Notes

Physiological variants in the aortic mid-foot branching design using CT angiography: an offer for any different morphological group along with specialized medical relevance.
Limited population-based data have explored perianal involvement in Crohn's disease (CD) and compared the disease course between severe and non-severe perianal CD (PCD). We aimed to explore the disease course of these phenotypes in a population-based study of CD.

Cases were identified from the epi-IIRN cohort and included 2 Israeli health maintenance organizations covering 78% of the population. We validated specific algorithms to identify fistulizing PCD and to differentiate severe from non-severe disease by medication utilization, International Classification of Disease, 9th Revision codes, and perianal procedures.

A total of 12,904 CD patients were included in an inception cohort from 2005 (2186 pediatric-onset, 17%) providing 86,119 person-years of follow-up. Fistulizing PCD was diagnosed in 1530 patients (12%) (574 with severe PCD, 4%). The prevalence of PCD was 7.9%, 9.4%, 10.3%, and 11.6% at 1, 3, 5, and 10 years from CD diagnosis, respectively. At 5 years, PCD patients were more likely to be hospitalized (36% in non-PCD vs 64% in PCD; P < .001), undergo inflammatory bowel disease-related surgeries (9% vs 38%, respectively; P < .001), and develop anorectal cancer (1.2/10,000 person-years for non-PCD vs 4.2/10,000 for PCD; P= .01). Severe PCD was associated with poorer outcomes compared with non-severe PCD, as shown for hospitalizations (61% in non-severe PCD vs 73% in severe; P= .004) and surgeries (35% vs 43%; P= .001).

Despite higher utilization of immunomodulators and biologics, PCD is associated with poor disease outcomes, especially in severe PCD.
Despite higher utilization of immunomodulators and biologics, PCD is associated with poor disease outcomes, especially in severe PCD.
The mechanisms underlying premature ventricular contraction (PVC)-induced cardiomyopathy (PIC) remain unknown. Transient receptor potential vanilloid-1 (TRPV1) afferent fibers are implicated in the reflex processing of cardiac stress.

The purpose of this study was to determine whether cardiac TRPV1 afferent signaling promote PIC.

A PIC swine model (50% PVC burden) was created via an implanted pacemaker. We selectively depleted cardiac TRPV1 afferent fibers using percutaneous epicardial application of resiniferatoxin (RTX). Animals were randomized to PVC only (n = 11), PVC+RTX (n = 11), or control (n = 6). We examined early-stage (4 weeks after implantation; n = 5) and late-stage PIC (8 weeks after implantation; n = 6). At terminal experimentation, animals underwent echocardiography, serum sampling, and physiological and autonomic reflex testing.

Depletion of cardiac TRPV1 afferents by RTX treatment was confirmed by absent sensory fibers and absent functional responses to TRPV1 activators. Left ventricular ejection fraction was worse in late-stage than early-stage PIC (P <.01). At 4 weeks (early stage), left ventricular ejection fraction was higher in PVC+RTX vs PVC animals (51.7% ± 1.6% vs 45.0% ± 2.1%; P = .030), whereas no significant difference between PVC and PVC+RTX was observed at 8 weeks (late stage). Histologic studies demonstrated reduced fibrosis in PVC+RTX vs PVC alone at 4 weeks (2.27% ± 0.14% vs 3.01% ± 0.21%; P = .020), suggesting that RTX mitigated profibrotic pathways induced by persistent PVCs.

TRPV1 afferent depletion alleviates left ventricular dysfunction in early- but not late-stage PIC. This temporal effect suggests that multiple pathways promote PIC, of which TRPV1 afferents are a part.
TRPV1 afferent depletion alleviates left ventricular dysfunction in early- but not late-stage PIC. This temporal effect suggests that multiple pathways promote PIC, of which TRPV1 afferents are a part.
Marked variations in survival rates have brought into question whether standard clinicopathologic classification should be applied to patients presenting with multiple primary lung cancers (MPLCs). This study investigated the genetic profiles of MPLCs in a cohort of patients using next-generation sequencing and correlated results to clinicopathologic data and patient outcome.

Patients treated surgically with curative intent fortwo putative primaries of similar histopathology from January 2000 to December 2019 at St Vincent's Hospital Melbourne. DNA and RNA was extracted from formalin-fixed, paraffin-embedded tumor tissue and sequenced on an IonTorrent Personal Genome Machine system. Patient outcome was determined by overall survival and disease-free survival.

A total of 40 cases fulfilled the inclusion criteria. Mutational profiling was concordant with clinicopathologic diagnosis in most cases; however, seven cases (17.5%) revealed shared mutations suggesting metastatic disease and this was associated with a substantial reduction in overall survival (p < 0.05).

Our results suggest that gene sequencing technologies are potentially a more accurate diagnostic and prognostic tool compared with traditional histopathologic evaluation in patients presenting with suspected MPLCs, which could better guide management and predict outcomes.
Our results suggest that gene sequencing technologies are potentially a more accurate diagnostic and prognostic tool compared with traditional histopathologic evaluation in patients presenting with suspected MPLCs, which could better guide management and predict outcomes.Monoclonal antibodies that target immune checkpoint proteins, so-called immune checkpoint inhibitors, prevent tumor evasion of the immune system and are often effective in the treatment of lung cancer. Studies have revealed improved objective response rates, progression-free survival, and overall survival with immune checkpoint inhibitors when used in both first and subsequent-line settings. Unfortunately, only a subset of unselected patients with lung cancer responds to these therapies. An important area of ongoing research is to identify biomarkers that can predict which patients are most likely to derive clinical benefit. FM19G11 This review will discuss established and emerging biomarkers from some of the clinical trials that have demonstrated the efficacy of immune checkpoint inhibitors for the treatment of both NSCLC and SCLC.
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