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Establishing a means to prevent osteonecrosis after corticosteroid administration is an important theme. We asked whether pulsed electromagnetic field stimulation, a noninvasive treatment, could prevent osteonecrosis. Ninety rabbits were divided into four treatment groups: (1) exposure of 10 hours per day to electromagnetic stimulation for 1 week, followed by injection of methylprednisolone (20 mg/kg), and exposure of 10 hours per day to electromagnetism for a further 4 weeks (n = 40); (2) methylprednisolone injection only (n = 40); (3) no treatment (n = 5); and (4) exposure of 10 hours per day to electromagnetism for 5 weeks (n = 5). After 5 weeks, we harvested and histologically examined femurs bilaterally. The frequency of osteonecrosis was lower in the steroid-electromagnetism group (15/40) than in the steroid-only group (26/40). No necrotic lesions were found in the two control groups. We observed no clear effects of electromagnetism on the number, location, extent, and repair of necrotic lesions and intramedullary fat cell size in affected rabbits. Pulsed electromagnetic field stimulation reportedly augments angiogenesis factors and dilates blood vessels; these effects may lower the frequency of osteonecrosis. Exposure to pulsed electromagnetic field stimulation before corticosteroid administration could be an effective means to reduce the risk of osteonecrosis. [ABSTRACT FROM AUTHOR]

Objective: For early diagnosis and inquiry into the pathophysiology of Sjögren disease (SjD), salivary secretion and component levels, and salivary glands' uptakes in sialoscintigraphy were examined, in this cross-sectional study., Methods: Patients who visited our hospital with suspected SjD between April 2016 and March 2020 were checked for unstimulated salivary secretion and β2-microglobulin, Na+, and cortisol levels in saliva. The patients who showed any abnormal salivary test results underwent sialoscintigraphy; the uptakes in the parotid, submandibular, and thyroid glands were compared using paired t test., Results: Sixty-five patients (female/male 51/14, 64.5 ± 13.7 years) were checked for saliva. The secretion was 0.39 ± 0.43 mL/min. The component levels were 1.98 ± 1.45 mg/dL for β2-microglobulin (n = 61), 15.9 ± 15.3 mEq/L for Na+ (n = 61), and 0.20 ± 0.18 μg/dL for cortisol (n = 56). A significant negative correlation was observed between the secretion and each component level. A significant positive correlation was found between the 2 out of the 3 component levels. Sialoscintigraphy of 52 patients showed significantly lower uptake in the submandibular glands than in the parotid glands (submandibular/parotid ratio: 0.51 ± 0.36, left; 0.54 ± 0.39, right). The total uptake in the 4 salivary glands was lower, but not significantly, than that in the thyroid gland., Conclusions: In patients with suspected SjD, a decreased salivary secretion correlated with a high level of any of β2-microglobulin, Na+, and cortisol; the 2 of the 3 levels correlated positively. Sialoscintigraphy showed that the submandibular glands were involved to a greater extent than the parotid glands were. The total salivary gland uptake may be lower than that in thyroid., Competing Interests: The authors declare no conflict of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: None.

Background: Cabozantinib is highly effective against advanced renal cell carcinoma (RCC). However, approximately 60% of the patients require a dose reduction due to severe adverse events. Although associations between trough concentrations of cabozantinib and its efficacy and safety have been reported in other countries, reports on Japanese patients are unavailable. Therefore, we investigated the association of cabozantinib trough concentration with therapeutic efficacy and adverse events in Japanese patients with RCC and evaluated the usefulness of therapeutic drug monitoring., Methods: In this prospective observational study, we measured the trough concentrations of cabozantinib in 10 Japanese patients with RCC enrolled between May 2022 and September 2023. The associations of trough concentration with treatment response, as determined by RECIST 1.1, and the occurrence of grade 2 or higher adverse events were assessed., Results: Trough concentration was higher in patients with controlled cancer than in those with progressive cancer (1024 ± 352 versus 457 ± 216 ng/mL, P = 0.035). In addition, patients with grade 2 or higher adverse events showed a significantly higher trough concentration than those without (1560 ± 513 versus 807 ± 319 ng/mL, P = 0.032). In particular, grade 2 or higher dysgeusia, anorexia, fatigue, and dyspepsia significantly correlated with trough concentrations., Conclusions: This is the first clinical study to demonstrate a correlation between cabozantinib trough concentration, therapeutic efficacy, and adverse events in Japanese patients with RCC. The therapeutic drug monitoring of cabozantinib could be useful for improving therapeutic efficacy and avoiding serious adverse events., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The aim of this study was to investigate how preoperative chemotherapy affected the serum zinc concentrations in patients with pancreatic cancer (PC)., Methods: Two hundreds and thirty-one patients with PC who underwent pancreatectomy at our department from 2013 to 2019 were enrolled in this study and measured for the serum zinc concentrations before pancreatectomy. Patient characteristics, course of treatment, and laboratory data were analyzed., Results: One hundred thirty-five patients underwent upfront pancreatectomy and 58 received preoperative Gemcitabine + S1 (GEM + S1) and 29 received Gemcitabine + nab-Paclitaxel (GEM + nab-PTX). Comparing the serum zinc concentrations before and after preoperative treatment, it was found to decrease after treatment with statistical difference (79.3 μg/dl vs. 68.7 μg/dl, p < 0.001). The result was consistent with the investigation for both the patients who received GEM + S1 and those who received GEM + nab-PTX (p = 0.019, p < 0.001, respectively)., Conclusions: The preoperative chemotherapy consistently reduced the serum zinc concentrations in the PC patients, regardless of their regimen such as GEM + S1 and GEM + nab-PTX. Monitoring the serum zinc concentration and appropriate zinc supplementation may be essential for PC patients undergoing preoperative chemotherapy and pancreatectomy., Competing Interests: Conflict of Interest: The authors declare that they have no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Nintedanib, a multi-intracellular tyrosine kinase inhibitor, reduces progression of idiopathic pulmonary fibrosis (IPF) and has been approved to use in other progressive fibrosing interstitial lung diseases (ILD) recently. However, the factors that affect the discontinuation of treatment due to adverse events is uncertain. The dorsal muscle group area at the T12 vertebral level (T12DMA) assessed on computed tomography (CT) images has been reported to be associated with mortality in chronic obstructive pulmonary disease (COPD) and other diseases. The relationship between T12DMA and the discontinuation of nintedanib remains unclear., Methods: 39 patients with IPF or other progressive fibrosing ILDs who started nintedanib at a regular dose (300 mg/day) were enrolled. We compared the characteristics between patients who stopped nintedanib at a regular dose before 6 months and/or continue to take nintedanib at a low dose (150 mg/day) and patients who were still taking nintedanib at a regular dose over 6 months. This study retrospectively investigated clinical parameters including T12DMA index (T12DMA/height2) to evaluate whether these parameters might serve as risk factor for the tolerability of nintedanib in patients with IPF and other progressive fibrosing ILDs., Results: Discontinuation or dose reductions of nintedanib due to adverse events were observed in 14 (35.8%) patients. A multiple logistic regression model showed T12DMA index to be the only significant risk factor for predicting for the early termination of nintedanib (odd rate, 0.549; 95% confidence interval, 0.327-0.922; P = .023)., Conclusions: This study revealed that T12DMA index was a risk factor for the early termination of nintedanib. The initial dose of nintedanib adjusted to the differences in skeletal muscle mass and careful management of adverse events may contribute to the longer nintedanib treatment, which would lead to a better clinical outcome., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Current cardiovascular magnetic resonance sequences cannot discriminate between different myocardial extracellular space (ECSs), including collagen, noncollagen, and inflammation. We sought to investigate whether cardiovascular magnetic resonance radiomics analysis can distinguish between noncollagen and inflammation from collagen in dilated cardiomyopathy., Methods: We identified data from 132 patients with dilated cardiomyopathy scheduled for an invasive septal biopsy who underwent cardiovascular magnetic resonance at 3 T. Cardiovascular magnetic resonance imaging protocol included native and postcontrast T 1 mapping and late gadolinium enhancement (LGE). Radiomic features were computed from the midseptal myocardium, near the biopsy region, on native T 1 , extracellular volume (ECV) map, and LGE images. Principal component analysis was used to reduce the number of radiomic features to 5 principal radiomics. Moreover, a correlation analysis was conducted to identify radiomic features exhibiting a strong correlation (r>0.9) with the 5 principal radiomics. Biopsy samples were used to quantify ECS, myocardial fibrosis, and inflammation., Results: Four histopathological phenotypes were identified: low collagen (n=20), noncollagenous ECS expansion (n=49), mild to moderate collagenous ECS expansion (n=42), and severe collagenous ECS expansion (n=21). Noncollagenous expansion was associated with the highest risk of myocardial inflammation (65%). Although native T 1 and ECV provided high diagnostic performance in differentiating severe fibrosis (C statistic, 0.90 and 0.90, respectively), their performance in differentiating between noncollagen and mild to moderate collagenous expansion decreased (C statistic: 0.59 and 0.55, respectively). Integration of ECV principal radiomics provided better discrimination and reclassification between noncollagen and mild to moderate collagen (C statistic, 0.79; net reclassification index, 0.83 [95% CI, 0.45-1.22]; P <0.001). There was a similar trend in the addition of native T 1 principal radiomics (C statistic, 0.75; net reclassification index, 0.93 [95% CI, 0.56-1.29]; P <0.001) and LGE principal radiomics (C statistic, 0.74; net reclassification index, 0.59 [95% CI, 0.19-0.98]; P =0.004). Five radiomic features per sequence were identified with correlation analysis. They showed a similar improvement in performance for differentiating between noncollagen and mild to moderate collagen (native T 1 , ECV, LGE C statistic, 0.75, 0.77, and 0.71, respectively). These improvements remained significant when confined to a single radiomic feature (native T 1 , ECV, LGE C statistic, 0.71, 0.70, and 0.64, respectively)., Conclusions: Radiomic features extracted from native T 1 , ECV, and LGE provide incremental information that improves our capability to discriminate noncollagenous expansion from mild to moderate collagen and could be useful for detecting subtle chronic inflammation in patients with dilated cardiomyopathy., Competing Interests: Disclosures None.

Objectives: Pancreatic ductal adenocarcinoma is an intractable disease with frequent recurrence after resection and adjuvant therapy. The present study aimed to clarify whether artificial intelligence-assisted analysis of histopathological images can predict recurrence in patients with pancreatic ductal adenocarcinoma who underwent resection and adjuvant chemotherapy with tegafur/5-chloro-2,4-dihydroxypyridine/potassium oxonate., Materials and Methods: Eighty-nine patients were enrolled in the study. Machine-learning algorithms were applied to 10-billion-scale pixel data of whole-slide histopathological images to generate key features using multiple deep autoencoders. Areas under the curve were calculated from receiver operating characteristic curves using a support vector machine with key features alone and by combining with clinical data (age and carbohydrate antigen 19-9 and carcinoembryonic antigen levels) for predicting recurrence. Supervised learning with pathological annotations was conducted to determine the significant features for predicting recurrence., Results: Areas under the curves obtained were 0.73 (95% confidence interval, 0.59-0.87) by the histopathological data analysis and 0.84 (95% confidence interval, 0.73-0.94) by the combinatorial analysis of histopathological data and clinical data. Supervised learning model demonstrated that poor tumor differentiation was significantly associated with recurrence., Conclusions: Results indicate that machine learning with the integration of artificial intelligence-driven evaluation of histopathological images and conventional clinical data provides relevant prognostic information for patients with pancreatic ductal adenocarcinoma., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Previous studies have demonstrated the benefit of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) for preventing longitudinal geographic miss (LGM). However, it is yet unclear whether IVUS guidance is useful for robotic-PCI (robotic-assisted perctaneous coronary intervention [R-PCI])., Methods: A total of 58 consecutive patients with stable angina who underwent IVUS-guided R-PCI were enrolled. The stent landing position was angiographically marked using a balloon marker before stenting, followed by measurements of the expected stent length using balloon pullback. Subsequently, prestenting IVUS was performed to determine stent landing. All pre-PCI IVUS images were assessed for lesion length and percent plaque volume (%PV) using both IVUS and angiographic marking. LGM was defined as a residual %PV >50% at either the distal or proximal stent edge, any stent edge dissection, or additional stent deployment immediately after stenting., Results: The included patients had an average age of 67.1 ± 10.1 years. IVUS guidance had significantly longer lesion lengths compared with angiographic marking. Based on IVUS-guided stent deployment, nine cases exhibited LGM immediately after stenting. IVUS-marked landing points had a significantly smaller %PV and significantly larger lumen area compared with those for angiography., Conclusion: IVUS-guided R-PCI was well-tolerated and may be better at preventing LGM compared with angiography-guided R-PCI., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Disclosures None.

Purpose: To examine 1-year outcomes of metamorphopsia and tangential retinal displacement after epiretinal membrane surgery and identify predictors for metamorphopsia score at 1 year and its improvement from baseline., Methods: M-CHARTS were used to measure metamorphopsia. Distances between the intersections of two sets of retinal vessels were measured with infrared or autofluorescence images. Predictors for metamorphopsia scores at 1 year after surgery and their differences from baseline were identified with multivariate regression analysis., Results: Ninety-two eyes of 90 consecutive patients were included. The vertical and horizontal distances continued expanding for 1 year ( P < 0.001). Both vertical and horizontal metamorphopsia scores improved 3 months after surgery ( P = 0.025 and P < 0.001, respectively), and horizontal scores continued improving for a year. Horizontal metamorphopsia scores correlated with retinal displacement more strongly than vertical scores. Higher metamorphopsia score at baseline is predictive for that at 1 year. Older age and being male are predictive for less improvement of the score at 1 year from baseline., Conclusion: Metamorphopsia correlates with tangential retinal displacement at 1 year after epiretinal membrane surgery. Horizontal metamorphopsia scores keep improving until 1 year postoperatively. Being male and older age are both independent predictors for poor improvement of metamorphopsia after epiretinal membrane surgery.

Abstract: In this single-center retrospective study, we intended to evaluate the frequencies and characteristics of computed tomography findings of pancreatobiliary inflammation (PBI) in patients treated with lenvatinib and the relationship of these findings with treatment-planning changes.We included 78 patients (mean ± standard deviation, 69.8 ± 9.4 years, range: 39-84 years, 62 men) with hepatocellular carcinoma (n = 62) or thyroid carcinoma (n = 16) who received lenvatinib (June 2016-September 2020). Two radiologists interpreted the posttreatment computed tomography images and assessed the radiological findings of PBI (symptomatic pancreatitis, cholecystitis, or cholangitis). The PBI effect on treatment was statistically evaluated.PBI (pancreatitis, n = 1; cholecystitis, n = 7; and cholangitis, n = 2) was diagnosed in 11.5% (9/78) of the patients at a median of 35 days after treatment initiation; 6 of 9 patients discontinued treatment because of PBI. Three cases of cholecystitis and 1 of cholangitis were accompanied by gallstones, while the other 5 were acalculous. The treatment duration was significantly shorter in patients with PBI than in those without (median: 44 days vs. 201 days, P = .02). Overall, 9 of 69 patients without PBI showed asymptomatic gallbladder subserosal edema.Lenvatinib-induced PBI developed in 11.5% of patients, leading to a significantly shorter treatment duration. Approximately 55.6% of the PBI cases were acalculous. The recognition of this phenomenon would aid physicians during treatment planning in the future., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Carcinomatous meningitis (CM) is a critical issue for physicians. However, no study has reported a simple and useful diagnostic or predictive marker for CM.This study aimed to elucidate the potential markers for diagnosing CM derived from cerebrospinal fluid (CSF).We retrospectively enrolled 78 lung cancer patients with suspected CM during the clinical course, including 42 CM and 36 non-CM patients. We compared the clinical and CSF findings, including carcinoembryonic antigen (CEA), between CM and non-CM patients, and explored the diagnostic markers for early identification of CM as well as the contributing factors for mortality.On CSF analysis, with cutoff values of CEA ≥5 ng/ml, total protein (TP) in CSF ≥45 g/dl, and total cell count (TCC) ≥7 cells/μL, the sensitivity, specificity, and area under the curve (AUC) for CM were 85.7%, 84.6%, and 0.887 (95% CI: 0.758-1.0, P < .001); 80.5%, 69.4%, and 0.755 (95% CI: 0.646-0.865, P < .001); and 56.1%, 100%, and 0.817 (95% CI: 0.722-0.912, P < .001), respectively. TP levels in CSF ≥the patients' age had a sensitivity, specificity, and an AUC of 48.8%, 77.8%, and 0.633 (95% CI: 0.722-0.912, P = .045) for CM, respectively. Among CM patients, patients with 'TP in CSF (>patients' age)" (n = 19, P = .008) showed significantly shorter 90-day survival probability than the residual patients (n = 20). None of the CSF parameters could predict the risk of mortality on Cox regression analysis.The cutoff value of CEA ≥5 ng/ml in CSF is a simple and useful method with a high diagnostic value for CM diagnosis, but not a suitable predicting factor for mortality. 'TP in CSF >patients' age" might be a novel factor for assessing short-term mortality., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Immune checkpoint inhibitors (ICIs) have emerged as evolutionary treatments for malignant diseases. Although ICIs can cause immune-related adverse events (irAEs) in various organs, precise timing after ICI initiation has been scarcely reported. Elucidating the effects of irAEs, such as time to onset, involvement of major organs, influence on progression-free survival (PFS), and overall survival (OS), are critical issues for physicians. Furthermore, lung-irAE as a whole is not well known.We conducted a retrospective study of 156 patients who were treated with ICIs and compared 82 irAE patients with 74 non-irAE patients.This study clearly demonstrated that the preferred period after induction of ICIs was significantly longer in lung-irAE than in other major organs (skin, digestive tract, and endocrine). The effect of irAEs on PFS and OS was evident PFS in the irAE group (n = 82) (median 128 days, interquartile range [IQR] 62-269 days, P = .002) was significantly longer than that in the non-irAE group (n = 74) (median 53 days, IQR 33-151 days). Similarly, OS was significantly longer in the irAE group (median 578 days, IQR 274-1027 days, P = .007) than in the non-irAE group (median 464 days, IQR: 209-842 days). However, this positive effect of irAEs in the lungs was not proportional to the extent of severity.Lung-irAEs can occur at a later phase than non-lung-irAEs and seemed not to prolong OS and PFS. However, further studies are needed to support these findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

To evaluate the utility of unenhanced postmortem computed tomography (PMCT) for the investigation of in-hospital nontraumatic death in children up to 3 years of age.This study included the cadavers of children who died from intrinsic diseases before 3 years of age. The major underlying disease and the main organ-disease systems associated with the immediate causes of death were determined by clinical evaluation, PMCT, and autopsy, which were used as a reference standard. The rates of concordance between the former two methods and autopsy were calculated for all cases.In total, 22 cadavers (12 male and 10 female; mean age, 6.1 ± 8.2 months) were included. The rates of concordance between clinical evaluation/PMCT and autopsy for diagnosis of the major underlying disease and main organ-disease systems associated with the immediate causes of death were 100%/36% (P = .0015) and 59%/41% (P = .37), respectively. In cases where the respiratory system was associated with the immediate cause of death, PMCT showed greater diagnostic sensitivity (90%) than did clinical evaluation (20%). In contrast, the diagnostic sensitivity of PMCT was lower than that of clinical evaluation in cases involving disorders of the cardiac system and multiple organ systems (0% vs 100% for both).The findings of this study suggest that the use of unenhanced PMCT with clinical evaluation can result in improved detection of the immediate cause of death in select cases of in-hospital nontraumatic death before 3 years of age.

Background: Somatic stem cell (SC) therapy can improve cardiac performance following ischemic injury. In this study, we investigated whether induced pluripotent SC-derived cardiomyocytes (iPS-CMs) are more effective than somatic SCs, such as skeletal myoblasts (SM) and mesenchymal (M)SCs, in promoting functional recovery upon transplantation in a porcine model of myocardial infarction., Methods: Myocardial injury was induced by ameroid ring placement in immunosuppressed female mini pigs; after 1 month, epicardial cell transplantation was performed with iPS-CMs (n = 7), SMs (n = 7), and MSCs (n = 7). Control pigs underwent sham operation (n = 8)., Results: Cell therapy improved functional recovery 2 months after myocardial infarction, as evidenced by increased ejection fraction (iPS-CM, +7.3% ± 2.2% and SM, +5.8% ± 5.4% vs control, -4.4% ± 3.8%; P < 0.05). The analysis of regional contractile function in the infarcted zone revealed an increase in transverse peak strain (iPS-CM, +4.6% ± 2.2% vs control, -3.8% ± 4.7%; P < 0.05). The C-11 acetate kinetic analysis by positron emission tomography showed that the work-metabolic cardiac energy efficacy increased by the transplantation of iPS-CMs, but was reduced by the other cell types. This was accompanied by decreased myocardial wall stress in the infarcted zone (iPS-CM, -27.6 ± 32.3 Pa and SM, -12.8 ± 27 Pa vs control, +40.5 ± 33.9 Pa; P < 0.05)., Conclusions: The iPS-CM is superior to other somatic cell sources in terms of improving regional contractile function and cardiac bioenergetic efficiency, suggesting greater clinical benefits in severely damaged myocardium.

Objectives: The aim of this study was to evaluate the diagnostic and prognostic impact of systemic inflammatory markers for IPMN with high-grade dysplasia (HGD)/invasive carcinoma., Methods: Neutrophil-to-lymphocyte ratio (NLR), derived NLR, platelet-to-lymphocyte ratio, and C-reactive protein-to-albumin ratio were compared across the different histological grades of 205 IPMN cases. We also tested the diagnostic performance for IPMN with HGD/invasive carcinoma., Results: The median (interquartile range) preoperative NLR was higher in IPMN with HGD/invasive carcinoma (2.03 [1.48-2.93]) than IPMN with low-grade dysplasia (1.74 [1.42-2.24], P = 0.0137). The C-reactive protein-to-albumin ratio and derived NLR values were also significant higher in cases with HGD/invasive carcinoma. A combination assay of NLR, carcinoembryonic antigen, and carbohydrate antigen 19-9 revealed a 58.8% sensitivity and 76.8% specificity. Among the cases with worrisome features, the high NLR values increased the positive predictive value (68.8%) compared with low values (31.8%). In IPMN cases with the associated invasive carcinoma, high NLR values showed association with the deeper vertical invasion and shorter survival periods., Conclusions: Preoperative NLR, combined with tumor markers and image findings, can be a useful predictive marker for the presence of HGD/invasive carcinoma in IPMNs. Preoperative NLR also predicts the long-term outcomes in IPMN cases with invasive carcinoma.

Rationale: Because most patients with familial Mediterranean fever (FMF) have attacks without any prodromal symptoms, and since it is suggested that patients with FMF have subclinical inflammation even during remission, a daily continuous administration of colchicine is recommended for patients with FMF even during remission. However, it is possible that intermittent colchicine therapy only during FMF attacks prevents the attacks completely in patients with FMF with expectable attacks., Patient Concerns: A 31-year-old Japanese woman suffered high fever and arthralgia lasting for 2 to 3 days after each menstrual period's start. She was admitted to our hospital, and colchicine was administered immediately after her next period's start, and the febrile attack was completely prevented., Diagnoses: We eventually diagnosed typical FMF., Interventions: Her remission has been maintained by intermittent colchicine therapy., Outcomes: The genetic analysis revealed the G304R heterozygous mutation in exon 2 of the MEFV gene. Cytokine analysis suggested subclinical inflammation during the remission period., Lessons: This case suggests that taking an extensive medical history (including the relationship between fever attack and menstruation) is important in the diagnosis of female patients with FMF. This case also suggests that a continuous administration of colchicine may have to be considered to regulate subclinical inflammation even in patients with FMF with completely expectable attacks.

Rationale: Most cases of lymphoepithelial carcinoma (LEC) occur in the nasopharynx, and LEC in the sinonasal tract is extremely rare; thus, the clinical characteristics of sinonasal LEC are not well known., Patient Concerns: A 63-year-old Japanese man presented with a three-week history of left cheek pain, nasal obstruction and cheek swelling., Diagnoses: Enhanced CT and MRI revealed a tumor of the left maxillary sinus that invaded the left orbit and hard palate, with multiple swollen left cervical lymph nodes. Open biopsy was performed, and the specimen was diagnosed as LEC., Interventions: Alternating chemoradiotherapy (ALCRT) followed by salvage surgery was performed., Outcomes: Our patient has been disease free for 5 years., Lessons: A literature review of the epidemiology, etiology, clinical course and management of sinonasal LEC is highlighted. We believe ALCRT followed by salvage surgery to be a highly optimal treatment for sinonasal LEC from the viewpoint of a balance between quality of life and a high curative effect.

Rationale: Among all dermatomyositis (DM) patients, antimelanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) positive patients have significantly poor short-term mortality, whereas they experience less relapses over the long term after the remission. We report the case of a patient with anti-MDA5 Ab-positive clinically amyopathic dermatomyositis (CADM) with the recurrence of interstitial lung disease (ILD) after 7 years of remission. There has been no case report of an anti-MDA5 Ab-positive DM patient with the recurrence of ILD after 7 years of long-term remission., Patient Concerns: A 70-year-old Japanese woman was diagnosed with anti-MDA5 Ab-positive CADM and ILD. After achieving 7 years long-term remission, she was admitted to our department with erythema on the fingers and interstitial pneumonia. Her anti-MDA5 Ab titer was elevated., Diagnoses: We diagnosed recurrent CADM complicated with ILD., Interventions: We successfully treated her with 1,000 mg of methyl-prednisolone pulse and intravenous cyclophosphamide therapy followed by prednisolone 50 mg/day and an increase of cyclosporine., Outcomes: After that treatment, the patient's skin symptoms and interstitial pneumonia were relieved. All laboratory investigations such as ferritin, the serum markers of interstitial pneumonia (i.e., SP-A, SP-D), and the titer of anti-MDA5 Ab showed signs of improvement., Lessons: Her case suggests that careful physical examinations and monitoring the serum markers are important even after long-term remission is achieved.

Rationale: As the initial treatment of rapidly progressive interstitial lung disease (RPILD) with antimelanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab)-positive dermatomyositis (DM) patients, a combination of corticosteroids, cyclophosphamide, and calcineurin inhibitor is recommended. However, some of these patients have poor prognoses despite such intensive treatment. Other more effective treatments are desired. We report the case of an anti-MDA5 Ab-positive DM patient who had developed RPILD despite intensive treatments; she was treated successfully by a short-term plasma exchange (PE)., Patient Concerns: A 71-year-old Japanese woman was admitted to the rheumatology department of another hospital with progressive muscle weakness of the limbs and erythema on both upper eyelids and the fingers of both hands. She was suspected of having classical DM (CDM) based on the findings of typical skin and myositis. Although a chest computed tomography (CT) examination showed no findings of interstitial pneumonia at the first visit to the department, she newly presented interstitial pneumonia during her admission and her anti-MDA5 Ab titer was elevated., Diagnoses: She was diagnosed with interstitial lung disease (ILD) with anti-MDA5 Ab-positive DM., Interventions: She was treated with 1000 mg of methyl-prednisolone pulse, 500 mg of intravenous cyclophosphamide therapy (IVCY) followed by prednisolone 40 mg/day with tapering, and oral cyclosporine 200 mg/day. However, her interstitial pneumonia worsened with increasing breathing difficulty and an increasing serum ferritin level. She was transferred to our department, and we initiated PE as an additional treatment., Outcomes: After the PE treatment, all laboratory findings, for example, ferritin, KL-6, and the titer of anti-MDA5 Ab showed marked improvement, and the patient's skin symptoms and active interstitial pneumonia were relieved., Lessons: Our patient's case suggests that PE may be effective for RPILD in anti-MDA5 Ab-positive DM patients.

Background: Optical coherence tomographic (OCT) morphologies associated with lesion progression are not well studied. The aim of this study was to determine the morphological change for untreated lesion progression using both OCT and intravascular ultrasound (IVUS)., Methods and Results: We used baseline and 8-month follow-up 3-vessel OCT and IVUS to assess 127 nonculprit lesions (IVUS plaque burden ≥40%) in 45 patients with stable angina after target lesion treatment. Lesion progression was defined as an IVUS lumen area decrease >0.5 mm 2 . A layered pattern was identified as a superficial layer that had a different optical intensity and a clear demarcation from underlying plaque. Lesion progression was observed in 19% (24/127) lesions, and its pattern was characterized into 3 types: type I, new superficial layered pattern at follow-up that was not present at baseline (n=9); type II, a layered pattern at baseline whose layer thickness increased at follow-up (n=7); or type III, no layered pattern at baseline or follow-up (n=8). The increase of IVUS plaque+media area was largest in type I and least in type III (1.9 mm 2 [1.6-2.1], 1.1 mm 2 [0.9-1.4], and 0.3 mm 2 [-0.2 to 0.8], respectively; P =0.002). Type III, but not types I or II, showed negative remodeling during follow-up (IVUS vessel area; from 14.3 mm 2 [11.4-17.2] to 13.5 mm 2 [10.4-16.7]; P =0.02). OCT lipidic plaque was associated with lesion progression (odds ratio, 13.6; 95% confidence interval, 3.7-50.6; P <0.001)., Conclusions: Lesion progression was categorized to distinct OCT morphologies that were related to changes in plaque mass or vessel remodeling., (© 2017 American Heart Association, Inc.)

Purpose: To determine whether the degree of metamorphopsia significantly correlated with the distance of the tangenital retinal displacement after epiretinal membrane surgery., Methods: The M-CHARTS were used to measure the vertical metamorphopsia score and the horizontal score. The distances between the intersections of two sets of retinal vessels situated vertically or horizontally were measured in the near-infrared Spectralis images., Results: Fifty eyes of 50 patients (22 men; age, 69.5 ± 7.8 years) were retrospectively studied. The vertical and horizontal metamorphopsia scores significantly improved at 1 month after the surgery, and the vertical and horizontal retinal distances increased. The baseline horizontal and vertical metamorphopsia scores significantly correlated with the ratio of the pre- and postoperative vertical and horizontal retinal displacements, respectively (P = 0.038 and P = 0.015 at 1 week; P = 0.036 and P = 0.036 at 1 month). The postoperative horizontal metamorphopsia score at 1 month and the vertical metamorphopsia score at 3 months significantly correlated with the vertical displacement at 1 month (P = 0.034) and the horizontal displacement at 3 months (P = 0.001), respectively., Conclusion: The degree of metamorphopsia significantly correlated with the tangential retinal displacement. Dislocated Müller cells may stimulate the photoreceptors located away from original positions, which consequently results in the sensation of metamorphopsia in patients with an epiretinal membrane.

Objective: The aim of the study was to evaluate the relationship between hospital volume and outcome after pancreaticoduodenectomy (PD)., Summary Background Data: Previous reviews for the hospital volume-outcome relationship after pancreatic resection were limited owing to clinical or methodological heterogeneity, resulting from differences in surgical procedures and high-volume hospital (HVH) definitions across studies., Methods: We conducted a rigorous meta-analysis on the influence of hospital volume on various outcomes after PD using strict inclusion criteria and single cutoff values for HVHs., Results: Thirteen studies based on nationwide databases from 11 countries, and including 58,023 patients in total, were included in this study. The overall pooled odds ratio (OR) for mortality favoring the HVH group was 2.37 [95% confidence interval (CI): 1.95-2.88] with high heterogeneity (I = 63%). We therefore classified all included studies into categories according to the cutoff values for HVH as defined in each individual study. The pooled OR for each category of 1 to 19, 20 to 29, and ≥30 PDs per year was 1.94, 2.34, and 4.05, respectively. There were significant differences among these categories (I = 58.9%, P = 0.09). The 2 former categories showed no statistical interstudy heterogeneities. The data did not suggest publication bias. These trends persisted in all subgroup analyses. Postoperative length of stay in the HVH group was significantly shorter with mild interstudy heterogeneity., Conclusions: This meta-analysis included studies from different countries with disparate health care systems and provided strong evidence for an inverse association between higher hospital volume and lower mortality after PD. Variations in HVH cutoff values across studies majorly influenced the overall heterogeneity.

Objectives: The occurrence of hepatic steatosis after pancreatectomy is known to be associated with the remnant pancreatic function. However, other risk factors for hepatic steatosis after pancreatectomy remain unknown. The aims of this study were to identify other risk factors in addition to the remnant pancreatic function and elucidate the relationship between postoperative hepatic steatosis and pancreatic exocrine insufficiency in totally pancreatomized patients., Methods: Forty-three patients who underwent total pancreatectomy were analyzed. Hepatic steatosis was defined as the attenuation of unenhanced computed tomography values. Clinical findings and laboratory data were compared between patients with and without hepatic steatosis., Results: Sixteen (37.2%) patients developed hepatic steatosis after total pancreatectomy, with marked declines in the Controlling Nutritional Status score and body mass index. Multiple linear regression analysis revealed that the attenuation of computed tomography values was correlated with female sex (P = 0.002), early postoperative serum albumin levels (P = 0.003), and pancreatic enzyme replacement therapy with high-dose pancrelipase (P = 0.032)., Conclusions: Postoperative hepatic steatosis after pancreatectomy is associated with sex, malnutrition, and pancreatic exocrine insufficiency. High-dose pancreatic enzyme replacement therapy may have preventive effects on hepatic steatosis occurring after pancreatectomy.

Purpose: To determine the clinical significance of retinal pigment epithelium (RPE) undulations in the acute stage of Vogt-Koyanagi-Harada disease., Methods: Retinal pigment epithelium undulations were detected and classified into 3 grades: Grade 1, slight; Grade 2, moderate; and Grade 3, severe undulations, in the enhanced depth imaging optical coherence tomographic images. The relationship between the clinical characteristics and the presence of RPE undulations was investigated., Results: Among the 61 eyes of 31 patients with Vogt-Koyanagi-Harada disease, 40 eyes had some degree of RPE undulations (Grade 1 = 12, Grade 2 = 15, and Grade 3 = 13). The patients with RPE undulations in both eyes were significantly older at the onset (P = 0.0002). The eyes with RPE undulations were more likely to develop posterior recurrences (P = 0.032) and have worse vision at 12 months (P = 0.043). Multiple regression analysis revealed that RPE undulations were an independent predictor of posterior recurrences (P = 0.009) and poor visual outcomes (P = 0.035)., Conclusion: Retinal pigment epithelium undulations detected by enhanced depth imaging optical coherence tomographic are relatively frequent occurrences at the acute stage of Vogt-Koyanagi-Harada, and their presence is a predictor of posterior recurrences and poor visual outcomes after high-dose steroid therapy.

Background: Nerve growth factor (NGF), which plays important roles in promoting growth and differentiation of nerve cells, has recently been reported as a regulator in pancreatic β cells in terms of insulin releasing function. In this study, we examined whether NGF stimulation would promote islet graft survival and function in islet transplantation., Methods: We found that supplementation of cultured islets with NGF improved the viability of islet cells and induced the production of insulin, vascular endothelial growth factor, and cellular proliferative markers. Because a specific inhibitor of TrkA, K252a, blocked all these effects, we propose that the TrkA receptor is the mediator of NGF stimulation., Results: After transplantation to the kidney subcapsule and liver of syngenic diabetic mice, a higher rate of normoglycemic achievement, increased serum insulin, and improved glucose tolerance were observed in the mice transplanted with NGF-pretreated islet grafts. Histological analysis revealed higher expression of insulin and vascular endothelial growth factor, an increase in proliferative β cells, and revascularization in NGF-pretreated islet grafts without activation of any inflammatory cells., Conclusions: The NGF treatment can therefore serve as a new and promising therapeutic tool for improving islet graft viability and function in islet transplantation.

To evaluate radiographic features of endotracheal/endobronchial fluid in the airway (FA) observed on postmortem computed tomography (PMCT). We studied 164 subjects who died at our hospital between April 2009 and September 2012. Fluid in the airway was considered positive when fluid was identified in the lumen of 1 of the 2 main bronchi in continuity with a segmental bronchus. Pleural effusion and atelectasis/consolidation of the lung lower lobes were also evaluated. Fluid in the airway was observed in 60 (71%) of 84 subjects with unilateral or bilateral pleural effusion, and in 44 (55%) of 80 subjects without pleural effusion (P = 0.029). Of the latter, 41 (93%) had atelectasis/consolidation of the lower lung lobes. Among subjects without pleural effusion, average times after death to PMCT of subjects with and without FA were 501 and 314 minutes, respectively (P = 0.01). Time-course analysis showed that cases with FA on PMCT largely correlated with time after death (R = 0.7966). Fluid in the airway is frequently observed on PMCT in subjects with pleural effusion or atelectasis/consolidation of the lung. No FA in subjects without pleural effusion correlated to shorter times after death. In addition, FA frequency on PMCT increased over time after death.

Colloid carcinoma, characterized by the presence of a large amount of extracellular mucin that results in the formation of mucous lakes with a relative paucity of neoplastic glandular cells within them, is extremely rare in the uterine cervix. Herein, we report an additional case of colloid carcinoma of the cervix and discuss the immunohistochemical characteristics and histogenesis of this extremely rare tumor. A 47-year-old Japanese female without any history of carcinomas was found to have a bulky mass in the cervix. Biopsy from the cervix revealed adenocarcinoma; subsequently, total hysterectomy was performed. Histopathologic study demonstrated that columnar or cuboidal neoplastic glandular cells forming cribriform or tubular structures floated within the mucous lakes involving almost the entire layer of the cervical wall. Adenocarcinoma in situ (AIS) component was also observed. Immunohistochemically, tumor cells of the colloid carcinoma were positive for cytokeratin 7, MUC5AC, MUC6, and p16 (diffuse), but negative for cytokeratin 20, MUC2, and cdx-2. In addition, human papillomavirus 16 was detected in both colloid carcinoma and AIS components. This is the first reported case of endocervical type colloid carcinoma, and the second documented case of cervical colloid carcinoma with immunohistochemical analyses of mucin. The present case had an endocervical type AIS component, which suggests that AIS may be a precursor lesion of colloid carcinoma. Moreover, this case clearly demonstrates that the occurrence of cervical colloid carcinoma correlates with high-risk human papillomavirus.