An Autopsy Case of Multiple Jejunal Diverticula Showing Severe Malabsorption

A rare autopsy case of multiple jejunal diverticula showing severe malabsorption is reported. A 56-year-old man was admitted due to vomiting and leg edema. On admission, his height was 160cm, his body weight was 39kg, and laboratory data revealed severe hypoproteinemia (TP: 4.0g/dl, ALB: 2.1g/dl). On the 14th day of admission, agonal breathing and disturbance of consciousness occurred after massive vomiting of gastric juice, and the patient died of respiratory failure. At autopsy, on abdominal sectioning, multiple diverticula situated on the mesenterium side of the enteron extending 70cm in length from the proximal jejunum were identified. However there were no findings suggesting perforation or diverticulitis. Histologically, the diverticula were lined by ordinal jejunum mucosa associated with muscularis mucosa, but the muscularis propria was not involved in the diverticular walls. The diverticula were identified as false diverticula. In both lower lungs, aspiration pneumonia was widely seen. The cause of death was considered to be aspiration pneumonia due to the vomiting caused by multiple jejunal diverticula.Only 16 case reports of multiple jejunal diverticulosis in Japan could be found in the literature however most of the reported complications were perforation and diverticulitis, and there were no reports of malabsorption. Therefore, the present case is significant concerning the cause of malabsorption in routine explorations

A Clinicopathological Study of Primary Small Intestinal Cancer with Emphasis on Cellular Characteristics

We examined the clinicopathological profiles and cellular characteristics of 10 cases of surgically resected primary small intestinal cancers (excluding duodenal cancers). Histological examination revealed nine adenocarcinomas and one sarcomatoid carcinoma. Invasion depth was subserosal in five cases, serosal in four cases and to the adjacent transverse colon in the remaining case. Metastasis was present in lymph node in seven cases, in distant organs in six, and in the peritoneum in seven cases. Of the 10 cases, 7 underwent postoperative chemotherapy, and 6 of the eight traceable patients died from the disease (mean period of survival: 386 days). Histomorphologically, eight of nine adenocarcinomas showed an intestinal phenotype (unclassifiable in the other) in the upper layer, while in the lower layer, there showed an intestinal phenotype and five a non-intestinal phenotyp. Immunohistochemistry revealed a mean positive rate in the upper/lower layers as follows: 93%/86% and 38%/29% by intestinal markers CDX2 and MUC2; 19%/28% and 13%/32% by pancreatobiliary markers CK7 and MUC1; and 4%/19% and 2%/9% by gastric markers MUC5AC and MUC6, respectively. Thus, the intestinal phenotype predominated in almost all small intestinal cancer in this study, although some showed a transformation to non-intestinal or hybrid phenotypes with tumor progression. Flexible management for the diversity and transformation of cellular characteristics is therefore recommended treating and diagnosing small intestinal cancers

A Case of Unusual Polypoid Mixed Hemangioma of the Sigmoid Colon: Possibly an Angioadenomatous Polyp

Herein, we report on an unusual case of polypoid mixed hemangioma of the sigmoid colon. An 85-year-old woman who underwent colonoscopic examination was found to have a smooth, red polypoid tumor, 6mm in diameter, in the sigmoid colon. The polyp was resected endoscopically. Microscopically, the polyp contained two pathologic components: (i) adenomatous proliferative glands as the epithelial component; and (ii) mixed hemangioma as the mesenchymal component. On the basis of these findings, a pathological diagnosis of angioadenomatous polyp was made. Although seven previous cases of polypoid hemangioma located in the submucosa have been reported in the literature, the present case is the first in which the hemangioma is localized only in the mucosa. The mixed hemangioma may be the pathogen stimulating the adenomatous proliferation of the glands

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

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

A Case of Orbital Metastasis as Disease Progression of Anaplastic Lymphoma Kinase-Positive Lung Cancer Treated with Crizotinib

Orbital metastasis of lung cancer is rare. It often causes visual disorder. To date, there are only a few case reports. Crizotinib is an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor that leads to responses in most patients with ALK-positive non-small-cell lung cancer. Visual disorder is one of the popular adverse events of crizotinib, but the symptom almost decreases over time. We report a case of orbital metastasis as the disease progression of ALK-positive lung cancer treated with crizotinib. It should be kept in mind that orbital metastasis can be the disease progression of lung adenocarcinoma with ALK translocation treated with crizotinib. When physicians encounter a patient receiving crizotinib with visual disorder, we must distinguish between adverse events and orbital metastasis

Case report: continued treatment with alectinib is possible for patients with lung adenocarcinoma with drug-induced interstitial lung disease

Abstract Background Alectinib, a second-generation anaplastic lymphoma kinase (ALK) inhibitor, is a key drug for ALK rearranged lung adenocarcinoma. Interstitial lung disease (ILD) is an important adverse effect of alectinib, which generally requires termination of treatment. However, we treated two patients with drug-induced ILD who continued to receive alectinib. Case presentation Patient 1 was a 57-year-old male with an ALK-rearranged Stage IV lung adenocarcinoma who was administered alectinib as first-line therapy. Computed tomography (CT) detected asymptomatic ground-glass opacity (GGO) on day 33 of treatment. Alectinib therapy was therefore discontinued for 7 days and then restarted. GGO disappeared, and the progression of ILD ceased. Patient 2 was a 64-year-old woman with an ALK-positive lung adenocarcinoma who was administered alectinib as third-line therapy. One year later, CT detected GGO; and she had a slight, nonproductive cough. Alectinib therapy was continued in the absence of other symptoms, and GGO slightly diminished after 7 days. Two months later, CT detected increased GGO, and alectinib therapy was continued. GGO diminished again after 7 days. The patient has taken alectinib for more than 2 years without progression of ILD. Conclusions Certain patients with alectinib-induced ILD Grade 2 or less may continue alectinib therapy if they are closely managed

Alkaline phosphatase flare phenomenon following epidermal growth factor receptor-tyrosine kinase inhibitor treatment of non-small cell lung cancer: Report of a case and case review

Alkaline phosphatase (ALP) flare phenomenon documented as scintigraphic flare phenomenon due to elevated serum ALP levels produced by osteoblasts reflects an osteoblastic reaction in response to the effective therapy of non-small cell lung cancer (NSCLC). Here, we report a case of ALP flare following gefitinib treatment for NSCLC. We also retrospectively analyzed the prevalence of ALP flare in lung cancer patients treated via epidermal growth factor receptor-tyrosine kinase inhibitor in our hospital. Recognition of this phenomenon is important for physicians treating NSCLC patients to avoid discontinuation of a potentially beneficial treatment because of misdiagnosis for refractory multiple bone metastasis or adverse effect

Highly asymmetric lamellar nanostructures from nanoparticle-linear hybrid block copolymers

The highly asymmetric lamellar (A-LAM) nanostructure is one of the most important template geometries for block copolymer (BCP) lithography. However, A-LAM is unattainable from conventional BCPs, and there is no general molecular design strategy for A-LAM-forming BCP. Herein, a nanoparticle-linear hybrid BCP system is reported, which is designed based on the intramolecular crosslinking technique, as a remarkably effective platform to obtain the A-LAM morphology. The hybrid BCPs consisting of polystyrene single-chain nanoparticles and linear polylactide segments show a remarkable capability to form the A-LAM morphology in bulk, where a maximum width ratio of 4.1 between the two domains is obtained. This unusual phase behavior is attributed to the bulky and rigid characteristics of the nanoparticle block. Furthermore, the thin films of these hybrid BCPs show perpendicularly oriented A-LAM morphology on a chemically modified Si substrate, allowing promising application in the fabrication of asymmetric line-and-space nanopatterns

The negative effect of initial high-dose methylprednisolone and tapering regimen for acute respiratory distress syndrome: a retrospective propensity matched cohort study

Abstract Background The efficacy of corticosteroid use in acute respiratory distress syndrome (ARDS) remains controversial. Generally, short-term high-dose corticosteroid therapy is considered to be ineffective in ARDS. On the other hand, low-dose, long-term use of corticosteroids has been reported to be effective since they provide continued inhibition of the systemic inflammatory response syndrome (SIRS) that accompanies ARDS. Thus far, no reports have been published on the efficacy of initiating treatment with a high-dose corticosteroid regimen with tapering. Methods We conducted a retrospective observational study involving 186 patients treated at a teaching hospital (68% had sepsis, pneumonia, or aspiration pneumonia). ARDS was diagnosed according to the Berlin definition. Patients were divided into a high-dose (n = 21) or low-dose corticosteroid group (n = 165) to compare the effectiveness of a down-titration regimen. The primary medical team chose which treatment a patient would receive. We were careful to conduct a differential diagnosis of interstitial pneumonia (e.g., acute eosinophilic pneumonia) since corticosteroid treatment has been proven effective in that patient population. The primary outcome was the 60-day mortality rate. The secondary outcome was the number of ventilator-free days (VFD). Results Those started on a high-dose regimen had a significantly higher 60-day mortality rate (P = 0.031) with significantly fewer VFD (P = 0.021). Propensity scores were used to adjust patient backgrounds in a variable analysis that also showed the high-dose regimen was a factor in decreasing VFD (OR, 95.63; 95% CI, 1.74–5271.07; P = 0.026) and worsening the 60-day mortality rate (OR, 2.54; 95% CI, 0.92–7.02; P = 0.072). Conclusions A tapering regimen after high-dose corticosteroids is likely to increase ventilator dependency and might aggravate the prognosis of patients with ARDS diagnosed according to the Berlin definition