Endoscopic Thoracic Sympathectomy: At What Level Should You Perform Surgery?

Several interventions are possible on the sympathetic chain and the nomenclature has been confusing. The authors propose a uniform nomenclature for each procedure, mainly, sympathectomy for resection or ablation of the ganglion, sympathicotomy for the transaction of the chain, ramicotomy for the procedure preserving the chain and ganglia and severing the rami, and finally, sympathetic block for clipping above and below the ganglia. They recommend intervention on the T2 ganglia for facial hyperhidrosis and rubor, on the T3 ganglia for palmar hyperhidrosis, and on the T3 and T4 ganglia for axillary hyperhidrosis.     

Irofulven as first line therapy in recurrent or metastatic gastric cancer: a phase II multicenter study by the Cancer Therapeutics Research Group (CTRG)

Background The purpose of this study was to evaluate the tolerability and efficacy of irofulven, a DNA interacting acylfulvene analog, as first line therapy for patients with recurrent or metastatic gastric cancer. Patients and methods Twenty-three patients with recurrent or metastatic gastric cancer received irofulven at a dose of 0.45 mg/kg administered intravenously over 30-min infusion (up to a maximum of 50 mg), on days 1 and 8, every 3 weeks. Results The median number of cycles delivered per patient was 2 (range 1–6). Two patients (9%) had ≥ 1-week delay in administration of subsequent cycle of chemotherapy. For the day 8 chemotherapy, dose reductions were required in seven patients (30%); dose omitting occurred in five patients (22%). Grade 3/4 anemia and neutropenia occurred in 22 and 17% of patients, respectively. There was no grade 4 thrombocytopenia and no neutropenic fever was observed. Of the 20 evaluable patients, there were no responses observed, 3 patients had stable disease after 2 cycles of treatment which was not confirmed by a further assessment. Median overall survival was 6.05 months (95% CI 4.55–9.39). Conclusions Irofulven was tolerated at the dose of 0.45 mg/kg on days 1 and 8, every 3 weeks but showed no evidence of antitumor activity in patients with advanced gastric cancer.     

5-Substituted imidazole-4-acetic acid analogues: synthesis, modeling, and pharmacological characterization of a series of novel gamma-aminobutyric acid(C) receptor agonists

A series of ring-substituted analogues of imidazole-4-acetic acid (IAA, 4), a partial agonist at both GABAA and GABAC receptors (GABA = gamma-aminobutyric acid), have been synthesized. The synthesized compounds 8a-l have been evaluated as ligands for the alpha1beta2gamma2S GABAA receptors and the rho1 GABAC receptors using the FLIPR membrane potential (FMP) assay and by electrophysiology techniques. None of the tested compounds displayed activity at the GABAA receptors at concentrations up to 1000 microM. However, the 5-Me, 5-Ph, 5-p-Me-Ph, and 5-p-F-Ph IAA analogues, 8a,c,f,g, displayed full agonist activities at the rho1 receptors in the FMP assay (EC50 in the range 22-420 microM). Ligand-protein docking identified the Thr129 in the alpha1 subunit and the corresponding Ser168 residue in rho1 as determinants of the selectivity displayed by the 5-substituted IAA analogues. The fact that GABA, 4, and 8a displayed decreased agonist potencies at a rho1Ser168Thr mutant compared to the WT rho1 receptor strongly supported this hypothesis. However, in contrast to GABA and 4, which exhibited increased agonist potencies at a alpha1(Thr129Ser)beta2gamma2 mutant compared to WT GABAA receptor, the data obtained for 8a at the WT and mutant receptors were nonconclusive.     

Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer

The phase 3 KEYNOTE-177 study evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite-instability-high (MSI-H)/mismatch-repair-deficient (dMMR) metastatic colorectal cancer (mCRC). Primary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints were overall response rate (ORR) per RECIST v1.1 by BICR and safety. Here, we report results from the post hoc analysis of patients who were enrolled in Asia from the final analysis (FA) of KEYNOTE-177. A total of 48 patients from Japan, Korea, Singapore, and Taiwan (pembrolizumab, n = 22; chemotherapy, n = 26) were included. At FA, median time from randomization to data cutoff (February 19, 2021) was 45.3 (range 38.1–57.8) months with pembrolizumab and 43.9 (range 36.6–55.1) months with chemotherapy. Median PFS was not reached (NR; 95% confidence interval [CI] 1.9 months–NR) with pembrolizumab versus 10.4 (95% CI 6.3–22.0) months with chemotherapy (hazard ratio [HR] 0.56, 95% CI 0.26–1.20). Median OS was NR (range 13.8 months–NR) versus 30.0 (14.7–NR) months (HR 0.65, 95% CI 0.27–1.55) and ORR was 50% (95% CI 28–72) versus 46% (95% CI 27–67). Grade 3/4 treatment-related adverse events (TRAEs) were reported by two patients (9%) in the pembrolizumab arm and 20 (80%) in the chemotherapy arm. Immune-mediated adverse events or infusion reactions were reported by six patients (27%) and 10 patients (40%), respectively. No deaths due to TRAEs occurred. These data support first-line pembrolizumab as a standard of care for patients from Asia with MSI-H/dMMR mCRC. ClinicalTrials.gov identifier: NCT02563002.     

Imagining Consequences of Excessive Smartphone Use via a Character-Based Mobile Application

Excessive use of smartphones or other electronic screen products and the associated symptoms of addiction among youngsters have sparked concerns. This study explores possibilities of preventing adolescents or young adults from excessive smartphone use via a character-based mobile application stimulating their imagination and reflection. The character responds contingently to a user’s act of switching on or off the screen, causing one to associate the effects on the character with excessive use. This approach, grounded in the embodied cognition thesis, combines behavior with imaginative consequences for one to experience, which combat the rewarding neural pathways activated in addictive behaviors. The application was deployed in a field trial. Each participant’s usage was tracked via automated logging, and cognitive responses were probed through in-depth interviews. Interview data were analyzed, followed by comparison with logged data. Overall, about half of the participants attributed imaginative consequences to their ways of using phones. One third of the participants showed evidence of positive change in using phones. These two groups substantially overlapped. The results suggest that experientially grounded association of virtual consequences with physical acts could correlate with behavior change. Using figurative representation as feedback could be promising in supporting individuals for healthy habits.     

Pyrolysis Temperature-Dependent Changes in the Characteristics of Biochar-Borne Dissolved Organic Matter and Its Copper Binding Properties

Bulletin of Environmental Contamination and Toxicology - The dissolved organic matter (DOM) samples from biochars produced from Jerusalem artichoke stalks by pyrolysis at 300, 500, and...