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Background: Facial aberrant reinnervation syndrome (FARS) is a common sequelae of facial nerve injury followed by aberrant reinnervation and recovery. Patients with FARS can present with different patterns of facial synkinesis, facial muscle hypertonicity, and facial spasm/twitching. 1 Synkinesis associated with FARS is described as undesired muscle contraction when a voluntary movement is triggered. One of the most common and bothersome types of facial synkinesis is oral-ocular synkinesis, where patients experience unwanted eyelid closure with movement of the mouth such as smiling or pursing the lips. First-line treatment options for FARS include facial physical therapy and botulinum toxin selective chemodenervation. For patients with persistent or more significant symptoms, there are surgical options, including selective neurectomy and selective myectomy of the involved facial nerve branches and muscles. 2 , 3 Selective myectomy of the orbicularis oculi muscle has been shown to be an effective surgical treatment option for oral-ocular synkinesis. 3 – 4 There is nuance to this procedure, including deciding whether to target the upper eyelid, lower eyelid, or both, as well as which segments and how much of the orbicularis oculi muscle to remove, balancing the goals of improving synkinesis and hypertonicity while avoiding the creation of lagophthalmos. The novel implementation of autologous microfat grafting to the procedure can help improve postoperative eyelid volume and contour and may help prevent the cut edges of the muscle from fusing, thus reducing the likelihood of persistent or recurrent ocular synkinesis. Objective: To describe a selective myectomy of the orbicularis oculi with the novel addition of autologous microfat grafting for the treatment of oral-ocular synkinesis. Methods: This video demonstrates the procedural steps for a selective myectomy of the orbicularis oculi with autologous microfat grafting for a patient with oral-ocular synkinesis due to FARS. In addition, it demonstrates the preparation of harvested abdominal fat that is utilized for the autologous microfat grafting. Results: Selective myectomy of the orbicularis oculi with autologous microfat grafting has been routinely performed safely and effectively by the senior author for treatment of oral-ocular synkinesis. Postoperative aesthetic eyelid shape and functional results have been reassuring with improvements up to 1 year postoperative and a need for additional long-term follow-up. Conclusion: To the authors’ knowledge, a selective myectomy of the orbicularis oculi with autologous microfat grafting has not been demonstrated in video documentation. Autologous microfat grafting may be a helpful addition to selective myectomy of the orbicularis oculi to enhance both eyelid aesthetics and function. Patient Consent Statement: All patients included in the video have consented to the use of videos and photographs of their faces for research and educational purposes. Funding and Conflicts of Interest: The authors have no funding, financial relationships, or conflicts of interest to disclose. Runtime of video: 7 mins 11 secs.

Abstract Metformin is well‐established as a treatment for type 2 diabetes in non‐pregnant individuals. The low cost, acceptability and broad tolerability of metformin have also made it an attractive option for research into the treatment of other conditions associated with insulin resistance. Despite almost 50 years of clinical experience with the use of metformin to treat diabetes in pregnancy, many questions remain regarding its precise effectiveness in different maternal subgroups, as well as potential short‐term and long‐term effects on the offspring. In this narrative review, we present the current evidence for the use of metformin during pregnancy in various maternal subgroups, including women living with overweight and obesity, women at risk of gestational diabetes, women diagnosed with gestational diabetes and women with pregestational diabetes, including type 2 diabetes. Our specific focus is on the impact of metformin on short‐term maternal, fetal and neonatal outcomes. We also consider the evidence for other emerging indications for metformin in pregnancy, such as the prevention and management of pre‐eclampsia. Plain Language Summary This article looks at research on how metformin use in pregnancy affects mothers and newborns in the short term. Doctors have prescribed metformin since the 1970s for the treatment of diabetes in pregnancy. Despite years of use, there are still questions about how safe and effective metformin is for mothers and their children. Metformin taken during pregnancy moves through the placenta into the foetus's bloodstream. The short‐term and long‐term effects of metformin on offspring need careful attention. The studies that have looked at the link between metformin use and birth defects have not found any strong link between taking metformin in pregnancy and birth defects, however close attention will continue to be paid in this area. Some large studies have examined the use of metformin in pregnant women who do not have diabetes, but who do live with overweight or obesity. The studies are difficult to compare. Some, but not all, of these studies have shown less weight gain for the mother if metformin is taken by these women during pregnancy. Other large studies have looked at whether metformin can prevent gestational diabetes. The results are mostly disappointing. They suggest that metformin does not stop gestational diabetes from developing. However, the participants in these studies were mostly from white backgrounds and metformin may help prevent gestational diabetes in women of different ethnic backgrounds. However, more research is needed. Metformin has been widely studied as an alternative to insulin for the treatment of gestational diabetes. Because different countries diagnose and treat GDM differently, this makes comparing study results difficult. Women with gestational diabetes seem to gain less weight during pregnancy if they use metformin rather than insulin. Using metformin instead of insulin may result in lower average birth weights for babies from these pregnancies. Also, the use of metformin may lead to fewer babies being born abnormally large. Similarly, large trials have examined the use of metformin in pregnant women who are living with type 2 diabetes. These studies show that metformin can lower a mother's insulin needs. It can also help control weight gain and reduce the risk of having a large baby. One study found that metformin use in women living with Type 2 diabetes might increase the risk of having smaller babies. This was especially true if the mother had high blood pressure or kidney disease. This finding requires further investigation. Metformin might help prevent pre‐eclampsia, but this is still unclear. Research is ongoing into a potential role for metformin in the treatment of pre‐eclampsia. In conclusion, metformin has been studied in many groups of pregnant women. Women with gestational diabetes or type 2 diabetes may see benefits like less weight gain and better blood sugar/glucose control. Current evidence suggests that metformin shouldn't be used if there are foetal growth issues. It is also not recommended for mothers with high blood pressure or kidney disease. Future studies might find specific groups of pregnant women who would benefit the most from metformin.

Background/Purpose APS ACTION Registry was created to study the natural course of antiphospholipid syndrome (APS) over 10 years in persistently antiphospholipid antibody (aPL) positive patients with or without systemic autoimmune rheumatic diseases (SARDs). Our primary objective was to compare the characteristics of aPL-positive patients with or without thrombocytopenia (TP) and/or autoimmune hemolytic anemia (AIHA). Methods The registry inclusion criteria are positive aPL based on the Revised Sapporo APS Classification Criteria, tested at least twice within 1 year prior to enrollment. For the primary comparison of demographic, clinical, and serologic characteristics in this retrospective study, we divided patients into two groups: TP/AIHA ever and never. Thrombocytopenia was defined as a platelet count of <100,000 x 10 9 /L tested twice at least 12 weeks apart, and AIHA was defined as anemia with hemolysis and a positive direct antiglobulin test (DAT). For the secondary analysis, we compared patients with TP versus AIHA, and the immunosuppressive use stratified by systemic lupus erythematosus (SLE) classification. Results As of April 2022, of 1,039 patients (primary aPL/APS: 618 [59%]; SLE classification: 334 [31%]) included in the registry, 228 (22%) had baseline (historical or current) TP and/or AIHA (TP only: 176 [17%]; AIHA only: 35 [3%], and both: 17 [2%]). Thrombocytopenia and/or AIHA was significantly associated with Asian race, SLE classification, cardiac valve disease, catastrophic/microvascular APS, triple aPL (lupus anticoagulant, anticardiolipin antibody, and anti-β 2 -glycoprotein-I antibody) positivity, and SLE-related serologic and inflammatory markers. When 101/618 (16%) primary aPL/APS patients and 101/334 (34%) SLE patients with TP and/or AIHA were compared, azathioprine and mycophenolate mofetil were more commonly reported in lupus patients, however corticosteroid, intravenous immunoglobulin, and rituximab use were similar between groups. Conclusion In our large multi-center international cohort of persistently aPL-positive patients, approximately one-fifth had active or historical TP and/or AIHA at registry entry; half of these patients had additional SLE. Cardiac valve disease, catastrophic/microvascular APS, and triple aPL-positivity were aPL-related clinical and laboratory manifestations associated with TP and/or AIHA, suggesting a more severe APS clinical phenotype in aPL-patients with TP and/or AIHA.

Background: Various medial patellofemoral ligament (MPFL) reconstruction techniques have been developed to minimize risks to the physis in skeletally immature patients. Purpose: To examine outcomes of MPFL reconstruction (MPFLR) based on fixation technique in skeletally immature patients. Study Design: Systematic review; Level of evidence, 4. Methods: PubMed, Scopus, Ovid, Cochrane Library, and CINAHL databases were searched for the literature on outcomes of MPFLR in the pediatric population, utilizing various anatomic and nonanatomic techniques. Primary outcomes were postoperative redislocation rates, return-to-sports (RTS) rates, and patient-reported outcomes (PROs). Moreover, outcomes involving sequela of growth plate disturbance were collected. Results: The final analysis included 17 studies—2 using sling-based techniques, 3 using surface-based techniques, 5 using soft tissue realignments, and 7 utilizing transosseous femoral fixations. Higher rates of postoperative redislocation were found in the sling-based (14.8%) and distal soft tissue realignment using semitendinosus tenodesis (38%) techniques, while lower rates were noted with surface-based (1.3%) and transosseous (3.4%) techniques. For PROs, there were large amounts of heterogeneity among studies, but all reported postoperative improvements, with more positive PROs generally seen in anatomic reconstructions. The RTS rate was 100% for surface-based techniques, 79.4% for distal soft tissue realignments, 79.5% for soft tissue realignment techniques, and 83.2% for transosseous techniques. No negative outcomes as a sequela of growth plate disturbance were reported. Conclusion: Nonanatomic techniques—such as sling-based and distal soft tissue realignment techniques—have higher rates of redislocation and lower RTS rates in skeletally immature patients undergoing MPFLR. Surface-based and transosseous tunnel-based techniques were shown to have lower redislocation and higher RTS rates. Clinical Relevance: This review provides insight into the most appropriate surgical management of patellar instability in patients with open growth plates.

Background: No biomechanical study has established the effect of different graft positions or bone block options on anterior glenohumeral joint stability. Purpose/Hypothesis: The purpose of this study was to compare graft choice (distal clavicular vs coracoid autograft for Latarjet) and position on stability of the bone block for anterior glenohumeral instability. It was hypothesized that both grafts would be comparable if flush with the glenoid but that the sling effect of the Latarjet procedure would lead to greater stability in case of graft medialization. Study Design: Controlled laboratory study. Methods: Eight cadaveric shoulders were included. Defects stabilized using a distal clavicular graft and a coracoid graft were consecutively positioned at 0, 4, and 8 mm medially. The starting position was determined by the humeral head’s being seated at its most medial position on the glenoid surface. Each experiment comprised maximal external rotation and glenohumeral abduction at 60° while applying a constant 50-N medial compressive force to the humerus under all conditions. The conjoint tendon was routed through a split in the subscapularis and loaded with a 5-N weight using a pulley system for all Latarjet trials to simulate the sling effect. Results: Regarding the clavicular graft, the stability ratio significantly decreased versus the intact condition at all medial offsets ( P = .007 for 0 mm, P < .001 for 4 mm, and P < .001 for 8 mm), and it was significantly lower in the 4-mm versus 0-mm position ( P = .008), significantly higher in the 4-mm versus 8-mm position ( P < .001), and significantly lower in the 8-mm versus 0-mm position ( P < .001). Regarding the coracoid graft, the stability ratio was comparable with intact for the 0-mm position ( P = .12), while it was significantly lower in the 4-mm and 8-mm positions ( P < .001 for both). The distal clavicular graft at 0-mm offset was comparable with the coracoid graft at 0-mm offset. Conclusion: In shoulders with anterior glenoid bone loss, the coracoid and distal clavicular autografts were biomechanically comparable when placed flush with the glenoid. The distal clavicle at 0-mm offset did not restore stability compared with the intact specimen, but the Latarjet at 0-mm offset was not significantly different from the intact condition. Clinical Relevance: The Latarjet procedure provides higher stability compared with distal clavicular autograft when medialized.

Abstract Objective: Patients with Opioid Use Disorder (OUD) are prone to Multidrug-Resistant Organism (MDRO) colonization and infections, thus at risk for worse outcomes during critical illness. Understanding the prevalence and predictors of MDRO infections is essential to optimize interventions and treatments. Design: Retrospective cohort study. Methods: The study evaluated the prevalence of MDRO isolation among adults with OUD admitted to an intensive care unit (ICU) between January 1, 2018, and July 31, 2023. It included adults admitted to an ICU with bacterial infections and positive cultures obtained within 48 hours of admission. Demographics, clinical traits, and MDRO isolation rates were analyzed using descriptive statistics, univariate methods, and Least Absolute Shrinkage and Selection Operator (LASSO) regression. Results: MDRO isolation occurred in 178 of 790 patients (22.5%), with methicillin-resistant Staphylococcus aureus as the most frequently isolated organism. LASSO regression identified housing insecurity (OR: 1.79, 95% CI 1.09–2.93, P = .022), no receipt of medications for OUD treatment (OR: 1.56, 95% CI 1.06–2.29, P = .023), positive hepatitis C virus (HCV) status (OR: 2.19, 95% CI 1.19–4.03, P = .012), and intravenous antibiotic use in the prior 90 days (OR: 1.04 per 24 h, 95% CI 1.01–1.07, P = .007) as significant predictors of MDRO isolation. Conclusions: The study highlights a high prevalence of MDRO isolation in critically ill OUD patients admitted for infection-related issues with positive cultures obtained within 48 hours of admission, influenced by factors like housing insecurity, no receipt of medications for OUD treatment, HCV status, and prior antibiotic use.

Abstract Chronically elevated circulating excess free fatty acids (ie, lipotoxicity) is a pathological process implicated in several metabolic disorders, including obesity-driven type 2 diabetes (T2D). Lipotoxicity exerts detrimental effects on pancreatic islet β-cells by reducing glucose-stimulated insulin secretion (GSIS), altering β-cell transcriptional identity, and promoting apoptosis. While β-cell-derived small extracellular vesicles (sEV) have been shown to contribute to β-cell failure in T2D, their specific role in lipotoxicity-mediated β-cell failure remains to be elucidated. In this work, we demonstrate that lipotoxicity enhances the release of sEVs from β-cells, which exhibit altered proteomic and lipidomic profiles. These palmitate (PAL)-exposed extracellular vesicles (EVs) induce β-cell dysfunction in healthy mouse and human islets and trigger significant islet transcriptional changes, including the upregulation of genes associated with the TGFβ/Smad3 pathway, as noted by RNA sequencing. Importantly, pharmacological inhibition of the TGFβI/II receptor improved PAL EV-induced β-cell dysfunction, underscoring their involvement in activating the TGFβ/Smad3 pathway during this process. We have comprehensively characterized lipotoxic β-cell sEVs and implicated their role in inducing β-cell functional failure in T2D. These findings highlight potential avenues for therapeutic interventions targeting sEV-mediated pathways to preserve β-cell health in metabolic disorders.

PURPOSE Predictive biomarkers to better tailor therapy for patients with early-stage human epidermal growth factor 2 (HER2)-positive breast cancer are a priority. We hypothesized that HER2 and immune-based biomarkers would be predictive of pathologic complete response (pCR) to preoperative trastuzumab/pertuzumab (HP). MATERIALS AND METHODS Patients with stage II/III, estrogen receptor (ER)-negative, HER2-positive breast cancer received neoadjuvant HP in the TBCRC026 clinical trial. The pCR after receiving HP alone was 22% (18/83). Tumor biopsies were performed at baseline. Secondary correlative objectives were to determine the relationship between HER2-based biomarkers and immune processes with pCR. NanoString code sets BC360 and IO360 were used to compare differential gene expression in baseline tumors that underwent pCR versus no pCR. NanoString GeoMx digital spatial profiling was used to assess immune protein abundance in intraepithelial and stromal segments. Stromal tumor-infiltrating lymphocytes and Ki67 were evaluated by hematoxylin and eosin and immunohistochemistry, respectively. RESULTS Intraepithelial HER2 protein abundance was significantly associated with pCR ( P = .001). Low HER2 abundance tumors were primarily basal-like, and essentially all (19/20) failed to achieve pCR. High HER2 abundance tumors that achieved pCR (14/51) exhibited a high degree of immune cell activity, whereas high HER2 abundance tumors that failed to achieve pCR tumors (37/51) were enriched for M-phase processes and epidermal growth factor receptor signaling. Baseline Ki67 was significantly higher in nonresponders ( P = .04). CONCLUSION ER-negative, HER2-positive breast cancer has unique molecular and immunologic features that may predict pCR after neoadjuvant HP. Validation of these potential biomarkers and composite biomarker analyses may guide design of future clinical trials.

Objectives: Early identification of patients living with cancer at higher risk of death from an infection is critical in infection mortality prevention. We characterize patients living with cancer at the highest risk of dying from an infection. Methods: 7,529,481 US cancer survivors (1992 to 2015) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized mortality ratios (SMRs) and 95% CIs were calculated. Fine-gray survival analysis was performed to calculate hazard ratios by adjusting for the effects of competing risks (eg, deaths due to causes other than infection). Results: Among 7,529,481 patients living with cancer (1992 to 2015), 101,167 (1.3%) died of infection. The rate of infection-specific mortality was 27.19/10,000 person-years, with an SMR of 3.29 (95% CI: 3.26-3.32, P <0.001). Patients who were older, male, black, and unmarried were at a greater risk of fatal infection. Overall, the risk of infection-specific mortality for patients living with cancer is greatest 1 year after diagnosis compared with the general population (SMR: 8.68, 95% CI: 8.53-8.84; P< 0.0001), and this risk decreases with follow-up time (SMR at >10 y after diagnosis: 2.93, 95% CI: 2.87-3.00; P< 0.0001). Among patients with Hodgkin Lymphoma, Non-Hodgkin Lymphoma, and Kaposi Sarcoma, 9.2%, 11.5%, and 82.2% of all deaths within the first year after cancer diagnosis occurred due to acute infectious disease. In contrast, for patients with liver cancer, the relative percentage of infection-specific mortality increases with follow-up time from 3.5% at <1 year after cancer diagnosis and 10.4% at 10+ years of follow-up. Conclusion: The results of this study characterize infection mortality in patients living with cancer, which can guide more targeted research and interventions in this population.