Mixed germ cell tumor infiltrating the pineal gland without elevated tumor markers: illustrative case

BACKGROUND: Tumors in the pineal region consist of various histological types, and correct diagnosis from biopsy specimens is sometimes difficult. The authors report the case of a patient with a mixed germ cell tumor infiltrating into the pineal gland despite showing no elevation of tumor markers. OBSERVATIONS: An 18-year-old man complained of headache and nausea and showed disturbance of consciousness. Magnetic resonance imaging showed hydrocephalus associated with a cystic pineal tumor. The patient underwent tumor biopsy followed by endoscopic third ventriculostomy for hydrocephalus in a local hospital. A pineocytoma was diagnosed, and the patient was referred to the authors' hospital for treatment. Concentrations of placental alkaline phosphatase, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin in cerebrospinal fluid were not elevated. However, the authors' review of the tumor specimen revealed some immature cells infiltrating the pineal gland. These cells were positive for AFP, Sal-like protein 4, and octamer-binding transcription factor 3/4; and the diagnosis was changed to mixed germ cell tumor. Chemoradiotherapy was initiated, followed by surgical removal of the residual tumor. LESSONS: Careful examination of all tumor specimens and immunohistochemical analyses are important for accurate diagnosis of pineal tumors

The putative ceramide-conjugation protein Cwh43 regulates G0 quiescence, nutrient metabolism and lipid homeostasis in fission yeast

Cellular nutrient states control whether cells proliferate, or whether they enter or exit quiescence. Here, we report characterizations of fission yeast temperature-sensitive (ts) mutants of the evolutionarily conserved transmembrane protein Cwh43, and explore its relevance to utilization of glucose, nitrogen source and lipids. GFP-tagged Cwh43 localizes at ER associated with the nuclear envelope and the plasma membrane, as in budding yeast. We found that cwh43 mutants failed to divide in low glucose and lost viability during quiescence under nitrogen starvation. In cwh43 mutants, comprehensive metabolome analysis demonstrated dramatic changes in marker metabolites that altered under low glucose and/or nitrogen starvation, although cwh43 cells apparently consumed glucose in the culture medium. Furthermore, we found that cwh43 mutant cells had elevated levels of triacylglycerols (TGs) and coenzyme A, and that they accumulated lipid droplets. Notably, TG biosynthesis was required to maintain cell division in the cwh43 mutant. Thus, Cwh43 affects utilization of glucose and nitrogen sources, as well as storage lipid metabolism. These results may fit a notion developed in budding yeast stating that Cwh43 conjugates ceramide to glycosylphosphatidylinositol (GPI)-anchored proteins and maintains integrity of membrane organization

Switching to Dupilumab from Other Biologics without a Treatment Interval in Patients with Severe Asthma: A Multi-Center Retrospective Study

Background: Dupilumab is a fully humanized monoclonal antibody that blocks interleukin4 and interleukin-13 signals. Several large clinical trials have demonstrated the efficacy of dupilumab in patients with severe asthma. However, few studies have examined a switch to dupilumab from other biologics. Methods: This retrospective, multi-center observational study was conducted by the Okayama Respiratory Disease Study Group. Consecutive patients with severe asthma who were switched to dupilumab from other biologics without a treatment interval between May 2019 and September 2021 were enrolled. Patients with a treatment interval of more than twice the standard dosing interval for the previous biologic prior to dupilumab administration were excluded. Results: The median patient age of the 27 patients enrolled in this study was 57 years (IQR, 45-68 years). Eosinophilic chronic rhinosinusitis (ECRS)/chronic rhinosinusitis with nasal polyp (CRSwNP) was confirmed in 23 patients. Previous biologics consisted of omalizumab (n = 3), mepolizumab (n = 3), and benralizumab (n = 21). Dupilumab significantly improved FEV1 (median improvement: +145 mL) and the asthma control test score (median improvement: +2). The overall response rate in patients receiving dupilumab for asthma as determined using the Global Evaluations of Treatment Effectiveness (GETE) was 77.8%. There were no significant differences in the baseline characteristics of the GETE-improved group vs. the non-GETE-improved group. ECRS/CRSwNP improved in 20 of the 23 patients (87.0%). Overall, 8 of the 27 patients (29.6%) developed transient hypereosinophilia (>1500/ mu L), but all were asymptomatic and able to continue dupilumab therapy. Conclusions: Dupilumab was highly effective for the treatment of severe asthma and ECRS/CRSwNP, even in patients switched from other biologics without a treatment interval

Alteration of the immune environment in bone marrow from children with recurrent B cell precursor acute lymphoblastic leukemia

Due to the considerable success of cancer immunotherapy for leukemia, the tumor immune environment has become a focus of intense research; however, there are few reports on the dynamics of the tumor immune environment in leukemia. Here, we analyzed the tumor immune environment in pediatric B cell precursor acute lymphoblastic leukemia by analyzing serial bone marrow samples from nine patients with primary and recurrent disease by mass cytometry using 39 immunophenotype markers, and transcriptome analysis. High-dimensional single-cell mass cytometry analysis elucidated a dynamic shift of T cells from naïve to effector subsets, and clarified that, during relapse, the tumor immune environment comprised a T helper 1-polarized immune profile, together with an increased number of effector regulatory T cells. These results were confirmed in a validation cohort using conventional flow cytometry. Furthermore, RNA transcriptome analysis identified the upregulation of immune-related pathways in B cell precursor acute lymphoblastic leukemia cells during relapse, suggesting interaction with the surrounding environment. In conclusion, a tumor immune environment characterized by a T helper 1-polarized immune profile, with an increased number of effector regulatory T cells, could contribute to the pathophysiology of recurrent B cell precursor acute lymphoblastic leukemia. This information could contribute to the development of effective immunotherapeutic approaches against B cell precursor acute lymphoblastic leukemia relapse

Capability and Limitations of Recent Diagnostic Criteria for Autoimmune Pancreatitis

Because a diagnostic serological marker is unavailable, autoimmune pancreatitis (AIP) is diagnosed based on unique features. The diagnostic capabilities and potential limitations of four sets of diagnostic criteria for AIP (Japanese diagnostic criteria 2006 and 2011, Asian diagnostic criteria, and international consensus diagnostic criteria (ICDC)) were compared among 85 patients who were diagnosed AIP according to at least one of the four sets. AIP was diagnosed in 87%, 95%, 95%, and 95% of the patients according to the Japanese 2006, Asian, ICDC, and Japanese 2011 criteria, respectively. The ICDC can diagnose types 1 and 2 AIP independently and show high sensitivity for diagnosis of AIP. However, as the ICDC are rather complex, diagnostic criteria for AIP should perhaps be revised and tailored to each country based on the ICDC

A Case of Super-giant Basal Cell Carcinoma Initially Diagnosed as Multiple Traumas

Basal cell carcinoma (BCC), which is relatively easy to diagnose in a clinical setting, is the most common malignant tumor in the skin. Conversely, a giant BCC, a tumor beyond 5 cm in diameter, is a rare disease. In particular, a giant BCC beyond 20 cm in diameter is called a super-giant BCC, which frequently invades into deeper tissues, including the dermis, bones, or muscles. Here, we present a case of a 71-year-old patient who was initially diagnosed with multiple traumas with a large periosteal defect of the head. The ulcer was surrounded by malodorous necrotic tissue and slough, and several bacteria that caused necrotizing fasciitis were detected. Mapping biopsies after extensive debridement yielded BCC, and therefore, he was finally diagnosed with a super-giant BCC. A careful consultation revealed a history of ulcer on the head after a head injury approximately 10 years ago. He underwent radical dissection including the external table of the skull, followed by a free latissimus dorsi muscle flap with a meshed split-thickness skin graft. Because of the slow and chronic development of a super-giant BCC, accurate diagnosis is often difficult. Careful attention should be paid in patients with long-sustained ulcers

デントウ ケンチク デントウ コウゲイ ノ ギジュツ ト ブンカ ノ ケイショウ ニ カンスル タクミ リョウイキ ノ キョウイク ケンキュウ

　伝統的な建築・工芸についての知識と基本技能を修得し、現代社会と呼応しうる新たなデザインを生み出す人材を養成することを目的に、2019年デザイン学科に匠領域が増設された。2017年から継続している伝統建築を通した教育・研究・地域連携の成果、「工芸」「匠」の位置づけ、匠ものデザインプロジェクト、遠州地域との関わりと「織」教育プログラム、旧田代家住宅を活用した学生作品展について報告し、伝統建築・工芸の技術と文化の継承という大きな課題の中での、デザイン教育における「匠」について検証するものである。　In 2019, the Department of Design was expanded to include the field of TAKUMI, with the aim of acquiring knowledge and basic skills in traditional architecture and crafts, cultivating human resources capable of creating new designs that can respond to modern society. This study reports on the results of education, research, and regional collaboration through traditional architecture that have been continuing since 2017, the positions of "KOUGEI" and "TAKUMI", the craftsmanship design project of “TAKUMIMONO”, the relationship with the Enshu region and the "weaving" education program, as well as the exhibition of student works using former Tashiro residence. It also examines "TAKUMI" in design education amid the major issue of inheriting traditional architecture, craft techniques, and culture

Superchargeを付加した腹直筋皮弁を用いた乳房再建

2013年以降、乳がん全摘後に保険適応となった人工ゲル充填乳房を用いた乳房再建術のまれな合併症として、T細胞型非ホジキンリンパ腫が報告され、同タイプの人工ゲル充填乳房は使用できなくなった。これを受けて、当院では自家組織を用いた乳房再建の症例が増加している。ボリュームのある乳房の場合、腹部を用いた有茎腹直筋皮弁、遊離皮弁が選択されることが多い。有茎皮弁では上腹壁動静脈を血管茎とするが、腹直筋の血行は深下腹壁動静脈優位のため血行が不十分と考えられる硬結が術後に生じることがある。これを改善するため、当科では可能な限り深下腹壁動静脈を胸部のレシピエント血管に吻合してsuperchargeを行い、血行の増強に努めている。遊離皮弁と異なり、皮弁の自由度が制限されるため血管吻合がやや困難であるが、術後は柔らかい乳房が再現されることが期待できる。With the onset of insurance coverage in 2013, implant-based techniques had been popular for breast reconstruction in Japan until fairly recently. However, possible complications of non-Hodgkin’s lymphoma caused by implant materials led a recall of textured-typed implants for breast reconstruction. Such situation led patients head for breast reconstruction using autologous tissue. In case of well-developed breasts, either rectus abdominal musculocutaneous flap or deep inferior epigastric perforator flap is frequently selected for breast reconstruction. The former flap is well-vascularized but rectus abdominal muscle is used to transpose the flap, which could cause the herniation of the abdominal wall as a complication at late-stage. In the latter flap, since abdominal fat tissue is used, reconstructed breasts are similar to original breasts, while operation periods are relatively long in order to anastomose vessels under microscopy. Besides, thrombosis in anastomosed vessels could cause the total necrosis of reconstructed breasts.To overcome the disadvantages of the both methods, rectus abdominal musculocutaneous flaps anastomosed with vessels in the recipient region (i.e., Supercharged flap) have been developed. Here, we will describe seven cases with supercharged flaps to reconstruct breasts performed in our hospital

Bone marrow-derived vasculogenesis leads to scarless regeneration in deep wounds with periosteal defects

Deep skin wounds with periosteal defects, frequently caused by traffic accidents or radical dissection, are refractory. Transplant surgery is frequently performed, but patients are subjected to stress for long operation periods, the sacrifice of donor regions, or several complications, such as flap necrosis or intractable ulcers. Even if the defects are covered, a scar composed of fibrous tissue remains in the body, which can cause itching, dysesthesia, or repeated ulcers because of the lack of distribution of peripheral nerves or hair follicles. Thus, treatments with the aim of regenerating lost tissue for deep wounds with periosteal defects are needed. Here, we show that the use of gelatin sponges (GS), which have been used as haemostatic materials in clinical practice, allowed the regeneration of heterogeneous tissues, including periosteum, skin, and skin appendages, when used as scaffolds in deep wounds with periosteal defects in rats. Bone marrow transplantation in rats revealed the mechanism by which the microenvironment provided by GS enabled bone marrow-derived cells (BMDCs) to form a vascular niche, followed by regeneration of the periosteum, skin, or skin appendages such as hair follicles by local cells. Our findings demonstrated that vascular niche formation provided by BMDCs is crucial for heterogeneous tissue regeneration

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target