Granulosa cell metabolism at ovulation correlates with oocyte competence and is disrupted by obesity and aging.

STUDY QUESTION: Is oocyte developmental competence associated with changes in granulosa cell (GC) metabolism? SUMMARY ANSWER: GC metabolism is regulated by the LH surge, altered by obesity and reproductive aging, and, in women, specific metabolic profiles are associated with failed fertilization versus increased blastocyst development. WHAT IS KNOWN ALREADY: The cellular environment in which an oocyte matures is critical to its future developmental competence. Metabolism is emerging as a potentially important factor; however, relative energy production profiles between GCs and cumulus cells and their use of differential substrates under normal in vivo ovulatory conditions are not well understood. STUDY DESIGN, SIZE, DURATION: This study identified metabolic and substrate utilization profiles within ovarian cells in response to the LH surge, using mouse models and GCs of women undergoing gonadotropin-induced oocyte aspiration followed by IVF/ICSI. PARTICIPANTS/MATERIALS, SETTING, METHODS: To comprehensively assess follicular energy metabolism, we used real-time metabolic analysis (Seahorse XFe96) to map energy metabolism dynamics (mitochondrial respiration, glycolysis, and fatty acid oxidation) in mouse GCs and cumulus-oocyte complexes (COCs) across a detailed time course in the lead up to ovulation. In parallel, the metabolic profile of GCs was measured in a cohort of 85 women undergoing IVF/ICSI (n = 21 with normal ovarian function; n = 64 with ovarian infertility) and correlated with clinical parameters and cycle outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: Our study reveals dynamic changes in GC energy metabolism in response to ovulatory LH, with mitochondrial respiration and glycolysis differentially affected by obesity versus aging, in both mice and women. High respiration in GCs is associated with failed fertilization (P < 0.05) in a subset of women, while glycolytic reserve and mitochondrial ATP production are correlated with on-time development at Day 3 (P < 0.05) and blastocyst formation (P < 0.01) respectively. These data provide new insights into the cellular mechanisms of infertility, by uncovering significant associations between metabolism within the ovarian follicle and oocyte developmental competence. LIMITATIONS, REASONS FOR CAUTION: A larger prospective study is needed before the metabolic markers that were positively and negatively associated with oocyte quality can be used clinically to predict embryo outcomes. WIDER IMPLICATIONS OF THE FINDINGS: This study offers new insights into the importance of GC metabolism for subsequent embryonic development and highlights the potential for therapeutic strategies focused on optimizing mitochondrial metabolism to support embryonic development. STUDY FUNDING/COMPETING INTEREST(S): National Health and Medical Research Council (Australia). The authors have no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Physeal Closure and Fracture Pattern in Adolescent Transitional Distal Radius Fractures.

PURPOSE: To show a correlation between grade of physeal closure and fracture pattern in adolescent transitional distal radius fractures. METHODS: A retrospective chart review was performed of 490 distal radius fractures, ages 14 to 18, at a single institution between 2007 and 2020. A board-certified orthopaedic hand surgeon reviewed all images. Thirty-six distal-radius fractures were considered adolescent transitional fractures. The review included Salter-Harris classification, fracture fragments, and grade of physeal closure. RESULTS: Distal radial physeal closure is 50 times more likely to be of a higher grade in the presence of Salter-Harris type IV fractures ( P <0.001). Closure of the physis is also 7.37 and 13.08 times more likely to be of higher grade in the absence of a dorsal metaphyseal fracture and in the presence of an ulnar corner fracture, respectively ( P =0.011 and 0.021). CONCLUSION: Adolescent transitional fractures of the distal radius occur when the growth plate has a partial closure. The closure pattern of the distal radial physis begins centrally, with subsequent ulnar and then radial closure. In this cohort, there is a correlation between grade of physeal closure and fracture pattern in adolescent transitional distal radius fractures. LEVEL OF EVIDENCE: Level IV-diagnostic.

Obesity and oocyte quality: significant implications for ART and emerging mechanistic insights.

The prevalence of obesity in adults worldwide, and specifically in women of reproductive age, is concerning given the risks to fertility posed by the increased risk of type 2 diabetes, metabolic syndrome, and other noncommunicable diseases. Obesity has a multi-systemic impact in female physiology that is characterized by the presence of oxidative stress, lipotoxicity, and the activation of pro-inflammatory pathways, inducing tissue-specific insulin resistance and ultimately conducive to abnormal ovarian function. A higher body mass is linked to Polycystic Ovary Syndrome, dysregulated menstrual cycles, anovulation, and longer time to pregnancy, even in ovulatory women. In the context of assisted reproductive technology (ART), compared to women of normal body mass index, obese women have worse outcomes in every step of their journey, resulting in reduced success measured as live birth rate. Even after pregnancy is achieved, obese women have a higher chance of miscarriage, gestational diabetes, pregnancy complications, birth defects, and most worryingly, a higher risk of stillbirth and neonatal death. The potential for compounding effects of ART on pregnancy complications and infant morbidities in obese women has not been studied. There is still much debate in the field on whether these poorer outcomes are mainly driven by defects in oocyte quality, abnormal embryo development, or an unaccommodating uterine environment, however the clinical evidence to date suggests a combination of all three are responsible. Animal models of maternal obesity shed light on the mechanisms underlying the effects of obesity on the peri-conception environment, with recent findings pointing to lipotoxicity in the ovarian environment as a key driver of defects in oocytes that have not only reduced developmental competence but long-lasting effects in offspring health.

Non-invasive, label-free optical analysis to detect aneuploidy within the inner cell mass of the preimplantation embryo.

STUDY QUESTION: Can label-free, non-invasive optical imaging by hyperspectral autofluorescence microscopy discern between euploid and aneuploid cells within the inner cell mass (ICM) of the mouse preimplantation embryo? SUMMARY ANSWER: Hyperspectral autofluorescence microscopy enables discrimination between euploid and aneuploid ICM in mouse embryos. WHAT IS KNOWN ALREADY: Euploid/aneuploid mosaicism affects up to 17.3% of human blastocyst embryos with trophectoderm biopsy or spent media currently utilized to diagnose aneuploidy and mosaicism in clinical in vitro fertilization. Based on their design, these approaches will fail to diagnose the presence or proportion of aneuploid cells within the foetal lineage ICM of some blastocyst embryos. STUDY DESIGN, SIZE, DURATION: The impact of aneuploidy on cellular autofluorescence and metabolism of primary human fibroblast cells and mouse embryos was assessed using a fluorescence microscope adapted for imaging with multiple spectral channels (hyperspectral imaging). Primary human fibroblast cells with known ploidy were subjected to hyperspectral imaging to record native cell fluorescence (4-6 independent replicates, euploid n = 467; aneuploid n = 969). For mouse embryos, blastomeres from the eight-cell stage (five independent replicates: control n = 39; reversine n = 44) and chimeric blastocysts (eight independent replicates: control n = 34; reversine n = 34; 1:1 (control:reversine) n = 30 and 1:3 (control:reversine) n = 37) were utilized for hyperspectral imaging. The ICM from control and reversine-treated embryos were mechanically dissected and their karyotype confirmed by whole genome sequencing (n = 13 euploid and n = 9 aneuploid). PARTICIPANTS/MATERIALS, SETTING, METHODS: Two models were employed: (i) primary human fibroblasts with known karyotype and (ii) a mouse model of embryo aneuploidy where mouse embryos were treated with reversine, a reversible spindle assembly checkpoint inhibitor, during the four- to eight-cell division. Individual blastomeres were dissociated from control and reversine-treated eight-cell embryos and either imaged directly or used to generate chimeric blastocysts with differing ratios of control:reversine-treated cells. Individual blastomeres and embryos were interrogated by hyperspectral imaging. Changes in cellular metabolism were determined by quantification of metabolic co-factors (inferred from their autofluorescence signature): NAD(P)H and flavins with the subsequent calculation of the optical redox ratio (ORR: flavins/[NAD(P)H + flavins]). Autofluorescence signals obtained from hyperspectral imaging were examined mathematically to extract features from each cell/blastomere/ICM. This was used to discriminate between different cell populations. MAIN RESULTS AND THE ROLE OF CHANCE: An increase in the relative abundance of NAD(P)H and decrease in flavins led to a significant reduction in the ORR for aneuploid cells in primary human fibroblasts and reversine-treated mouse blastomeres (P < 0.05). Mathematical analysis of endogenous cell autofluorescence achieved separation between (i) euploid and aneuploid primary human fibroblast cells, (ii) control and reversine-treated mouse blastomeres cells, (iii) control and reversine-treated chimeric blastocysts, (iv) 1:1 and 1:3 chimeric blastocysts and (v) confirmed euploid and aneuploid ICM from mouse blastocysts. The accuracy of these separations was supported by receiver operating characteristic curves with areas under the curve of 0.97, 0.99, 0.87, 0.88 and 0.93, respectively. We believe that the role of chance is low as mathematical features separated euploid from aneuploid in both human fibroblasts and ICM of mouse blastocysts. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Although we were able to discriminate between euploid and aneuploid ICM in mouse blastocysts, confirmation of this approach in human embryos is required. While we show this approach is safe in mouse, further validation is required in large animal species prior to implementation in a clinical setting. WIDER IMPLICATIONS OF THE FINDINGS: We have developed an original, accurate and non-invasive optical approach to assess aneuploidy within the ICM of mouse embryos in the absence of fluorescent tags. Hyperspectral autofluorescence imaging was able to discriminate between euploid and aneuploid human fibroblast and mouse blastocysts (ICM). This approach may potentially lead to a new diagnostic for embryo analysis. STUDY FUNDING/COMPETING INTEREST(S): K.R.D. is supported by a Mid-Career Fellowship from the Hospital Research Foundation (C-MCF-58-2019). This study was funded by the Australian Research Council Centre of Excellence for Nanoscale Biophotonics (CE140100003) and the National Health and Medical Research Council (APP2003786). The authors declare that there is no conflict of interest.

Dysregulation of bisphosphoglycerate mutase during in vitro maturation of oocytes.

PURPOSE: Oxygen is vital for oocyte maturation; however, oxygen regulation within ovarian follicles is not fully understood. Hemoglobin is abundant within the in vivo matured oocyte, indicating potential function as an oxygen regulator. However, hemoglobin is significantly reduced following in vitro maturation (IVM). The molecule 2,3-bisphosphoglycerate (2,3-BPG) is essential in red blood cells, facilitating release of oxygen from hemoglobin. Towards understanding the role of 2,3-BPG in the oocyte, we characterized gene expression and protein abundance of bisphosphoglycerate mutase (Bpgm), which synthesizes 2,3-BPG, and whether this is altered under low oxygen or hemoglobin addition during IVM. METHODS: Hemoglobin and Bpgm expression within in vivo matured human cumulus cells and mouse cumulus-oocyte complexes (COCs) were evaluated to determine physiological levels of Bpgm. During IVM, Bpgm gene expression and protein abundance were analyzed in the presence or absence of low oxygen (2% and 5% oxygen) or exogenous hemoglobin. RESULTS: The expression of Bpgm was significantly lower than hemoglobin when mouse COCs were matured in vivo. Following IVM at 20% oxygen, Bpgm gene expression and protein abundance were significantly higher compared to in vivo. At 2% oxygen, Bpgm was significantly higher compared to 20% oxygen, while exogenous hemoglobin resulted in significantly lower Bpgm in the COC. CONCLUSION: Hemoglobin and 2,3-BPG may play a role within the maturing COC. This study shows that IVM increases Bpgm within COCs compared to in vivo. Decreasing oxygen concentration and the addition of hemoglobin altered Bpgm, albeit not to levels observed in vivo.

The BlastGen study: a randomized controlled trial of blastocyst media supplemented with granulocyte-macrophage colony-stimulating factor.

RESEARCH QUESTION: Does Embryogen®/BlastGen™ culture medium improve live birth rates compared with standard culture medium for women undergoing IVF and intracytoplasmic sperm injection (ICSI) with poor prognosis. DESIGN: Randomized clinical trial. A total of 100 couples undergoing IVF/ICSI were randomly allocated to having their inseminated oocytes incubated in either Embryogen®/BlastGen™ sequential culture media or standard Cleavage/Blastocyst sequential culture media for 5 days (ClinicalTrials.gov Identifier: NCT02305420). RESULTS: No statistically significant difference in live birth rate was found between the control group and the Embryogen®/BlastGen™ group (17 [34%] versus 11 [22%], respectively) (OR 0.55; 95% CI 0.22 to 1.32; P = 0.18). After adjustment for maternal age, body mass index and fertilization procedure, the blastulation rate reduced (40.6 ± 26.5 versus 24.6 ± 26.7; RR 0.70, CI 0.52 to 0.95; P < 0.05), and grade of the embryo transferred (OR 0.35, CI 0.16 to 0.77; P < 0.01) when Embryogen®/BlastGen™ medium was used. CONCLUSION: A significant reduction in day-5 embryo outcome parameters was found using Embryogen®/BlastGen™ compared with standard medium, and insufficient evidence of a difference in pregnancy outcomes. Taking into consideration the small samples size, study limitations and strict inclusion criteria of this single-centre study, further research is needed to determine the efficacy of Embryogen®/BlastGen™ medium in couples undergoing IVF/ICSI.

Fifty years of reproductive biology in Australia: highlights from the 50th Annual Meeting of the Society for Reproductive Biology (SRB).

The 2018 edition of the Society for Reproductive Biology's (SRB) Annual Meeting was a celebration of 50 years of Australian research into reproductive biology. The past 50 years has seen many important contributions to this field, and these advances have led to changes in practice and policy, improvements in the efficiency of animal reproduction and improved health outcomes. This conference review delivers a dedicated summary of the symposia, discussing emerging concepts, raising new questions and proposing directions forward. Notably, the symposia discussed in this review emphasised the impact that reproductive research can have on quality of life and the health trajectories of individuals. The breadth of the research discussed encompasses the central regulation of fertility and cyclicity, life course health and how the environment of gametes and embryos can affect subsequent generations, significant advances in our understanding of placental biology and pregnancy disorders and the implications of assisted reproductive technologies on population health. The importance of a reliable food supply and protection of endangered species is also discussed. The research covered at SRB's 2018 meeting not only recognised the important contributions of its members over the past 50 years, but also highlighted key findings and avenues for innovation moving forward that will enable the SRB to continue making significant contributions for the next 50 years.

Promotion of EGF receptor signaling improves the quality of low developmental competence oocytes.

Oocytes acquire developmental competence with progressive folliculogenesis. Cumulus oocyte complexes (COCs) from small antral follicles have inherent low competence and are poorly responsive to amphiregulin (AREG) which normally mediates oocyte maturation and ovulation. Using low competence porcine COCs, in an in vitro AREG-induced oocyte maturation system, the combined exposure to N(6),2'-O-dibutyryladenosine 3':5' cyclic monophosphate (cAMP) and bone morphogenetic protein 15 (B15) and growth differentiation factor 9 (G9) was necessary to enhance the rate of oocyte meiotic maturation and blastocyst formation. Furthermore, the combination of cAMP+B15+G9 enabled AREG-stimulated cumulus expansion and increased expression of the matrix-related genes HAS2, TNFIPA6 and PTGS2. Additionally, the combination enhanced p-ERK1/2 which is downstream of the EGF receptor. The enhanced nuclear maturation and blastocyst formation rates with the combinational treatment were ablated by an EGF receptor phosphorylation inhibitor. These results indicate that cAMP and oocyte-secreted factors cooperate to promote EGF receptor functionality in developing COCs, representing a key component of the acquisition of oocyte developmental competence.

Soft tissue release and bilobed flap for severe radial longitudinal deficiency.

PURPOSE: To report the hand position, range of motion, functional results, and radiographic outcomes associated with treating radial longitudinal deficiency with release of constricting or deforming soft tissue and resurfacing of the radial skin deficiency with a bilobed flap. METHODS: We recalled and reviewed patients with at least a 3-year follow-up who had undergone soft-tissue release and coverage with a bilobed flap. The study group consisted of 16 patients and 18 wrists. All patients underwent follow-up examination and radiographs. Outcome measures using Pediatric Outcomes Data Collection Instrument (PODCI), Disabilities of the Arm, Shoulder, and Hand (DASH), and visual analogue scale (VAS) scores were recorded. RESULTS: At a mean of 9.2 years follow-up, the average final resting wrist radial deviation angle was 64° compared with 88° preoperatively. The average active wrist flexion-extension arc was 73°. Average DASH score was 27 (range, 5-54). PODCI global was 88 (range, 75-97), PODCI happiness was 86 (range, 70-100), and VAS overall satisfaction (range, 0-10) was 1.2 (range, 0-8). At final follow-up, no physeal growth arrests were noted on radiographs, and no patients to date have required ulnocarpal arthrodesis. CONCLUSIONS: Soft-tissue release and coverage with a bilobed flap should be considered in the treatment algorithm for patients with radial longitudinal deficiency. Outcome measures show that these patients maintain useful active motion, and along with their parents, are satisfied with both the appearance and function. Some recurrence of radial deviation was noted, which was similar to results previously reported following centralization/radialization procedures, although with a lower inherent risk of both physeal injury to the ulna and stiffness. In addition, potential future procedures are not compromised by this surgical approach. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Evaluation of a Large Language Model's Ability to Assist in an Orthopedic Hand Clinic.

BACKGROUND: Advancements in artificial intelligence technology, such as OpenAI's large language model, ChatGPT, could transform medicine through applications in a clinical setting. This study aimed to assess the utility of ChatGPT as a clinical assistant in an orthopedic hand clinic. METHODS: Nine clinical vignettes, describing various common and uncommon hand pathologies, were constructed and reviewed by 4 fellowship-trained orthopedic hand surgeons and an orthopedic resident. ChatGPT was given these vignettes and asked to generate a differential diagnosis, potential workup plan, and provide treatment options for its top differential. Responses were graded for accuracy and the overall utility scored on a 5-point Likert scale. RESULTS: The diagnostic accuracy of ChatGPT was 7 out of 9 cases, indicating an overall accuracy rate of 78%. ChatGPT was less reliable with more complex pathologies and failed to identify an intentionally incorrect presentation. ChatGPT received a score of 3.8 ± 1.4 for correct diagnosis, 3.4 ± 1.4 for helpfulness in guiding patient management, 4.1 ± 1.0 for appropriate workup for the actual diagnosis, 4.3 ± 0.8 for an appropriate recommended treatment plan for the diagnosis, and 4.4 ± 0.8 for the helpfulness of treatment options in managing patients. CONCLUSION: ChatGPT was successful in diagnosing most of the conditions; however, the overall utility of its advice was variable. While it performed well in recommending treatments, it faced difficulties in providing appropriate diagnoses for uncommon pathologies. In addition, it failed to identify an obvious error in presenting pathology.

Risk Factors for Leaving Against Medical Advice in Patients Admitted for Upper Extremity Orthopedic Procedures.

INTRODUCTION: Patients who leave against medical advice (AMA) face increased risks of negative health outcomes, presenting a challenge for healthcare systems. This study examines demographic and hospital course factors associated with patients leaving AMA after an upper extremity (UE) orthopaedic procedure. METHODS: We analyzed 262,912 patients who underwent UE orthopaedic procedures between 2011 and 2020, using the Healthcare Cost and Utilization Project database. We then compared demographic and hospital course factors between patients who left AMA and those who did not leave AMA. RESULTS: Of 262,912 UE orthopaedic patients, 0.45% (1,173) left AMA. Those more likely to leave AMA were aged 30 to 49 (OR, 5.953, P < 0.001), Black (OR, 1.708, P < 0.001), had Medicaid (OR, 3.436, P < 0.001), and were in the 1st to 25th income percentile (OR, 1.657, P < 0.001). Female patients were less likely to leave AMA than male patients (OR, 0.647, P < 0.001). Patients leaving AMA had longer stays (3.626 versus 2.363 days, P < 0.001) and longer recovery times (2.733 versus 1.977, P < 0.001). CONCLUSION: We found that male, Black, younger than 49 years old, Medicaid-insured, and lowest income quartile patients are more likely to leave AMA after UE orthopaedic treatment.

Improved Outcomes in Operative Management of Concomitant Distal Radius and Scaphoid Fractures.

BACKGROUND: This study aims to investigate the characteristics of concomitant distal radius and scaphoid fractures and determine outcome differences of operative and nonoperative management. METHODS: A retrospective search of a level-1 trauma center's database over a 15-year period (2007-2022) for concomitant distal radius and scaphoid fractures in adult patients was completed. In all, 31 cases were reviewed for mechanism of injury, method of fracture management, distal radius fracture AO Foundation/Orthopaedic Trauma Association classification, scaphoid fracture classification, time to radiographic scaphoid union, time to motion, and other demographics. A multivariate statistical analysis was completed comparing outcomes in operative versus conservative management of the scaphoid fracture in these patients. Outcomes were defined as time to radiographic union and time to motion. RESULTS: In all, 22 cases of operative fixation of the scaphoid and 9 cases of nonoperative management of the scaphoid were reviewed. One case of nonunion was identified in the operative group. Operative management of scaphoid fractures resulted in a statistically significant reduction in time to motion (2-week reduction) and time to radiographic union (8-week reduction). CONCLUSIONS: This study demonstrates that operative management of scaphoid fractures in the setting of a concomitant distal radius fracture reduces the time to radiographic union and time to clinical motion. This suggests that operative management is ideal in patients who are good candidates for surgery and desire earlier return of motion. However, conservative management should be considered, as nonoperative care showed no statistical difference regarding union rates of scaphoid or distal radius fractures.

Impact of COVID-19 on Elective Orthopaedic Surgery Outcomes During the Peak of the Pandemic, an Uptick of Complications: An Analysis of the ACS-NSQIP.

INTRODUCTION: Since the World Health Organization declared a pandemic in March 2020, COVID-19 has pressured the healthcare system. Elective orthopaedic procedures for American seniors were canceled, delayed, or altered because of lockdown restrictions and public health mandates. We sought to identify differences in the complication rates for elective orthopaedic surgeries before and atfter the pandemic onset. We hypothesized that complications increased in the elderly during the pandemic. METHODS: We conducted a retrospective analysis of the American College of Surgeons-National Surgical Quality Improvement Program database in patients older than 65 years undergoing elective orthopaedic procedures from 2019 (prepandemic) and April to December 2020 (during the pandemic). We recorded readmission rates, revision surgery, and 30-day postoperative complications. In addition, we compared the two groups and adjusted for baseline features with standard multivariate regression. RESULTS: We included 146,430 elective orthopaedic procedures in patients older than 65 years (94,289 before the pandemic and 52,141 during). Patients during the pandemic had a 5.787 times greater chance of having delayed wait time to the operating room (P < 0.001), a 1.204 times greater likelihood of readmission (P < 0.001), and a 1.761 times increased chance of delayed hospital stay longer than 5 days (P < 0.001) when compared with prepandemic. In addition, during the pandemic, patients were 1.454 times more likely to experience any complication (P < 0.001) when compared with patients prepandemic undergoing orthopaedic procedures. Similarly, patients were also 1.439 times more likely to have wound complication (P < 0.001), 1.759 times more likely to have any pulmonary complication (P < 0.001), 1.511 times more likely to have any cardiac complication (P < 0.001), and 1.949 times more likely to have any renal complication (P < 0.001). CONCLUSION: During the COVID-19 pandemic, elderly patients faced longer wait times within the hospital and increased odds of complications after elective orthopaedic procedures than similar patients before the pandemic.

Implementation of entrustable professional activities in multiple surgical residencies: A quality improvement approach.

BACKGROUND: The COVID-19 pandemic decreased the operative case volume for surgical residents. Our institution implemented Entrustable Professional Activities (EPAs) in all core surgical training programs to document the competency of graduating residents. Continuation of this project aimed to improve implementation. METHODS: This project occurred at a large academic center with eight surgical specialties during the 2020-21 (Year 1) and 2021-22 (Year 2) academic years. Each specialty chose five EPAs, and residents were asked to obtain three micro-assessments per EPA. After the initial pilot year, program directors were surveyed regarding perceptions of EPA utility and barriers to implementation. RESULTS: Seventy senior residents completed 732/906 (80.8%) micro-assessments. Of these, 99.6% were deemed practice ready. Total micro-assessment completion rates in four specialties, four specific EPAs (including one EPA identified "at risk" due to the COVID-19 pandemic), and overall were significantly higher in Year 2 than Year 1 (p â€‹< â€‹0.05) CONCLUSIONS: Implementing EPAs in all core surgical specialties at an institution is achievable, though expectedly initially imperfect. An ongoing quality collaborative initiative focused on barriers to implementation can improve completion rates.

Socioeconomic Status Affects Pre- and Postoperative Two-point Discrimination in Patients with Carpal Tunnel Syndrome.

Carpal tunnel release is a life-changing procedure within hand surgery. Multiple factors may have an impact on the outcome following surgery. Methods: In this retrospective cohort study, we reviewed all patients who underwent carpal tunnel release in our institutional database from 2018 to 2020. We included patients with a minimum of 6-week follow-up. Patient demographics were identified, including insurance status and comorbidities. Patients were categorized as "improved" or "not improved" based on two-point test differences. Results were analyzed using the Fisher exact test. We ran a logistic regression model to analyze the relationship between income status (operationalized by having Medicaid/Carelink) and preoperative scores, and inferential statistics were computed with appropriate t tests. Results: Of the 125 patients who met the inclusion criteria, 47 (37.6%) had Medicaid or Carelink, and 79 (62.4%) had commercial insurance. Medicaid/ Carelink patients presented with worse two-point discrimination on initial presentation (P < 0.001). Compared to commercial insurance, Medicaid/Carelink patients were less likely to show improvement in postoperative two-point discrimination (P < 0.001). Male patients were also less likely to show improvement. Race, ethnicity, medical comorbidities, and age were not shown to have a significant effect on improvement in two-point discrimination. Conclusions: Although medical comorbidities did not have a significant effect on postoperative two-point, patients with low-income status (Medicaid/Carelink) may have a less predictable outcome. These socioeconomic considerations are critical in appropriately risk stratifying surgical candidates, and counseling patients in whom tactile acuity may be less predictable.

Restoring Sperm Quality Post-Cryopreservation Using Mitochondrial-Targeted Compounds.

While critical for male fertility preservation, cryopreservation damage reduces sperm quality and fertilization potential. This study investigated whether the addition of mitochondrial-targeted, antioxidant compounds, also known as Mitochondrial activators, to the cryopreservation medium could protect sperm quality during cryopreservation. For this, semen samples from men undergoing IVF/ICSI treatment, which were donated for research, underwent cryopreservation in the absence or presence of BGP-15, MitoQ and L-carnitine. Fresh semen and thawed sperm samples from the same participant were analyzed for indicators of sperm quality: sperm viability, kinetics, mitochondrial reactive oxygen species (ROS) levels, Mitochondrial Membrane Potential (MMP) and DNA damage. Cryopreservation significantly reduced sperm viability and motility and predicted mucous penetration. BGP-15, MitoQ and L-carnitine improved sperm motility, whilst the addition of L-Carnitine prevented the loss of sperm viability during cryopreservation. Both BGP-15 and L-carnitine reduced sperm DNA oxidative damage, but only BGP-15 significantly reduced DNA fragmentation. More importantly, BGP-15 increased sperm predictive mucous penetration and MMP and reduced DNA oxidation. Our results show that the addition of BGP-15 or L-carnitine to the cryopreservation medium improves sperm quality post-thawing, highlighting the potential of mitochondrial antioxidants to improve long-term fertility preservation in males.

Socioeconomic status does not change decision-making in the treatment of distal radius fractures at a level 1 trauma center.

Objectives: To compare operative rates, total hospital charges, and length of stay between different socioeconomic cohorts in treating distal radius fractures (DRFs). Design: A retrospective cohort study. Setting: Large public level 1 trauma center. Patients: A retrospective search of all trauma activations over a 7-year period (2013-2020) yielded 816 adult patients diagnosed with DRF. Patients were separated into cohorts of socioeconomic status based on 2010 US Census data and insurance status. Intervention: DRFs were treated either nonoperatively using closed reduction and splinting or operatively using open reduction and internal fixation, closed reduction percutaneous pinning, or external fixator application. Main Outcome Measurements: Operative rates of DRF, total hospital charges, and length of stay. Results: Patients who were uninsured or in the low-income socioeconomic cohort had no significant difference in operative rates, total hospital costs, or length of stay when compared with their respective insured or standard income groups. Younger patients and those with OTA/AO type C, bilateral, or open DRFs were more likely to undergo operative intervention. Conclusions: This study demonstrates that low socioeconomic status based on annual household income and insurance status was not associated with differences in operative rates on DRFs, length of stay, or total hospital charges. These results suggest that outcome disparities between groups may be caused by postoperative differences rather than treatment decision-making. Although this study investigates access to surgical care at a publicly funded level 1 trauma center, disparities may still exist in other models of care. Level of Evidence: Prognostic Level III.

Providing Orthopaedic Care to Vulnerably Underserved Patients: AOA Critical Issues.

ABSTRACT: Implementation of the Affordable Care Act has increased the number of Americans with health insurance. However, a substantial portion of the population is still considered underserved, including those who are uninsured, underinsured, and those who are enrolled in Medicaid. The patients frequently face substantial access-to-care issues. Many underlying social determinants of health impact this vulnerable, underserved population, and surgeons must understand the nuances of caring for the underserved. There are numerous opportunities to engage with this population, and providing care to the indigent can be rewarding for both the vulnerably underserved patient and their surgeon.

Subungual Exostosis of the Hand: A Case Report in a 5-Year-Old Boy and Literature Review.

Subungual exostosis is a relatively uncommon benign tumor that occurs at the distal end of the distal phalanx of the toes and rarely the hands. We present in this article a review of the currently published English literature and provide a case report of a 5 year old male with subungual exostosis of the thumb. A 5 year old male presented with a slow growing mass of the distal dorsal aspect of the left thumb. Radiographs showed dorsal calcifications on the thumb. Surgical removal of the mass and histopathological analysis was performed supporting a diagnosis of subungual exostosis. Post-operatively, the patient had complete excision of the mass, normal nail morphology, no reoccurrence, and no post-surgical complications. Subungual exostosis remains a rare entity especially in the upper extremity. Its cause is not fully understood, nor is there an agreed upon method of treatment. However, with careful dissection during surgical removal good outcomes can be obtained. To our knowledge, this is the largest literature review on subungual exostosis and our case report is an uncommon presentation in the youngest reported male patient. It is our hope that this literature review and case report lend to increased awareness of subungual exostosis and how to diagnose and treat this lesion.

The Cutting Edge: Surface Texture Analysis following Resection of Nerve Stumps Using Various Instruments.

BACKGROUND: Preparation of nerve ends is an essential part of nerve repair surgery. Multiple instruments have been described for this purpose; however, no consensus exists regarding which is the least traumatic for tissue handling. We believe that various instruments used for nerve-end excision will lead to different surface roughness. METHODS: Median and ulnar nerves from fresh frozen cadavers were dissected, and 1-2 cm lengths were excised using a No. 11 blade, a razor blade, or a pair of scissors. Using electron microscopy, 3-dimensional surface analysis of roughness (Sa) for each specimen was performed using ZeeScan optical hardware and GetPhase software (PhaseView, Buisson, France). An ANOVA or Kruskal-Wallis test compared roughness measures among cutting techniques. RESULTS: Forty nerves were included. Of these, 13 (32.5%) were cut using scissors, 15 (37.5%) using a razor blade, and 12 (30%) using a No. 11 blade. An ANOVA test showed statistical differences in Sa among the cutting techniques (P = 0.002), with the lowest mean Sa noted in the scissors group (7.2 µM, 95% CI: 5.34-9.06), followed by No. 11 blade (7.29 µM, 95% CI: 5.22-9.35), and razor blade (11.03 µM, 95% CI: 9.43-12.62). Median Ra (surface profile roughness) was 4.58 (IQR: 2.62-5.46). A Kruskal-Wallis test demonstrated statistical difference in Ra among techniques (P = 0.003), with the lowest by No. 11 blade (3 µM, IQR: 1.87-4.38), followed by scissors (3.29 µM, IQR: 1.56-4.96), and razor (5.41 µM, IQR: 4.95-6.21). CONCLUSION: This novel technique of 3-dimensional surface analysis found razor blade use demonstrated poor roughness, whereas a No. 11 blade or nerve-specific scissors led to equivocally smooth nerve ends.