 mRNA levels were determined using quantitative RT-PCR. RESULTS: Based on the ROC analysis, (GA)n alleles with ≥22 repeats were collectively defined as L alleles and alleles with ≤21 repeats as S alleles. (GA)n L alleles were significantly associated with susceptibility to SSc (P = 5.0e-04, odds ratio 1.34, additive model). Significant association was observed both in diffuse cutaneous and limited cutaneous SSc. Among the SSc, (GA)n L alleles were significantly enriched in the patients with a modified Rodnan total skin thickness score ≥10 compared with those with a score <10. FLI1 mRNA levels were significantly decreased in healthy controls carrying (GA)n L alleles as compared with non-carriers. CONCLUSION: Extended repeat alleles of FLI1 (GA)n microsatellite may be associated with lower FLI1 mRNA levels and susceptibility to human SSc.

Long-term outcomes of ocular adnexal lesions in IgG4-related ophthalmic disease.

AIMS: To determine the long-term outcomes of ocular adnexal lesions in immunoglobulin G4-related ophthalmic disease (IgG4-ROD). METHODS: This retrospective, non-randomised exploratory study included 82 patients with ocular adnexal lesions. We evaluated the long-term outcomes in 71 patients during the median follow-up period of 30 months, who underwent either watchful waiting (n=20; range 12-90 months) or systemic corticosteroid treatment, delivered according to consensus guidelines (n=51; range 9- 115 months). We also analysed factors that might contribute to recalcitrance to treatment. RESULTS: Of 82 patients, 40 (49%) were male, and the median patient age was 60 years old. Twenty-one (26%) patients with extraocular muscle (EOM) and/or trigeminal nerve branch (CN V) enlargements had a significantly high frequency of multiple ocular adnexal lesions (p<0.0001, Fisher's exact test). In addition, two patients developed EOM and/or CN V enlargements de novo over time. Twenty patients with solitary lacrimal gland enlargements preferred watchful waiting, due to mild symptoms. Of these, 18 (90%) lesions remained dormant throughout a median follow-up of 27 months. Among 51 patients treated with corticosteroids, 31 (61%) experienced relapses after treatment and required systemic low-dose maintenance treatment. A multivariate analysis indicated that EOM and/or CN V enlargements comprised a risk factor for relapse (HR 2.7; 95% CI 1.1 to 6.7). CONCLUSIONS: This exploratory study showed that different types of ocular adnexal lesions in IgG4-ROD displayed distinct proliferative activities. Our results suggested that EOM and/or CN V enlargements might be secondary lesions that confer refractoriness to systemic corticosteroid treatment recommended by consensus guidelines.

Strong correlation between cancer progression and anti-transcription intermediary factor 1γ antibodies in dermatomyositis patients.

OBJECTIVES: Transcription intermediary factor 1γ (ΤΙF1γ) protein is known as a tumour suppressor that promotes cellular differentiation. Autoantibodies to ΤΙF1γ have a strong clinical association with cancers associated with dermatomyositis (DM). This study aims to identify the clinical characteristics of cancers in anti-ΤΙF1γ antibody-positive adult patients with DM. METHODS: This retrospective analysis covered 160 adult DM patients who visited Nagoya University Hospital or collaborating medical centres between 2003 and 2016. Anti-TIF1γ antibody and other myositis-specific autoantibodies were detected by ELISA. Based on a review of medical charts, the cancers were staged according to the TNM Classification of Malignant Tumours of the Union for International Cancer Control and were divided into the two groups of "advanced" or "non-advanced" according to the stage classification. RESULTS: Forty-one of the 160 (26%) patients had cancer. The incidence was significantly higher in the anti-TIF1γ-positive patients than in the anti-TIF1γ-negative patients (23/34=68% vs. 18/126=14%, p<1x10-6). Anti-TIF1γ-positive patients with cancer were found more frequently in the "advanced" group than in the "non-advanced" group (21/23=91% vs. 9/18=50%, p<0.0046). The intervals between DM diagnosis and cancer diagnosis were significantly shorter in the anti-TIF1γ-positive patients than in the anti-TIF1γ-negative patients (p=0.047). CONCLUSIONS: Not only did anti-TIF1γ antibodies correlate strongly with malignancy in DM patients, but cancers were also significantly more advanced in anti-TIF1γ-positive DM patients than in anti-TIF1γ-negative patients. Cancers in such cases were very frequently found close to the time of the DM diagnosis.

Association of HLA-G 3' Untranslated Region Polymorphisms with Systemic Lupus Erythematosus in a Japanese Population: A Case-Control Association Study.

HLA-G plays a role in fetal-maternal tolerance as well as immunoregulation, and has been suggested to be involved in autoimmune diseases and cancers. HLA-G encodes two potentially functional polymorphisms in the 3' untranslated region, 14bp insertion/deletion (14bp indel, rs371194629) and a single nucleotide polymorphism rs1063320, previously reported to affect HLA-G expression level or splicing isoform and to be associated with susceptibility to systemic lupus erythematosus (SLE). However, the results of SLE association studies are inconsistent, probably due to the small sample size of each study and lack of consideration of linkage disequilibrium (LD) with HLA-class II haplotypes in each population. In this study, we performed association studies of these polymorphisms on 843 patients with SLE and 778 healthy controls in a Japanese population, in many of whom HLA-DRB1 alleles have been genotyped at the four-digit level. LD was detected between DRB1*13:02, protective against multiple autoimmune diseases in the Japanese, and the rs1063320 G (D' = 0.86, r2 = 0.02) and with 14bp del (D' = 0.62, r2 = 0.01), but not between SLE-susceptible DRB1*15:01 and HLA-G. Although significant association with overall SLE was not detected, 14bp ins allele was significantly associated with SLE with the age of onset <20 years, when compared with healthy controls (P = 0.0067, PFDR = 0.039, OR 1.44, additive model) or with SLE patients with the age of onset ≥20 (P = 0.033, PFDR = 0.0495, OR 2.09, additive model). This association remained significant after conditioning on DRB1*13:02 or DRB1*15:01. On the other hand, significant association was detected between rs1063320 C and anti-RNP antibody and anti-Sm antibody positive SLE, which was dependent on negative LD with DRB1*13:02. eQTL analysis showed reduced HLA-G mRNA level in 14bp ins/ins individuals. In conclusion, our observations showed that HLA-G 14bp ins allele represents a genetic contribution on early-onset SLE independent of DRB1.

A case of acute renal failure of multiple myeloma due to monoclonal type I cryoglobulinemia with thrombotic microangiopathy.

The term cryoglobulinemia (CG) is used to refer to vasculitis due to so-called mixed cryoglobulins containing immune complexes. Although most cases of monoclonal CG, called type I CG, are asymptomatic, purpura, skin ulcers, and renal failure develop in some cases. Hematological disorders are the underlying diseases in most cases, on which the therapeutic strategies available and the prognosis of patients depends. We here report a case of a 47-year-old man who had pain in both his ankles, with palpable purpura and epistaxis, and presented with acute renal failure. Monoclonal immunoglobulin (Ig) G-κ protein was detected and cryoglobulin was also positive. Renal biopsy revealed emboli with a fibrillar structure in the glomeruli and renal tubule lumina. The complication of thrombotic microangiopathy (TMA) occurred during the course. Therefore, plasma exchange and hemodialysis were added to methylprednisolone pulse therapy. The treatment was successful, dissipating the purpura. However, the purpura relapsed and renal dysfunction progressed when the administration of oral steroids was tapered. Bone marrow biopsy was performed again, which indicated an increase in abnormal plasma cells. The patient was finally diagnosed as multiple myeloma. Then, bortezomib-dexamethasone therapy was initiated. This is the first case of type I CG with monoclonal IgG complicated by TMA during the course; it provides insight into the pathogenesis of renal dysfunction associated with type I CG.

Serologic factors in early relapse of IgG4-related orbital inflammation after steroid treatment.

PURPOSE: To determine whether serologic factors correlate with early relapse in cases of IgG4-related orbital inflammation, a lymphoproliferative disorder. DESIGN: Retrospective cohort study. METHODS: We examined the orbital images and serum data of 30 patients with (n=24) or without (n=6) corticosteroid treatment before and after corticosteroid treatment and 6 months after discontinuation of corticosteroid treatment. RESULTS: Seven patients (23%) (all with corticosteroid treatment) had elevated serum levels of rheumatoid factor. Of the 24 patients with corticosteroid treatment, 24 (100%) showed regression of the lesion, but 8 of the 24 (33%) showed relapse. The serum IgG4 levels before and after corticosteroid treatment were not significantly different between the relapsed and nonrelapsed groups (P=.5 and P=.2, respectively). However, the incidence of patients who were rheumatoid factor-positive was significantly higher in the relapsed group (P=.02). The 6 patients without corticosteroid treatment showed minor proliferation or regression of the lesion at the 6-month follow-up. CONCLUSIONS: The serum rheumatoid factor level may correlate with proliferative activity in IgG4-related orbital inflammation.

[Case of thoracoabdominal stent graft with postoperative paralysis which showed dramatic recovery after re-institution of spinal drainage].

A 62-year-old man underwent stent graft insertion for thoracoabdominal aneurysm. We inserted a spinal drainage catheter at L3-4 and started drainage at 10 cmH2O at the beginning of surgery. Intravenous naloxone was started from the beginning of the operation. Intraoperative course was uneventful, and postoperatively no neurological symptoms/signs were noted. The next day, 90 minutes after removal of the drainage catheter, sensory loss and muscle weakness of bilateral lower limbs developed. A drainage catheter was reinserted, and muscle weakness of the right lower limb recovered after 115 minutes, and sensory loss of left lower limb recovered after 260 minutes. There was no muscle weakness or paralysis after 300 minutes. The drainage was continued for the next 48 hours and removed without subsequent neurological symptoms and the patient was discharged eight days after the operation.

Ocular adnexal IgG4-related lymphoplasmacytic infiltrative disorder.

OBJECTIVE: To determine the clinicopathological characteristics of patients with infiltration of IgG4-positive plasma cells into the ocular adnexa. METHODS: We designed a prospective study to evaluate 24 patients with ocular adnexal lymphoplasmacytic infiltrative lesions, including sclerosing inflammation and reactive lymphoid hyperplasia. We analyzed peripheral blood and biopsy specimens from all patients. The classification criteria for placement in the IgG4-related group included having both an elevated serum level of IgG4 of 135 mg/dL or greater and an IgG4:IgG ratio of infiltrating plasma cells of 30% or greater. RESULTS: Ten patients met the classification criteria (IgG4-related group), 9 patients did not meet the criteria (IgG4-unrelated group), and 5 patients met 1 but not both criteria (indeterminate group). Patients in the IgG4-related group had significantly higher bilateral involvement (P = .02), a higher number of allergic diseases (P = .01), and elevated IgE serum levels (P = .01). Of the 10 patients in the IgG4-related group, 3 also had polyclonal hypergammaglobulinemia, 6 had systemic lymphadenopathy or salivary gland enlargement, and 1 developed autoimmune pancreatitis. Patients in the IgG4-unrelated group did not have these serum and/or systemic abnormalities. CONCLUSION: The IgG4-related and IgG4-unrelated groups have different patterns of tissue involvement and systemic disease associations and possibly different prognoses.

[Thoracic epidural analgesia is effective in perioperative pain relief for uterine artery embolization].

BACKGROUND: Uterine artery embolization (UAE) has become widely employed in Japan. Although several methods of anesthesia and analgesia are performed for UAE, pain control does not appear to be satisfactory. We report a series of UAE, successfully managed using thoracic epidural analgesia. METHODS: Before UAE an epidural analgesic catheter was inserted at T 10-11. Local anesthetic and morphine sulfate were administered through the catheter. After the UAE patients received patient-controlled epidural analgesia (PCEA) for 24 hours. The next day, patients were treated with diclofenac sodium 25 mg suppository every 8 hours. RESULTS: In all cases, early pain was controlled well by epidural analgesia. Late pain was controlled by combining epidural analgesia with diclofenac sodium. Nausea and pruritus due to morphine sulfate occurred in some cases, but disappeared after discontinuation of PCEA. CONCLUSIONS: Several phases of severe pain are seen perioperatively in UAE. Because thoracic epidural analgesia is easily administered and the dosage of the drugs used effectively controlled, it is a practical method for perioperative pain control for UAE.