Faculty Bibliography

This work describes the synthesis, characterization, and preliminary evaluation of the anti-Plasmodium falciparum activity of a copper(II) coordination-complex derived from an imidazole-based ligand. This compound was characterized by Infrared, UV-Vis, Raman, high resolution mass spectrometry, fluorescence, Thermogravimetric analysis, and electrical conductivity allowing the elucidation of their structure and which was also confirmed by single-crystal X-ray diffraction. From the crystallographic analysis, it was found that the copper atom is situated in an octahedral environment, with both carboxylate ligands occupying equatorial positions and the ligands L located axially. Interestingly, the acetate ions act as bidentate ligands, but in an anisobidentate binding mode, where the oxygen atoms exhibit different bond distances to the metal center, resulting in asymmetric coordination. This phenomenon is attributed to strong hydrogen bonding within the crystal packing. Biological assays performed to test the complex revealed low hemocytotoxicity, with values ≤20% at concentrations above 500 µg/mL. When evaluated in vitro against Plasmodium falciparum (3D7 strain, chloroquine-sensitive), the complex exhibited significantly higher activity than the free ligand. These findings indicate that coordination to the metal center plays a substantial role in enhancing antiparasitic-activity, providing a solid foundation for future investigations aimed at elucidating the underlying mechanisms and advancing research on the anti-Plasmodium falciparum activity of metal complexes.

As the population ages, the incidence and prevalence of musculoskeletal degeneration, such as osteoarthritis, increase. While the currently accepted treatment options provide symptomatic and functional improvement, they do not halt the progression of osteoarthritis. This results in the eventual need for surgery for many patients with advanced osteoarthritis. Due to the seemingly inevitable progression of OA, many clinicians and researchers have shifted their focus to regenerative therapies. Orthobiologics, a specific type of regenerative therapy designed to treat orthopedic conditions, has been gaining traction in recent years due to the utilization of autologous biological substances and synthetic peptides in healing musculoskeletal injuries and degenerative conditions. Orthobiologics can be distinguished into one of four classes: cell-based, biologic fluids-based, matrix-based, molecular-based, and based on their composition. In this review, key examples of each class, mechanism of action, and current clinical data for each agent are examined. Limitations of current orthobiologics involve a lack of standardization in the preparation and administration of each agent, as well as uniformity in assessment endpoints across different clinical studies. Lastly, we will discuss future directions of orthobiologics as a therapy for the treatment of osteoarthritis.

INTRODUCTION/UNASSIGNED:To ensure Alzheimer's disease-modifying treatments can be initiated in diverse populations, efficient pathways to obtain timely diagnoses are required. METHODS/UNASSIGNED:This interim sub-analysis of a multicenter US study included cross-sectional surveys and interviews with neurologists at 12 diverse sites to assess real-world lecanemab use. RESULTS/UNASSIGNED:testing to inform risk/benefit decisions. Infusions usually started within 6 months of diagnosis. Delayed/incomplete referrals were identified as the most significant barrier in the current patient pathway. DISCUSSION/UNASSIGNED:These findings demonstrate the feasibility of lecanemab integration in diverse clinical settings and highlight the importance of primary care physician engagement, optimization of referral pathways, and expanding BBM use in improving timely diagnosis, equitable access, and early treatment initiation.

Many individuals hospitalized due to severe viral infections develop mental and physical sequelae, which could potentially be prevented by targeted interventions for those at risk. Our goal was to develop and externally validate an algorithm for predicting mental and physical symptoms after SARS-CoV-2 hospitalization utilizing routinely collected clinical data. Participants were included from two independent samples of the German National Pandemic Cohort Network (NAPKON): a model development sample (SUEP; N = 451; mean age: 55.6 ± 15.3; 36.2% female) and an external validation sample (HAP: N = 158; mean age: 55.1 ± 12.1; 39.9% female). Machine learning models leveraging demographic, clinical and biological variables collected at the time of admission were employed to predict Patient-Reported Outcomes Measurement Information System scores (PROMIS) across 7 domains (physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities, and pain) three months after SARS-CoV-2 hospitalization. Shapley Additive exPlanation values were used to provide interpretable information about key predictive factors. Approximately 15-20% of participants reported moderate to severe impairment in at least one PROMIS domain three months after hospitalization. For the mental health composite score, the best-performing model achieved RMSE = 1.833 ± 0.341 and R² = 0.927 ± 0.031 in SUEP and RMSE = 3.131 and R² = 0.893 in HAP. For the physical health composite, the best-performing model achieved RMSE = 2.908 ± 0.703 and R² = 0.824 ± 0.052 in SUEP and RMSE = 3.019 and R² = 0.850 in HAP. Furthermore, the models achieved high predictive performance across all individual PROMIS domain scores in both samples. We provide an externally validated methodology for accurately predicting mental and physical symptomatology following hospitalization due to a severe viral infection. This approach may facilitate the development of a brief risk stratification tool at the point of hospitalization, enabling early identification of at-risk patients, improving the prediction accuracy of subsequent psychological and physical sequelae, and supporting timely preventive interventions.

CONTEXT/UNASSIGNED:A subset of metabolic diseases is caused by rare monogenic variants. Next-generation sequencing offers a promising approach for identifying such variants, but its application in clinical diagnostics for metabolic disease is limited and the diagnostic yield is unknown. OBJECTIVE/UNASSIGNED:To determine the diagnostic yield of clinical genome sequencing (GS) in adults presenting with common metabolic diseases. METHODS/UNASSIGNED:We performed clinical GS on 560 adults seen in New York clinical practices between August 2020 and December 2023. Participants presented with hyperlipidemia/hypertriglyceridemia (HLD/HTG), pre-diabetes, Type 2 diabetes mellitus (T2DM), and/or metabolic dysfunction-associated fatty liver disease/steatohepatitis (MAFLD/MASH). Variants in a curated set of 90 genes associated with monogenic forms of these conditions were classified as Pathogenic (P), Likely Pathogenic (LP), or Variant of Uncertain Significance (VUS) using ACMG/ClinGen guidelines. P/LP variants in ACMG secondary findings (v3.1) genes were also reported with participant consent. RESULTS/UNASSIGNED:The cohort had a female-to-male ratio of 1.7, with 18.6% African American and 22.6% Latino participants. The most common enrollment diagnoses were HLD/HTG (25%), T2DM (9%), pre-diabetes (7%), and MAFLD/MASH (4%). Many participants had multiple conditions (42% with two, 12% with three). Approximately one-third had reportable variants, with 6% classified as P/LP. The most common P/LP variants were in APOB and LDLR. CONCLUSION/UNASSIGNED:The prevalence of clinically significant (P/LP) variants related to primary metabolic disease in this cohort was 6%. An additional 5.5% of participants had P/LP variants in ACMG secondary findings genes. Future studies should refine participant selection for genome sequencing to optimize its diagnostic and clinical value.

Patients with paroxysmal nocturnal hemoglobinuria (PNH) on anti-C5 often experience extravascular hemolysis with anemia. Iptacopan, the first oral proximal complement inhibitor targeting factor B, has shown efficacy and safety in PNH patients. APPULSE-PNH (NCT05630001), a phase 3b, single‑arm, open-label trial, enrolled adult patients with PNH and hemoglobin ≥10 g/dL on stable anti-C5 for ≥6 months. Patients switched to iptacopan monotherapy (200 mg twice daily; 24 weeks). Primary endpoint: mean hemoglobin change from baseline across four visits (Days 126-168). At baseline, 57.7% of patients had elevated absolute reticulocyte counts (ARCs; above ULN = 123 × 10⁹/L) and 50% had C3 deposition on red blood cells (RBCs) >10%, indicative of extravascular hemolysis. There was a statistically significant increase in hemoglobin during the trial; adjusted mean change from baseline (95% CI) was +2.0 g/dL (1.7-2.3) overall, and in patients with baseline hemoglobin <12 g/dL and ≥12 g/dL, +2.4 (2.0-2.7) and +1.4 (1.0-1.8), respectively. Patients maintained transfusion independence, 92.7% with hemoglobin ≥12 g/dL. Adjusted mean change from baseline (95% CI) in lactate dehydrogenase and ARC were -1.3% (-6.6 to 4.3) and -89.2 × 10⁹/L (-95.5 to -82.9), respectively. Mean (SD) proportion of C3d+ PNH RBCs, assessed by flow cytometry, decreased from 11.0% (8.6) to 0.2% (0.7) at Day 168. No patients had breakthrough hemolysis or major adverse vascular events. FACIT-Fatigue and treatment satisfaction scores improved by Days 84 and 168. Safety showed consistency with previous iptacopan PNH trials. Iptacopan improved hematologic outcomes in PNH patients with hemoglobin ≥10 g/dL on anti-C5, maintaining control of intravascular hemolysis and resolving extravascular hemolysis.

Existence of linguistic, gender and ethno-racial differences in patients with sepsis remains relatively unknown, especially in the public health domain. Retrospective analysis of data reported by a hospital in South Brooklyn to a New York State sepsis registry was undertaken over a 24-month period. Inclusion criteria were age over 18, available linguistic, gender and ethno-racial data, and registration in the New York State sepsis registry. Patients with missing data fields were excluded from the study. Primary outcome was the correlation of gender, race, ethnic & language-based differences with overall sepsis-based mortality. Secondary outcomes were the correlation of the same demographic variables with rates of mechanical ventilation, vasopressor use, intensive care unit (ICU) admission rates & overall incidence of sepsis and septic shock. Results: 677 patients were included in the final analysis in this single center retrospective observational cohort study and multiple statistically significant primary and secondary outcomes were found. Non-English-speaking patients had a higher incidence rate of sepsis-based mortality when compared to their English-speaking cohorts. The incidence rate difference is -0.36 (95% CI -0.49 to -0.22), with a P-value < 0.0001. A higher rate of vasopressor use was noted among non-English speaking patients when compared to their English speaking counterparts. The difference in incidence rates was -0.35, (95% CI -0.46 to -0.25) with a P-value of < 0.0001. Non-English-speaking patients had a higher incidence of receiving mechanical ventilation when compared to English-speaking cohorts. The incidence rate difference is -0.35 (95% CI -0.48 to -0.22), with a P-value < 0.0001. Non-English-speaking patients had a higher ICU admission rate with an incidence rate difference of -0.30, at a P value < 0.0001. Non-English-speaking patients had a higher sepsis incidence rate (0.70, 95% CI 0.63 to 0.78) compared to English-speaking patients (0.30, 95% CI 0.25 to 0.36), with a P-value of < 0.0001. Non-English-speaking patients experienced a higher incidence of septic shock (0.70, 95% CI 0.63 to 0.78) compared to English-speaking patients (0.30, 95% CI 0.25 to 0.36), with a P-value of < 0.0001. Caucasians showed statistically significant and higher rates across all primary and secondary outcomes albeit with greater statistical fragility. No significant differences were noted with regards to the impact of gender on all outcomes. Conclusion: Significant and multiple linguistic and ethno-racial differences were noted in this single center study with regards to sepsis-based morbidity and mortality outcomes. These differences need to be validated in larger, multi-center trials and could inform future efforts focused on identifying higher risk subsets in patients presenting with sepsis and septic shock in a public health setting.

BackgroundPostoperative care following endoscopic sinus surgery (ESS) aims to optimize mucosal healing, reduce inflammation, and minimize infectious complications. Although saline irrigation is considered standard of care, the potential benefit of adding topical antibiotics, such as mupirocin, during the early postoperative period remains uncertain.ObjectiveTo evaluate whether short-term postoperative mupirocin nasal irrigation improves clinical, endoscopic, and microbiological outcomes compared with saline irrigation alone following ESS.MethodsThis prospective, randomized, double-blinded, placebo-controlled trial included adults with chronic rhinosinusitis undergoing ESS. Patients were randomized to receive either mupirocin (0.05%) nasal irrigation or placebo saline irrigation twice daily for 21 days postoperatively. Outcomes assessed within the first 3 months included patient-reported symptoms using the sinonasal outcomes test (SNOT-22) and visual analog scale (VAS), endoscopic findings (mucosal edema, polyp formation, crusting, granulation tissue, and purulence), postoperative sinus culture results, and need for systemic antibiotics.ResultsSixty-eight patients were enrolled, and 56 completed follow-up. Both groups demonstrated significant postoperative improvement in SNOT-22 and VAS scores compared with preoperative baseline, without significant between-group differences. However, the mupirocin group showed significantly lower rates of endoscopic mucosal edema and polyp formation at 1 month postoperatively. Negative postoperative cultures were also more frequent in the mupirocin group, with reduced need for systemic oral antibiotics. No significant differences were observed in crusting, granulation tissue, purulence, steroid use, or pain medication requirements.ConclusionShort-term prophylactic postoperative mupirocin nasal irrigation after ESS does not confer additional improvement in patient-reported quality-of-life outcomes compared with saline alone but appears to reduce early inflammatory endoscopic changes, bacterial culture positivity, and need for systemic antibiotics. Larger studies with longer follow-up are needed to confirm these findings.