The effects of age, mature oocyte number, and cycle number on cumulative live birth rates after planned oocyte cryopreservation.

PURPOSE: To examine the effects of age, mature oocyte number, and cycle number on cumulative live birth rates after planned oocyte cryopreservation (OC), with the goal of developing a patient counselling tool. METHODS: We performed a retrospective cohort study of all patients with ≥ 1 autologous oocyte thaw at our university-affiliated fertility center before 12/31/2023. Patients were included if they (1) had a live birth or ongoing pregnancy > 12 weeks from OC, or (2) used all oocytes and euploid/untested embryos from OC. Primary outcome was cumulative live birth / ongoing pregnancy rate (CLBR). RESULTS: 527 patients with 1 OC cycle, 149 patients with 2 OC cycles, and 55 patients with ≥ 3 OC cycles were included. Overall CLBR was 43%. CLBR was > 70% among patients who thawed ≥ 20 mature oocytes that were cryopreserved at age < 38 years. Multiple logistic regression showed that age at first OC and total number of mature oocytes thawed independently predicted CLBR, but number of OC cycles did not. CONCLUSION: Patients must be counselled that younger age at OC and more mature oocytes improve CLBR. However, additional OC cycles do not independently improve CLBR. Our results can help patients decide whether to pursue additional OC cycles to obtain more oocytes.

Progression of brain injuries associated with methotrexate chemotherapy in childhood acute lymphoblastic leukemia.

BACKGROUND: Brain bases and progression of methotrexate-associated neurotoxicity and cognitive disturbances remain unknown. We tested whether brain abnormalities worsen in proportion to intrathecal methotrexate(IT-MTX) doses. METHODS: In this prospective, longitudinal study, we recruited 19 patients with newly diagnosed acute lymphoblastic leukemia 4-to-20 years of age and 20 matched controls. We collected MRI and neuropsychological assessments at a pre-methotrexate baseline and at week 9, week 22, and year 1 during treatment. RESULTS: Patients had baseline abnormalities in cortical and subcortical gray matter(GM), white matter(WM) volumes and microstructure, regional cerebral blood flow, and neuronal density. Abnormalities of GM, blood flow, and metabolites worsened in direct proportions to IT-MTX doses. WM abnormalities persisted until week 22 but normalized by year 1. Brain injuries were localized to dorsal and ventral attentional and frontoparietal cognitive networks. Patients had cognitive deficits at baseline that persisted at 1-year follow-up. CONCLUSIONS: Baseline abnormalities are likely a consequence of neuroinflammation and oxidative stress. Baseline abnormalities in WM microstructure and volumes, and blood flow persisted until week 22 but normalized by year 1, likely due to treatment and its effects on reducing inflammation. The cytotoxic effects of IT-MTX, however, likely contributed to continued, progressive cortical thinning and reductions in neuronal density, thereby contributing to enduring cognitive deficits. IMPACT: Brain abnormalities at a pre-methotrexate baseline likely are due to acute illness. The cytotoxic effects of intrathecal MTX contribute to progressive cortical thinning, reductions in neuronal density, and enduring cognitive deficits. Baseline white matter abnormalities may have normalized via methotrexate treatment and decreasing neuroinflammation. Corticosteroid and leucovorin conferred neuroprotective effects. Our findings suggest that the administration of neuroprotective and anti-inflammatory agents should be considered even earlier than they are currently administered. The neuroprotective effects of leucovorin suggest that strategies may be developed that extend the duration of this intervention or adapt it for use in standard risk patients.

Construct length analysis of type B and C cervical and thoracolumbar fractures.

Objectives: The purpose of this study is to identify if construct length affects the rate of surgical complications and instrumentation revision following surgical fixation of subaxial and thoracolumbar Type B and C fractures. This study evaluates the effect of ankylosing spondylitis/diffuse idiopathic skeletal hyperostosis (AS/DISH) within this population on outcomes. Methods: Retrospective review of 91 cervical and 89 thoracolumbar Type B and C fractures. Groups were divided by construct length for analysis: short-segment (constructs spanning two or less segments adjacent to the fracture) and long-segment (constructs spanning more than two segments adjacent to the vertebral fracture). Results: For cervical fractures, construct length did not impact surgical complications (P = 0.641), surgical hardware revision (P = 0.167), or kyphotic change (P = 0.994). For thoracolumbar fractures, construct length did not impact surgical complications (P = 0.508), surgical hardware revision (P = 0.224), and kyphotic change (P = 0.278). Cervical Type B fractures were nonsignificantly more likely to have worsened kyphosis (P = 0.058) than Type C fractures. Assessing all regions of the spine, a diagnosis of AS/DISH was associated with an increase in kyphosis (P = 0.030) and a diagnosis of osteoporosis was associated with surgical hardware failure (P = 0.006). Conclusion: Patients with short-segment instrumentation have similar surgical outcomes and changes in kyphosis compared to those with long-segment instrumentation. A diagnosis of AS/DISH or osteoporosis was associated with worse surgical outcomes.

Optimizing early phase clinical trial washout periods: a report from the therapeutic advances in childhood leukemia and lymphoma (TACL) consortium.

PURPOSE: The National Cancer Institute (NCI) issued a 2021 memorandum adopting the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) task force recommendations to broaden clinical study eligibility criteria. They recommended that washout periods be eliminated for most prior cancer therapy and when required, to utilize evidence/rationale-based criteria. The Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) consortium responded to this guidance. PROCESS: A TACL task force reviewed the consortium's research portfolio, the relevant literature and guidance documents from ASCO-Friends, NCI, and US Food and Drug Administration (FDA) to make expert consensus and evidence-based recommendations for modernizing, broadening and codifying TACL-study washout periods while ensuring consistency with pediatric ethics and federal regulations. TACL's screening log was reviewed to estimate the impact that updated washout periods would have on patient inclusivity and recruitment. RESULTS: Over a 19-year period, 42 patients (14.6% of all screened ineligible (n = 287) patients), were identified as excluded from TACL early-phase studies exclusively due to not meeting washout criteria. An additional six (2.1%) did not meet washout and at least one other exclusion criterion. A new TACL washout guidance document was developed/adopted for use. Where washout criteria were not eliminated, rationale/evidenced-based criteria were established with citation. CONCLUSION: In an effort to reduce unnecessary exclusion from clinical trials, TACL created rationale/evidenced-based washout period standards largely following guidance from the NCI/ASCO-Friends recommendations. These new, expanded eligibility criteria are expected to increase access to TACL clinical trials while maintaining safety and scientific excellence.

How emotion is experienced and expressed in multiple cultures: a large-scale experiment across North America, Europe, and Japan.

Core to understanding emotion are subjective experiences and their expression in facial behavior. Past studies have largely focused on six emotions and prototypical facial poses, reflecting limitations in scale and narrow assumptions about the variety of emotions and their patterns of expression. We examine 45,231 facial reactions to 2,185 evocative videos, largely in North America, Europe, and Japan, collecting participants' self-reported experiences in English or Japanese and manual and automated annotations of facial movement. Guided by Semantic Space Theory, we uncover 21 dimensions of emotion in the self-reported experiences of participants in Japan, the United States, and Western Europe, and considerable cross-cultural similarities in experience. Facial expressions predict at least 12 dimensions of experience, despite massive individual differences in experience. We find considerable cross-cultural convergence in the facial actions involved in the expression of emotion, and culture-specific display tendencies-many facial movements differ in intensity in Japan compared to the U.S./Canada and Europe but represent similar experiences. These results quantitatively detail that people in dramatically different cultures experience and express emotion in a high-dimensional, categorical, and similar but complex fashion.

Impact of Preoperative Intervertebral Disc Degeneration on Patient-Reported Outcome Measures After Lumbar Fusion.

OBJECTIVE: The Pfirrmann scoring system classifies lumbosacral disc degeneration based on MRI signal intensity. The relationship between pre-existing disc degeneration and PROMs after one-level lumbar fusion is not well documented. The purpose of this study was to investigate the relationship between the severity of preoperative intervertebral disc degeneration and pre- and postoperative patient-reported outcome measures (PROMs) in patients undergoing one-level lumbar fusion. METHODS: All adult patients underwent posterior lumbar decompression and fusion (PLDF) or transforaminal lumbar interbody fusion (TLIF) between 2014-2022 were included. Patient demographics, and comorbidities were extracted from medical records. Lumbar intervertebral discs on sagittal MRI T2-weighted images were assessed by two independent graders utilizing Pfirrmann criteria. Grades I-III were categorized as low-grade disc degeneration, while IV-V were considered high-grade. Multivariable linear regression assessed the impact of disc degeneration on PROMS. RESULTS: A total of 150 patients were included, of which, 69 (46%) had low grade disc degeneration, while 81 (54%) had high grade degeneration. Patients with high-grade degeneration had increased preoperative VAS-Leg scores (6.10 vs. 4.54, p=0.005) and displayed greater one-year postoperative improvements in VAS-Back scores (-2.11 vs -0.66, p=0.002). Multivariable regression demonstrated Pfirrmann scores as independent predictors for both preoperative VAS-Leg scores (p=0.004) and postoperative VAS-Back improvement (p=0.005). CONCLUSIONS: In patients undergoing one-level lumbar fusion, higher Pfirmann scores were associated with increased preoperative leg pain and greater one-year postoperative improvement in back pain. Further studies into the relationship of pre-operative disc degeneration and their impact on postoperative outcomes may help guide clinical decision making and patient expectations.

The Effect of Patient Resilience on Postoperative Scores After One and Two-level Anterior Cervical Discectomy and Fusion.

OBJECTIVE: The purpose is to investigate the association between resilience and outcomes of pain and neck-related disability after single- and two-level anterior cervical discectomy and fusion (ACDF). METHODS: Patients who underwent single- or two-level ACDF were sent a survey between six months and two years following surgery. The survey included the Brief Resilience Scale (BRS), Visual Analogue Scale (VAS) for pain, Neck Disability Index (NDI), and Pain Self-Efficacy Questionnaire (PSEQ-2). Patients completed the VAS and NDI twice, once describing preoperative pain and disability and once describing current pain and disability. Respondents were classified as high resilience (HR), medium resilience (MR), or low resilience (LR). Demographics, PSEQ-2 scores, pre- and postoperative VAS and NDI scores, and change in VAS (ΔVAS) and NDI (ΔNDI) scores were compared between groups. RESULTS: Thirty-three patients comprised the HR group, 273 patients comprised the MR group, and 47 patients comprised the LR group. All groups demonstrated postoperative improvement in VAS and NDI scores that exceeded previously established MCID values. The HR group demonstrated greater improvement in pain compared to the LR group (ΔVAS: -5.8 for HR vs -4.4 for LR, p=0.05). Compared to the MR group, the LR group demonstrated greater postoperative pain (VAS: 3.2 for LR vs 2.5 for MR, p=0.02) and disability (NDI: 11.9 for LR vs 8.6 for MR, p=0.02). CONCLUSIONS: Patients demonstrated improvement in pain and neck-related disability after single- and two-level ACDF, regardless of resilience score. Patients with greater resilience may be expected to demonstrate more improvement in pain after ACDF.

Which North American spine society disc herniation morphology descriptors are most associated with improvements in clinical outcomes after microdiscectomy?

Background: The North American Spine Society (NASS) assembled the first ever comprehensive naming system for describing lumbar disc disease, including lumbar disc herniation. The objectives of this study were (1) to determine which NASS descriptors are most predictive of independent patient-reported outcomes after microdiscectomy and (2) to identify the inter-rater reliability of each NASS descriptor. Methods: Adult patients (≥18 years) who underwent a lumbar microdiscectomy from 2014-2021 were retrospectively identified. Patient-reported outcome measures (PROMs) were collected at preoperative, 3-month, and 1-year postoperative time points. Lumbar disc herniations were evaluated and classified on preoperative MRI using the NASS lumbar disc nomenclature specific to disc herniation. Results: About 213 microdiscectomy patients were included in the final analysis. Herniation descriptors exhibiting the greatest reliability included sequestration status (κ=0.83), axial disc herniation area (κ=0.83), and laterality (κ=0.83). The descriptor with the lowest inter-rater reliability was direction of migration (κ=0.53). At 3 months, a sequestered herniation was associated with lower odds of achieving the minimal clinically important difference (MCID) for ODI (p=.004) and MCS (p=.032). At 12 months, a similar trend was observed for Oswestry Disability Index (ODI) MCID achievement (p=.001). At 3 months, a herniation with larger axial area was a predictor of MCID achievement in ODI (p=.004) and the mental component summary (MCS) (p=.009). Neither association persisted at 12 months; however, larger axial disc herniation area was able to predict MCID achievement in the Visual Analogue Scale (VAS) leg (p=.031) at 12 months. Conclusions: The utility of the NASS nomenclature system in predicting postoperative outcomes after microdiscectomy has yet to be studied. We showed that sequestration status and disc area are both reliable and able to predict the odds of achieving MCID in certain clinical outcomes at 3 months and 12 months after surgery. Hence, preoperative imaging analysis of lumbar disc herniations may be useful in accurately setting patient expectations.

Ex vivo biomechanical evaluation of tissue construct strength in an equine colopexy model.

OBJECTIVE: To compare strength of left paramedian colopexies using various techniques in equine ex vivo models. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Equine cadavers euthanized for nongastrointestinal pathology (36 specimens derived from 9 horses). METHODS: Colopexies were performed after euthanasia. Suture pattern (horizontal mattress vs. cruciate) and incorporation of dorsal sheath of the rectus abdominis (partial-thickness) versus incorporation of dorsal and ventral sheath of the rectus abdominis (full-thickness) were evaluated. Single cycle load to failure, work to peak load, stiffness, and mode of failure of colopexy tissue constructs were assessed. RESULTS: Mean load to failure of all constructs ranged from 102.26 to 166.38 N. Partial-thickness bites demonstrated a mean load to failure and standard deviation (SD) of 111.91 (35.88) N and 102.26 (30.06) N (p < .05) which was significantly lower than the mean and SD of full-thickness bites (166.3 [72.42] N and 163.21 [51.40 N]), respectively. All full-thickness bites regardless of suture pattern and over half of partial-thickness bites failed at the colonic wall. There was no significant difference in load to failure compared to mode of failure. CONCLUSION: A stronger colopexy was achieved with a full-thickness bite regardless of the suture pattern. The most common mode of failure was the colon wall. CLINICAL SIGNIFICANCE: Incorporating ventral and dorsal fascia of the rectus abdominus provided a stronger colopexy structure, which may necessitate a second incision or subcutaneous palpation of the needle when performing a colopexy. The lateral band of the colon failed in most constructs (77%) regardless of technique, which could weaken the colonic wall and risk colonic rupture.

Progerin Can Induce DNA Damage in the Absence of Global Changes in Replication or Cell Proliferation.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic condition characterized by features of accelerated aging, and individuals with HGPS seldom live beyond their mid-teens. The syndrome is commonly caused by a point mutation in the LMNA gene which codes for lamin A and its splice variant lamin C, components of the nuclear lamina. The mutation causing HGPS leads to production of a truncated, farnesylated form of lamin A referred to as "progerin." Progerin is also expressed at low levels in healthy individuals and appears to play a role in normal aging. HGPS is associated with an accumulation of genomic DNA double-strand breaks (DSBs) and alterations in the nature of DSB repair. The source of DSBs in HGPS is often attributed to stalling and subsequent collapse of replication forks in conjunction with faulty recruitment of repair factors to damage sites. In this work, we used a model system involving immortalized human cell lines to investigate progerin-induced genomic damage. Using an immunofluorescence approach to visualize phosphorylated histone H2AX foci which mark sites of genomic damage, we report that cells engineered to express progerin displayed a significant elevation of endogenous damage in the absence of any change in the cell cycle profile or doubling time of cells. Genomic damage was enhanced and persistent in progerin-expressing cells treated with hydroxyurea. Overexpression of wild-type lamin A did not elicit the outcomes associated with progerin expression. Our results show that DNA damage caused by progerin can occur independently from global changes in replication or cell proliferation.

Factors Related to Clinical Performance in Spine Surgery Fellowship: Can We Predict Success.

INTRODUCTION: The factors most important in the spine fellowship match may not ultimately correlate with quality of performance during fellowship. This study examined the spine fellow applicant metrics correlated with high application rank compared with the metrics associated with the strongest clinical performance during fellowship. METHODS: Spine fellow applications at three academic institutions were retrieved from the San Francisco Match database (first available to 2021) and deidentified for application review. Application metrics pertaining to research, academics, education, extracurriculars, leadership, examinations, career interests, and letter of recommendations were extracted. Attending spine surgeons involved in spine fellow selection at their institutions were sent a survey to rank (1) fellow applicants based on their perceived candidacy and (2) the strength of performance of their previous fellows. Pearson correlation assessed the associations of application metrics with theoretical fellow rank and actual performance. RESULTS: A total of 37 spine fellow applications were included (Institution A: 15, Institution B: 12, Institution C: 10), rated by 14 spine surgeons (Institution A: 6, Institution B: 4, Institution C: 4). Theoretical fellow rank demonstrated a moderate positive association with overall research, residency program rank, recommendation writer H-index, US Medical Licensing Examination (USMLE) scores, and journal reviewer positions. Actual fellow performance demonstrated a moderate positive association with residency program rank, recommendation writer H-index, USMLE scores, and journal reviewer positions. Linear regressions identified journal reviewer positions (ß = 1.73, P = 0.002), Step 1 (ß = 0.09, P = 0.010) and Step 3 (ß = 0.10, P = 0.002) scores, recommendation writer H-index (ß = 0.06, P = 0.029, and ß = 0.07, P = 0.006), and overall research (ß = 0.01, P = 0.005) as predictors of theoretical rank. Recommendation writer H-index (ß = 0.21, P = 0.030) and Alpha Omega Alpha achievement (ß = 6.88, P = 0.021) predicted actual performance. CONCLUSION: Residency program reputation, USMLE scores, and a recommendation from an established spine surgeon were important in application review and performance during fellowship. Research productivity, although important during application review, was not predictive of fellow performance. LEVEL OF EVIDENCE: III. STUDY DESIGN: Cohort Study.

DNA sequence and chromatin differentiate sequence-specific transcription factor binding in the human malaria parasite Plasmodium falciparum.

Development of the malaria parasite, Plasmodium falciparum, is regulated by a limited number of sequence-specific transcription factors (TFs). However, the mechanisms by which these TFs recognize genome-wide binding sites is largely unknown. To address TF specificity, we investigated the binding of two TF subsets that either bind CACACA or GTGCAC DNA sequence motifs and further characterized two additional ApiAP2 TFs, PfAP2-G and PfAP2-EXP, which bind unique DNA motifs (GTAC and TGCATGCA). We also interrogated the impact of DNA sequence and chromatin context on P. falciparum TF binding by integrating high-throughput in vitro and in vivo binding assays, DNA shape predictions, epigenetic post-translational modifications, and chromatin accessibility. We found that DNA sequence context minimally impacts binding site selection for paralogous CACACA-binding TFs, while chromatin accessibility, epigenetic patterns, co-factor recruitment, and dimerization correlate with differential binding. In contrast, GTGCAC-binding TFs prefer different DNA sequence context in addition to chromatin dynamics. Finally, we determined that TFs that preferentially bind divergent DNA motifs may bind overlapping genomic regions due to low-affinity binding to other sequence motifs. Our results demonstrate that TF binding site selection relies on a combination of DNA sequence and chromatin features, thereby contributing to the complexity of P. falciparum gene regulatory mechanisms.

Immediate Versus Delayed Venous Thromboembolism Prophylaxis Following Spine Surgery: Increased Rate of Unplanned Reoperation for Postoperative Hematoma with Immediate Prophylaxis.

BACKGROUND CONTEXT: There is significant variability in postoperative chemoprophylaxis protocols amongst spine providers due to perceived risks and benefits, but limited data on the topic. At our institution, both orthopaedic spine and neurosurgery departments utilize unfractionated subcutaneous heparin in identical dosages and frequency, with the only difference being time to initiation postoperatively. PURPOSE: To evaluate the rate of symptomatic venous thromboembolism (VTEs) and unplanned reoperation for hematoma based on timing of chemoprophylaxis initiation. STUDY DESIGN/SETTING: Single institution retrospective cohort study PATIENT SAMPLE: Patients undergoing elective spine surgery, excluding patients undergoing surgery in the setting of trauma, malignancy, or infection OUTCOME MEASURES: Outcome measures included the diagnosis of a venous thromboembolism within 90 days of surgery and unplanned reoperation for a hematoma METHODS: Patients undergoing elective spine surgery from 2017 to 2021 were grouped based on chemoprophylaxis protocol. In the "immediate" group, patients received subcutaneous heparin 5000 units every 8 hours starting immediately after surgery, and in the "delayed" group, patients received chemoprophylaxis starting postoperative day (POD)-2 for any decompressions and/or fusions involving a spinal cord level (i.e., L2 and above) and POD-1 for those involving only levels below the spinal cord (i.e., L3 to pelvis). A cox proportional hazards model was created to assess independent predictors of venous thromboembolic events, while a logistic regression was utilized for unplanned reoperations for hematoma. RESULTS: Of 8,704 patients, a total of 98 (1.13%) VTE events occurred, of which 43 (0.49%) were pulmonary embolism. Fifty-four patients (0.62%) had unplanned reoperations for postoperative hematomas. On cox proportional hazards model analysis, immediate chemoprophylaxis was not protective of a venous thromboembolism (Hazard Ratio: 1.18, p=0.436), but, it was a significant independent predictor for unplanned reoperation for hematoma on multivariable logistic regression modeling (Odds Ratio: 3.29, p<0.001). CONCLUSIONS: Both chemoprophylaxis protocols in our study resulted in low rates of VTE and postoperative hematoma. However, our findings suggest that the delayed chemoprophylaxis protocol may mitigate postoperative hematoma formation without increasing the risk for a thrombotic event.

Physical and Psychological Impact of Scar Cosmesis after Cervical Spine Fusion Surgery.

INTRODUCTION: Patients' and surgeons' perceptions of cutaneous scarring can vary, causing unpleasant physical and psychological outcomes. This study aims to bridge the current scientific literature gap and understand the impact of patient-perceived scar cosmesis after anterior and posterior cervical spine surgery. METHODS: Retrospective review of patients ≥18 years old who underwent anterior or posterior cervical spine surgery from 2017 to 2022 at a large, urban academic group. To select patients with adequate time for surgical scar maturation, only patients who were greater than six months post-surgery were included. The SCAR-Q survey, a surgical scar assessment tool, was administered to patients to assess patient perceptions of scar symptomatology, appearance, and psychosocial impact. Scores range from 0 to 100, with 100 as the best outcome. An additional 5-item Likert scale question was administered to assess overall surgical satisfaction. RESULTS: All 854 respondents who completed the survey were stratified into two groups"Unsatisfied vs Satisfied." Patients who were "unsatisfied" with their surgery had the lowest outcome scores for SCAR-Q appearance, symptom, and psychosocial scores than those who were "satisfied" (p<0.001). Females had significantly higher/"more favorable" responses for SCAR-Q Appearance (77.5 vs. 82.8 p<0.001) and Psychosocial (87.4 vs. 94.3 p<0.001) scores compared to males. Regression analysis performed for each component score showed that increases in all three component scores were significant in patients in the satisfied group. CONCLUSIONS: Our study demonstrates that cervical spine surgery patients unsatisfied with their surgical outcome have lower scar-related scores, highlighting the impact of cosmetic closure and appearance.

Improved Clinical Outcomes After Partial Repair and In-Situ Biceps Tenodesis for the Treatment of Massive Irreparable Rotator Cuff Tears.

PURPOSE: The aim of this study was to present the short-term outcomes of arthroscopic in-situ biceps tenodesis combined with partial rotator cuff repair in patients with massive irreparable rotator cuff tears (MIRCT) and minimal arthritis. METHODS: A retrospective review was conducted utilizing prospectively maintained institutional databases to identify patients who had undergone a partial rotator cuff repair with in-situ biceps tenodesis between March 2017 to December 2022. Patients were included if they (1) were diagnosed pre- or intra-operatively with MIRCT, and (2) had complete pre-operative and minimum 1-year post-operative patient-reported outcome measures. RESULTS: Thirty-nine patients met the eligibility criteria and were included for analysis. The mean age of the study participants was 65 ± 7 years (range: 46 - 76) with 76.9% (n = 30) being male. The average follow-up was 21 ± 12 months (range: 12 - 58). Patients experienced significant improvement in visual analog scale for pain (VAS), American Shoulder and Elbow Surgeons (ASES) score, and subjective assessment numeric evaluation (SANE) score (p < 0.001 for all comparisons). The pre- to post-operative improvement was 3.1 ± 2.3 for VAS, 27.5 ± 20.6 for ASES, and 31.3 ± 24.8 for SANE. Postoperatively, the average scores for VAS, ASES, and SANE were 1.3 ± 1.5, 79.5 ± 17.0, and 69.6 ± 20.1, respectively. Twenty-six patients (66.7%) achieved the minimal clinically important difference (MCID) for VAS, thirty-three patients (84.6%) achieved the MCID for ASES, and thirty patients (76.9%) achieved the MCID for SANE.. CONCLUSIONS: Partial rotator cuff repair with in-situ biceps tenodesis is an effective treatment for MIRCT, leading to significant improvements in patient-reported outcome and range of motion measures compared to preoperative conditions.

Postoperative opioid consumption patterns diverge between propensity matched patients undergoing traumatic and elective cervical spine fusion.

BACKGROUND CONTEXT: Prolonged opioid therapy following spine surgery is an ongoing postoperative concern. While prior studies have investigated postoperative opioid use patterns in the elective cervical surgery patient population, to our knowledge, opioid use patterns in patients undergoing surgery for traumatic cervical spine injuries have not been elucidated. PURPOSE: The purpose of this study was to compare opioid use and prescription patterns in the postoperative pain management of patients undergoing traumatic and elective cervical spine fusion surgery. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Adult patients with traumatic cervical injuries who underwent primary anterior cervical discectomy and fusion (ACDF) or posterior cervical decompression and fusion (PCDF) during their initial hospital admission. The propensity matched, control group consisted of adult elective cervical fusion patients who underwent primary ACDF or PCDF. OUTCOME MEASURES: Demographic data, surgical characteristics, spinal disease diagnosis, location of cervical injury, procedure type, operative levels fused, and Prescription Drug Monitoring Program (PDMP) data. PDMP data included the number of opioid prescriptions filled, preoperative opioid use, postoperative opioid use, and use of perioperative benzodiazepines, muscle relaxants, or gabapentin. Opioid consumption data was collected in morphine milligram equivalents (MME) and standardized per day. METHODS: A 1:1 propensity match was performed to match traumatic injury patients undergoing cervical fusion surgery with elective cervical fusion patients. Traumatic injury patients were matched based on age, sex, CCI, procedure type, and cervical levels fused. Pre- and postoperative opioid, benzodiazepine, muscle relaxant, and gabapentin use were assessed for the traumatic injury and elective patients. T- or Mann-Whitney U tests were used to compare continuous data and Chi-Squared or Fisher's Exact were used to compare categorical data. Multivariate stepwise regression using MME per day 0 - 30 days following surgery as the dependent outcome was performed to further evaluate associations with postoperative opioid use. RESULTS: A total of 48 patients underwent fusion surgery for a traumatic cervical spine injury and 48 elective cervical fusion with complete PDMP data were assessed. Elective patients were found to fill more prescriptions (3.19 vs. 0.65, p=.023) and take more morphine milligram equivalents (MME) per day (0.60 vs. 0.04, p=.014) within 1 year prior to surgery in comparison to traumatic patients. Elective patients were also more likely to use opioids (29.2% vs. 10.4%, p=.040) and take more MMEs per day (0.70 vs. 0.05, p=.004) within 30 days prior to surgery. Within 30 days postoperatively, elective patients used opioids more frequently (89.6% vs. 52.1%, p<.001) and took more MMEs per day (3.73 vs. 1.71, p<.001) than traumatic injury patients. Multivariate stepwise regression demonstrated preoperative opioid use (Estimate: 1.87, p=.013) to be correlated with higher postoperative MME per day within 30 days of surgery. Surgery after traumatic injury was correlated with lower postoperative MME use per day within 30 days of surgery (Estimate: -1.63 p=.022). CONCLUSION: Cervical fusion patients with a history of traumatic spine injury consume fewer opioids in the early postoperative period in comparison to elective cervical fusion patients, however both cohorts consumed a similar amount after the initial 30-day postoperative period. Preoperative opioid use was also a risk factor for higher consumption in the short-term postoperative period. These results may aid physicians in further understanding patients' postoperative care needs based on presenting injury characteristics and highlights the need for enhanced follow-up care for traumatic cervical spine injury patients after fusion surgery.

Maternal vitamin D levels during pregnancy and offspring schizophrenia.

BACKGROUND: Findings from previous studies on maternal 25(OH)D levels during pregnancy and offspring schizophrenia are limited and inconsistent. METHODS: We used nationwide population-based register data with a nested case-control design to examine the association between maternal 25(OH)D levels during pregnancy and offspring schizophrenia. The cases of schizophrenia (n = 1145) were born from 1987 to 1997, and received a diagnosis of schizophrenia by 2017, and were matched with equal number of controls. A quantitative immunoassay was used to measure maternal 25(OH)D in archived maternal serum in the national biobank of the Finnish Maternity Cohort, collected during the first and early second trimesters. Conditional logistic regression models examined the association between maternal 25(OH)D levels and offspring schizophrenia. RESULTS: No significant association was found between log-transformed maternal 25(OH)D levels and schizophrenia in unadjusted (OR 0.96, 95 % CI 0.78-1.17, p = 0.69) or adjusted analyses (aOR 0.98, 95 % CI 0.79-1.22, p = 0.89). Analyses by quintiles also revealed no association between the lowest quintile of maternal 25(OH)D levels and schizophrenia (OR 1.09, 95 % CI 0.81-1.45, p = 0.55; aOR 1.06, 95 % CI 0.78-1.45, p = 0.71). Maternal 25(OH)D levels, measured in categories, either in deficient category (OR 1.07 (0.85-1.35), p = 0.52; aOR 1.05 (0.81-1.34), p = 0.88) or insufficient category (OR 1.13, 95 % CI 0.92-1.40, p = 0.23; aOR 1.13, 95 % CI 0.90-1.41, p = 0.27) were also not associated with offspring schizophrenia. CONCLUSIONS: Maternal vitamin D levels in early pregnancy were not associated with offspring schizophrenia. Future studies measuring vitamin D during different stages of gestation are needed to draw firm conclusions.

PKD1 mutant clones within cirrhotic livers inhibit steatohepatitis without promoting cancer.

Somatic mutations in non-malignant tissues are selected for because they confer increased clonal fitness. However, it is uncertain whether these clones can benefit organ health. Here, ultra-deep targeted sequencing of 150 liver samples from 30 chronic liver disease patients revealed recurrent somatic mutations. PKD1 mutations were observed in 30% of patients, whereas they were only detected in 1.3% of hepatocellular carcinomas (HCCs). To interrogate tumor suppressor functionality, we perturbed PKD1 in two HCC cell lines and six in vivo models, in some cases showing that PKD1 loss protected against HCC, but in most cases showing no impact. However, Pkd1 haploinsufficiency accelerated regeneration after partial hepatectomy. We tested Pkd1 in fatty liver disease, showing that Pkd1 loss was protective against steatosis and glucose intolerance. Mechanistically, Pkd1 loss selectively increased mTOR signaling without SREBP-1c activation. In summary, PKD1 mutations exert adaptive functionality on the organ level without increasing transformation risk.

Riluzole for Degenerative Cervical Myelopathy: A Secondary Analysis of the CSM-PROTECT Trial.

Importance: The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. Objective: To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. Design, Setting, and Participants: This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical trial conducted from January 2012 to May 2017. Adult surgical patients with DCM with moderate to severe myelopathy (mJOA scale score of 8-14) were randomized to receive either riluzole or placebo. The present study was conducted from July to December 2023. Intervention: Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery. Main Outcomes and Measures: The primary outcome measure was a difference in clinical improvement from baseline to 1-year follow-up, assessed using a global statistical test (GST). The 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS), arm and neck pain numeric rating scale (NRS) scores, American Spinal Injury Association (ASIA) motor score, and Nurick grade were combined into a single summary statistic known as the global treatment effect (GTE). Results: Overall, 290 patients (riluzole group, 141; placebo group, 149; mean [SD] age, 59 [10.1] years; 161 [56%] male) were included. Riluzole showed a significantly higher probability of global improvement compared with placebo at 1-year follow-up (GTE, 0.08; 95% CI, 0.00-0.16; P = .02). A similar favorable global response was seen at 35 days and 6 months (GTE for both, 0.07; 95% CI, -0.01 to 0.15; P = .04), although the results were not statistically significant. Riluzole-treated patients had at least a 54% likelihood of achieving better outcomes at 1 year compared with the placebo group. The ASIA motor score and neck and arm pain NRS combination at 1 year provided the best-fit parsimonious model for detecting a benefit of riluzole (GTE, 0.11; 95% CI, 0.02-0.16; P = .007). Conclusions and Relevance: In this secondary analysis of the CSM-PROTECT trial using a global outcome technique, riluzole was associated with improved clinical outcomes in patients with DCM. The GST offered probability-based results capable of representing diverse outcome scales and should be considered in future studies assessing spine surgery outcomes.

The attainment of a patient acceptable symptom state in patients undergoing revision spine fusion.

INTRODUCTION: Revision lumbar fusion is most commonly due to nonunion, adjacent segment disease (ASD), or recurrent stenosis, but it is unclear if diagnosis affects patient outcomes. The primary aim of this study was to assess whether patients achieved the patient acceptable symptom state (PASS) or minimal clinically important difference (MCID) after revision lumbar fusion and assess whether this was influenced by the indication for revision. METHODS: We retrospectively identified all 1-3 level revision lumbar fusions at a single institution. Oswestry Disability Index (ODI) was collected at preoperative, three-month postoperative, and one-year postoperative time points. The MCID was calculated using a distribution-based method at each postoperative time point. PASS was set at the threshold of ≤ 22. RESULTS: We identified 197 patients: 56% with ASD, 28% with recurrent stenosis, and 15% with pseudarthrosis. The MCID for ODI was 10.05 and 10.23 at three months and one year, respectively. In total, 61% of patients with ASD, 52% of patients with nonunion, and 65% of patients with recurrent stenosis achieved our cohort-specific MCID at one year postoperatively with ASD (p = 0.78). At one year postoperatively, 33.8% of ASD patients, 47.8% of nonunion patients, and 37% of patients with recurrent stenosis achieved PASS without any difference between indication (p = 0.47). CONCLUSIONS: The majority of patients undergoing revision spine fusion experience significant postoperative improvements regardless of the indication for revision. However, a large proportion of these patients do not achieve the patient acceptable symptom state. While revision spine surgery may offer substantial benefits, these results underscore the need to manage patient expectations.