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Frailty is a complex biological process that is associated with adverse outcomes in community-dwelling and hospitalized patients. While clinical evaluation is the current gold standard for screening and diagnosis, such an approach is not without its limitations (such as personnel and resource requirement). In this review, we will discuss prospective biomarkers for frailty. Opportunistic and deliberate radiological testing could provide important information that complements clinical frailty evaluation. Novel biochemical panels may yield additional methods for frailty screening in the future. It is known that early frailty intervention could lead to better outcomes for patients. Integration of electronic medical records, laboratory and radiological results, as well as clinical informatics infrastructure could result in augmented clinical decision-making and more optimized healthcare resources utilization.

Background This study investigates the association between preoperative leukopenia and leukocytosis with 30-day postoperative complications following noninfectious revision total shoulder arthroplasty (TSA). Methods The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients who underwent noninfectious revision TSA from 2015 to 2022. The study population was divided into three groups based on preoperative white blood cell (WBC) count: normal (WBC 4500–11,000), leukopenia (WBC ≤ 4500), and leukocytosis (WBC ≥ 11,000). Logistic regression analysis was conducted to investigate the relationship between WBC count and postoperative complications. Results Compared to normal WBC counts, leukocytosis was independently associated with an increased likelihood of experiencing any complication (OR 1.71, 95% CI 1.13–2.59; P  = 0.012), sepsis (OR 5.31, 95% CI 1.38–20.37; P  = 0.015), non-home discharge (OR 2.18, 95% CI 1.18–4.05; P  = 0.013), readmission (OR 2.76, 95% CI 1.36–5.63; P  = 0.005), and LOS > 2 days (OR 1.68, 95% CI 1.06–2.66; P  = 0.028). Compared to normal WBC counts, leukopenia was independently associated with an increased likelihood of experiencing pneumonia (OR 14.98, 95% CI 2.32–96.56; P  = 0.004) and readmission (OR 2.78, 95% CI 1.49–5.17; P  = 0.001). Conclusion The present study identified preoperative leukocytosis and leukopenia as independent risk factors for 30-day postoperative complications following revision TSA. Integrating WBC count into preoperative assessments can enhance the identification of patients at risk for postoperative complications, allowing for more tailored management strategies and potentially improving overall patient outcomes.

Purpose The aim of this study is to explore potential complications and risk factors associated with revision TSA in patients with congestive heart failure (CHF). Methods This study examined all individuals who underwent revision total shoulder arthroplasty (TSA) from 2015 to 2022, sourced from the American College of Surgeons National Surgical Quality Improvement database. The analysis encompassed patient demographics, comorbidities, and 30-day postoperative complications. Logistic regression was employed to analyze the postoperative complications linked to patients with preoperative CHF. Results Compared to patients without CHF, patients with CHF were significantly associated with dependent functional status (P  < .001), chronic obstructive pulmonary disease (P  < .001), and hypertension ( P  = .002). Compared to patients without CHF, patients with CHF were independently associated with a significantly greater likelihood of experiencing any complication (OR 2.19, 95% CI 1.12–4.29; P  = .022) and non-home discharge (OR 3.02, 95% CI 1.37–6.65; P  = .006). Conclusion Congestive heart failure was identified as an independent risk factor for experiencing any complication and non-home discharge in patients undergoing revision TSA. Awareness of the cardiovascular health status of a patient and its severity can influence the decision-making process when considering revision TSA. Level of evidence III Retrospective Cohort Comparison Using Large Database; Prognosis Study.

Abstract Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut and immunohistochemically (IHC) stained for Ki67 (MIB-1 antibody). The QuPath platform was used to evaluate tumoral Ki67 expression. Calibration of the DIA method was performed as in published studies. A guideline for building an automated Ki67 scoring algorithm was sent to participating labs. Very high correlation and no systematic error ( p = 0.08) was found between consecutive Ki67 IHC sections. Ki67 scores were higher for core biopsy slides compared to paired whole sections from resections ( p ≤ 0.001; median difference: 5.31%). The systematic discrepancy between core biopsy and corresponding whole sections was likely due to pre-analytical factors (tissue handling, fixation). Therefore, Ki67 IHC should be tested on core biopsy samples to best reflect the biological status of the tumor.

The recent emergence of the omicron variant of the SARS-CoV-2 virus with large numbers of mutations has raised concern about a potential new surge in infections. Here we use molecular dynamics to study the biophysics of the interface of the omicron spike protein binding to (i) the ACE2 receptor protein, (ii) antibodies from all known binding regions, and (iii) the furin binding domain. Our simulations suggest that while there is significant reduction of antibody binding strength corresponding to escape, the omicron spike pays a cost in terms of weaker receptor binding. The furin cleavage domain is the same or weaker binding than the alpha variant, suggesting less viral load and disease intensity than the extant delta variant. Competing Interest Statement M.Z. Jawaid received summer research support via a gift from Protein Architects Corp to UC Davis.

We demonstrate that AlphaFold and AlphaFold Multimer, implemented within the ColabFold suite, can accurately predict the structures of the furin enzyme with known six residue inhibitory peptides. Noting the similarity of the peptide inhibitors to polybasic furin cleavage domain insertion region of the SARS-CoV-2, which begins at P681, we implement this approach to study the wild type furin cleavage domain for the virus and several mutants. We introduce mutations in silico for alpha, omicron, and delta variants, for several sequences which have been rarely observed, for sequences which have not yet been observed, for other coronaviruses (NL63, OC43, HUK1a, HUK1b, MERS, and 229E), and for the H5N1 flu. We show that interfacial hydrogen bonds between the furin cleavage domain and furin are a good measure of binding strength that correlate well with endpoint binding free energy estimates, and conclude that among all candidate viral sequences studied, delta is near the very top binding strength within statistical accuracy. However, the binding strength of several rare sequences match delta within statistical accuracy. We find that the furin S1 pocket is optimized for binding arginine as opposed to lysine. This residue, typically at sequence position five, contains the most hydrogen bonds to the furin, and hydrogen bond count for just this residue shows a strong positive correlation with the overall hydrogen bond count . We demonstrate that the root mean square backbone C-alpha fluctuation of the first residue in the furin cleavage domain has a strong negative correlation with the interfacial hydrogen bond count. We show by considering the variation with the number of basic residues that the maximum mean number of interfacial hydrogen bonds expected is 15.7 at 4 basic residues. Competing Interest Statement M.Z. Jawaid received summer support from a gift to UC Davis by Protein Architects. G.G. receives support from a gift to UC Davis by Protein Architects. RLD and DLC are officers of Protein Architects but have received no support from this study. Footnotes * https://dlcox.files.wordpress.com/2022/01/furin_cleavage_domain-si.pdf