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The identification of CD30 expression by immunohistochemistry is essential for the treatment of lymphomas using an antibody-drug conjugate targeting CD30. However, no standardized protocol for CD30 staining has been available. In this study, we compared three common automated immunostaining platforms {Bond III (B III), Dako Omnis (DO) and Ventana BenchMark ULTRA (VBMU)}. A primary antibody for CD30, the Ber-H2 clone, was diluted 50- to 400-fold for B III and DO, and ready-to-use antibody was used for VBMU. An enhancement step using a linker was introduced in all protocols. First, several candidate dilutions were selected for each platform by staining six cases. These candidate conditions were then confirmed with 60 cases of various types of peripheral T-cell lymphomas (PTCLs). The concordance rates of CD30 expression among platforms differed depending on cutoff values and antibody dilutions, except for anaplastic large cell lymphoma. The concordance rates among three platforms in the evaluation of "positive" or "negative" were 100% and 97% when the cutoff values were 1% and 10% respectively, if using 400-diluted antibody in B III and 100-diluted antibody in DO. This study demonstrated the feasibility of equalizing CD30 staining of PTCLs among different platforms by adjusting protocols., (Pathology International© 2024 The Author(s). Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Background: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP., Methods: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis., Result: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed., Conclusion: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications., Competing Interests: Declaration of competing interest Hiroshi Mukae received lecture honoraria and research grants from KYORIN Pharmaceutical Co., Ltd. Outside of the submitted work., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) are diseases caused by Aspergillus infection, and CPA can develop from ABPA in some cases. We herein report a patient with CPA overlapping with ABPA. Serum cytokine levels were evaluated at 4 time points: the ABPA diagnosis, CPA diagnosis, 6 months after the start of voriconazole (VRCZ), and 12 months after re-administration of VRCZ. Interleukin (IL)-13 levels decreased upon glucocorticoid treatment, whereas IL-25 and IL-33 levels decreased rapidly with the initiation of antifungals. Early antifungal therapy may be important to control disease progression and prevent CPA overlap.

Background: Evidence regarding the association of the usage of biologic agents (Etanercept, Tocilizumab, adalimumab and so on), such as anti-tumor necrosis factor α, with the incidence and risk factors of non-tuberculous Mycobacteria (NTM) infection is limited. Therefore, this study aimed to investigate the incidence and risk factors of NTM and their associations with biologic agents' usage, and also investigated the potential of Mycobacterium avium complex (MAC) antibodies as a predictor of NTM infection development., Methods: This retrospective study included 672 patients with autoimmune diseases from four hospitals in Nagasaki, Japan, from January 1, 2011, to June 30, 2019, who fulfilled the inclusion criteria., Results: Of the 672 patients, 9 (1.3%) developed complicated NTM infection, including two with disseminated infection, after the introduction of biologic agents. Of the nine patients, two died due to NTM infection but none tested positive for MAC antibodies prior to initiation of biologic agents. The mortality rate was higher in patients complicated with NTM than without NTM (22.2% vs 2.6%, P = 0.024). The corticosteroids dosage at the time of initiating the biologic agents was significantly higher in the NTM group than in the non-NTM group (median, 17 mg vs 3 mg, P = 0.0038)., Conclusion: In the patients undergoing therapy with biologic agents, although NTM complication was rare, it could be fatal. In particular, for patients on a relatively high dose corticosteroids, careful observation is essential for identifying NTM complication, even if the MAC antibody test is negative., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Invasive aspergillosis (IA) and mucormycosis are life-threatening diseases, especially among immunocompromised patients. Drug-resistant Aspergillus fumigatus strains have been isolated worldwide, which can pose a serious clinical problem. As IA mainly occurs in patients with compromised immune systems, the ideal therapeutic approach should aim to bolster the immune system. In this study, we focused on Vγ9Vδ2 T cells that exhibit immune effector functions and examined the possibility of harnessing this unconventional T cell subset as a novel therapeutic modality for IA. A potent antifungal effect was observed when A. fumigatus ( Af293 ) hyphae were challenged by Vγ9Vδ2 T cells derived from peripheral blood. In addition, Vγ9Vδ2 T cells exhibited antifungal activity against hyphae of all Aspergillus spp., Cunninghamella bertholletiae , and Rhizopus microsporus but not against their conidia. Furthermore, Vγ9Vδ2 T cells also exhibited antifungal activity against azole-resistant A. fumigatus , indicating that Vγ9Vδ2 T cells could be used for treating drug-resistant A. fumigatus . The antifungal activity of Vγ9Vδ2 T cells depended on cell-to-cell contact with A. fumigatus hyphae, and degranulation characterized by CD107a mobilization seems essential for this activity against A. fumigatus . Vγ9Vδ2 T cells could be developed as a novel modality for treating IA or mucormycosis., Importance: Invasive aspergillosis (IA) and mucormycosis are often resistant to treatment with conventional antifungal agents and have a high mortality rate. Additionally, effective antifungal treatment is hindered by drug toxicity, given that both fungal and human cells are eukaryotic, and antifungal agents are also likely to act on human cells, resulting in adverse effects. Therefore, the development of novel therapeutic agents specifically targeting fungi is challenging. This study demonstrated the antifungal activity of Vγ9Vδ2 T cells against various Aspergillus spp. and several Mucorales in vitro and discussed the mechanism underlying their antifungal activity. We indicate that adoptive immunotherapy using Vγ9Vδ2 T cells may offer a new therapeutic approach to IA., Competing Interests: Y.T. is a co-inventor of JP2014-257451 (on the method for expanding γδ T cells using PTA) and JP2014-73475 (on the method for a nonradioactive cellular cytotoxicity assay). The other authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

Due to the widespread appearance of viruses, antibiotic-resistant bacteria (ARBs), and antibiotic resistance genes (ARGs) in the aquatic environment, more powerful oxidation processes such as ozonation are needed to enhance the efficiency of their inactivation and removal during wastewater treatment. However, information is lacking on the elimination rates of viruses, ARBs, cell-associated ARGs (ca-ARGs), and cell-free ARGs (cf-ARGs) during ozonation. This study examined the kinetics and dose-dependent inactivation of a virus (MS2 coliphage) and an ARB (Ampicillin-resistant [Amp R ] E. coli) and the removal of ca- and cf-ARGs (plasmid-encoded bla TEM ) by ozonation in a filtered secondary effluent (SE) of a municipal sewage treatment plant (STP). In addition, the ozonation kinetics of carbamazepine (CBZ) and metoprolol (MTP)-ubiquitous organic micropollutants with different removal rate constants-were also investigated in order to monitor their effectiveness as indicators for the abovementioned biological risk factors. Our results showed that ozonation was an efficient way to remove MS2, Amp R E. coli, ARGs, CBZ, and MTP. We investigated the kinetics of their inactivation/removal with respect to exposure in terms of CT (dissolved ozone concentration C and contact time T) value, and found their inactivation/removal constants were in the following order: MS2 (8.66 ×10 3 M -1 s -1 ) ≈ Amp R E. coli (8.19 ×10 3 M -1 s -1 ) > cf-ARG (3.95 ×10 3 M -1 s -1 ) > CBZ ( 3.21 ×10 3 M -1 s -1 ) > ca-ARG (2.48 ×1 0 3 M -1 s -1 ) > MTP (8.35 ×10 2 M -1 s -1 ). In terms of specific ozone dose, > 5 - log inactivation of MS2 was observed at > 0.30 mg O3/mg DOC, while > 5-log inactivation of Amp R E. coli was confirmed at 1.61-2.35 mg O3/mg DOC. Moreover, there was almost no removal of ca-ARG when the specific ozone dose was < 0.68 mg O3/mg DOC. However, 2.86-3.42-log removal of ca-ARG was observed at 1.27-1.31 mg O3/mg DOC, while 1.14-1.36-log removal of cf-ARG was confirmed at 3.60-4.30 mg O3/mg DOC. As alternative indicators, > 4-log removal of CBZ was observed at > 1.00 mg O3/mg DOC, while > 2-log removal of MTP was confirmed at > 2.00 mg O3/mg DOC. Thus, it was observed that inactivation of E. coli needs a greater ozone dose to achieve the same level of inactivation of Amp R E. coli; for ARGs, cf-ARG can persist longer than ca-ARG if low dosages of ozone are applied in the filtrated SE, CBZ might act as an indicator with which to monitor the inactivation of viruses and ARBs, while MTP might act as an indicator with which to monitor removal of ARGs. Moreover, cf-ARG cannot be neglected even after ozonation due to the possibility that ca-ARGs can become cf-ARGs during ozonation and be discharged with the final effluent, posing a potential risk to the receiving environment., Competing Interests: Declaration of Competing Interest All authors of the submitted paper titled “Comparison on removal performance of virus, antibiotic-resistant bacteria, cell-associated and cell-free antibiotic resistance genes, and indicator chemicals by ozone in the filtrated secondary effluent of a sewage treatment plant” disclosed any financial and personal relationships with other people or organizations., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Currently, no established marker exists for predicting peritoneal metastasis progression during chemotherapy, although they are major interruptive factors in sequential chemotherapy in patients with advanced gastric cancer (AGC). This multicenter retrospective study was conducted from June 2015 to July 2019, analyzing 73 patients with AGC who underwent taxane-plus-ramucirumab (TAX/RAM) therapy and had their serum carbohydrate antigen 125 (CA125) concentrations measured. Of 31 patients with elevated CA125 levels above a cutoff of 35 U/mL, 25 (80.6%) had peritoneal metastasis. The CA125 concentrations before TAX/RAM treatment were associated with ascites burden. The overall survival was significantly shorter in the CA125-elevated group. CA125 kinetics, measured at a median of 28 days after chemotherapy, were associated with the ascites response (complete or partial response: -1.86%/day; stable disease: 0.28%/day; progressive disease: 2.33%/day). Progression-free survival in the CA125-increased group, defined by an increase of 0.0067%/day using receiver operating characteristic curve analysis, was significantly poorer among patients with peritoneal metastases. In conclusion, this study highlights that CA125 kinetics can serve as an early predictor for the progression of peritoneal metastasis during TAX/RAM treatment.

(1) Background : Nivolumab plus chemotherapy is established as a first-line treatment for advanced gastric cancer (AGC). While mFOLFOX6 is commonly used for AGC with severe peritoneal metastasis, the efficacy of nivolumab combined with it remains uncertain. We evaluated the outcomes of nivolumab plus mFOLFOX6 for AGC with severe peritoneal metastasis in clinical practice. (2) Methods : This multicenter retrospective study was conducted between December 2021 and June 2023. We investigated AGC patients with massive ascites or inadequate oral intake due to severe peritoneal metastasis and who received nivolumab plus mFOLFOX6. (3) Results : Among 106 patients treated with nivolumab plus chemotherapy, 21 (19.8%) had severe peritoneal metastasis, with 14 receiving nivolumab plus mFOLFOX6. The median progression-free survival was 7.4 months (95%CI 1.9-10.1), and the median overall survival was 10.7 months (95%CI 5.3-NA), with four patients (28.5%) surviving more than 12 months. Improved ascites and oral intake were observed in 6/14 patients (42.8%) and 10/11 patients (90.9%), respectively. The major grade 3 or more adverse events included leukopenia (28.5%) and neutropenia (21.4%), with no severe immune-related adverse events reported. (4) Conclusions : The safety and moderate efficacy of nivolumab plus mFOLFOX6 were suggested even in AGC patients with severe peritoneal metastasis.

Background: Cryptococcal meningitis (CM) is an invasive fungal infection with a poor prognosis that often occurs in both healthy individuals and compromised hosts, such as patients infected with human immunodeficiency virus (HIV). Unlike CM in HIV patients, evidence regarding CM in non-HIV patients is limited to small retrospective studies., Objective: To identify the pretreatment prognostic factors for CM in non-HIV patients., Methods: We conducted a large retrospective analysis of CM in non-HIV patients using data from a nationwide Japanese database. The study included hospitalized patients diagnosed with CM between 1 April 2010 and 31 March 2017. All-cause mortality was compared between patients with CM with and without HIV infection. Poor diagnostic factors were analysed in the non-HIV CM group., Results: Overall, 533 (64 HIV and 469 non-HIV) patients met the criteria. The mortality rate at 90 days was significantly lower in the HIV group (6.3% vs. 25.4% p = .0002). In a logistic regression analysis of the non-HIV group, age ≥ 65 y (odds ratio [OR] 2.37, 95% CI 1.17-4.78), impaired consciousness (Japan Coma Scale ≥1) (OR 2.25, 95% CI 1.29-3.93), haemodialysis (OR 3.53, 95% CI 1.12-11.20) and previous corticosteroid usage (OR 2.40, 95% CI 1.37-4.19) were associated with poor prognosis at 30 days after diagnosis., Conclusion: More caution is suggested when treating non-HIV with CM in older patients with impaired consciousness, previous corticosteroid usage and haemodialysis., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Congenital pulmonary lymphangiectasia (CPL) is associated with fetal pulmonary venous obstructive physiology. The precise morbidity of CPL is unknown as CPL is generally fatal in neonates. Here, we report an infant with secondary CPL in total anomalous pulmonary venous connection (TAPVC). He developed severe pulmonary hypertension (PH) after corrective surgery for TAPVC. However, cardiac catheterization showed mild left pulmonary venous obstruction (PVO), which was deemed unnecessary for re-intervention. He died at 11 months-old due to an exacerbation of PH. Autopsy revealed medial hypertrophy of the pulmonary arteries, mild left PVO, and marked dilatation and proliferation of the pulmonary lymphatics which might have been involved in the PH, although CPL was not conclusively identified based on the previous biopsy findings. We should be aware of the possibility of CPL in addition to postoperative PVO when encountering patients with fetal pulmonary venous obstructive physiology. Furthermore, a cautious approach to the interpretation of lung biopsy results is warranted.