Validation of the Diagnostic Criteria for IgG4-Related Periaortitis/Periarteritis and Retroperitoneal Fibrosis (IgG4PA/RPF) 2018, and Proposal of a Revised 2023 Version for IgG4-Related Cardiovascular/Retroperitoneal Disease.

BACKGROUND: In 2018, diagnostic criteria were introduced for IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis (PA/RPF). This study assessed the existing criteria and formulated an improved version.Methods and Results: Between August 2022 and January 2023, we retrospectively analyzed 110 Japanese patients diagnosed with IgG4-related disease (IgG4-RD) involving cardiovascular and/or retroperitoneal manifestations, along with 73 non-IgG4-RD patients ("mimickers") identified by experts. Patients were stratified into derivation (n=88) and validation (n=95) groups. Classification as IgG4-RD or non-IgG4-RD was based on the 2018 diagnostic criteria and various revised versions. Sensitivity and specificity were calculated using experts' diagnosis as the gold standard for the diagnosis of true IgG4-RD and mimickers. In the derivation group, the 2018 criteria showed 58.5% sensitivity and 100% specificity. The revised version, incorporating "radiologic findings of pericarditis", "eosinophilic infiltration or lymphoid follicles", and "probable diagnosis of extra-PA/-RPF lesions", improved sensitivity to 69.8% while maintaining 100% specificity. In the validation group, the original and revised criteria had sensitivities of 68.4% and 77.2%, respectively, and specificities of 97.4% and 94.7%, respectively. CONCLUSIONS: Proposed 2023 revised IgG4-related cardiovascular/retroperitoneal disease criteria show significantly enhanced sensitivity while preserving high specificity, achieved through the inclusion of new items in radiologic, pathological, and extra-cardiovascular/retroperitoneal organ categories.

Risk of infection from glucocorticoid and methotrexate interaction in patients with rheumatoid arthritis using biologics: A retrospective cohort study.

AIMS: This retrospective cohort study aimed to evaluate the effect of the interaction between methotrexate and glucocorticoids on the risk of developing bacterial infections in patients with rheumatoid arthritis (RA) using biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: We used the 2005-2018 JMDC claims database, a nationwide claims database in Japan. From the database of 7 175 048 patients, study patients were obtained by applying the following exclusion criteria: no use of bDMARDs; without information on the date of prescription; without RA as a disease; other than the new users of bDMARDs; and age <18 years. The exposures were glucocorticoids and methotrexate, and the outcome was bacterial infection. The interaction effects were examined using multivariate Cox regression analysis. Bacterial infections were identified according to antibiotic prescription and International Statistical Classification of Diseases and Related Health Problems, 10th revision codes. RESULTS: A total of 2837 RA patients were identified, with a median age of 50 years. The incidence of infection was 16.8% (95% confidence interval: 15.5-18.3). The interaction term for the doses of glucocorticoids and methotrexate was significant. Additionally, a higher dose of glucocorticoid was a significant risk factor for developing bacterial infections on the side of high doses of methotrexate. The incidence of bacterial infections tended to increase significantly with increasing methotrexate doses coprescribed with glucocorticoids ≥5 mg or glucocorticoid doses coprescribed with methotrexate ≥8 mg. CONCLUSION: Our results indicate a potential association between methotrexate dose and bacterial infections during bDMARDs administration with glucocorticoids in patients with RA.

Prescribed probiotic usage to prevent Clostridioides difficile infection among older patients receiving antibiotics: A retrospective cohort study.

OBJECTIVES: Clostridioides difficile infection (CDI) is a leading cause of antimicrobial-associated colitis and is a global clinical concern. Probiotics are considered a CDI-preventive measure; however, highly inconsistent data have been previously reported. Thus, we evaluated the CDI-preventive effect of prescribed probiotics in high-risk older patients receiving antibiotics. METHODS: Older patients (aged ≥65 years) admitted to the emergency department who received antibiotics between 2014 and 2017 were enrolled in this single-center retrospective cohort study. Propensity score-matched analysis was used to compare the CDI incidence in patients who took the prescribed probiotics within 2 days of receiving antibiotics for at least 7 days with those who did not. The rates of severe CDI and associated hospital mortality were also evaluated. RESULTS: Among 6148 eligible patients, 221 were included in the prescribed probiotic group. A propensity score-matched (221 matched pairs) well-balanced for patient characteristics was obtained. The incidence of primary nosocomial CDI did not differ significantly between the prescribed and non-prescribed probiotic groups (0% [0/221] vs. 1.0% [2/221], p = 0.156). Of the 6148 eligible patients, 0.5% (30/6148) developed CDI, with a severe CDI rate of 33.3% (10/30). Furthermore, no CDI-associated in-hospital mortality was observed in the study cohort. CONCLUSIONS: The evidence from this study does not support recommendations for the routine use of prescribed probiotics to prevent primary CDI in older patients receiving antibiotics in situations where the CDI is infrequent.

[Surgical Treatment of Congenital Absence of the Pericardium Found by Chance at Pulmonary Surgery:Report of a Case].

Absence of the pericardium is generally asymptomatic rare congenital disorder. However, it may be life-threatening problem due to cardiac deviation or herniation after the pulmonary resection. We described a case of complete defect of the pericardium found at surgery for metastatic lung cancer. Since the left lower lobectomy was necessary, the pericardium was reconstructed with an ePTFE sheet. Postoperative course was uneventful without any symptoms at two years post-surgery.

The Usefulness of a Simple Classification for Bronchoscopic Findings for Diagnosis of Peripheral Pulmonary Tumour.

BACKGROUND: Normal bronchial epithelium has been described in terms of transparency and smoothness. No studies have compared bronchoscopic and pathological findings in the identification of bronchial epithelium. OBJECTIVES: This study aimed to classify bronchoscopic findings for peripheral pulmonary tumour (PPT) for accurate bronchoscopic diagnosis accounting for the presences of bronchial epithelium and bronchial stenosis using an ultrathin bronchoscope. METHODS: We performed endocytoscopy using narrow-band imaging (NBI) of specimens immediately after lobectomy to investigate the normal bronchial epithelium under the physiological saline injection technique (PSIT) prior to classification of PPT. A retrospective study to classify bronchoscopic findings included 46 patients diagnosed with malignancy by bronchoscopy for PPT. RESULTS: We recognized a "light blue line" (LBL) with NBI under PSIT, corresponding to strong reflection of short-wavelength light by cilia on the epithelial surface in an ex vivo endocytoscopic study. Bronchoscopic findings of PPT were classified morphologically into stenotic type (ST) and non-stenotic type (NonST). Tumours were also classified as exposed type (ET) and non-exposed type (NonET) based on the presence of epithelium. Most ST and NonET lesions (74%) were adenocarcinoma. Among squamous cell carcinoma, 55% were categorized as ST and ET. All NonST and NonET cases were adenocarcinoma. A significant difference in the presence of LBL was seen between ET and NonET. CONCLUSIONS: Our simple classification based on the appearance of stenosis and LBL in PPT may facilitate pathological diagnosis.

[Cavernous Hemangioma Originating in the Left Atrial Appendage:Report of a Case].

A 66-year-old male with hypertension was referred for evaluation of abnormal find chest X-ray. A computed tomography (CT) scan revealed a solitary pericardial mass with a diameter of 5 cm, located in the left atrioventricular groove. It showed solid but unevenly enhanced contents suggesting a well vascularized tumor originating in either a part of the left heart or the pericardium. As magnetic resonance imaging showed a clear boundary between the tumor and the pericardium, cardiac origin was suspected. Surgical removal of the tumor was performed via median sternotomy. The tumor originated from the lateral aspect of the left atrial appendage, having a base of 10 mm in diameter. The tumor was fully excised with an associated left atrial cuff under cardiopulmonary bypass. The postoperative course was uneventful. The tumor was histopathologically diagnosed as cavernous hemangioma originating in the left atrial wall. There has been no sign of recurrence for four years following surgery.

Observational study to determine the optimal dose of daptomycin based on pharmacokinetic/pharmacodynamic analysis.

High doses of daptomycin (DAP) (>6 mg/kg/day) have been preliminarily recommended in recent practical guidelines for methicillin-resistant Staphylococcus aureus infection, to achieve better clinical effects. While such doses can elevate the plasma trough concentration (Cmin) of DAP, there is an associated risk of creatine phosphokinase (CPK) elevation warranting further investigation. In the current study relationships between DAP Cmin and CPK elevation were investigated, and optimal DAP doses were determined. Plasma DAP concentrations were measured in 20 patients. Logistic regression analysis was performed to assess relationships between DAP Cmin and CPK elevation, then a population pharmacokinetic model of DAP was developed. To determine an optimal DAP dose a Monte Carlo simulation (MCS) was performed to minimize the risk of CPK elevation and maximize the probability of successful treatment. In logistic regression analysis DAP Cmin was significantly associated with CPK elevation (odds ratio 1.21, p = 0.048). With respect to dose-dependent increases in the probability of CPK elevation and exposure to DAP, MCS estimated an optimal DAP dose of 4-6 mg/kg/day, corresponding to a minimum inhibitory concentration (MIC) of ≤0.5 µg/mL. For an MIC of 1 µg/mL, MCS estimated an optimal DAP dose of 10 mg/kg/day. However, the probability of CPK elevation associated with high doses of DAP was higher than that associated with the approved doses. In cases where high doses of DAP are administered, close CPK monitoring is required and therapeutic drug monitoring of DAP may be desirable.

A surgical case of primary perivascular epithelioid cell tumor of the heart.

BACKGROUND: We encountered an extremely rare case of perivascular epithelioid cell tumor (PEComa) of the heart. CASE REPORT: A 54-year-old woman was admitted to our hospital because a solid mass developing in the left atrioventricular groove by computed tomography scans of the chest. Histologic examination of the resected tumor revealed that the tumor had proliferating fusiform or spheroid cells with clear cytoplasm. Immunostaining showed positive results for α-smooth muscle actin, a myogenic marker, and human melanin black-45 (HMB-45), leading to a diagnosis of PEComa. The patient was discharged uneventfully, and there was no recurrence for the last thirteen years postoperatively. CONCLUSIONS: We experienced a surgical case of PEComa primarily occurring in the heart. Although no sign of a recurrence is observed to date, we consider it necessary to follow up the case carefully.

Outcomes of Thoracic Aortic Surgery in Patients With Coronary Artery Disease　- Based on the Japan Adult Cardiovascular Surgery Database.

BACKGROUND: Coronary artery disease (CAD) is associated with increased morbidity and mortality after open repair of thoracic aorta. Nevertheless, the efficacy of preoperative coronary angiography (CAG) and revascularization is controversial. The aim of this study was to clarify the effect of preoperative CAD on surgical outcome by reviewing the Japan Adult Cardiovascular Database. Methods and Results: This study involved 4,596 patients who underwent open surgery for true thoracic aortic aneurysm between 2004 and 2009. After excluding patients with concomitant cardiac operation, except coronary artery bypass grafting (CABG), the remaining 1,904 patients with coronary artery stenosis included 995 cases of simultaneous CABG. The prevalence of CAD was significantly higher in patients with diabetes, renal dysfunction, hyperlipidemia, cerebrovascular disorders, peripheral artery lesions, old myocardial infarction (MI), and coronary intervention. Patients with simultaneous CABG had severe CAD compared with those without, with no other major differences in patient background noted. Thirty-day postoperative and in-hospital mortalities were higher in CAD patients. Incidence of perioperative MI was higher in patients who underwent open aortic repair with simultaneous CABG, but simultaneous CABG did not affect operative mortality. CONCLUSIONS: In patients with surgically treated true aortic aneurysm, CAD was frequently observed, suggesting that aggressive preoperative coronary evaluation is needed.

IgG4-Positive Plasmacytic Infiltration in Aortic Wall and Aortic Valve Surgical Samples and Its Relation to Preoperative Serum IgG4 Levels.

The prevalence and extent of immunoglobulin G4 (IgG4)-positive cell infiltration were investigated in 282 surgical samples of aortic wall and aortic valve. Tissue infiltration of IgG4-positive cells was observed in 24 (17.3%) of 139 aortic valve samples and 46 (32%) of 143 aortic wall samples, and the condition of IgG4-positive cell infiltration > 30/hpf together with IgG4/CD138 ratio > 40% was observed in 2 (1.4%) of aortic valve samples and 14 (9.8%) of aortic wall samples. Among 275 patients, preoperative serum IgG4 level was available in 48 patients (50 samples), and it was > 135 mg/dL in only one patient. Of these 48 patients with serum IgG4 measurement, 29 patients had aortic valve stenosis and 12 had aortic aneurysm. Compared with 23 aortic stenosis patients without tissue infiltration of IgG4-positive cells in the aortic valve, six patients with IgG4-positive cell infiltration had a more prevalent smoking history (26% versus 83%) and borderline significantly higher serum IgG4 (median, 24.5 mg/dL versus 55.5 mg/dL), although either preoperative peak pressure gradient between left ventriculum and aorta or aortic valve area did not differ significantly between groups. Compared with six aortic aneurysm patients without tissue infiltration of IgG4-positive cells in the aortic wall, six patients with IgG4-positive cell infiltration had borderline significantly higher serum IgG4 (median, 28.9 mg/dL versus 68.2 mg/dL). The current study showed that tissue IgG4-positive infiltration is not a rare occurrence in the aortic stenosis and aortic aneurysm. Clinical significance of tissue IgG4-postive cell infiltration in these patients requires further investigation.

Development of a new surgical sheet containing both silk fibroin and thermoplastic polyurethane for cardiovascular surgery.

PURPOSE: The surgical sheets that are currently used for congenital cardiovascular surgery have several drawbacks, including material deterioration, calcification, and pseudo-intimal proliferation resulting in hemodynamic disturbance. The aim of this study was to evaluate a newly developed sheet made from a combination of silk fibroin (SF) and a synthetic polymer, thermoplastic polyurethane (TPU), for surgical use. METHODS: The hybrid SF/TPU sheet was a non-woven fabric with nanofibers that was made using the electrospinning method. The mechanical properties of the SF/TPU sheet were characterized. To determine its biocompatibility, part of the wall of the canine descending aorta was replaced with a SF/TPU sheet as a patch. The patches were removed after 3 months and a histological examination was performed. RESULTS: The flexibility, water permeability, and suture retention strength of the SF/TPU sheet were excellent and equivalent to those of existing sheets. The SF/TPU sheet had excellent handling properties and fit well into the vascular wall without needle hole bleeding. The histological examination revealed that the intimal tissue was restored well over the intraluminal surface of the explanted SF/TPU sheet, the absence of calcium deposition, and minimal inflammatory reaction, without signs of degradation. CONCLUSION: The SF/TPU sheet had excellent mechanical properties and tissue biocompatibility. These favorable features and possible biodegradability of the SF portion warrant a long-term follow-up study.

A Case of Aortic Stenosis with Serum IgG4 Elevation, and IgG4-Positive Plasmacytic Infiltration in the Aortic Valve, Epicardium, and Aortic Adventitia.

A 74-year-old man was admitted for preoperative screening of aortic stenosis. Five months before this admission, he was found to have elevated serum immunoglobulin G4 (IgG4; 2,010 mg/dL). Computed tomography (CT) showed a soft tissue mass surrounding the abdominal aorta, suggestive of IgG4-related periaortitis. CT coronary angiography showed perivascular thickening of the right coronary artery, and subsequent coronary angiography showed a multi-vessel disease. The patient underwent aortic valve replacement and coronary bypass surgery. Immunohistochemical analysis showed IgG4-positive plasmacytic infiltration in specimens from the aortic valve, epicardium, and aortic adventitia, suggestive of the possible role of IgG4-related immune inflammation for the pathogenesis.

IgG4-positive cell infiltration in various cardiovascular disorders - results from histopathological analysis of surgical samples.

BACKGROUND: The diagnosis of Immunoglobulin G4 (IgG4)-related disease (IgG4-RD), in general, depends on serum IgG4 concentrations and histopathological findings; therefore, diagnosis of IgG4-RD in cardiovascular organs/tissues is often difficult owing to the risk of tissue sampling. METHODS: Prevalence of IgG4-positive lymphoplasmacytic infiltration in 103 consecutive cardiovascular surgical samples from 98 patients with various cardiovascular diseases was analyzed immunohistochemically. RESULTS: The diagnoses of the enrolled patients included aortic aneurysm (abdominal, n = 8; thoracic, n = 9); aortic dissection (n = 20); aortic stenosis (n = 24), aortic regurgitation (n = 10), and mitral stenosis/regurgitation (n = 17). In total, 10 (9.7%) of the 103 specimens showed IgG4-positive cell infiltration with various intensities; five of these were aortic valve specimens from aortic stenosis, and IgG4-positive cell infiltration was present at >10 /HPF in three of them. In one aortic wall sample from an abdominal aortic aneurysm, various histopathological features of IgG4-RD, such as IgG4-positive cell infiltration, obliterating phlebitis, and storiform fibrosis, were observed. CONCLUSIONS: IgG4-positive cell infiltration was observed in 9.7% of the surgical cardiovascular specimens, mainly in the aortic valve from aortic stenosis and in the aortic wall from aortic aneurysm. Whether IgG4-positive cell infiltration has pathophysiological importance in the development or progression of cardiovascular diseases should be investigated in future studies.

[Localized Nodular Pulmonary Amyloidosis after Resection of Lung Cancer;Report of a Case].

A 79-year-old man had undergone endoscopic colorectal resection for colon cancer and partial resection of right S2 for lung cancer in 2007. Two years later, enlargement of a small nodule in the right S10 detected by chest computed tomography was noted. Partial lung resection was performed in April 2009, and the pathological diagnosis was localized nodular pulmonary amyloidosis.

[Concomitant Operations for Thoracic Aortic Aneurysm and Myasthenia Gravis;Report of a Case].

A 77-year-old man, who had been under medical treatment for myasthenia gravis without thymoma, was diagnosed with aortic arch aneurysm. He underwent total aortic arch replacement and total resection of the thymus through median sternotomy. His symptoms relating to myasthenia gravis dramatically disappeared after the surgery. The serum anti-acetyl chorine receptor antibody decreased from 2.7 to 0.7 nmol/l (N<0.2) with the reduction of oral predonisolone from 12.5 to 5 mg/day at 4 years after the surgery. The concomitant operations significantly improved his quality of life.

[Three Surgical Cases of Quadricuspid Aortic Valve].

Quadricuspid aortic valve is a rare congenital disease. We experienced 3 surgical cases of quadricuspid aortic valve. Patient 1 was a 72-year-old man who was noted to have a quadricuspid aortic valve associated with aortic regurgitation and an ascending aortic aneurysm(51 mm in diameter). He underwent replacement of the aortic valve and the ascending aorta. Patient 2 was a 71-year-old man with severe aortic stenosis, regurgitation, and coronary triple vessel disease. He underwent aortic valve replacement and coronary artery bypass grafting. Preoperative echocardiography revealed no abnormalities in the number of valve leaflets, but quadricuspid aortic valve was identified during surgery. Patient 3 was a 79-year-old man with severe aortic regurgitation, who underwent aortic valve replacement. In all patients, the 4 valve cusps were approximately of the same size. Multi-detector computed tomography is useful for evaluation of valve morphology. Indication of prophylactic ascending aorta replacement in patients with aortic dilatation requires further study.

Surgical treatment of a mycotic pseudoaneurysm of the transverse arch using a rifampicin-impregnated dacron patch in an infant.

We describe a case of successful treatment of mycotic pseudoaneurysm of the transverse aortic arch in a male infant. The aneurysm was resected and the defect was repaired using a patch made from a rifampicin-impregnated Dacron graft.

[Influence of the Site of Port Insertion on the Flow Velocity of 5-FU Continuous Intravenous Injection by Using a Compression-Type Portable Continuous Infuser for Colorectal Cancer Patients].

For the continuous intravenous injection off luorouracil (5-FU) over 46 hours in a chemotherapeutic regimen for colorectal cancer, a compression-type portable continuous infuser is used. However, there is an error in the flow velocity. Errors in the dose or time of administration completion may influence the efficacy and safety of 5-FU. Therefore, it is necessary to reduce the error in the flow velocity. The type of diluent, air temperature, and concentration of 5-FU are reportedly factors influencing the flow velocity. However, no study has examined the influence of the site of port insertion. In this study, we investigated factors associated with the flow velocity of 5-FU continuously and intravenously injected by using an infuser in patients with colorectal cancer, among whom the site of port insertion differed. The results showed that the site of port insertion influenced the flow velocity during the continuous intravenous injection of 5-FU using an infuser. It is important to reduce the error in the flow velocity by considering the site of port insertion in addition to the concentration of 5-FU and the air temperature.

[Aortic regurgitation in a patient with polyarteritis nodosa].

Polyarteritis nodosa (PN) is vasculitis of small- to medium-sized arteries. A 57-year-old woman with PN developed aortic valve regurgitation. Aortic valve replacement (AVR) was performed. We found inflammatory change of the ascending aorta which was rarely involved in PN. Abnormal thickness of the aortic wall was recognized during operation, which had not been detected by preoperative computed tomography. Perioperative course was uneventful, and the patient underwent anti-inflammatory therapy after the operation. No perivalvular leakage has been detected for 3 years since AVR. We should consider the possibility of aortitis, when cardiovascular operations are performed in patients with vasculitis for small- to medium-sized arteries.