Mutations in the nonstructural proteins of SARS-CoV-2 may contribute to adverse clinical outcome in patients with COVID-19.

BACKGROUND: From late March through April 2021, we experienced a cluster of patients with COVID-19, named "Cluster K", with rapid severe illness compared with those who were infected before. METHODS: Patients with COVID-19 who were enrolled in this study were divided into two groups: 66 patients from November 2020 to March 2021 (group A) and 37 patients whose infection links were traced from Cluster K (group B). The primary outcome was mortality rate, and the secondary outcome was maximal oxygen flow rate as the severity of the disease. Viral genome sequences were compared between the two groups. RESULTS: Mortality rates were 6.1% in group A and 16.2% in group B (odds ratio: 2.97, 95% confidence interval: 0.65-15.38). The patients in group B required high oxygen flow rate (O2 ≥10 l/min) in the earlier clinical course (P = 0.029). Viral genome sequences revealed five amino acid mutations; of these, four were found on three nonstructural proteins (NSPs): one in nsp3 and nsp15, two in nsp6 (one of them is near the potential sites under positive selective pressure). Another one was on the S protein. CONCLUSION: This study suggests that mutations in NSPs, especially nsp6, are associated with adverse clinical outcome in patients with COVID-19.

Low-reflective wire-grid polarizers with absorptive interference overlayers.

Wire-grid (WG) polarizers with low reflectivity for visible light have been successfully developed. We theoretically consider the optical properties of simple sandwich structures of absorptive layer/transparent layer (gap layer)/high-reflective mirrors and found that it is possible to develop an antireflection (AR) coating owing to the interference along with the absorption in the absorptive layer. A wide variety of materials can be used for AR coatings by tuning the thicknesses of both the absorptive and the gap layers. This AR concept has been applied to reduce the reflectance of WG polarizers of Al. FeSi(2) as an absorptive layer has been deposited by the glancing angle deposition technique immediately on the top of Al wires covered with a thin SiO(2) layer as a gap layer. For the optimum combination of the thicknesses of FeSi(2) and SiO(2), the reflectance becomes lower than a few per cent, independent of the polarization, whereas the transmission polarization properties remain good. Because low-reflective (LR) WG polarizers are completely composed of inorganic materials, they are useful for applications requiring high-temperature durability such as liquid crystal projection displays.

[Synchronous double invasive ductal carcinomas of the pancreas with multifocal branch duct intraductal papillary mucinous neoplasms of the pancreas].

A 52-year-old man with a history of distal gastrectomy for gastric cancer was admitted to our hospital because of jaundice. CT scan revealed double tumors in the pancreatic head and body concomitant with multicystic lesions of the pancreas. Total pancreatectomy with splenectomy and remnant gastrectomy was performed. Final histological diagnosis was double invasive ductal carcinomas of the pancreas head and tail with multifocal branch duct intraductal papillary mucinous adenomas of the pancreas. The present case suggests that entire pancreas might have malignant potential in patients with intraductal papillary mucinous neoplasms.

Rare Clinical Course of Immunoglobulin G4-Related Inflammatory Abdominal Aortic Aneurysm with Multiple Rare Complications.

Immunoglobulin G4- (IgG4-) related inflammatory abdominal aortic aneurysm (AAA) has been recognized as a manifestation of IgG4-related disease (IgG4-RD). We experienced one patient with multiple consecutive manifestations before and after endovascular stent grafting for IgG4-related inflammatory AAA (IAAA). A 71-year-old man was diagnosed with IgG4-RD due to increased IgG4 serum concentration, typical findings of parotid gland biopsy, and periaortitis in another hospital 2 years and 7 months before visiting our hospital. He came to our hospital because of abdominal pain and IAAA. He developed paraplegia after hospitalization and underwent endovascular stent grafting for the IAAA. About one month after stent grafting, he developed perforation of the sigmoid colon due to enteritis. He also had myocardial infarction. Finally, he died of intestinal bleeding. Here, we describe this case with rare, multiple, consecutive manifestations of IgG4-RD, some of which might be caused by IgG4-related IAAA or side effects of treatments rather than by IgG4-RD itself. We report this case because the clinical course seemed rare for IgG4-RD or IgG4-related IAAA. For treating IgG4-RD with IgG4-related IAAA, we should consider factors causing the symptoms and carefully select the proper treatment.

[ALK-negative primary gastric anaplastic large cell lymphoma].

A 56-year-old Japanese woman was admitted to our hospital with upper abdominal pain. Gastroendoscopy revealed a Borrmann III type tumor which was diagnosed from the biopsied specimen as an anaplastic large cell lymphoma (ALCL). CT scan revealed para-aortic and left-supra clavicular lymph node swelling, so her clinical stage was defined as IIIE according to the Ann Arbor classification. The patient first of all received CHOP therapy, however her lymphoma lesions increased in size. Therefore she underwent salvage chemotherapy regimens and autologous peripheral blood stem cell transplantation (APBSCT). She has remained in complete clinical remission (CCR) for eleven months after the APBSCT.

Solitary thymic metastasis of breast cancer 13 years after surgery.

A 59-year-old woman was noted to have an anterior mediastinal mass on computed tomography at a regular follow-up 13 years after initial surgery for left breast cancer. Magnetic resonance imaging showed an anterior mediastinal mass. A total thymectomy with excision of surrounding lymphoid tissue was performed. Pathological examination of the resected tumor confirmed the diagnosis of thymic metastasis from breast cancer. The patient has been alive for 6 years after thymectomy. Metastases to the thymus are rare, but long-term survival can be expected with appropriate treatment.

[A case of thrombotic thrombocytopenic purpura with systemic lupus erythematosus].

We described a case of thrombotic thrombocytopenic purpura (TTP) with systemic lupus erythematosus (SLE). A-60-year old woman was admitted to our hospital because of fever, disconsciousness, and general fatigue. 32 years ago, she was diagnosed as SLE with Raynaud's phenomenon, rash, photosensitivity, arthritis, lymphocytopenia, and ANA. Her SLE was well controlled with 10 mg predonisolone as a maintance dose until several weeks ago. On admission, severe thrombocytopenia (0.7x10(4)/microl) and other laboratory data revealed microangiopathic hemolytic anemia and renal dysfunction, Immediately after diagnosed as TTP, plasma exchange and corticosteroid therapy started. In spite of the treatment, disconsciousness progressed and systemic convulsion occurred and died 4 days after admission. Autopsied examination revealed diffuse microvascular hyalinized thrombi in heart, kidney, liver, spleen, and pancreas. Some microvascular thrombi were detected in lymph nodes, bone marrow, intestine. Pathological diagnosis of TTP was made on microvascular hyalinized platelet thrombi in organs. Von Willebrand factor-cleaving protease (VWF-CP) activity in plasma on set is less than 0.5 percent of normal and inhibitor for VWF-CP was detected. We here report a valuable case for analysis of pathogenesis in SLE-TTP.

Pyoderma gangrenosum complicated with myelodysplastic syndrome followed by rapidly progressing pyothorax-associated lymphoma: a case report.

This report describes a patient with pyoderma gangrenosum (PG) complicated with myelodysplastic syndrome (MDS) followed by rapidly progressing pyothorax-associated lymphoma (PAL). A 74-year-old man was admitted with cutaneous gangrene associated with MDS. We diagnosed him as having PG, and high-dose oral prednisolone was started. Two months after admission he developed lymphoma rapidly. The patient died in spite of radiation therapy. On autopsy, the pathological diagnosis was diffuse large cell lymphoma. Epstein-Barr virus (EBV)-encoded RNA, and EBV-encoded nuclear antigen (EBNA) were detected in lymphoma cells. This case suggested that immunosuppressive therapy might favour the clonal proliferation of EBV-infected cells.

Diagnostic clues for recurrent hepatocellular carcinoma: comparison of tumour markers and imaging studies.

OBJECTIVE: To elucidate the usefulness of monitoring Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) and des-gamma-carboxy prothrombin detected with a revised kit (DCP-R) as clues to the diagnosis of recurrent hepatocellular carcinoma (HCC). METHODS: A total of 57 patients with HCC were enrolled in the study. They were classified into two groups: group A comprised 27 patients in whom the diagnostic clue to recurrent HCC appeared before November 1997; these patients were monitored by ultrasonography, computed tomography (CT), AFP and des-gamma-carboxy prothrombin detected with a conventional kit (DCP-C). Group B comprised 30 patients in whom the diagnostic clue to recurrent HCC was detected after November 1997; these patients were monitored by ultrasound, CT, AFP, AFP-L3 and DCP-R. RESULTS: In group A, 22 and five HCC recurrences were recognized initially by imaging studies and tumour markers, respectively. In group B, 17 and 13 HCC recurrences were recognized initially by imaging studies and tumour markers, respectively. The number of patients in whom tumour markers were the first clue to the diagnosis of recurrent HCC was significantly higher in group B than in group A. CONCLUSIONS: Periodic examination of AFP-L3 and DCP-R may be useful for the early detection of recurrent HCC.

[A case treated successfully with low-dose CDDP and 5-FU for the treatment of liver and para-aortic lymph node metastases and second metastasis to anterior mediastinum lymph nodes from gastric cancer after gastrectomy].

A 64-year-old-male had recurrent paraaortic lymph node and liver metastases eight months after total gastrectomy and with distal pancreatectomy and splenectomy for advanced gastric cancer. Combined chemotherapy with 5-FU and a low-dose of CDDP was effective and the both lesions disappeared. Thirteen months later, a second recurrence of anterior mediastinum lymph node metastases occurred. After the same protocol, the lesions showed a partial response and lymph node dissection was performed. Histopathological examination showed that the resected lymph nodes had 99% necrosis and fibrotic change. Immunohistochemical examination of p53 of the primary gastric cancer showed negative staining. The patient has been followed for three years after the operation, and has no recurrent lesions.

Unruptured cystic artery pseudoaneurysm accompanied by Mirizzi syndrome: a report of a case.

Pseudoaneurysm of the cystic artery is a rare complication of cholecystitis. 34 cases have been reported from 1976 to 2012, searched on MEDLINE and most of the cases have presented with gastrointestinal bleeding. We report the third case of an unruptured pseudoaneurysm of the cystic artery associated with calculous cholecystitis. An 85-year-old female presented to the emergency unit with epigastric pain and jaundice. Laboratory data and contrast-enhanced computed tomography (CT) revealed calculous cholecystitis and Mirizzi syndrome accompanied by a pseudoaneurysm in the gallbladder. Color Doppler ultrasonography (US) clearly demonstrated the pulsatile pseudoaneurysm. After biliary drainage and antimicrobial therapy, selective hepatic angiography with the aim of providing transcatheter arterial embolization was performed but the pseudoaneurysm had already thrombosed spontaneously. Open cholecystectomy was successfully carried out. Histological specimens demonstrated the pseudoaneurysm with organized thrombus in the epithelial wall of the gallbladder thickened with severe fibrosis. It is suggested that cholecystitis with unusual symptoms such as gastrointestinal bleeding requires immediate enhanced CT and US with Doppler imaging in order not to overlook a rare but life-threatening pseudoaneurysm.

Two novel NKG2D ligands of the mouse H60 family with differential expression patterns and binding affinities to NKG2D.

H60, originally described as a dominant minor histocompatibility Ag, is an MHC class I-like molecule that serves as a ligand for the NKG2D receptor. In the present study, we identified two novel mouse chromosome 10-encoded NKG2D ligands structurally resembling H60. These ligands, which we named H60b and H60c, encode MHC class I-like molecules with two extracellular domains. Whereas H60b has a transmembrane region, H60c is a GPI-anchored protein. Recombinant soluble H60b and H60c proteins bound to NKG2D with affinities typical of cell-cell recognition receptors (K(d) = 310 nM for H60b and K(d) = 8.7 muM for H60c). Furthermore, expression of H60b or H60c rendered Ba/F3 cells susceptible to lysis by NK cells, thereby establishing H60b and H60c as functional ligands for NKG2D. H60b and H60c transcripts were detected only at low levels in tissues of healthy adult mice. Whereas H60b transcripts were detectable in various tissues, H60c transcripts were detected mainly in the skin. Infection of mouse embryonic fibroblasts with murine cytomegalovirus induced expression of H60b, but not H60c or the previously known H60 gene, indicating that transcriptional activation of the three types of H60 genes is differentially regulated. The present study adds two new members to the current list of NKG2D ligands.

Enhanced production of p24 Gag protein in HIV-1-infected rat cells fused with uninfected human cells.

Although many human molecules have been suggested to affect replication of human immunodeficiency virus type 1 (HIV-1), the distribution of such cofactors in human cell types is not well understood. Rat W31/D4R4 fibroblasts expressing human CD4 and CXCR4 receptors were infected with HIV-1. The provirus was integrated in the host genome, but only a limited amount of p24 Gag protein was produced in the cells and culture supernatants. Here we found that p24 production was significantly increased by fusing HIV-1-infected W31/D4R4 cells with uninfected human cell lines of T-cell, B-cell, or macrophage lineages. These findings suggest that human cellular factors supporting HIV-1 replication are distributed widely in cells of lymphocyte and macrophage lineages. We also examined whether the amount of p24 produced by rat-human hybrid cells was correlated with expression levels of specific human genes. The results suggested that HP68 and MHC class II transactivator (CIITA) might up- and down-regulate p24 production, respectively. It was also suggested that HIV-1 replication is affected by molecules other than those examined in this study, namely, cyclin T1, cyclin-dependent kinase 9, CRM1, HP68, and CIITA.

Granulocytic sarcoma of the gingiva: two case reports.

The intraoral occurrence of granulocytic sarcoma is extremely rare. This article describes 2 cases of granulocytic sarcoma of the gingiva in different clinical situations: one as a precursor to acute myeloid leukemia in a 50-year-old man and the other as a sign of blast crisis in a 59-year-old man with chronic myelomonocytic leukemia. Clinicians and oral surgeons should consider the possibility of tumorous lesion and systemic disease when an intractable ulcer is encountered in an oral cavity. Early diagnosis may improve prognosis and increase expectancy of survival.

Pseudomyxoma peritonei due to mucinous cystadenocarcinoma in situ of the urachus presenting as an inguinal hernia.

Pseudomyxoma peritonei is generally caused by appendiceal and ovarian tumors. Other primary sites have been rarely reported. We describe herein the second reported case of pseudomyxoma peritonei due to mucinous cystadenocarcinoma of the urachus. A 54-year-old man was admitted with a left inguinal hernia that had developed several months prior to his admission. During herniorrhaphy, we found a large amount of gelatinous mucinous material in the indirect-hernia sac and made a diagnosis of pseudomyxoma peritonei on cytological grounds. At re-operation, the origin of the pseudomyxoma peritonei proved to be a ruptured urachal cyst. The urachal cyst and the dome of the urinary bladder were excised. In addition, we removed as much of the gelatinous material as possible. On histological examination, a unilocular cyst was found to consist of noninvasive mucinous adenocarcinoma. We succeeded in removing the rest of the mucinous material by postoperative intraperitoneal lavage with dextran solution, and have observed no evidence of recurrence for 7 years since the operation.

Surveillance program for early detection of hepatocellular carcinoma in Japan: results of specialized department of liver disease.

OBJECTIVE: Surveillance of cirrhotic patients enables early detection of hepatocellular carcinoma (HCC) and possibly prolongs survival. The aim of this study was to explore whether early-stage HCC can be detected earlier at a specialized department of liver disease than in other institutions. METHODS: The study subjects were 574 patients with HCC. Patients were subdivided into 3 groups according to the manner of HCC detection: group A, HCC was detected in 91 patients during periodic examination at Kurume University School of Medicine; group B, HCC was detected in 301 patients during periodic examination at other institutions; group C, HCC was detected incidentally or because of symptoms in 182 patients. RESULTS: The HCC detected in group A was significantly of smaller size (20.4 mm) compared with groups B (27.1 mm, P<0.0001) and C (57.8 mm, P<0.0001). The frequency of receiving treatment (surgery or local ablation therapy) was significantly higher in group A (73%) than in groups B (52%, P=0.002) and C (26%, P<0.0001). The 5-year survival rates were 52% for group A, 40% for group B, and 23% for group C, respectively. The survival of group A was significantly better than that of groups B (P=0.0157) and C (P<0.0001). CONCLUSIONS: Surveillance for HCC at specialized Department of Liver Disease can detect early-stage HCC, resulting in a higher chance of receiving promising treatment.

Value of fusing PET plus CT images in hepatocellular carcinoma and combined hepatocellular and cholangiocarcinoma patients with extrahepatic metastases: preliminary findings.

BACKGROUND/AIMS: This study aimed to evaluate the usefulness of (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) and PET plus computed tomography (CT) fusion images for the detection of extrahepatic metastases of hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma (combined HCC/CC). METHODS: Twenty-one patients with HCC and combined HCC/CC were enrolled in the study from December 2004 to February 2005. In all patients, PET and CT of the chest to pelvis region were performed. The sensitivity of PET plus CT fusion images was compared with the sensitivity of PET, CT, and bone scintigraphy. RESULTS: In 14 patients, a total of 58 extrahepatic metastases were diagnosed. The detection rate of PET plus CT fusion images, PET, CT, and bone scintigraphy was 98.2% (57 of 58 metastases), 89.6% (52 of 58 metastases), 91.2% (52 of 57 metastases), and 68.7% (11 of 16 bone metastases), respectively. No extrahepatic metastases were detected in the other seven patients. The detection rate of PET was 10/18 (55.6%) for intrahepatic lesions of HCC and combined HCC/CC. CONCLUSIONS: The fusion of PET plus CT images is useful in detecting extrahepatic metastases in HCC and combined HCC/CC patients.

Evaluation of malignancy using Ki-67 labeling index for gastric stromal tumor.

BACKGROUND: Assessment of malignant potential in gastrointestinal stromal tumors (GISTs) is still problematic. The maximum tumor diameter and the mitotic index are generally used as an index of malignancy of GISTs. The Ki-67 labeling index has recently been used as an index of cell growth, and the prognosis of GISTs was reported to be significantly poor when the value of this index was 10% or higher. METHODS: Clinicopathological and immunohistological factors were analyzed in 15 patients who underwent surgical resection of gastric stromal tumors at our department between April 1997 and July 2002. The patients were divided into "metastasis/recurrence" and "benign" groups. Also, the relationship of changes in the Ki-67 labeling index to the degree of malignancy in recurrent lesions was assessed in an 84-year-old woman who underwent five reoperations because of recurrences in the peritoneum. RESULTS: Significant differences were noted between the metastasis/recurrence and benign groups in relation to the mean maximum tumor diameter (186.7 +/- 80.8 mm vs 41.3 +/- 22.9 mm), mitotic index (88.3 +/- 5.0/50 high-power fields [HPF] vs 3.0 +/- 2.9/50 HPF), and the Ki-67 labeling index (11.4 +/- 2.5% vs 0.01 +/- 0.51%). In the patient who had metastasis to the liver 3.5 years after initial operation and underwent five reoperations before death, the intervals until detection of recurrence tended to be shortened gradually. The Ki-67 labeling index varied with each operation, and tended to be higher at the time of reoperations than at the initial operation. CONCLUSION: The maximum tumor diameter, mitotic index, and Ki-67 labeling index were useful as an index of malignancy for gastric stromal tumor. The efficacy of surgical resection alone may be insufficient in patients with disseminated metastasis to the peritoneum.

Unilateral renal cortical necrosis with contralateral hydronephrosis after surgery for uterus carcinoma.

Renal cortical necrosis (RCN) represents a rare cause of acute renal failure that is characterized by necrosis of the renal cortex with sparing of the medulla. Most previous RCN cases reported have been bilateral and have occurred in pregnancy. Unilateral RCN is a quite rare disorder. Here, we report a case of unilateral RCN with contralateral hydronephrosis after surgery for uterus carcinoma. In this patient it seems that hydronephrosis had been present before RCN occurrence. It is suggested that ureteric obstruction protects against RCN development.