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Surgery is the standard of care for early-stage non-small cell lung cancer (NSCLC), with SBRT reserved for patients who are not surgical candidates or decline surgery. The role of SBRT for medically operable early-stage NSCLC is not defined. We hypothesized overall survival (OS), lung cancer-specific survival (LCSS), progression free survival (PFS), and recurrence rates following SBRT or surgery in medically operable patients with Stage I NSCLC from the Veterans' Health Care System (VAHS) would be equivalent. Medically operable patients diagnosed with Stage I NSCLC between 2000-2020 from the VAHS, determined by an FEV1 or DLCO > 60% of predicted and Charlson comorbidity index (CCI) of 0 or 1, treated with SBRT or surgery were identified. SBRT patients were propensity score matched for age, diagnosis year, sex, race, smoking status, tumor stage, FEV1, and CCI in a 1:1:1 ratio (SBRT:lobectomy:sub-lobar resection). OS, LCSS, and PFS were compared using log-rank and Kaplan-Meier analyses. PFS was calculated as the time from treatment start to recurrence or death, whichever occurred first. Local recurrence was defined as any new lung tumor, regional as spread to intrathoracic lymph nodes, and distant as spread beyond these sites. Hazard ratios were calculated using Cox regression. Recurrence was compared via a chi-squared test. 103 patients were included in each cohort. 97% of patients were male, 86% were white, and 89% were diagnosed from 2011-2020. 82% of patients had a CCI of 0 and the mean percent predicted FEV1 was 88%. 52% of SBRT patients received 50-60 Gy in 5 fractions and 69% of sub-lobectomy patients were treated with a wedge resection. Median follow-up was 4.32 years. For all patients, 5-year OS was 51% (95% CI 46-57%). After matching, OS, LCSS, and PFS were significantly worse with SBRT compared to either surgical cohort (Table 1). Regional recurrence was significantly higher following SBRT (15.5% vs 6.8% or 4.9%; p < 0.05), but there was no significant difference in local (28.2% vs 21.4% or 21.4%; p > 0.05) or distant recurrence (10.7% vs 9.7% or 13.6%; p > 0.05) when compared to lobectomy or sub-lobar resection, respectively. In medically operable patients, OS, LCSS, and PFS following either lobectomy or sub-lobar resection were superior to that for SBRT for Stage I NSCLC, likely due in part to higher regional recurrence following SBRT. This suggests that pulmonary function test results and comorbidity calculations alone are insufficient to define a cohort of medically operable patients suited for SBRT. These data also support trials investigating strategies to overcome regional recurrences seen with SBRT. [ABSTRACT FROM AUTHOR]

Z TIP: It is critical for insurers to evaluate the language of their policies and to understand how those policies might subject the insurers to litigation in various foreign forums. With regard to insureds suing their insurance companies for denial of coverage, establishing a court's personal jurisdiction over the insurance company is accomplished by showing either (1) general personal jurisdiction or (2) specific personal jurisdiction. The Path Forward While courts are closing the door on general personal jurisdiction arguments regarding insurers, the window of specific personal jurisdiction seemingly remains open. [Extracted from the article]

Routine activity situations on an Alzheimer's disease (AD) special care unit were examined with respect to residents' social and physical environmental interactions, time use, and apparent affect. Using a computer-assisted observational tool, observers recorded prevailing activity situations and corresponding behaviors and affects of seven residents every 10 minutes, from 8:00 AM to 8:00 PM, across four days. Although meals/snacks and some activity groups were positively associated with use of physical objects and engagement in activities, residents were predominantly environmentally disengaged, inactive, or without positive affects during the most prevalent activity situations of background media, downtime, and television. Findings suggest that routine activity situations may act as potent environmental influences on the quality of life (QOL) of people with AD and mediate the effectiveness of other environmental interventions undertaken on their behalf. [ABSTRACT FROM AUTHOR]

Bovine herpes virus type 1 (BHV-1) gIII is a major virion glycoprotein with homology to the immunoglobulin superfamily. We have investigated the possibility that gIII is related to host molecules and have identified a gIII-specific monoclonal antibody (mAb) that cross-reacts with normal bovine cells. The cross-reactive entity was expressed mainly on monocyte/macrophages (Mφ), polymorphonuclear leucocytes (PMN) and platelets, and was identified as a 43,000-63,000 molecular weight (MW) cell-surface glycoprotein. For Mφ, the glycoprotein appears to be a general lineage marker, rather than a maturation or activation marker, and may be a functional receptor, as evidenced by its endocytosis via coated pits and its involvement in proliferation of mononuclear cells in vitro. This novel leucocyte marker was also detected on subsets of human, ovine and canine Mφ. Competitive binding assays with sera from cattle immunized with BHV-1 or gIII revealed apparent low responsiveness to the cross-reactive epitope. The results suggest that BHV-1 gIII is antigenically related to a novel host leucocyte receptor and that evasion and/or interference with leucocyte function may be a consequence of this molecular mimicry relationship. [ABSTRACT FROM AUTHOR]

Multiparametric magnetic resonance imaging (mpMRI) is not currently included in prostate cancer (PC) staging. The purpose of this study was to test the association between mpMRI detected prostate capsule involvement and extraprostatic extension (EPE) with metastasis free survival (MFS) and overall survival (OS) in patients with localized PC treated with radiation. Patients diagnosed with localized PC between 2000-2021 from the Veterans Affairs Prostate Date Core with an mpMRI prior to definitive radiation were identified. Reports were assessed for minor or significant capsular abutment (defined as greater than or equal to 1.5 cm of capsular contact or radiologist's mention of long segment abutment), extracapsular extension (ECE), seminal vesicle invasion (SVI), or adjacent organ invasion (OI). mpMRI findings' impact on MFS by multivariable Fine-Gray competing-risks regression and OS by Cox regression were assessed. Overall, 1,547 patients were included. Most pre-treatment mpMRIs (84%) occurred after 2016. 692 (45%) patients were Black. 1,113 (72%) patients had non-palpable disease. Median follow-up was 5 years. The 5-year cumulative incidence of metastasis was 10% (95% confidence interval (CI) 8-12%) and death was 9% (95% CI = 7-11%). There were 390 (25%) patients with minor capsular abutment, 134 (9%) with significant capsular abutment, 129 (8%) with ECE, 56 (4%) with SVI, and 17 (1%) with OI. After controlling for age, race, prostate specific antigen, grade group, and comorbidities, the presence of significant capsular abutment, ECE, SVI, and OI were independently associated with MFS, but minor capsular abutment was not. On multivariable analysis controlling for the same factors, EPE (ECE, SVI, or OI) was associated with worse OS. In a modern, real-world cohort of localized PC patients treated with radiation from the largest integrated health system in the United States, significant capsule abutment and EPE on mpMRI are independently prognostic of MFS, but minor capsular abutment is not. EPE is associated with inferior OS. mpMRI should be widely available for patients with PC as it adds prognostic information. Studies are ongoing to define its role as a standard staging tool. [ABSTRACT FROM AUTHOR]

Previous research has shown that exposure to ergot alkaloids found in endophyte-infected (Epichloë coenophiala) tall fescue (Lolium arundinaceum) results in decreased vasoactivity. Little is known regarding the effect ergot alkaloid exposure during gestation may have on vasculature supporting the fetus. The objective of this study was to evaluate contractile responses of uterine and umbilical arteries collected from ewes consuming ergot alkaloids during gestation. On d 35 of gestation, 36 Suffolk ewes (78.24 ±9.5 kg) were randomly assigned to endophyte-infected (E+) or endophyte-free (E-) tall fescue seed treatments that were fed either throughout or switched on d 86 of gestation, creating four seed treatments E+E+, E+E-, E-E+, E-E-. Ewes were fed E+ tall fescue seed to provide 1.77 mg of total ergovaline/head/d with E- ewes receiving the same quantity of E- seed. Gestation was terminated on d 133, and sections of uterine artery and umbilical cord were surgically collected. Only collections from 28 ewes (n = 7/treatment) were of sufficient viability to proceed with the contractility experiments. Arteries were cleaned, sliced into 2-mm cross sections, and suspended in multi-myograph chambers containing 5 mL of continuously oxygenated Krebs-Henseleit buffer. Vessels were exposed to increasing concentrations (5x10-8 to 1x10-4 M) of norepinephrine, serotonin, ergotamine, and ergovaline (5x10-9 to 1x10-5 M; extract of tall fescue seed) in 15-min intervals. Data were normalized as a percentage of the maximum contractile response induced by a reference dose of 120 mM KCl. Data from each artery were analyzed using mixed models of SAS as a split-plot with seed and myograph treatments as the whole and sub-plot treatments, respectively. Increasing concentrations of norepinephrine generated a moderate contractile response by the uterine artery (P < 0.05), but no response in the umbilical artery. Increasing concentrations of serotonin resulted in negligible responses in uterine preparations, whereas umbilical artery preparations were very responsive (P < 0.05) to serotonin. Ewes receiving E+E+ and E-E+ treatments had decreased vasoactivity in umbilical arteries to serotonin with a dextral shift in concentrations where the response curve initiated (P < 0.05). Interestingly, uterine arteries were not responsive to exposure to ergotamine or ergovaline, whereas umbilical arteries were very responsive. Umbilical arteries collected from ewes receiving E-E- and E+E- were more vasoactive to ergot alkaloids (P < 0.05) than other treatments. These findings indicate that maternal blood supply to the placenta is protected from negative effects of ergot alkaloids; however, umbilical vasculature is not and this could negatively affect fetal growth. [ABSTRACT FROM AUTHOR]

A previous study using a contractility bioassay determined that 5HT2A receptors in bovine lateral saphenous veins play a role in ergot alkaloid-induced vascular contraction in steers grazing endophyte-infected (Epichloë coenophiala) tall fescue (Lolium arundinaceum). Ergot alkaloids have also been shown to be vasoactive in gut vasculature. To determine what 5HT receptors are involved in vasoconstriction of gut vasculature, contractility of ruminal and mesenteric arteries and veins collected from cattle were evaluated in the presence of agonists selective for 5HT1D (L694-247), 5HT2A (TCB-2), 5HT2B (BW723C86), and 5HT7 (LP44) receptors. Segments of vein and artery were collected from 18 mixed-breed and -gender animals between 10 and 30 mo of age (531 ± 29 kg). Vessels were sliced into 2- to 3-mm cross-sections and suspended in a multimyograph containing 5 mL of continuously oxygenated Krebs-Henseleit buffer (95% O2/5% CO2, pH = 7.4, and 37°C). Vessels were equilibrated to 1.0 g for 90 min followed by the addition of 120 mM KCl. Tissues were exposed to increasing concentrations of 5HT agonists every 15 min. Contractile response data were normalized as a percentage of the maximum contractile response induced by KCl. Analysis of variance was evaluated using mixed models procedure of SAS for effects of agonist concentration for each vessel type. BW723C86, L694-247, and LP44 did not induce a contractile response for ruminal or mesenteric vasculature. However, when exposed to BW723C86 or L694-247, mesenteric veins relaxed (P < 0.05). There was a trend for BW723C86 (P < 0.05), L694-257 (P = 0.06), and LP44 (P < 0.05) to induce a contractile response for ruminal arteries but at the lowest agonist concentration. This is an indication that the ruminal artery is still relaxing from exposure to KCl. Exposure of gut vasculature to TCB-2 induced vasoactivity. Onset was observed at addition of 5 × 10-5 M TCB-2 for the mesenteric artery and vein and the ruminal vein (P < 0.05). The mesenteric artery reached a maximal response when exposed to 5 × 10-5 M TCB-2 and did not differ from the highest (1 × 10-4 M) TCB-2 concentration addition (P > 0.05). For the ruminal artery, a contractile response was observed at 5 × 10-6 M TCB-2 (P < 0.05). The findings of this study indicate that 5HT1D and 5HT2B are present in mesenteric veins and may play a role in vasorelaxation. Furthermore, 5HT2A is present in ruminal and mesenteric vasculature, plays a role in vasoconstriction of blood flow, and could be influenced by ergot alkaloid exposure as has been demonstrated in peripheral blood vessels. [ABSTRACT FROM AUTHOR]