Early gastric cancer with RhoGAP fusion is linked to frequent nodal metastasis and a part of microtubular-mucocellular histology.

INTRODUCTION: Gastric cancer with fusion genes involving the Rho GTPase-activating protein domain (RhoGAP-GC) is mainly included in the genomically stable type of The Cancer Genome Atlas classification. Clinical implications and histological characteristics of RhoGAP-GC in the early phase remain unclear. METHODS: We analyzed 878 consecutive pT1b GCs for RhoGAP and its partner genes using fluorescence in situ hybridization assay. RESULTS: RhoGAP fusion was detected in 57 (6.5%) GCs. Univariate analysis revealed that female sex, middle-lower third tumor location, advanced macroscopic type, tumor diameter > 2 cm, pT1b2, lymphatic invasion, venous invasion, negative EBER-ISH, and RhoGAP fusion were significantly associated with lymph node metastasis (LNM). Multivariate analysis presented RhoGAP fusion, lymphatic invasion, tumor diameter > 2 cm, advanced macroscopic type, venous invasion, and middle-lower third tumor location as independent risk factors for LNM. Notably, RhoGAP fusion had the highest odds ratio (3.92) for LNM among analyzed parameters (95% CI 2.12-7.27; p < 0.001). Compared to non-RhoGAP-GCs, RhoGAP-GCs were significantly frequent in younger females and showed the highest incidence of lymphatic invasion (56.2%) and LNM (49.1%) (p < 0.001). Histologically, microtubular architecture with pseudo-trabecular interconnection and small aggregations of tumor cells with a varied amount of cytoplasmic mucin, named "microtubular-mucocellular (MTMC) histology," was found in 93.0% (53 of 57) of RhoGAP-GCs in the intramucosal area. MTMC histology showed high sensitivity and negative predictive value (93.0% and 99.4%, respectively) for RhoGAP fusion, albeit positive predictive value is low (34.9%). CONCLUSION: RhoGAP-GC is linked to a characteristic MTMC histology and a high incidence of LNM.

Prognostic significance of antifibrotic agents in idiopathic pulmonary fibrosis after initiation of long-term oxygen therapy.

BACKGROUND AND AIM: Idiopathic pulmonary fibrosis (IPF) is a fatal and progressive interstitial lung disease with varying degrees of hypoxemia. Long-term oxygen therapy (LTOT) is frequently used to treat hypoxemia, however the prognostic factors for better survival in IPF patients after initiation of LTOT remain unknown. METHODS: We retrospectively investigated favorable factors of survival in consecutive 55 IPF patients with chronic respiratory failure who were introduced LTOT. RESULTS: The 6-, 12-, 18-, and 24-month survival rates in IPF patients after introduction of LTOT were 70.9%, 49.0%, 45.2%, and 32.3%, respectively. Univariate analysis demonstrated that low Glasgow Prognostic Score (GPS) (hazard ratio [HR] 0.482, p=0.043) and treatment with antifibrotic agents (HR 0.401, p=0.013) were associated with favorable survival, while multivariate analysis revealed that treatment with antifibrotic agents was the independent predictor (HR 0.449, p=0.032). Moreover, IPF patients treated with antifibrotic agents with LTOT had significantly longer survival than those without antifibrotic agents (p = 0.0106). CONCLUSION: In IPF patients who were introduced LTOT, treatment with antifibrotic agents was the independent factor for favorable survival. Treatment with antifibrotic agents may improve prognosis of IPF even after initiation of LTOT.

Pembrolizumab-induced secondary adrenal insufficiency due to adrenocorticotrophic hormone deficiency in a patient with non-small-cell lung carcinoma: a case report.

BACKGROUND: Pembrolizumab can cause immune-related adverse events such as adrenal insufficiency (AI). However, there is no consensus regarding appropriate monitoring of adrenal function during subsequent chemotherapy in patients who have received immune checkpoint inhibitors (ICIs) such as pembrolizumab. CASE PRESENTATION: In this report, we discuss the case of a 60s-year-old male patient with non-small cell lung cancer receiving chemotherapy who developed secondary AI due to adrenocorticotrophic hormone (ACTH) deficiency 8 months after the discontinuation of pembrolizumab, which was 17 months after the initiation of pembrolizumab immunotherapy. After 5 months of chemotherapy, he developed fever and diarrhoea, after which chemotherapy was discontinued. Thereafter, he was hospitalised owing to the development of general fatigue and anorexia. Although cortisol and ACTH levels were not measured during chemotherapy, they were measured before hospitalisation, and secondary AI was suspected. After admission, a detailed endocrine workup was performed, and the patient was diagnosed with secondary AI due to ACTH deficiency. Treatment with hydrocortisone was initiated, which markedly improved his general fatigue and anorexia. The patient showed no evidence of progressive disease 9 months after the discontinuation of pembrolizumab. CONCLUSIONS: Although rare, the possibility of AI should be considered in patients who have received ICIs when nonspecific symptoms develop during or after subsequent chemotherapy, and measurements of endocrine function (including cortisol and ACTH levels) should be performed.

Detection of TRAF1-ALK fusion in skin lesions of systemic ALK+ anaplastic large cell lymphoma initially involving the skin and the draining lymph node.

A case of cytoplasmic anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) initially involving the skin in a 44-year-old Japanese female is reported. The patient had a hemorrhagic erythematous tumor on the right thigh without any systemic symptoms. Pathology showed diffuse infiltration of CD30-positive anaplastic large cells positive for epithelial membrane antigen and cytoplasmic ALK. The right inguinal lymph node showed infiltration of tumor cells in the marginal sinus. Only 2 weeks after radiation therapy, the patient developed multiple subcutaneous nodules and lung involvement. Even after subsequent multichemotherapy sessions, cutaneous recurrence occurred. Literature review of cytoplasmic ALK-positive ALCL initially involving in the skin revealed that skin lesions were mostly seen in the extremities and that half of the cases developed extracutaneous lesions. Radiation and chemotherapy were effective for most cases. Inverse RT-PCR identified a tumor necrosis factor receptor-associated factor (TRAF)1-ALK fusion in our case. Most reported cases with this translocation experienced repeated changes in chemotherapy, suggesting poorer prognosis. Although ALK-positive ALCL generally responds well to chemotherapy, the presence of a TRAF1-ALK fusion may suggest resistance to treatment. Detection of fusion partners of ALK is important for predicting clinical courses and deciding treatment options.

Eosinophil-rich variant of nodal marginal zone lymphoma: a clinicopathological study of 11 cases.

AIMS: Tissue eosinophilia is commonly observed in T-cell and classic Hodgkin lymphomas, but rarely in B-cell lymphomas. Herein, we present the first report of a case series on nodal marginal zone lymphoma (NMZL) with tissue eosinophilia. METHODS AND RESULTS: All 11 patients in this study had nodal disease at primary presentation. The mean age at diagnosis was 64 years. The mean follow-up period was 39 months, and all patients were alive. Nine of the 11 patients (82%) showed no recurrence, but the other two patients experienced recurrence in the lymph nodes or skin. Marked eosinophilic infiltration was observed in all biopsied lymph nodes. Nine of the 11 patients had a preserved nodular architecture with expanded interfollicular areas. The other two patients showed diffuse lymphoma cell infiltration with effacement of nodal architecture. One of them was diagnosed as having diffuse large B-cell lymphoma transformed from NMZL because large cells accounted for >50% of the lymphoma cells and formed sheet-like patterns. Cells were positive for CD20 and BCL2 and negative for CD5, CD10, and BCL6. Some patients showed myeloid cell nuclear differentiation antigen (MNDA) positivity. All patients showed B-cell monoclonality via flow cytometry, southern blotting, and/or polymerase chain reaction (PCR). CONCLUSION: All patients showed distinctive morphological features and could be misdiagnosed with peripheral T-cell lymphoma due to their eosinophil-rich backgrounds. The predominance of B cells, absence of histiocytes, and high endothelial venules in the interfollicular areas are key factors for diagnosis. B-cell monoclonality is the most reliable evidence of differentiation. We designated this type of lymphoma as an eosinophil-rich variant of NMZL.

Clinicopathologic and genetic characterization of angiofibroma of soft tissue: a study of 12 cases including two cases with AHRR::NCOA3 gene fusion.

AIMS: Angiofibroma of soft tissue (AFST) is a benign tumour characterised by prominent arborizing blood vessels throughout the lesion. Approximately two-thirds of AFST cases were reported to have AHRR::NCOA2 fusion, and only two cases have been reported to have other gene fusions: GTF2I::NCOA2 or GAB1::ABL1. Although AFST is included in fibroblastic and myofibroblastic tumours in the World Health Organization's 2020 classification, histiocytic markers, especially CD163, have been reported to be positive in almost all examined cases, and it still remains the possibility of a fibrohistiocytic nature of the tumour. Therefore, we aimed to clarify the genetic and pathological spectrum of AFST and identify whether histiocytic marker-positive cells were true neoplastic cells. METHODS AND RESULTS: We evaluated 12 AFST cases, which included 10 cases with AHRR::NCOA2 and two with AHRR::NCOA3 fusions. Pathologically, nuclear palisading, which has not been reported in AFST, was detected in two cases. Furthermore, one tumour resected by additional wide resection revealed severe infiltrative growth. Immunohistochemical analysis indicated varying levels of desmin-positive cells in nine cases, whereas CD163- and CD68-positive cells were diffusely distributed in all 12 cases. We also performed double immunofluorescence staining and immunofluorescence in situ hybridisation in four resected cases with >10% desmin-positive tumour cells. The results suggested that the CD163-positive cells differed from desmin-positive cells with AHRR::NCOA2 fusion in all four cases. CONCLUSION: Our findings suggested that AHRR::NCOA3 could be the second most frequent fusion gene, and histiocytic marker-positive cells are not genuine neoplastic cells in AFST.

ALK rearrangement-associated renal cell carcinoma morphologically mimicking mucinous tubular and spindle cell carcinoma: a case report.

BACKGROUND: Anaplastic lymphoma kinase rearrangement-associated renal cell carcinoma (ALK-RCC) is an extremely rare tumor and ALK-RCC that mimics mucinous tubular and spindle cell carcinoma (MTSCC) has been very reported only in one instance. CASE PRESENTATION: A 42-year-old Japanese woman was admitted to our hospital for the treatment of a left renal tumor measuring 5 cm in maximum dimension. She underwent a laparoscopic left nephrectomy. Histologically, the tumor formed tubular or focally papillary structures with a small amount of spindle-shaped tumor cells against the background of prominent extracellular mucin. Although the tumor cells were negative for immunohistochemistry (IHC) of alpha-methylacyl-CoA racemase (AMACR) and lymph node metastasis was presented (these are atypical findings for MTSCC), we initially diagnosed the tumor as MTSCC based on its morphological characteristics with mucin deposition. However, an additional IHC analysis revealed that the tumor cells were diffusely positive for ALK-IHC. In addition, TPM3 exon 8 - ALK exon 20 fusion gene was detected by RNA sequencing. The tumor was thus correctly diagnosed as ALK rearrangement-associated renal cell carcinoma (ALK-RCC). CONCLUSIONS: Since the use of molecular targeted therapy with an ALK inhibitor for ALK-RCC is promising, the correct pathological diagnosis of ALK-RCC is quite important. We strongly recommend that ALK-IHC be routinely performed for renal tumors with negative AMACR staining that mimic MTSCC.

Surfactant protein D: A useful biomarker for distinguishing COVID-19 pneumonia from COVID-19 pneumonia-like diseases.

Introduction: Computed tomography is useful for the diagnosis of coronavirus disease (COVID-19) pneumonia. However, many types of interstitial lung diseases and even bacterial pneumonia can show abnormal chest shadows that are indistinguishable from those observed in COVID-19 pneumonia. Thus, it is necessary to identify useful biomarkers that can efficiently distinguish COVID-19 pneumonia from COVID-19 pneumonia-like diseases. Herein, we investigated the usefulness of serum Krebs von den Lungen 6 (KL-6) and surfactant protein D (SP-D) for identifying patients with COVID-19 pneumonia among patients with abnormal chest shadows consistent with COVID-19 pneumonia. Method: This was a retrospective cohort study of consecutive patients who underwent evaluation of serum KL-6 and SP-D at a single center from February 2019 to December 2020. A total of 54 patients with COVID-19 pneumonia and 65 patients with COVID-19 pneumonia-like diseases were enrolled in this study from the source population. Serum KL-6 and SP-D levels in both groups were analyzed. Result: The serum levels of KL-6 and SP-D in patients with COVID-19 pneumonia were significantly lower than those in patients with COVID-19 pneumonia-like disease (median [interquartile range]: 208.5 [157.5-368.5] U/ml vs. 430 [284.5-768.5] U/ml, p < 0.0001 and 24.7 [8.6-51.0] ng/ml vs. 141 [63.7-243.5] ng/ml, p < 0.0001, respectively). According to receiver operating characteristic (ROC) analysis, the areas under the ROC curves (95% confidence intervals) of serum KL-6 and SP-D levels for distinguishing COVID-19 pneumonia from COVID-19 pneumonia-like diseases were 0.761 (0.675-0.847) and 0.874 (0.812-0.936), respectively. The area under the ROC curve of serum SP-D was significantly larger than that of serum KL-6 (p = 0.0213), suggesting that serum SP-D can more efficiently distinguish COVID-19 pneumonia from COVID-19 pneumonia-like diseases. Conclusion: Serum SP-D is a promising biomarker for distinguishing COVID-19 pneumonia from COVID-19 pneumonia-like diseases. Serum SP-D can be useful for the management of patients with abnormal chest shadow mimicking COVID-19 pneumonia.

High prevalence of TERT aberrations in myxoid liposarcoma: TERT reactivation may play a crucial role in tumorigenesis.

Myxoid liposarcoma (MLPS) is genetically characterized by FUS-DDIT3 or EWSR1-DDIT3 gene fusion and the high frequency of hotspot mutations (C228T or C250T) in the promoter region of telomerase reverse transcriptase (TERT) that encodes the TERT protein. The latter leads to telomerase reactivation, a mechanism of telomere maintenance. Although the TERT promoter hotspot mutation is a poor prognostic factor in various tumors, its effect on MLPS has not been reported in detail. In the present study, we examined the clinicopathological characteristics, prognosis, and telomere maintenance mechanisms in 83 primary tumor samples of MLPS, which were resected surgically at the Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, from 2008 to 2020. TERT promoter hotspot mutations were observed in 77% (63/82) cases, and alternative lengthening of telomeres (ALT) was absent in all cases. Among the cases without TERT promoter hotspot mutations, TERT rearrangements, and minor point mutations in the TERT promoter region were found in 3 and 2 cases, respectively. TERT mRNA expression was observed consistently even in patients for whom no genomic TERT aberrations were detected, and the presence of TERT promoter hotspot mutation did not correlate significantly with either overall and metastasis-free survival (P = .56, P = .83, respectively) or clinicopathological features. Therefore, patients with MLPS characteristically shows TERT expression and a high prevalence of TERT aberrations. Our findings suggest that TERT aberration is not prognostic factor, but might occur at an early stage and play a key role in tumorigenesis.

Distinct Clinicopathologic Features and Possible Pathogenesis of Localized ALK-positive Histiocytosis of the Breast.

Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a rare emerging entity characterized by systemic or localized proliferation of histiocytes harboring ALK rearrangements. Breasts are reportedly affected by ALK-positive histiocytosis. Here, we evaluated 2 localized cases of breast ALK-positive histiocytosis through a comprehensive clinicopathologic, molecular, and genomic analysis to further delineate this entity and better understand its pathogenesis. The cases involved 2 undiagnosed ALK-positive spindle-cell breast lesions. Both cases were Asian women aged 30s to 40s who underwent excisions for asymptomatic breast masses. Macroscopically, both lesions were well-circumscribed, solid masses. Microscopically, both lesions were predominantly composed of fascicles with uniform, bland spindle cells, admixed with epithelioid histiocyte-like cells and lymphoid aggregates. Immunohistochemically, the spindle and epithelioid cells coexpressed ALK and histiocytic markers (eg, CD68, CD163). Genetically, both lesions harbored KIF5B-ALK, confirmed by fluorescence in situ hybridization and polymerase chain reaction-direct sequencing analyses. Combining these results, both cases were successfully diagnosed as ALK-positive histiocytosis. Furthermore, no common or previously annotated somatic alterations were identified by whole-exome sequencing. One case harbored clonal immunoglobulin gene rearrangements according to the polymerase chain reaction-based BIOMED-2 protocol. Therefore, ALK-positive histiocytosis can be accurately diagnosed through a combination of morphologic, immunohistochemical, and molecular analyses. In this entity, breast cases may have distinct clinicopathologic features: Asian women aged 30s to 40s, asymptomatic masses, and predominant spindled morphology. For pathogenesis, ALK rearrangements could be the driver alteration, and a subset of ALK-positive histiocytosis may harbor a lymphoid lineage. These findings can be utilized to improve the diagnosis of ALK-positive histiocytosis and better understand its pathogenesis.

Impact of sarcopenia on chemotherapy-triggered exacerbation of interstitial lung disease in patients with non-small cell lung cancer.

BACKGROUND: While recent evidence has suggested that sarcopenia could predict chemotoxicity, its association with chemotherapy-triggered interstitial lung disease (ILD) exacerbations has yet to be investigated. Thus, the present study sought to determine whether sarcopenia could predict ILD exacerbations and overall survival (OS) in patients with ILD-complicated non-small cell lung cancer (NSCLC). METHODS: From January 2010 to July 2020, 74 patients with ILD-complicated NSCLC who received chemotherapy were retrospectively investigated. After categorizing patients according to the presence or absence of sarcopenia based on the psoas muscle index, ILD exacerbation rates and OS were evaluated. RESULTS: Among the patients in the study, 39 were included in the sarcopenia group. Moreover, 17 (22.9%) patients developed ILD exacerbations, with the sarcopenia and nonsarcopenia groups having an exacerbation rate of 33.3% and 11.4%, respectively (p = 0.025). Multivariate analysis identified sarcopenia as an independent predictor of ILD exacerbations (p = 0.039). Furthermore, patients with sarcopenia demonstrated a significantly shorter median OS compared to those without the same (9.2 vs. 13.3 months; p = 0.029). CONCLUSIONS: Sarcopenia predicted chemotherapy-triggered ILD exacerbation and OS in patients with ILD-complicated NSCLC, suggesting its utility in determining treatment approaches.

Early intervention of plasma exchange combined with intensive immunosuppressive treatment for anti-MDA-5 antibody-positive rapidly progressive interstitial pneumonia: Two case reports.

BACKGROUND: Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) has to be reported to often cause rapidly progressive interstitial lung disease (RP-ILD) especially in East Asian countries. Even with the recommended rapid administration of immunosuppressive agents with high-dose corticosteroids, intravenous pulse cyclophosphamide, and calcineurin inhibitors, the prognosis of anti-MDA5 Ab-related RP-ILD is poor. Plasma exchange (PE) has been reported to be effective for steroid-refractory RP-ILD with anti-MDA5 Ab. However, the timing, frequency, and interval of PE for the treatment of RP-ILD with anti-MDA5 Ab have not yet been established. CASE PRESENTATION: We report two cases of RP-ILD with anti-MDA5 Ab treated by early intervention of PE combined with immunosuppressive treatment. Blood biomarkers including titers of anti-MDA5 Ab, serum KL-6 and ferritin were promptly decreased after each session of PE. Clinical symptoms, oxygenation and chest computed tomography abnormalities were completely improved after immunosuppressive treatment with PE. CONCLUSION: Early intervention of PE combined with immunosuppressive treatment may prevent the development to lethal severe respiratory failure in RP-ILD with anti-MDA5 Ab.

Glasgow prognostic score for prediction of chemotherapy-triggered acute exacerbation interstitial lung disease in patients with small cell lung cancer.

BACKGROUND: Predicting the incidence of chemotherapy-triggered acute exacerbation of interstitial lung disease (AE-ILD) in patients with lung cancer is important because AE-ILD confers a poor prognosis. The Glasgow prognostic score (GPS), which is an inflammation-based index composed of serum levels of C-reactive protein and albumin, predicts prognosis in patients with small cell lung cancer (SCLC) without ILD. In this study, we investigated AE-ILD and survival outcome based on the GPS in patients with ILD associated with SCLC who were receiving chemotherapy. METHODS: Medical records of patients who received platinum-based first-line chemotherapy between June 2010 and May 2019 were retrospectively reviewed to compare the incidence of AE-ILD and overall survival (OS) between GPS 0, 1, and 2. RESULTS: Among our cohort of 31 patients, six (19.3%) experienced chemotherapy-triggered AE-ILD. The AE-ILD incidence increased from 9.5% to 25.0% and 50.0% with increase in GPS of 0, 1, and 2, respectively. Univariate and multivariate analyses revealed remarkable associations between GPS 2 and both AE-ILD (odds ratio for GPS 2, 18.69; p = 0.046) and prognosis (hazard ratio of GPS 2, 13.52; p = 0.002). Furthermore, median OS in the GPS 0, 1, and 2 groups was 16.2, 9.8, and 7.1 months, respectively (p < 0.001). CONCLUSIONS: Our results suggest that GPS 2 is both a predictor of risk of chemotherapy-triggered AE-ILD and a prognostic indicator in patients with ILD associated with SCLC. We propose that GPS may be used as a guide to distinguish chemotherapy-tolerant patients from those at high risk of AE-ILD.

Serum Neutrophil Gelatinase-associated Lipocalin (NGAL) Is Elevated in Patients with Asthma and Airway Obstruction.

Neutrophilic airway inflammation is one of the features of severe asthma. Neutrophil gelatinase-associated lipocalin (NGAL), or lipocalin-2, is a glycoprotein associated with neutrophilic inflammation and can be detected in blood. Recently, blood NGAL levels have been reported to be elevated in chronic obstructive pulmonary disease. However, the clinical significance of serum NGAL levels in patients with asthma has not been elucidated. The aim of this study was to explore the association between serum NGAL level and clinical parameters in patients with asthma. Sixty-one non-smoking people with stable asthma were enrolled in this study. All patients underwent blood collection and pulmonary function tests. The associations between serum NGAL levels and clinical parameters were analyzed retrospectively. Serum NGAL levels in patients with asthma and obstructive ventilatory defect were higher than those in patients with asthma without obstructive ventilatory defect (76.4±51.4 ng/mL vs. 39.3±27.4 ng/mL, P=0.0019). Serum NGAL levels were correlated with forced expired flow at 50% of vital capacity %predicted and forced expired flow at 75% of vital capacity %predicted (r=-0.3373, P=0.0078 and r=-0.2900, P=0.0234, respectively). Results of a multiple regression analysis demonstrated that serum NGAL level was independently associated with obstructive ventilatory defect. Serum NGAL levels were elevated in patients with asthma and obstructive ventilatory defect. NGAL may be involved in airway remodeling possibly mediated by neutrophilic inflammation in asthma.

Glasgow Prognostic Score predicts chemotherapy-triggered acute exacerbation-interstitial lung disease in patients with non-small cell lung cancer.

BACKGROUND: Interstitial lung disease (ILD) in patients with non-small cell lung cancer (NSCLC) worsens the prognosis for overall survival (OS) due to chemotherapy-triggered acute exacerbation (AE)-ILD. The Glasgow Prognostic Score (GPS), which is based on serum C-reactive protein and albumin levels, has been suggested as a reliable prognostic tool for mortality in cancer patients, including NSCLC. In this study, we investigated whether GPS is a predictor for chemotherapy-triggered AE-ILD and the prognosis in patients with NSCLC and pre-existing ILD. METHODS: We conducted a retrospective review on 56 NSCLC and ILD patients at our hospital who received platinum agent-based treatment as first-line chemotherapy between June 2010 and May 2019. We categorized these patients according to their GPS (0-2) and compared the incidence of chemotherapy-triggered AE-ILD and OS. RESULTS: The GPS 0, 1, and 2 groups included 31, 16, and nine patients, respectively, out of 56. A total of 12 (21.4%) patients showed chemotherapy-triggered AE-ILD. The median OS was at 11.5 months (95% confidence interval: 8.0-15.1). The incidence of chemotherapy-triggered AE-ILD within the first year of chemotherapy in the GPS 0, 1, and 2 groups was three (9.6%), four (25.0%), and five (55.5%), and the median OS time was 16.9, 9.8 and 7.6 months, respectively. Univariate and multivariate analyses indicated that only GPS 2 could predict both chemotherapy-triggered AE-ILD and OS (P < 0.05). CONCLUSIONS: GPS assessment of patients with NSCLC and pre-existing ILD is a valuable prognostic tool for predicting chemotherapy-triggered AE-ILD and OS. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: We found that GPS 2 was an independent risk factor for chemotherapy-triggered AE-ILD and prognosis in patients with ILD associated with NSCLC. WHAT THIS STUDY ADDS: GPS may potentially enable the discrimination of patients tolerant of chemotherapy from those at an increased risk of AE-ILD and predict the prognosis in patients with NSCLC and ILD receiving chemotherapy.

Prognostic Factors for Axial Length Elongation and Posterior Staphyloma in Adults With High Myopia: A Japanese Observational Study.

PURPOSE: To identify prognostic factors for axial length (AL) elongation and incidence of posterior staphyloma (PS) in adult Japanese patients with high myopia. DESIGN: Retrospective, observational cohort study. METHODS: Six-year follow-up data for 345 patients (620 eyes with AL ≥ 26.5 mm and spherical equivalent [SE] ≤- 8.00 diopters) admitted to the Tokyo Medical and Dental University Hospital from 2007 to 2017 were analyzed retrospectively. Main outcome measures were change in AL from baseline, factors associated with AL, categorization of eyes with high myopia, factors associated with incidence of PS, and impact of PS on myopic maculopathy and visual function. RESULTS: The mean annual increase in AL was 0.03 mm. Presence of optic nerve disc conus (P = .025), steeper corneal curvature, lower SE, and decreased choroidal thickness (CT) (all P < .001) were associated with increased AL in univariate and multivariate analyses. Younger age (P = .003) and no use of intraocular pressure-lowering medications (P = .046) were associated with increased AL. Eyes with high myopia were categorized using factor analysis as associated with glaucoma, severe pathologic myopia, and mild-to-moderate pathologic myopia. Older age, increased AL, glaucoma, and choroidal thinning (all P ≤ .001) were identified as significant risk factors for the incidence of PS in univariate and/or multivariate analyses. Incidence of PS was a precursor for myopic maculopathy and visual field defects. CONCLUSIONS: Optic nerve disc conus, steeper corneal curvature, lower SE, decreased CT, and no use of intraocular pressure-lowering medications were prognostic factors for increased AL. Older age, increased AL, glaucoma, and decreased CT were prognostic factors for PS.

Polymyxin B haemoperfusion treatment for respiratory failure and hyperferritinaemia due to COVID-19.

A 69-year-old man with a history of type 2 diabetes and high blood pressure was diagnosed with coronavirus disease 2019 (COVID-19). He had hyperferritinaemia and respiratory failure. Despite the initiation of favipiravir and high-dose corticosteroid and ceftriaxone, his respiratory failure progressed and serum ferritin levels increased. After polymyxin B-immobilized fibre column direct haemoperfusion (PMX-DHP) therapy, there was improvement of the respiratory failure and hyperferritinaemia. We report the first case of COVID-19-induced hyperferritinaemia and severe respiratory failure successfully treated by PMX-DHP.

Primary intramucosal synovial sarcoma of the sigmoid colon in a patient with a germline mutation in the MSH2 gene: A case report.

Synovial sarcoma is a high-grade soft tissue sarcoma that occurs primarily in the deep soft tissue of extremities, and primary colorectal synovial sarcoma is extremely rare. In this report, we present a synovial sarcoma mostly located within the mucosa of the sigmoid colon. The patient was a man in his forties with a germline deletion in the MSH2 gene. He had experienced undifferentiated pleomorphic sarcoma of the left forearm 7 years before and adenocarcinoma of the transverse colon 6 years before, both of which were successfully treated and exhibited no recurrence to date. A surveillance colonoscopy for Lynch syndrome revealed the tumor which had a submucosal tumor-like appearance with central erosion and endoscopic resection was performed. Histologically, it was composed of monotonous proliferation of spindle cells arranged in cellular fascicles; these findings were compatible with monophasic fibrous synovial sarcoma. In the tumor cells, the presence of the SS18-SSX1 fusion gene was confirmed. Protein expression of mismatch repair genes was intact in the tumor cells, indicating the association between microsatellite instability and synovial sarcoma was weak. The present case highlights a rare primary site of synovial sarcoma in a patient with Lynch syndrome.

Favipiravir-induced fever in coronavirus disease 2019: A report of two cases.

Favipiravir, an antiviral agent, is undergoing clinical trials for treating novel coronavirus disease 2019 (COVID-19). Here, we report two cases of COVID-19 with favipiravir-induced fever. In both cases, pyrexia was observed following the administration of favipiravir despite improvements in symptoms of COVID-19. No other cause for fever was evident after careful physical examination and laboratory investigation. The fever subsided in both patients after the discontinuation of favipiravir. To the best of our knowledge, this is the first report of favipiravir-induced fever in COVID-19 patients.