High Failure Rates for Unicompartmental Knee Arthroplasty in Morbidly Obese Patients: A Two-Year Minimum Follow-Up Study.

BACKGROUND: Several recent studies have recommended offering unicompartmental knee arthroplasty (UKA) to all patients regardless of body mass index (BMI). The aim of this investigation was to evaluate the proposition that UKA can indeed be offered to the morbidly-obese and super-obese (morbidly-obese, BMI ≥ 40 kg/m2) without compromising results or survivorship. METHODS: We retrospectively reviewed mobile-bearing medial UKA procedures performed at our facility from January 2012 to May 2015 with a minimum of 2-year follow-up. The study cohort was divided into patients with morbid obesity (BMI ≥ 40 kg/m2) and those without morbid obesity (BMI < 40 kg/m2). A detailed medical record review was performed. Extracted outcome data included the frequency of (1) major revision procedures (components revised), (2) minor secondary procedures (components not revised), (3) infection procedures, and (4) recommendations for revision. RESULTS: We found 152 patients (190 knees) who met criteria for inclusion. Mean follow-up duration was 3.4 years (range: 2.0-6.8 years). Major revision surgery occurred more frequently in the morbid-obesity UKA group (15.7% vs 3.0%, P < .01). Rates of minor secondary surgery and infection were comparable for both groups. Most failures in the morbid-obesity UKA group (85.7%) were due to disease progression involving other compartments or mobile-bearing instability. CONCLUSION: We found the rate of early major revision surgery in morbidly-obese patients undergoing UKA to be over 5-times greater than that of other patients. Failure was predominantly due to disease progression in other compartments or mobile-bearing instability. Further study is warranted and needed before expanding UKA indications to the morbidly-obese population.

A web-based tool to predict acute kidney injury in patients with ST-elevation myocardial infarction: Development, internal validation and comparison.

BACKGROUND: In ST-elevation myocardial infarction (STEMI), acute kidney injury (AKI) may increase subsequent morbidity and mortality. Still, it remains difficult to predict AKI risk in these patients. We sought to 1) determine the frequency and clinical outcomes of AKI and, 2) develop, validate and compare a web-based tool for predicting AKI. METHODS & FINDINGS: In a racially diverse series of 1144 consecutive STEMI patients, Stage 1 or greater AKI occurred in 12.9% and was severe (Stage 2-3) in 2.9%. AKI was associated with increased mortality (5.7-fold, unadjusted) and hospital stay (2.5-fold). AKI was associated with systolic dysfunction, increased left ventricular end-diastolic pressures, hypotension and intra-aortic balloon counterpulsation. A computational algorithm (UT-AKI) was derived and internally validated. It showed higher sensitivity and improved overall prediction for AKI (area under the curve 0.76) vs. other published indices. Higher UT-AKI scores were associated with more severe AKI, longer hospital stay and greater hospital mortality. CONCLUSIONS: In a large, racially diverse cohort of STEMI patients, Stage 1 or greater AKI was relatively common and was associated with significant morbidity and mortality. A web-accessible, internally validated tool was developed with improved overall value for predicting AKI. By identifying patients at increased risk, this tool may help physicians tailor post-procedural diagnostic and therapeutic strategies after STEMI to reduce AKI and its associated morbidity and mortality.

Nanoparticle formulation of ormeloxifene for pancreatic cancer.

Pancreatic cancer is the fourth most prevalent cancer with about an 85% mortality rate; thus, an utmost need exists to discover new therapeutic modalities that would enhance therapy outcomes of this disease with minimal or no side effects. Ormeloxifene (ORM), a synthetic molecule, has exhibited potent anti-cancer effects through inhibition of important oncogenic and proliferation signaling pathways. However, the anti-cancer efficacy of ORM can be further improved by developing its nanoformulation, which will also offer tumor specific targeted delivery. Therefore, we have developed a novel ORM encapsulated poly(lactic-co-glycolic acid) nanoparticle (NP) formulation (PLGA-ORM NP). This formulation was characterized for particle size, chemical composition, and drug loading efficiency, using various physico-chemical methods (TEM, FT-IR, DSC, TGA, and HPLC). Because of its facile composition, this novel formulation is compatible with antibody/aptamer conjugation to achieve tumor specific targeting. The particle size analysis of this PLGA-ORM formulation (∼100 nm) indicates that this formulation can preferentially reach and accumulate in tumors by the Enhanced Permeability and Retention (EPR) effect. Cellular uptake and internalization studies demonstrate that PLGA-ORM NPs escape lysosomal degradation, providing efficient endosomal release to cytosol. PLGA-ORM NPs showed remarkable anti-cancer potential in various pancreatic cancer cells (HPAF-II, AsPC-1, BxPC-3, Panc-1, and MiaPaca) and a BxPC-3 xenograft mice model resulting in increased animal survival. PLGA-ORM NPs suppressed pancreatic tumor growth via suppression of Akt phosphorylation and expression of MUC1, HER2, PCNA, CK19 and CD31. This study suggests that the PLGA-ORM formulation is highly efficient for the inhibition of pancreatic tumor growth and thus can be valuable for the treatment of pancreatic cancer in the future.