Citations

Cerebral embolic protection devices (CEPD) during transcatheter aortic valve replacement (TAVR) have been shown to lower the risk of stroke during the procedure. However, their long-term and clinical effects on neuro-cognition are unknown. Therefore, we hypothesized the benefit of CEPD in TAVR patients with a prior history of stroke or transient ischemic attack (TIA). National Inpatient Sample (2019) and International Classification of Diseases, 10th Revision codes were used to identify patients undergoing TAVR with prior stroke or TIA. Propensity-matched analysis was performed to adjust for baseline characteristics and comorbidities. Primary outcome measures were postoperative stroke and all-cause mortality. Length of stay and hospital cost were secondary outcomes. Of 8450 unmatched TAVR patients with prior stroke or TIA in 2019, 1095 (13%) utilized CEPD. After propensity matching previous myocardial infarction (MI), coronary artery bypass grafting, and drug abuse were higher in the TAVR-only cohort. Postoperative stroke rate (1.4% vs 2.2%; P = 0.081) and odds [adjusted odds ratio (aOR), 0.48; 95% confidence interval (CI), 0.11–2.17; P = 0.341] were lower in the CEPD group. There was no difference in all-cause in-hospital mortality between the 2 groups (0.9% vs 1.0%). Length of stay (3 vs 2 days, P <0.001) and hospital expenditure ($172,711 vs $162,284; P = 0.002) were higher for the TAVR-only cohort. CEPD in TAVR patients with prior stroke or TIA did not show statistically significant postoperative stroke benefits. However, further larger-scale prospective studies are needed to evaluate the long-term neurocognitive benefits of CEPD in these patients. As the use of TAVR continues to expand, optimizing peri-procedural strategies such as the use of CEPD remains a critical area of research to improve patient outcomes.

Abstract Background: Mechanical thrombectomy (MT) has revolutionized the treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO), but its efficacy and safety in medium vessel occlusion (MeVO) remain less explored. This multicenter, retrospective study aims to investigate the incidence and clinical outcomes of vessel perforations (confirmed by extravasation during an angiographic series) during MT for AIS caused by MeVO. Methods: Data were collected from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. A total of 1373 AIS patients with MeVO underwent MT. Baseline characteristics, procedural details, and clinical outcomes were analyzed. Results: The incidence of vessel perforation was 4.8% (66/1373). Notably, our analysis indicates variations in perforation rates across different arterial segments: 8.9% in M3 segments, 4.3% in M2 segments, and 8.3% in A2 segments (p = 0.612). Patients with perforation had significantly worse outcomes, with lower rates of favorable angiographic outcomes (TICI 2c-3: 23% vs 58.9%, p &lt; 0.001; TICI 2b-3: 56.5% vs 88.3%, p &lt; 0.001). Functional outcomes were also worse in the perforation group (mRS 0–1 at 3 months: 22.7% vs 36.6%, p = 0.031; mRS 0–2 at 3 months: 28.8% vs 53.9%, p &lt; 0.001). Mortality was higher in the perforation group (30.3% vs 16.8%, p = 0.008). Conclusion: This study reveals that while the occurrence of vessel perforation in MT for AIS due to MeVO is relatively rare, it is associated with poor functional outcomes and higher mortality. The findings highlight the need for increased caution and specialized training in performing MT for MeVO. Further prospective research is required for risk mitigation strategies.

Objective: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). Background: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. Methods: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines. Results: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population (https://rediscover.unipi.it/). Conclusions: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.

Key Points In heme protein–mediated AKI (HP-AKI), a senescence phenotype promptly occurs, and increased expression of p16 Ink4a contributes to HP-AKI. Renal p16 Ink4a expression is induced by hemoglobin, myoglobin, and heme in vivo and in renal epithelial cells exposed to heme in vitro . Impairing the binding or degradation of heme by hemopexin deficiency or heme oxygenase-1 deficiency, respectively, further upregulates p16 Ink4a . Background Understanding the pathogenetic basis for AKI involves the study of ischemic and nephrotoxic models of AKI, the latter including heme protein–mediated AKI (HP-AKI). Recently, interest has grown regarding the role of senescence as a mechanism of kidney injury, including AKI. We examined whether senescence occurs in HP-AKI and potential inducers of and the role of a key driver of senescence, namely, p16 Ink4a , in HP-AKI. Methods The long-established murine glycerol model of HP-AKI was used, and indices of senescence were examined. To evaluate the interaction of heme and p16 Ink4a expression, murine models of genetic deficiency of hemopexin ( HPX ) and heme oxygenase-1 ( HO-1 ) were used. To determine the involvement of p16 Ink4a in HP-AKI, the population of p16 Ink4a -expressing cells was reduced using the INK-ATTAC model. Results Using multiple indices, a senescence phenotype appears in the kidney within hours after the induction of HP-AKI. This phenotype includes significant upregulation of p16 Ink4a . p16 Ink4a is upregulated in the kidney after the individual administration of myoglobin, hemoglobin, and heme, as well as in renal epithelial cells exposed to heme in vitro . Genetic deficiencies of HPX and HO-1 , which, independently, are expected to increase heme content in the kidney, exaggerate induction of p16 Ink4a in the kidney and exacerbate HP-AKI, the latter shown in the present studies involving HPX −/− mice and in previous studies involving HO-1 −/− mice. Finally, reduction in the population of p16 Ink4a -expressing cells in the kidney improves renal function in HP-AKI even within 24 hours. Conclusions The pathogenesis of HP-AKI involves senescence and the induction of p16 Ink4a , the latter driven, in part, by hemoglobin, myoglobin, and heme.

Abstract In a great partnership, the Federation of European Neuroscience Societies (FENS) and the Hertie Foundation organized the FENS‐Hertie 2022 Winter School on ‘Neuro‐immune interactions in health and disease’. The school selected 27 PhD students and 13 postdoctoral fellows from 20 countries and involved 14 faculty members experts in the field. The Winter School focused on a rising field of research, the interactions between the nervous and both innate and adaptive immune systems under pathological and physiological conditions. A fine‐tuned neuro‐immune crosstalk is fundamental for healthy development, while disrupted neuro‐immune communication might play a role in neurodegeneration, neuroinflammation and aging. However, much is yet to be understood about the underlying mechanisms of these neuro‐immune interactions in the healthy brain and under pathological scenarios. In addition to new findings in this emerging field, novel methodologies and animal models were presented to foment research on neuro‐immunology. The FENS‐Hertie 2022 Winter School provided an insightful knowledge exchange between students and faculty focusing on the latest discoveries in the biology of neuro‐immune interactions while fostering great academic and professional opportunities for early‐career neuroscientists from around the world.

This study aimed to analyze early revisits (within 48 hours of discharge) in an Emergency Department. Among the 178,295 visits, 11,686 were revisits, resulting in a rate of 6.55% (95%CI 6.43-6.67). A total of 1,410 revisits required hospitalization, and 252 were due to preventable errors (17.87%). These errors were mainly related to an inadequate therapeutic plan at discharge (47.22%), an incomplete diagnostic process (29.37%), and misdiagnoses (13.10%). These findings represent a technology-enabled clinical audit tool. Electronic Healthcare Records have the potential to: provide quality metrics of hospital performance, help to keep revisit rates updated (assessment through a real-time dashboard), and improve clinical management (by transparency initiatives about errors, and a supportive learning environment regarding lessons learned).

AbstractAimLocally advanced rectal cancer (LARC) is commonly treated with neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME) to reduce local recurrence (LR) and improve survival. However, LR, particularly associated with lateral lymph node (LLN) involvement, remains a concern. The aim of this study was to investigate preoperative factors associated with LLN involvement and their impact on LR rates in LARC patients undergoing nCRT and curative surgery.MethodThis multicentre retrospective study, including four academic high‐volume institutions, involved 301 consecutive adult LARC patients treated with nCRT and curative surgery between January 2014 and December 2019 who did not undergo lateral lymph node dissection (LLND). Baseline and restaging pelvic MRIs were evaluated for suspicious LLNs based on institutional criteria. Patients were divided into two groups: cLLN+ (positive nodes) and cLLN– (no suspicious nodes). Primary outcome measures were LR and lateral local recurrence (LLR) rates at 3 years.ResultsAmong the cohort, 15.9% had suspicious LLNs on baseline MRI, and 9.3% had abnormal LLNs on restaging MRI. At 3 years, LR and LLR rates were 4.0% and 1.0%, respectively. Ten out of 12 (83.3%) patients with LR showed no suspicious LLNs at the baseline MRI. Abnormal LLNs on MRI were not independent risk factors for LR, distant recurrence or disease‐free survival.ConclusionAbnormal LLNs on baseline and restaging MRI assessment did not impact LR and LLR rates in this cohort of patients with LARC submitted to nCRT and curative TME surgery.

The LMNA gene encodes lamin A and lamin C, which play important roles in nuclear organization. Pathogenic variants in LMNA cause laminopathies, a group of disorders with diverse phenotypes. There are two main groups of disease-causing variants: missense variants affecting dimerization and intermolecular interactions, and heterozygous substitutions activating cryptic splice sites. These variants lead to different disorders, such as dilated cardiomyopathy and Hutchinson–Gilford progeria (HGP). Among these, the phenotypic terms for LMNA-associated cardiocutaneous progeria syndrome (LCPS), which does not alter lamin A processing and has an older age of onset, have been described. Here, we present the workup of an LMNA variant of uncertain significance, NM_170707.2 c. 4G>A, p.(Glu2Lys), in a 36-year-old female with severe calcific aortic stenosis, a calcified mitral valve, premature aging, and a family history of similar symptoms. Due to the uncertainty of in silico predictions for this variant, an assessment of nuclear morphology was performed using the immunocytochemistry of stable cell lines to indicate whether the p.(Glu2Lys) had a similar pathogenic mechanism as a previously described pathogenic variant associated with LCPS, p.Asp300Gly. Indirect immunofluorescence analysis of nuclei from stable cell lines showed abnormal morphology, including lobulation and occasional ringed nuclei. Relative to the controls, p.Glu2Lys and p.Asp300Gly nuclei had significantly (p < 0.001) smaller average nuclear areas than controls (mean = 0.10 units, SD = 0.06 for p.Glu2Lys; and mean = 0.09 units, SD = 0.05 for p.Asp300Gly versus mean = 0.12, SD = 0.05 for WT). After functional studies and segregation studies, this variant was upgraded to likely pathogenic. In summary, our findings suggest that p.Glu2Lys impacts nuclear morphology in a manner comparable to what was observed in p.Asp300Gly cells, indicating that the variant is the likely cause of the LCPS segregating within this family.