Continuation of Oral Antidiabetic Medications Was Associated With Better Early Postoperative Blood Glucose Control Compared to Sliding Scale Insulin After Total Knee Arthroplasty.

BACKGROUND: This study evaluated blood glucose (BG), creatinine levels, metabolic issues, length of stay (LOS), and early postoperative complications in diabetic primary total knee arthroplasty (TKA) patients. It examined those who continued home oral antidiabetic medications and those who switched to insulin postoperatively. The hypothesis was that continuing home medications would lead to lower BG levels without metabolic abnormalities. METHODS: Patients who had diabetes who underwent primary TKA from 2013 to 2022 were evaluated retrospectively. Diabetic patients who were not on home oral antidiabetic medications or who were not managed as an inpatient postoperatively were excluded. Patient demographics and laboratory tests collected preoperatively and postoperatively as well as 90-day emergency department visits and 90-day readmissions, were pulled from electronic records. Patients were grouped based on inpatient diabetes management: continuation of home medications versus new insulin coverage. Acute postoperative BG control, creatinine levels, metabolic abnormalities, LOS, and early postoperative complications were compared between groups. Multivariable regression analyses were performed to measure associations. RESULTS: A total of 867 primary TKAs were assessed; 703 (81.1%) patients continued their home oral antidiabetic medications. Continuing home antidiabetic medications demonstrated lower median maximum inpatient BG (180.0 mg/dL versus 250.0 mg/dL; P < .001) and median average inpatient BG (136.7 mg/dL versus 173.7 mg/dL; P < .001). Logistic regression analyses supported the presence of an association (odds ratio = 17.88 [8.66, 43.43]; P < .001). Proportions of acute kidney injury (13.5 versus 26.7%; P < .001) were also lower. There was no difference in relative proportions of metabolic acidosis (4.4 versus 3.7%; P = .831), LOS (2.0 versus 2.0 days; P = .259), or early postoperative complications. CONCLUSIONS: Continuing home oral antidiabetic medications after primary TKA was associated with lower BG levels without an associated worsening creatinine or increase in metabolic acidosis. LEVEL III EVIDENCE: Retrospective Cohort Study.

Diversity Within the Field of Orthopedic Sports Medicine: A Systematic Review.

BACKGROUND: Orthopedic surgery is among the least diverse specialties in medicine. This systematic review analyzes gender, racial, and ethnic diversity within orthopedic sports medicine and aims to raise awareness and provide guidance for future strategies that support underrepresented minorities in medicine (URMs) and women in joining the orthopedic sports medicine workforce. We hypothesize that at all tiers of training, there is a lack of gender, racial, and ethnic parity in academic rank, leadership positions, and research productivity. METHODS: A search of all published literature in the English language from PubMed, Embase, Cochrane, and Scopus databases, between January 1, 2010, and August 18, 2023, was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included studies presented demographics regarding diversity within orthopedic sports medicine and provided trends in applicants, attendings, leadership, and/or research. Bias was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) study checklist. RESULTS: Thirteen studies published between 2016 and 2023 with STROBE scores 15.5 to 21.5 (70.5% to 97.7%) met criteria, and pertinent data were extracted. The percent of female orthopedic sports medicine surgeons from 2010 to 2019 increased from 5% (n = 138) to 6% (n = 206) with a compound annual growth rate of 0.2% (r2 = 0.97; p < 0.001). Females and URMs are underrepresented at the highest levels of orthopedic sports medicine leadership including department chair (female: 0% [n = 0]), division chief (female: 4% [n = 4]; URM: 3% [n = 3]), and fellowship director (female: 3.3% [n = 3]; URM: 4.4% [n = 4]). Studies from prominent orthopedic sports medicine journals (American Journal of Sports Medicine, Arthroscopy, Journal of Shoulder and Elbow Surgery, and Sports Health) show a 12.1% increase in female involvement in orthopedic sports medicine research from 1972 to 2018; however, this increase captures 59.3% (n = 2,953) females with degrees other than an MD. CONCLUSIONS: Although increasingly more females and underrepresented minorities are joining orthopedic sports medicine, the rate of diversification remains slow and current involvement in leadership and research is minimal. Targeted efforts aimed at increasing research opportunities and inspiring interest through mentorship for URMs and females in orthopedics is essential to drive change toward parity. LEVEL OF EVIDENCE: Level IV. Systematic Review. See Instructions for Authors for a complete description of levels of evidence.

Arthroscopy and Microfracture for Osteochondritis Dissecans of the Capitellum in Adolescent Athletes Shows Favorable Return to Sport: A Systematic Review.

PURPOSE: To assess return to sport (RTS) in the high-risk young athlete population with capitellar osteochondritis dissecans (OCD) undergoing arthroscopic microfracture (MFX) with or without debridement as well as associated indications, clinical outcomes, radiographic outcomes, and complications. METHODS: A literature search of all published literature in the English language from PubMed, EMBASE, Scopus, and Cochrane from database inception to April 4, 2022, was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included studies presented demographics and outcomes for adolescent (<21 years old) patients diagnosed with capitellar OCD who underwent arthroscopic MFX (or drilling/subchondral drilling) or MFX (or drilling/subchondral drilling) with debridement (or loose body removal/chondroplasty). Studies containing multiple surgical techniques that did not distinguish characteristics and outcomes of individual patients by surgical technique were excluded. Additionally, if there was overlap in patient populations between 2 studies, the study with less outcome data was excluded. Extracted data included study properties, patient demographics, lesion characteristics, surgery details, and patient outcomes, including range of motion, outcome scores, and RTS rates. Bias was assessed via the Methodological Index for Non-Randomized Studies (MINORS). RESULTS: Nine studies of 136 patients and 138 elbows met criteria. Included articles were published between 2005 and 2020 with MINORS scores of 8 to 14 (50% to 88%). The age ranged from 12.7 to 15.7 years with most patients being involved in baseball or gymnastics and a rate of dominant elbow involvement of 55% to 100%. Patient follow-up ranged from 16 to 138 months. All 9 studies reported RTS, ranging from 65% to 100%. Six of these studies categorized the level to which the patient returned, with patients RTS at the same level of competition ranging from 60% to 100%. Six studies reported complications, with a range rate of 0% to 43%; there were a total of 10 complications, 7 of which required reoperations. CONCLUSIONS: Arthroscopic MFX with or without arthroscopic debridement is a safe and effective treatment for OCD lesions of the capitellum in young, athletic patients. Included studies reported improved clinical, radiographic, and patient-reported outcomes. Aside from 1 study reporting an RTS of 65%, the rate of RTS ranged from 86% to 100%. The percentage of patients returning to sport at the same level of competition ranged from 60% to 100% with a time to RTS ranging from 4.1 to 5 months. A single study reported a complication rate of 43%, while remaining studies reported complication rates between 0% and 19%, with loose bodies being the most common complication requiring reoperation. Follow-up ranged from 16 to 138 months.

Arthroscopic treatment for intra-articular fibroma of the tendon sheath in a teenager.

An adolescent female patient presented with atraumatic left knee pain and limited flexion. MRI demonstrated evidence of a soft tissue lesion abutting the posterior cruciate ligament. Differential diagnosis included pigmented villonodular synovitis (PVNS) and fibroma of the tendon sheath (FTS). Following arthroscopic biopsy, histopathological evaluation confirmed FTS. The tumour was then excised via an arthroscopic approach. This case report provides a unique example of FTS abutting the cruciate ligaments in an uncommonly young female patient. It highlights the importance of including benign processes, such as FTS, in the differential with more aggressive-type diagnoses like PVNS. Furthermore, this case exemplifies an appropriate surgical indication for FTS. Finally, it emphasises the importance of communication and collaboration among orthopaedic subspecialists in providing safe and effective arthroscopic treatment of this unique tumour presentation.

Nuclear Lamin A/C Expression Is a Key Determinant of Paclitaxel Sensitivity.

Paclitaxel is a key member of the Taxane (paclitaxel [originally named taxol], docetaxel/Taxotere) family of successful drugs used in the current treatment of several solid tumors, including ovarian cancer. The molecular target of paclitaxel has been identified as tubulin, and paclitaxel binding alters the dynamics and thus stabilizes microtubule bundles. Traditionally, the anticancer mechanism of paclitaxel has been thought to originate from its interfering with the role of microtubules in mitosis, resulting in mitotic arrest and subsequent apoptosis. However, recent evidence suggests that paclitaxel operates in cancer therapies via an as-yet-undefined mechanism rather than as a mitotic inhibitor. We found that paclitaxel caused a striking break up of nuclei (referred to as multimicronucleation) in malignant ovarian cancer cells but not in normal cells, and susceptibility to undergo nuclear fragmentation and cell death correlated with a reduction in nuclear lamina proteins, lamin A/C. Lamin A/C proteins are commonly lost, reduced, or heterogeneously expressed in ovarian cancer, accounting for the aberration of nuclear shape in malignant cells. Mouse ovarian epithelial cells isolated from lamin A/C-null mice were highly sensitive to paclitaxel and underwent nuclear breakage, compared to control wild-type cells. Forced overexpression of lamin A/C led to resistance to paclitaxel-induced nuclear breakage in cancer cells. Additionally, paclitaxel-induced multimicronucleation occurred independently of cell division that was achieved by either the withdrawal of serum or the addition of mitotic inhibitors. These results provide a new understanding for the mitotis-independent mechanism for paclitaxel killing of cancer cells, where paclitaxel induces nuclear breakage in malignant cancer cells that have a malleable nucleus but not in normal cells that have a stiffer nuclear envelope. As such, we identify that reduced nuclear lamin A/C protein levels correlate with nuclear shape deformation and are a key determinant of paclitaxel sensitivity of cancer cells.

Host-Informed Expression of CRISPR Guide RNA for Genomic Engineering in Komagataella phaffii.

There is growing interest in the use of nonmodel microorganisms as hosts for biopharmaceutical manufacturing. These hosts require genomic engineering to meet clinically relevant product qualities and titers, but the adaptation of tools for editing genomes, such as CRISPR-Cas9, has been slow for poorly characterized hosts. Specifically, a lack of biochemical characterization of RNA polymerase III transcription has hindered reliable expression of guide RNAs in new hosts. Here, we present a sequencing-based strategy for the design of host-specific cassettes for modular, reliable, expression of guide RNAs. Using this strategy, we achieved up to 95% gene editing efficiency in the methylotrophic yeast Komagataella phaffii. We applied this approach for the rapid, multiplexed engineering of a complex phenotype, achieving humanized product glycosylation in two sequential steps of engineering. Reliable extension of simple gene editing tools to nonmodel manufacturing hosts will enable rapid engineering of manufacturing strains tuned for specific product profiles and potentially decrease the costs and timelines for process development.