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An autopsied case of extramammary Paget's disease associated with the elevation of serum CFA level is reported. An abnormally high level of serum CEA was found in 46% of patients with this disease. [ABSTRACT FROM AUTHOR]

Sixty-three patients with lacunar-type of acute capsular infarction were treated in our service during the last 2 years. Their lesions were identified by computed tomography (CT) and classified into six types according to their locations: anterior, lateral, posterior, superior, inferior and multiple. The lesions were thought to be in the watershed areas of the regional arterial supplies, and the areas were considered to be prone to ischemia. The clinical course of each type showed characteristic features of ischemic strokes. In the majority of the patients with the lateral type, reversible ischemic neurological deficit (RIND) was seen as the predominant symptom, transient ischemic attack (TIA) was noted in the patients with the superior type, and major completed stroke was observed in those with posterior type. [ABSTRACT FROM AUTHOR]

Abstract: Signaling pathways such as the pre-TCR and Wnt pathways regulate α/β T cell differentiation in thymus. Mice lacking an essential component of the pre-TCR exhibit arrest at the (CD4−CD8−) (CD44−CD25+) stage (DN3) of thymocyte development, and introduction of p53 deficiency into those mice abrogates this arrest, resulting in transition to the (CD4+CD8+) double-positive (DP) stage. This paper examines the effect of inactivation of p53 on thymocyte development in Bcl11b−/− mice that exhibit arrest at the DN3 or (CD4−CD8+) immature single-positive (ISP) stage. No DP thymocytes were detected in thymocytes of adoptive transfer experiments in scid mice that were derived from p53−/−Bcl11b−/− precursors but ISP thymocytes increased in the proportion and in the cell number approximately three times higher than those from Bcl11b−/− precursors. Consistently, the level of apoptosis decreased to the level of wild-type precursors. These results suggest that inactivation of p53 is sufficient for DN3 thymocytes to differentiate into the ISP, but not to DP, stage of thymocyte development in Bcl11b−/− mice. This provides evidence for a novel p53-mediated checkpoint that regulates the transition from the DN3 to ISP stage of thymocyte development. [Copyright &y& Elsevier]

Background: The global impact of the coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality. Immunocompromised patients, particularly those treated for B-cell lymphoma, have shown an increased risk of persistent infection with SARS-CoV-2 and severe outcomes and mortality. Multi-mutational SARS-CoV-2 variants can arise during the course of such persistent cases of COVID-19. No optimal, decisive strategy is currently available for patients with persistent infection that allows clinicians to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation. We introduced a novel treatment combining antivirals, neutralizing antibodies, and genomic analysis with frequent monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection. The aim of this retrospective study was to report and evaluate the efficacy of our novel treatment for immunocompromised B-cell lymphoma patients with persistent COVID-19 infection., Methods: This retrospective descriptive analysis had no controls. Patients with B-cell lymphoma previously receiving immunotherapy including anti-CD20 antibodies, diagnosed as having COVID-19 infection, and treated in our hospital after January 2022 were included. We selected anti-SARS-CoV-2 monoclonal antibodies according to subvariants. Every 5 days, viral load was tested by RT-PCR, with antivirals continued until viral shedding was confirmed. Primary outcome was virus elimination. Independent predictors of prolonged viral shedding time were determined by multivariate Cox regression., Results: Forty-four patients were included in this study. Thirty-five patients received rituximab, 19 obinutuzumab, and 26 bendamustine. Median treatment duration was 10 (IQR, 10-20) days; 22 patients received combination antiviral therapy. COVID-19 was severe in 16 patients, and critical in 2. All patients survived, with viral shedding confirmed at median 28 (IQR, 19-38) days. Bendamustine use or within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma significantly prolonged time to viral shedding., Conclusions: Among 44 consecutive patients treated, anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antiviral drugs, switching, and combination therapy resulted in virus elimination and 100% survival. Bendamustine use, within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma were the significant independent predictors of prolonged viral shedding time., (© 2024. The Author(s).)

Background: The efficacy of antiviral drugs that neutralize antibody drugs and fight against SARS-COV-2 is reported to be attenuated by genetic mutations of the virus in vitro. When B-cell immunocompromised patients are infected with SARS-COV-2, the infection can be prolonged, and genetic mutations can occur during the course of treatment. Therefore, for refractory patients with persistent COVID-19 infection, genomic analysis was performed to obtain data on drug resistance mutations as a reference to determine which antiviral drugs and antibody therapies might be effective in their treatment., Methods: This was a descriptive analysis with no controls. Patients were diagnosed as having COVID-19, examined, and treated in the Kansai Medical University General Medical Center between January 2022 and January 2023. The subjects of the study were B-cell immunocompromised patients in whom genome analysis of SARS-CoV-2 was performed., Results: During the study period, 984 patients with COVID-19 were treated at our hospital. Of those, 17 refractory cases underwent genomic analysis. All 17 patients had factors related to immunodeficiency, such as malignant lymphoma or post-organ transplantation. Eleven patients started initial treatment for COVID-19 at our hospital, developed persistent infection, and underwent genomic analysis. Six patients who were initially treated for COVID-19 at other hospitals became persistently infected and were transferred to our hospital. Before COVID-19 treatment, genomic analysis showed no intrahost mutations in the NSP5, the NSP12, and the RBD regions. After COVID-19 treatment, mutations in these regions were found in 12 of 17 cases (71%). Sixteen patients survived the quarantine, but one died of sepsis., Conclusions: In genomic analysis, more mutations were found to be drug-resistant after COVID-19 treatment than before COVID-19 treatment. Although it was not possible to demonstrate the usefulness of genome analysis for clinical application, the change of the treatment drug with reference to drug resistance indicated by genomic analysis may lead to good outcome of immunocompromised COVID-19 patients., (© 2023. The Author(s).)

Primary autoimmune neutropenia in young children is characterized by chronic neutropenia and positivity for antibodies against human neutrophil antigens (HNAs). This study analyzed the clinical characteristics of 402 children with neutropenia to identify differences between those with and without HNA-1 antibodies (HNA1abs). HNAabs in sera were detected by granulocyte immunofluorescence testing using flow cytometry. Relative fluorescence intensity (RFI) values were used to divide patients into positive (PG, n = 302), borderline (BG, n = 34), and negative (NG, n = 66) groups. The antibodies reacted to HNA-1a alone (59%), HNA-1b alone (1%), and HNA-1a/1b (40%). The PG had a significantly lower absolute neutrophil count before definitive diagnosis and a 1.6- to 2-times greater risk of hospitalization during neutropenia than the other groups. The median duration of neutropenia was longest in the PG at 25 months, followed by 20 months in the BG and 14 months in the NG. This large-scale cohort characterizes clinically distinct groups using the RFI value for HNA1abs in young children with neutropenia. Detection of HNA1abs may aid in understanding the clinical characteristics of children with neutropenia., (© 2023. Japanese Society of Hematology.)

Background: Preoperative computed tomography-guided marking can help identify small non-palpable pulmonary nodules during surgery. However, this technique is associated with the risk of air embolism. We retrospectively evaluated whether small pulmonary nodules could be intraoperatively localized using cone-beam computed tomography (CBCT)., Methods: A hybrid operating room permitting stable lateral positioning and scanning from the pulmonary apex to the base was used in all patients. CBCT images were obtained using a 10-s protocol with 180º rotation of the C-arm flat panel detector around the patient. Clips were placed on the visceral pleura to help guide pulmonary nodule localization. Partial pulmonary resection was performed using video-assisted thoracoscopic surgery at the predicted nodule site., Results: Between July 2013 and June 2019, 132 patients with 145 lesions underwent this procedure at our center. The detection rate of lesions on CBCT was 100%. The pathological diagnoses were primary lung cancer, metastatic pulmonary tumors, and benign lesions. The average consolidation-to-tumor ratio was 0.65 for all nodules, with ratios of 0.33, 0.96, and 0.70 for primary lung cancer, metastatic pulmonary tumors, and benign lesions, respectively. No complications related to this localization method were observed., Conclusions: CBCT-guided intraoperative localization is safe and feasible for non-palpable small pulmonary nodules. This technique may eliminate the risk of serious complications such as air embolism.

Somaclonal variation was studied by whole-genome sequencing in rice plants ( Oryza sativa L., 'Nipponbare') regenerated from the zygotes, mature embryos, and immature embryos of a single mother plant. The mother plant and its seed-propagated progeny were also sequenced. A total of 338 variants of the mother plant sequence were detected in the progeny, and mean values ranged from 9.0 of the seed-propagated plants to 37.4 of regenerants from mature embryos. The natural mutation rate of 1.2 × 10 -8 calculated using the variants in the seed-propagated plants was consistent with the values reported previously. The ratio of single nucleotide variants (SNVs) among the variants in the seed-propagated plants was 91.1%, which is higher than 56.1% previously reported, and not significantly different from those in the regenerants. Overall, the ratio of transitions to transversions of SNVs was lower in the regenerants as shown previously. Plants regenerated from mature embryos had significantly more variants than different progeny types. Therefore, using zygotes and immature embryos can reduce somaclonal variation during the genetic manipulation of rice., (Copyright © 2023 by JAPANESE SOCIETY OF BREEDING.)

Purpose: The purpose of this study was to find useful imaging features on non-contrast-enhanced magnetic resonance imaging (MRI) that can divide patients with thymic epithelial tumor (TET) into clinical stage I-II and III-IV groups under assumption that contrast media are contraindicated., Materials and Methods: This retrospective study included 106 patients (median age, 60 years; range, 27-82 years; 62 women) with surgically resected TET who underwent MRI between August 1986 and July 2015. All cases were classified according to the 2015 WHO classification and staged using the eighth edition of the TNM system. Two radiologists independently evaluated 14 categories of MRI findings; the findings in patients with stage I-II were compared with those of patients with stage III-IV using a logistic regression model. Disease-specific survival associated with significant findings was calculated using the Kaplan-Meier method., Results: Univariate analysis showed that stage III-IV patients were more likely to have tumors with an irregular contour, heterogeneity on T1WI, low-signal intensity on T2WI, irregular border with lung, findings of great vessel invasion (GVI) (hereafter, GVI sign), pericardial thickening/nodule, and lymphadenopathy (all, P < 0.01). On multivariable analysis, only two findings, irregular border between tumor and lung (odds ratio [OR], 272.8; 95% CI 26.6-2794.1; P < 0.001) and positive GVI sign (OR, 49.3; 95% CI 4.5-539.8; P = 0.001) remained statistically significant. Patients with one or both features had significantly worse survival (log-rank test, P < 0.001)., Conclusion: For patients with TET who are unable to receive contrast for preoperative staging, the two image findings of an irregular border between tumor and lung and the positive GVI sign on non-contrast-enhanced MRI could be helpful in determining stage III-IV disease which is associated with a worse survival., (© 2022. The Author(s).)

This paper describes the nickel-catalyzed reductive alkylation of aroyl fluorides with alkyl bromides in a decarbonylative manner. In this reaction, various functional groups are well tolerated and the C( sp 2 )-C( sp 3 ) bond can be constructed directly without the use of organometallic reagents. The present reaction is a cross-electrophile coupling via the radical pathway, affording the corresponding alkylarenes in moderate to good yields.

Robotic gastrectomy (RG) is an alternative minimally invasive surgical technique that has gradually come into use for the treatment of gastric cancer (GC). This study aimed to assess the feasibility and safety of RG for the treatment of GC. We retrospectively reviewed the use of RG in 47 patients with GC, and clinicopathological features and surgical outcomes were evaluated. The median age and body mass index of the patients were 68 years and 21.9 kg/m 2 , respectively. Distal gastrectomy, total gastrectomy, and proximal gastrectomy were performed in 39 (83.0%), 5 (10.6%), and 3 (6.4%) patients, respectively. The median operative time was 354 (256- 603) min. None of the operations were converted to open or laparoscopic procedures. The median blood loss was 15 (2-350) ml. None of the patients required blood transfusion. The mean number of resected lymph nodes was 43 (7-93). The median duration of postoperative hospital stay was 13 (9-37) days. Approximately 4.3% and 2.1% of the patients had anastomotic leakage and pancreatic fistula, respectively. One (2.1%) patient had Clavien-Dindo classification grade IIIa surgical complication (anastomotic leakage). No treatment-related deaths were observed. These findings suggest that RG might be a safe and feasible procedure for the treatment of GC.

The post-transplant development of donor-specific antibodies (DSAs) initiates the antibody-mediated rejection, which is associated with an increased rate of graft loss. Therefore, risk prediction of de novo DSA (dnDSA) is important for understanding long-term prognostic implications for kidney transplantation outcomes. Cytotoxic T lymphocyte antigen-4 (CTLA-4), a cell surface molecule, suppresses T cell responses. Single-nucleotide polymorphisms (SNPs) in CTLA-4 are known to be associated with acute rejection; however, their association with dnDSA formation is not established. In the present study, we investigated the impact of CTLA-4 SNPs on dnDSA formation after kidney transplantation (KT) by analyzing three CTLA-4 SNPs (rs231775, rs3087243, and rs5742909) in 88 recipients. Patients with the GG genotype of CTLA-4 SNPs rs231775 and rs3087243 had higher rates of dnDSA formation than patients with the AA genotype or heterozygous genotypes. In conclusion, our findings indicate that CTLA-4 SNPs are predisposing factors for dnDSA formation after KT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)