Comparison of traditional two-injection dorsal digital block versus transthecal and subcutaneous single-injection digital block: A systematic review and meta-analysis.

Digital nerve block is a common procedure with several techniques, including the traditional digital nerve block, transthecal digital nerve block, and single subcutaneous palmar digital nerve block. This review aimed to evaluate the efficacy of these three methods. A systematic search was performed in the PubMed, Scopus, and Cochrane Library databases. The risk of bias of the studies was assessed using the Cochrane Collaboration's tool for assessing the risk of bias and the Risk of Bias Assessment Tool for Non-Randomized Studies. Fourteen prospective randomized controlled studies and one prospective comparative study were included. The three methods of digital block showed similar onset times, durations, injection pain and incidence of incomplete anesthesia. This review confirmed that all three methods of digital block are equally effective. Considering that patients prefer a single injection and the potential risk of complications, the single subcutaneous digital block could be more widely used.

Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial.

BACKGROUND: Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in a phase I/II multicenter trial (NCT01631552) in patients with advanced epithelial cancers. This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously. PATIENTS AND METHODS: Patients with refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic parameters with investigator-evaluated objective response rate (ORR per RECIST 1.1), duration of response, clinical benefit rate, progression-free survival, and overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and castrate-resistant prostate cancer. RESULTS: In the OSP (n = 495, median age 61 years, 68% female; UGT1A1∗28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently discontinued treatment due to adverse events (AEs). Most common treatment-related AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade ≥3 neutropenia and febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. Neutropenia (all grades) was numerically more frequent in UGT1A1∗28 homozygotes (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1∗1 wild type (59/177; 33.3%). There was one treatment-related death due to an AE of aspiration pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant prostate cancer patient had a complete response (n = 1/11; 9.1% ORR). CONCLUSIONS: SG demonstrated a toxicity profile consistent with previous published reports. Efficacy was seen in several cancer cohorts, which validates Trop-2 as a broad target in solid tumors.

A case report and epidemiological investigation of axillary lymph node abscess caused by Corynebacterium ulcerans in an HIV-1-positive patient.

A human immunodeficiency virus-1 (HIV-1)-positive male undergoing antiretroviral therapy was diagnosed with an axillary lymph node abscess caused by Corynebacterium ulcerans, and an environmental survey revealed that the patient's cat as the source of infection.

Functional morphology of the aardvark tail.

The musculoskeletal system of the aardvark (Orycteropus afer) tail was morphologically examined in two adult specimens. The tail musculature comprised three muscular groups, viz. a dorsal sacrocaudal system that consisted of the irregularly oriented Musculus sacrocaudalis dorsalis medialis and M. sacrocaudalis dorsalis lateralis, a lateral inter-vertebral connecting system, and a ventral sacrocaudal system characterized by the thick M. sacrocaudalis ventralis lateralis and M. sacrocaudalis ventralis medialis. Both the dorsal and ventral systems possessed large tendon groups that strengthened the tail structure. Computed tomography (CT) examination showed the presence of large but homogeneous cartilaginous inter-vertebral discs, whereas V-shaped bones were situated at the ventral aspect of the caudal vertebrae at the level of the inter-vertebral discs. CT visualization of the tendons and V-shaped bones in various tail positions suggested that these structures contribute to the tunnel digging action by bearing the trunk weight and lending force when the aardvark are displacing the soil by means of the forelimbs.

Efficacy and immunomodulatory actions of ONO-4641, a novel selective agonist for sphingosine 1-phosphate receptors 1 and 5, in preclinical models of multiple sclerosis.

ONO-4641 is a next-generation sphingosine 1-phosphate (S1P) receptor agonist selective for S1P receptors 1 and 5. The objective of the study was to characterize the immunomodulatory effects of ONO-4641 using preclinical data. ONO-4641 was tested in both in-vitro pharmacological studies as well as in-vivo models of transient or relapsing-remitting experimental autoimmune encephalomyelitis (EAE). In vitro, ONO-4641 showed highly potent agonistic activities versus S1P receptors 1 and 5 [half maximal effective concentration (EC(50) ) values of 0·0273 and 0·334 nM, respectively], and had profound S1P receptor 1 down-regulating effects on the cell membrane. ONO-4641 decreased peripheral blood lymphocyte counts in rats by inhibiting lymphocyte egress from secondary lymphoid tissues. In a rat experimental autoimmune encephalomyelitis (EAE) model, ONO-4641 suppressed the onset of disease and inhibited lymphocyte infiltration into the spinal cord in a dose-dependent manner at doses of 0·03 and 0·1 mg/kg. Furthermore, ONO-4641 prevented relapse of disease in a non-obese diabetic mouse model of relapsing-remitting EAE. These observations suggest that ONO-4641 may provide therapeutic benefits in the treatment of multiple sclerosis.

IFNß-1b may severely exacerbate Japanese optic-spinal MS in neuromyelitis optica spectrum.

BACKGROUND: Interferon-ß-1b (IFNß-1b) has been used to prevent exacerbation of relapsing-remitting multiple sclerosis (RRMS) including optic-spinal multiple sclerosis (OSMS) in Japan. We encountered 2 patients with OSMS with unexpectedly severe exacerbation soon after the initiation of IFNß-1b therapy. The experience urged us to retrospectively review the patients with RRMS who had been treated with IFNß-1b to identify similar cases. METHODS: At neurologic departments of 9 hospitals, the medical records of 56 patients with RRMS were reviewed to identify those who showed severe exacerbation soon after the initiation of IFNß-1b therapy. RESULTS: Of 56 patients with RRMS, we identified 7 who experienced severe exacerbation (exacerbation with increased scores of Expanded Disability Status Scale ≧7.0) within 90 days of the initiation of IFNß-1b therapy. In all 7 patients, the exacerbations after the initiation of IFNß-1b therapy were more severe than those experienced by the individual patients before the use of IFNß-1b, and seemed to have occurred unexpectedly in a short time after the initiation of INFß-1b therapy. A retrospective analysis revealed that all 7 patients had antibodies toward aquaporin 4, and the clinical features of all 7 patients after the exacerbation were consistent with those of neuromyelitis optica (NMO) spectrum. CONCLUSIONS: Our study suggests that IFNß-1b may trigger severe exacerbation in patients with the NMO spectrum. In INFß-1b therapy, cases in NMO spectrum should be carefully excluded.

Enhanced activity of the CREB co-activator Crtc1 in LKB1 null lung cancer.

Activation of Crtc1 (also known as Mect1/Torc1) by a t(11;19) chromosomal rearrangement underlies the etiology of malignant salivary gland tumors. As LKB1 is a target for mutational inactivation in lung cancer and was recently shown to regulate hepatic Crtc2/CREB transcriptional activity in mice, we now present evidence suggesting disruption of an LKB1/Crtc pathway in cancer. Although Crtc1 is preferentially expressed in adult brain tissues, we observed elevated levels of steady-state Crtc1 in thoracic tumors. In addition, we show that somatic loss of LKB1 is associated with underphosphorylation of endogenous Crtc1, enhanced Crtc1 nuclear localization and enhanced expression of the Crtc prototypic target gene, NR4A2/Nurr1. Inhibition of NR4A2 was associated with growth suppression of LKB1 null tumors, but showed little effect on LKB1-wildtype cells. These data strengthen the role of dysregulated Crtc as a bona fide cancer gene, present a new element to the complex LKB1 tumorigenic axis, and suggest that Crtc genes may be aberrantly activated in a wider range of common adult malignancies.

Isolation and characterization of 15 microsatellite loci for the Japanese gudgeon Sarcocheilichthys variegatus.

A microsatellite-enriched genomic library was obtained for the Japanese gudgeon Sarcocheilichthys variegatus microoculus, and 15 dinucleotide markers were successfully isolated and characterized. These markers were also available for other Japanese congeners, Sarcocheilichthys variegatus variegatus and Sarcocheilichthys biwaensis. In three populations of Sarcocheilichthys from Lake Biwa and the Ashida River in western Japan, seven to 27 alleles were observed for each locus. Linkage equilibrium was observed among most loci, and only one locus showed significant deviation from Hardy-Weinberg equilibrium in a population. These microsatellite markers will be useful for studies of the genetic structure of the Japanese gudgeons.

[Coronary malperfusion of left main trunk due to localized dissection of the ascending aorta].

Case 1. Forty nine years woman was given a diagnosis of acute myocardial infarction. Coronary angiography and trans-esophageal echocardiography showed left main trunk dissection due to local aortic root dissection. We operated surgical repair at left main trunk by pericardium after percutaneous coronary intervention. Case 2. Forty nine years man was given a diagnosis of acute myocardial infarction caused by left main trunk dissection due to traumatic local aortic root dissection. We operated coronary artery bypass grafting after insertion of perfusion catheter to left main trunk for maintain coronary perfusion. Although local dissection of aortic aorta is relatively rare, it is potentially complicated with coronary malperfusion. We describe 2 success a cases of surgical treatment for local acute type A aortic dissection complicated with coronary malperfusion.