Citations

Introduction: Lithium remains a gold standard treatment for bipolar disorder including during peripartum. Historically, guidelines advised against breastfeeding while taking lithium though recent data suggest it is acceptable for a healthy infant. Lack of awareness of acceptability contributes to decreased patient and clinician comfort and low breastfeeding rates. We report current breastfeeding rates, monitoring practices, and infant outcomes with lithium exposure in breastmilk at our institution. Methods: A retrospective chart review was conducted at a single academic medical center using records from 2013 to 2023. Electronic medical records were queried to identify patients prescribed lithium postpartum. Data were collected on timing of lithium initiation, lithium dose and concentration, breastfeeding status, and infant outcomes. Results: A total of 18 cases of lithium use in the postpartum period were identified. A total of 39% ( n = 7) of patients taking lithium postpartum breastfed. Most patients, 61% ( n = 11), initiated lithium prior to pregnancy, 11% ( n = 2) initiated during pregnancy and 27% ( n = 5) started postpartum. Four infant charts were reviewed with no reports of adverse events. Of these infants, average maternal lithium dose was 750 mg daily, with an average maternal serum lithium concentration of 0.62 mmol/L and average infant serum lithium concentration of 0.16 mmol/L. Conclusion: Our data demonstrate most patients using lithium postpartum have been taking lithium long-term and are not breastfeeding. Lithium exposure in breastmilk appears to be tolerated by healthy infants. There is a need for ongoing research and education on acceptability and infant monitoring recommendations to support patients who would like to breastfeed while on lithium.

Study Design: Cross-sectional study. Objective: To evaluate for areas of consensus and divergence of opinion within the spine community regarding the management of cervical spondylotic conditions and acute traumatic central cord syndrome (ATCCS) and the influence of the patient's age, disease severity, and myelomalacia. Summary of Background Data: There is ongoing disagreement regarding the indications for, and urgency of, operative intervention in patients with mild degenerative myelopathy, moderate to severe radiculopathy, isolated axial symptomatology with evidence of spinal cord compression, and ATCCS without myelomalacia. Methods: A survey request was sent to 330 attendees of the Cervical Spine Research Society (CSRS) 2021 Annual Meeting to assess practice patterns regarding the treatment of cervical stenosis, myelopathy, radiculopathy, and ATCCS in 16 unique clinical vignettes with associated MRIs. Operative versus nonoperative treatment consensus was defined by a management option selected by >80% of survey participants. Results: Overall, 116 meeting attendees completed the survey. Consensus supported nonoperative management for elderly patients with axial neck pain and adults with axial neck pain without myelomalacia. Operative management was indicated for adult patients with mild myelopathy and myelomalacia, adult patients with severe radiculopathy, elderly patients with severe radiculopathy and myelomalacia, and elderly ATCCS patients with pre-existing myelopathic symptoms. Treatment discrepancy in favor of nonoperative management was found for adult patients with isolated axial symptomatology and myelomalacia. Treatment discrepancy favored operative management for elderly patients with mild myelopathy, adult patients with mild myelopathy without myelomalacia, elderly patients with severe radiculopathy without myelomalacia, and elderly ATCCS patients without preceding symptoms. Conclusions: Although there is uncertainty regarding the treatment of mild myelopathy, operative intervention was favored for nonelderly patients with evidence of myelomalacia or radiculopathy and for elderly patients with ATCCS, especially if pre-injury myelopathic symptoms were present. Level of Evidence: Level V.

BACKGROUND Flap repair provides unique advantages in facial reconstruction but still carries the potential for undesirable postoperative cosmetic changes. OBJECTIVE The aims of this study were to describe postoperative vascular outcomes of patients undergoing flap repairs after Mohs micrographic surgery on facial tumors and to assess associations of baseline characteristics with outcomes. MATERIALS AND METHODS In this study, 7 dermatologists and 1 physician assistant in dermatology assessed preoperative and postoperative photographs of 57 patients who underwent facial Mohs micrographic surgery, evaluating vascular and pigment outcomes and number of telangiectasias. RESULTS There was a significant difference in number of telangiectasias according to body location (p = .002), where the number of telangiectasias was highest for nose surgery. CONCLUSION These data suggest that nasal flap repairs are associated with increased postoperative vascular changes. This highlights an opportunity for improved preoperative patient counseling and possible early laser treatment after nasal Mohs micrographic surgery.

Objective: The objective of this study was to measure potential associations between surgeon sex and number of days alive and at home (DAH). Background: Patients treated by female surgeons appear to have lower rates of mortality, complications, readmissions, and healthcare costs when compared with male surgeons. DAH is a validated measure, shown to better capture the patient experience of postoperative recovery. Methods: We conducted a retrospective study of adults (≥18 years of age) undergoing common surgeries between January 01, 2007 and December 31, 2019 in Ontario, Canada. The outcome measures were the number of DAH within 30-, 90-, and 365-days. The data was summarized using descriptive statistics and adjusted using multivariable generalized estimating equations. Results: During the study period, 1,165,711 individuals were included, of which 61.9% (N = 721,575) were female. Those managed by a female surgeon experienced a higher mean number of DAH when compared with male surgeons at 365 days (351.7 vs. 342.1 days; P < 0.001) and at each earlier time point. This remained consistent following adjustment for covariates, with patients of female surgeons experiencing a higher number of DAH at all time points, including at 365 days (343.2 [339.5–347.1] vs. 339.4 [335.9–343.0] days). Multivariable regression modeling revealed that patients of male surgeons had a significantly lower number of DAH versus female surgeons. Conclusions: Patients of female surgeons experienced a higher number of DAH when compared with those treated by male surgeons at all time points. More time spent at home after surgery may in turn lower costs of care, resource utilization, and potentially improve quality of life. Further studies are needed to examine these findings across other care contexts.

Abstract Objectives To examine the clinicopathologic features of patients with polymyalgia rheumatica (PMR) who had thoracic aorta repair surgery. Findings were compared with those of a cohort of patients with giant cell arteritis (GCA) requiring thoracic aorta repair. Methods All patients evaluated at Mayo Clinic in Rochester, MN, with Current Procedural Terminology (CPT) codes for thoracic aorta repair surgery between 2000–2021 were identified. All patients were screened for prior PMR diagnosis. Patients with PMR and no signs of GCA were categorized as clinically isolated PMR. The medical records of all patients were manually reviewed, and pathologists re-examined all the aortic tissues. Results Of the 4621 patients with at least one CPT code for thoracic aorta repair surgery, 43 patients were diagnosed with clinically isolated PMR before the surgery. Detailed histopathological examination of the aortic tissues revealed active inflammation in 30/43 (70%) patients after a median (IQR) of 10.0 (4.7–13.3) years from the PMR diagnosis. When compared with aortic tissue from patients with a prior diagnosis of GCA, the aorta of patients with PMR had more severe inflammation (Grade 3: 15/30 [50%] vs 5/34 [15%], P = 0.002). Patients with PMR and thoracic aorta repair may experience a 40% increased risk of mortality compared with the general population, but this did not reach statistical significance (standardized mortality ratio: 1.40; 95% CI: 0.91–2.07). Conclusions Some patients with PMR have subclinical aortic inflammation that is detectable many years after initial diagnosis and may contribute to the development of aortic aneurysm.

Abstract Context Multiple common genetic variants have been associated with type 2 diabetes, but the mechanism by which they predispose to diabetes is incompletely understood. One such example is variation in MTNR1B, which implicates melatonin and its receptor in the pathogenesis of type 2 diabetes. Objective To characterize the effect of diabetes-associated genetic variation at rs10830963 in the MTNR1B locus on islet function in people without type 2 diabetes. Design The association of genetic variation at rs10830963 with glucose, insulin, C-peptide, glucagon, and indices of insulin secretion and action were tested in a cohort of 294 individuals who had previously undergone an oral glucose tolerance test (OGTT). Insulin sensitivity, β-cell responsivity to glucose, and Disposition Indices were measured using the oral minimal model. Setting The Clinical Research and Translation Unit at Mayo Clinic, Rochester, MN. Participants Two cohorts were utilized for this analysis: 1 cohort was recruited on the basis of prior participation in a population-based study in Olmsted County. The other cohort was recruited on the basis of TCF7L2 genotype at rs7903146 from the Mayo Biobank. Intervention Two-hour, 7-sample OGTT. Main Outcome Measures Fasting, nadir, and integrated glucagon concentrations. Results One or 2 copies of the G-allele at rs10830963 were associated with increased postchallenge glucose and glucagon concentrations compared to subjects with the CC genotype. Conclusion The effects of rs10830963 on glucose homeostasis and predisposition to type 2 diabetes are likely to be partially mediated through changes in α-cell function.

OBJECTIVE The aims of this study were to 1) define the incidence of transforaminal lumbar interbody fusion (TLIF) interbody subsidence; 2) determine the relative importance of preoperative and intraoperative patient- and instrumentation-specific risk factors predictive of postoperative subsidence using CT-based assessment; and 3) determine the impact of TLIF subsidence on postoperative complications and fusion rates. METHODS All adult patients who underwent one- or two-level TLIF for lumbar degenerative conditions at a multi-institutional academic center between 2017 and 2019 were retrospectively identified. Patients with traumatic injury, infection, malignancy, previous fusion at the index level, combined anterior-posterior procedures, surgery with greater than two TLIF levels, or incomplete follow-up were excluded. Interbody subsidence at the superior and inferior endplates of each TLIF level was directly measured on the endplate-facing surface of both coronal and sagittal CT scans obtained greater than 6 months postoperatively. Patients were grouped based on the maximum subsidence at each operative level classified as mild, moderate, or severe based on previously documented < 2-mm, 2- to 4-mm, and ≥ 4-mm thresholds, respectively. Univariate and regression analyses compared patient demographics, medical comorbidities, preoperative bone quality, surgical factors including interbody cage parameters, and fusion and complication rates across subsidence groups. RESULTS A total of 67 patients with 85 unique fusion levels met the inclusion and exclusion criteria. Overall, 28% of levels exhibited moderate subsidence and 35% showed severe subsidence after TLIF with no significant difference in the superior and inferior endplate subsidence. Moderate (≥ 2-mm) and severe (≥ 4-mm) subsidence were significantly associated with decreases in cage surface area and Taillard index as well as interbody cages with polyetheretherketone (PEEK) material and sawtooth surface geometry. Severe subsidence was also significantly associated with taller preoperative disc spaces, decreased vertebral Hounsfield units (HU), the absence of bone morphogenetic protein (BMP) use, and smooth cage surfaces. Regression analysis revealed decreases in Taillard index, cage surface area, and HU, and the absence of BMP use predicted subsidence. Severe subsidence was found to be a predictor of pseudarthrosis but was not significantly associated with revision surgery. CONCLUSIONS Patient-level risk factors for TLIF subsidence included decreased HU and increased preoperative disc height. Intraoperative risk factors for TLIF subsidence were decreased cage surface area, PEEK cage material, bullet cages, posterior cage positioning, smooth cage surfaces, and sawtooth surface designs. Severe subsidence predicted TLIF pseudarthrosis; however, the causality of this relationship remains unclear.

Abstract Acute graft-versus-host disease (GVHD) grading systems that use only clinical symptoms at treatment initiation such as the Minnesota risk identify standard and high-risk categories but lack a low-risk category suitable to minimize immunosuppressive strategies. We developed a new grading system that includes a low-risk stratum based on clinical symptoms alone and determined whether the incorporation of biomarkers would improve the model’s prognostic accuracy. We randomly divided 1863 patients in the Mount Sinai Acute GVHD International Consortium (MAGIC) who were treated for GVHD into training and validation cohorts. Patients in the training cohort were divided into 14 groups based on similarity of clinical symptoms and similar nonrelapse mortality (NRM); we used a classification and regression tree (CART) algorithm to create three Manhattan risk groups that produced a significantly higher area under the receiver operating characteristic curve (AUC) for 6-month NRM than the Minnesota risk classification (0.69 vs 0.64, P = .009) in the validation cohort. We integrated serum GVHD biomarker scores with Manhattan risk using patients with available serum samples and again used a CART algorithm to establish 3 MAGIC composite scores that significantly improved prediction of NRM compared to Manhattan risk (AUC, 0.76 vs 0.70, P = .010). Each increase in MAGIC composite score also corresponded to a significant decrease in day 28 treatment response (80% vs 63% vs 30%, P &lt; .001). We conclude that the MAGIC composite score more accurately predicts response to therapy and long-term outcomes than systems based on clinical symptoms alone and may help guide clinical decisions and trial design.

Abstract The significance of biomarkers in second-line treatment for acute graft-versus-host disease (GVHD) has not been well characterized. We analyzed clinical data and serum samples at the initiation of second-line systemic treatment of acute GVHD from 167 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC) between 2016 and 2021. Sixty-two patients received ruxolitinib-based therapy, whereas 102 received other systemic agents. In agreement with prospective trials, ruxolitinib resulted in a higher day 28 (D28) overall response Frate than nonruxolitinib therapies (55% vs 31%, P = .003) and patients who received ruxolitinib had significantly lower nonrelapse mortality (NRM) than those who received nonruxolitinib therapies (point estimates at 2-year: 35% vs 61%, P = .002). Biomarker analyses demonstrated that the benefit from ruxolitinib was observed only in patients with low MAGIC algorithm probabilities (MAPs) at the start of second-line treatment. Among patients with a low MAP, those who received ruxolitinib experienced significantly lower NRM than those who received nonruxolitinib therapies (point estimates at 2-year: 12% vs 41%, P = .016). However, patients with high MAP experienced high NRM regardless of treatment with ruxolitinib or nonruxolitinib therapies (point estimates at 2-year: 67% vs 80%, P = .65). A landmark analysis demonstrated that the relationship between the D28 response and NRM largely depends on the MAP level at the initiation of second-line therapy. In conclusion, MAP measured at second-line systemic treatment for acute GVHD predicts treatment response and NRM. The outcomes of patients with high MAP are poor regardless of treatment choice, and ruxolitinib appears to primarily benefit patients with low MAP.

Abstract BACKGROUND H3K27-altered diffuse midline glioma (DMG) is a devastating pediatric brainstem tumor that affects 200-300 individuals in the US per year. Median survival is 9-11 months, and there are virtually no long-term survivors. Despite decades of clinical trials, radiation therapy remains standard of care, extending survival by 2-3 months. Elucidating the mechanisms that drive H3K27-altered DMG pathogenesis in order to uncover therapeutic vulnerabilities is of critical importance. Recent studies implicate MALT1 as a potential therapeutic target in gliomas. MALT1 is the effector molecule of the CARMA-BCL10-MALT1 (CBM) signalosome, a cytoplasmic protein complex that drives downstream pro-survival transcriptional activity. MALT1, which possesses scaffolding and protease functions, promotes cell viability, proliferation, and migration/invasion in multiple cancer types. We aim to evaluate the hypotheses that MALT1 promotes DMG cancer cell proliferation and migration and that MALT1 inhibition will abrogate tumor progression. METHODS/RESULTS We screened a panel of cells including astrocytes, neural stem cells, and DMG cell lines by Western blot and found that CBM complex members BCL10 and MALT1 are present in all cells tested. We next demonstrated that MALT1 is proteolytically active in DMG cell lines SF8628 and HSJD-DIPG-007. Specifically, we showed cleavage of the MALT1 protease substrate HOIL, which was abrogated by treatment with the MALT1 protease inhibitor MLT-748. We next generated multiple dox-inducible MALT1 shRNA DMG cell lines to assess the impact of MALT1 deficiency on DMG biology. Thus far, we find that shRNA knockdown of MALT1 does not impact SF8628 cell proliferation. CONCLUSIONS MALT1 is expressed and proteolytically active in DMG cells. Initial studies show that MALT1 knockdown does not affect proliferation of SF8628 cells. We will next evaluate the effect of MALT1 knockdown on proliferation of additional DMG cell lines, as well as the impact on other malignant features of DMG cells including migration/invasion.