Real-world efficacy and safety of interleukin-17 inhibitors for psoriasis: A single-center experience

We evaluated the efficacy and safety of interleukin (IL)-17 inhibitors (IL-17i) by analyzing 66 patients with psoriasis treated with secukinumab (n = 25), ixekizumab (n = 17) and brodalumab (n = 24) at Kurume University Hospital between December 2014 and June 2019. The mean Psoriasis Area and Severity Index (PASI) scores at baseline were 12.9, 13.4 and 9.9 in the secukinumab, ixekizumab and brodalumab groups (SECg, IXEg and BROg), respectively. At the 6-month evaluation, the mean PASI scores were 1.7, 1.1 and 0.5 in SECg, IXEg and BROg, respectively. The proportion of patients achieving PASI of 3.0 or less was significantly lower in SECg. Drug survivals showed no significant difference among the groups. Although one patient in IXEg died due to an unknown cause, no serious IL-17i-associated adverse event was observed. This study showed high efficacy and relatively low risk of the treatment with IL-17i.     

Angiotropic syringomatous carcinoma

Syringomatous carcinoma (SC) is a slow‐growing malignant skin tumor that usually affects the face or scalp. An 83‐year‐old female developed SC on the sole, a rare location. Histopathologically, numerous ducts with few keratinizing cysts were seen in the upper dermis, and cords, strands and nests with sclerotic stroma were seen in the deep dermis and subcutis. In addition to the perineural and intraneural invasion of the tumor, the tumor cells had also invaded the vessel walls. There was no intravasation of tumor cells or interruption of the endothelium. Because melanoma with vascular wall invasion without intravasation of melanoma cells or interruption of the endothelium has been called angiotropic melanoma, we termed the present tumor angiotropic SC. Tumor cells showed wide local invasion.     

Relation between white blood cell counts and myocardial reperfusion in patients with recanalized anterior acute myocardial infarction.

BACKGROUND: The clinical significance of the white blood cell (WBC) count on admission in relation to the duration of ischemia in acute myocardial infarction (AMI) remains unclear. METHODS AND RESULTS: The relationship of the WBC count on admission to myocardial reperfusion was examined in 135 patients with recanalization of an anterior AMI within 6 h of symptom onset. Patients were classified according to the WBC count on admission: Group L (n=75), WBC count <12,000 cells/mm(3) and group H (n=60), WBC count >or=12,000 cells/mm(3). Peak creatine kinase (CK) was higher and impaired myocardial reperfusion, defined as a myocardial blush grade of 0/1, was more frequent in group H than in group L. Among the patients in group H, those with early (3 h) recanalization; however, peak CK and the incidence of impaired myocardial reperfusion were similar in these subgroups of patients. Multivariate analysis showed that WBC count >or=12,000 cells/mm(3) on admission was an independent predictor of impaired myocardial reperfusion in patients with early recanalization (odds ratio 7.9, p=0.04), but not in those with late recanalization. CONCLUSIONS: A higher WBC count may be associated with progression of myocardial damage after recanalization in patients with early recanalization of an anterior AMI.     

Case of pneumothorax associated with pulmonary Mycobacterium fortuitum infection

A 39-year-old man with dyspnea was revealed to have severe pneumothorax and received partial resection of the left upper lobe after unsuccessful drainage. Necrotizing epitheloid granuloma was found in the resected lung and Mycobacterium fortuitum was detected from the lesion. Chemotherapy with levofloxacin and clarithromycin was started one year after surgery because of the newly found nodular shadow near the lesion. The case experienced pyothorax due to pulmonary tuberculosis three years before and Mycobacterium avium pleuritis one year before this episode. Three-time mycobacterial pleural infection in three years seems to be uncommon. Furthermore this is the first report of pneumothorax associated with pulmonary Mycobacterium fortuitum infection.     

Modulation of TNFR 1-triggered two opposing signals for inflammation and apoptosis via RIPK 1 disruption by geldanamycin in rheumatoid arthritis

Clinical Rheumatology - To evaluate the ability of geldanamycin to modulate two opposing TNFα/TNFR1-triggered signals for inflammation and cell death. The effects of geldanamycin on...     

Anti-myeloma effect of homoharringtonine with concomitant targeting of the myeloma-promoting molecules, Mcl-1, XIAP, and β-catenin

Since a variety of cell intrinsic and extrinsic molecular abnormalities cooperatively promote tumor formation in multiple myeloma (MM), therapeutic approaches that concomitantly target more than one molecule are increasingly attractive. We herein demonstrate the anti-myeloma effect of a cephalotaxus alkaloid, homoharringtonine (HHT), an inhibitor of protein synthesis, through the induction of apoptosis. HHT significantly reduced Mcl-1, a crucial protein involved in myeloma cell survival, in all three myeloma cell lines examined, whereas certain BH3-only proteins, such as Bim, Bik, and Puma, remained unchanged following HHT treatment, and their expression levels depended on the cell type. HHT also reduced the levels of c-FLIP(L/S), activated caspase-8, and induced active truncated-Bid. Thus, HHT-induced apoptosis appears to be mediated via both intrinsic and extrinsic apoptosis pathways, and the resultant imbalance between BH3-only proteins and Mcl-1 may be pivotal for apoptosis by HHT. In addition, HHT treatment resulted in reduced levels of beta-catenin and XIAP proteins, which also contribute to disease progression and resistance to chemotherapy in MM. In combination, HHT enhanced the effects of melphalan, bortezomib, and ABT-737. These results suggest that HHT could constitute an attractive option for MM treatment though its ability to simultaneously target multiple tumor-promoting molecules.     

Clinical analysis of primary lung cancer with a thin-walled cavity to explain the mechanism of thin-walled cavity formation]

We report 8 rare cases of primary lung cancer which showed a thin-walled cavity on chest X-ray and CT. We analyzed 8 cases (7 men, 1 woman) of primary lung cancer with thin-walled cavities admitted to our hospital between 1995 and 2006. The subjects were aged between 45 and 84 years of age (median: 72 years old). The reason for detection was treatment for tuberculosis in 1 case, ileus owing to metastasis to the small intestine in 1 case and tension pnumathorax 1 case, while 5 cases had abnormal chest x-ray film shadows without symptoms. Histologically, there were 5 cases of adenocarcinoma, 2 of squamous cell carcinoma, and 1 of adenosquamous cell carcinoma. Though various reports on the mechanism of the development of thin-walled cavity formation have been made, we suggest that it mainly develops by a check-valve mechanism, based on evaluation of the clinical course.