Potent, Gut-Restricted Inhibitors of Divalent Metal Transporter 1: Preclinical Efficacy against Iron Overload and Safety Evaluation.

Divalent metal transporter 1 (DMT1) cotransports ferrous iron and protons and is the primary mechanism for uptake of nonheme iron by enterocytes. Inhibitors are potentially useful as therapeutic agents to treat iron overload disorders such as hereditary hemochromatosis or ß-thalassemia intermedia, provided that inhibition can be restricted to the duodenum. We used a calcein quench assay to identify human DMT1 inhibitors. Dimeric compounds were made to generate more potent compounds with low systemic exposure. Direct block of DMT1 was confirmed by voltage clamp measurements. The lead compound, XEN602, strongly inhibits dietary nonheme iron uptake in both rats and pigs yet has negligible systemic exposure. Efficacy is maintained for >2 weeks in a rat subchronic dosing assay. Doses that lowered iron content in the spleen and liver by >50% had no effect on the tissue content of other divalent cations except for cobalt. XEN602 represents a powerful pharmacological tool for understanding the physiologic function of DMT1 in the gut. SIGNIFICANCE STATEMENT: This report introduces methodology to develop potent, gut-restricted inhibitors of divalent metal transporter 1 (DMT1) and identifies XEN602 as a suitable compound for in vivo studies. We also report novel animal models to quantify the inhibition of dietary uptake of iron in both rodents and pigs. This research shows that inhibition of DMT1 is a promising means to treat iron overload disorders.

Intrapartum ultrasound measurement of the lower uterine segment thickness in parturients with previous scar in labor: a cross-sectional study.

BACKGROUND: There is a lack of reliable methods to estimate the risk of uterine rupture or dehiscence during a trial of labor in women with previous cesarean sections. This study aimed to assess the lower uterine segment and myometrial thickness by ultrasonography in women with previous cesarean sections during labor and assess their association with the uterine defect. METHODS: A cross-sectional study was conducted on 161 women in the active phase of labor having one previous cesarean section. The study was conducted et al.-Azhar University Hospital, Assiut City, Egypt, from March 2018 to March 2019. Ultrasound measurements of lower uterine segment thickness and myometrial thickness were conducted by vaginal and abdominal ultrasound by two observers. The correlation of both thicknesses with the uterine defect was analyzed. RESULTS: Uterine defects were reported in 42 women (25.9%), uterine rupture in four women (2.5%), and dehiscence in 38 women (23.5%). The uterine defects were not associated with maternal factors (maternal age, gestational age at labor, body mass index, birth weight, interpregnancy, and inter-delivery interval). Receiver operating curve analysis demonstrated that lower uterine segment thickness was linked with uterine defect, with an area under the curve of 60% (95% CI, 51-70%, P = 0.044). Myometrial thickness was also linked to the uterine defect, with an area under the curve of 61% (95% CI, 52-71%, P = 0.025). Full lower uterine segment thickness of 2.3 mm and myometrial thickness of 1.9 mm were the cutoff value with the best combination of sensitivity and specificity for the uterine defect. Lower uterine segment thickness (OR = 0.49, 95%CI 0.24-0.96) and myometrial thickness (OR = 0.44, 95%CI 0.20-0.94) were significantly associated with the uterine defect. Lower uterine segment thickness (OR = 0.41, 95%CI 0.22-0.76) and myometrial thickness (OR = 0.33, 95%CI 0.16-0.66) were also significantly associated with cesarean section delivery. CONCLUSION: A lower uterine segment thickness of 2.3 mm and myometrial thickness of 1.9 mm during the first stage of labor are associated with a high risk of uterine defects during a labor trial. These measurements during labor can have a practical application in deciding the mode of delivery in women with previous cesarean sections and might reduce uterine rupture.

Magnetic resonance-guided focused ultrasound treatment for essential tremor shows sustained efficacy: a meta-analysis.

Although magnetic resonance-guided focused ultrasound (MRgFUS) is a viable treatment option for essential tremor, some studies note a diminished treatment benefit over time. A PubMed search was performed adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included if hand tremor scores (HTS), total Clinical Rating Scale for Tremor (CRST) scores, or Quality of Life in Essential Tremor Questionnaire (QUEST) scores at regular intervals following MRgFUS treatment for essential tremor were documented. Data analyses included a random effects model of meta-analysis and mixed-effects model of meta-regression. Twenty-one articles reporting HTS for 395 patients were included. Mean pre-operative HTS was 19.2 ± 5.0. Mean HTS at 3 months post-treatment was 7.4 ± 5.0 (61.5% improvement, p < 0.001). Treatment effect was mildly decreased at 36 months at 9.1 ± 5.4 (8.8% reduction). Meta-regression of time since treatment as a modifier of HTS revealed a downward trend in effect size, though this was not statistically significant (p = 0.208). Only 4 studies included follow-up ≥ 24 months. Thirteen included articles reported total CRST scores with standardized follow-up for 250 patients. Mean pre-operative total CRST score decreased by 46.2% at 3 months post-treatment (p < 0.001). Additionally, mean QUEST scores at 3 months post-treatment significantly improved compared to baseline (p < 0.001). HTS is significantly improved from baseline ≥ 24 months post-treatment and possibly ≥ 48 months post-treatment. There is a current paucity of long-term CRST and QUEST score reporting in the literature.

Clinico-Radiological Correlation in 26 Egyptian Children with Glutaric Acidemia Type 1.

BACKGROUND: Glutaric acidemia type 1 (GA1) is an inherited neurometabolic disease with significant morbidity. However, neuro-radiological correlation is not completely understood. OBJECTIVE: The study aimed to characterize the neuroimaging findings and their association with neurological phenotype in GA1 children. METHODS: Twenty-six Egyptian children (median age = 12 months) diagnosed with GA1 underwent clinical evaluation and brain magnetic resonance imaging (MRI). We objectively assessed the severity of neurological phenotype at the time of MRI using movement disorder (MD) and morbidity scores. Evaluation of brain MRI abnormalities followed a systematic and region-specific scoring approach. Brain MRI findings and scores were correlated with MD and morbidity scores, disease onset, and presence of seizures. RESULTS: Fifteen (57.7%) cases had insidious onset, eight (30.8%) manifested acute onset, whereas three (11.5%) were asymptomatic. Ten (38.5%) cases had seizures, five of which had no acute encephalopathic crisis. Putamen and caudate abnormalities (found in all acute onset, 93.3 and 73.3% of insidious onset, and one of three asymptomatic cases) were significantly related to MD (p = 0.007 and 0.013) and morbidity (p = 0.005 and 0.003) scores. Globus pallidus abnormalities (50% of acute onset, 46.7% of insidious onset, and one of three of asymptomatic cases) were significantly associated with morbidity score (p = 0.023). Other MRI brain abnormalities as well as gray and white matter score showed no significant association with neurological phenotype. Younger age at onset, acute onset, and seizures were significantly associated with worse neurological manifestations. CONCLUSION: Patients with GA1 manifest characteristic and region-specific brain MRI abnormalities, but only striatal affection appears to correlate with neurological phenotype.

Potent dual EGFR/Her4 tyrosine kinase inhibitors containing novel (1,2-dithiolan-4-yl)acetamides.

Modifications at C6 and C7 positions of 3-cyanoquinolines 6 and 7 led to potent inhibitors of the ErbB family of kinases particularly against EGFRWT and Her4 enzymes in the radioisotope filter binding assay. The lead (4, SAB402) displayed potent dual biochemical activities with EGFRWT/Her4 IC50 ratio of 80 due to its potent inhibition of Her4 activity (IC50 0.03 nM), however, the selectivity towards activating mutations (EGFRL858R, EGFRex19del) was decreased. Inhibitor 4 also exhibited excellent growth inhibition in seven different cancer types and reduced cell viability in female NMRI nude mice in the intraperitoneally implanted hollow fibers which have been loaded with MOLT-4 (leukemia) and NCI-H460 (NSCLC) cells in a statistically significant manner.

Depression and glioblastoma, complicated concomitant diseases: a systemic review of published literature.

Glioblastoma multiforme (GBM) is the most common primary brain cancer. Depression is a common co-morbidity of this condition. Despite this common interaction, relatively little research has been performed on the development of GBM-associated depression. We performed a literary search of the PubMed database for articles published relating to GBM and depression. A total of 85 articles were identified with 46 meeting inclusion criteria. Depression significantly impacts care, decreasing medication compliance, and patient survival. Diagnostically, because depression and GBM share intricate neuro-connectivity in a way that effect functionality, these diseases can be mistaken for alternative psychological or pathological disorders, complicating care. Therapeutically, anti-depressants have anti-tumor properties; yet, some have been shown to interfere with GBM treatment. One reason for this is that the pathophysiological development of depression and GBM share several pathways including altered regulation of the 5-HT receptor, norepinephrine, and 3':5'-cyclic monophosphate. Over time, depression can persist after GBM treatment, affecting patient quality of life. Together, depression and GBM are complicated concomitant diseases. Clinicians must be aware of their co-existence. Because of overlapping molecular pathways involved in both diseases, careful medication selection is imperative to avoid potential adverse interactions. Since GBMs are the most common primary brain cancer, physicians dealing with this disease should be prepared for the development of depression as a potential sequela of this condition, given the related pathophysiology and the known poor outcomes.

M2 segment thrombectomy is not associated with increased complication risk compared to M1 segment: A meta-analysis of recent literature.

INTRODUCTION: Recent clinical comparisons of M1 and M2 segment endovascular thrombectomy have reached incongruous results in rates of complication and functional outcomes. This study aims to clarify the controversy surrounding this rapidly advancing technique through literature review and meta-analysis. METHODS: A Pubmed search was performed (January 2015-September 2019) using the following keywords: "M2 AND ("stroke" OR "occlusion") AND ("thrombectomy" OR "endovascular")". Safety and clinical outcomes were compared between segments via weighted Student's t-test, Chi-square and odds ratio while study heterogeneity was analyzed using Cochran Q and I2 tests. RESULTS: Pubmed identified 208 articles and eleven studies were included after full-text analysis, comprising 2,548 M1 and 758 M2 mechanical thrombectomy segment cases. Baseline National Institutes of Health Stroke Scale scores were comparatively lower in patients experiencing an M2 occlusion (16 ± 1.25 vs 13.6 ± 0.96, p < 0.01). Patients who underwent M2 mechanical thrombectomy were more likely to experience both good clinical outcomes (modified Rankin Scale 0-2) (48.6% vs 43.5% respectively, OR 1.24; CI 1.05-1.47, p = 0.01) and excellent clinical outcomes (modified Rankin Scale 0-1) (34.7% vs. 26.5%%, OR 1.6; CI 1.28-1.99, p < 0.01) at 90 days compared to M1 mechanical thrombectomy. Neither recanalization rates (75.3% vs 72.8%, OR 0.92, CI 0.75-1.13, p = 0.44) nor symptomatic intracranial hemorrhage rates (5.6% vs 4.9%, OR 0.92; CI 0.61-1.39, p= 0.7) were significantly different between M1 and M2 cohorts. Mortality was less frequent in the M2 cohort compared to M1 (16.3% vs 20.7%, OR 0.73; CI 0.57-0.94, p = 0.01). M1 and M2 cohorts did not differ in symptom onset-to-puncture (238.1 ± 46.7 vs 239.8 ± 43.9 min respectively, p=0.488) nor symptom onset-to recanalization times (318.7 ± 46.6 vs 317.7 ± 71.1 min respectively, p = 0.772), though mean operative duration was shorter in the M2 cohort (61.8 ± 25.5 vs 54.6 ± 24 min, p < 0.01). CONCLUSIONS: Patients who underwent M2 mechanical thrombectomy had a higher prevalence of good and excellent clinical outcomes compared to the M1 mechanical thrombectomy cohorts. Additionally, our data suggest lower mortality rates in the M2 cohort and symptomatic intracranial hemorrhage rates that are similar to the M1 cohort. Therefore, M2 segment thrombectomy likely does not pose a significantly elevated operative risk and may have a positive impact on patient outcomes.

Treatment of Kienböck's Disease With Neutral Ulnar Variance by Distal Capitate Shortening and Arthrodesis to the Base of the Third Metacarpal Bone.

PURPOSE: We evaluated whether a surgical technique combining distal capitate shortening and arthrodesis to the base of the third metacarpal bone for the treatment of the early stages (stages II and IIIA) of Kienböck's disease with neutral ulnar variance resulted in pain relief, improvement in wrist motion, or changes in the radiographic evaluation. METHODS: This retrospective study reviewed 22 patients with early stages of Kienböck's disease with neutral ulnar variance, treated by distal capitate shortening and arthrodesis to the base of the third metacarpal bone. Patients were divided into 2 groups by disease stage: stage II (n = 12) and stage IIIA (n = 10). There were 8 women and 14 men, with an average age of 35.7 years. The following parameters were measured before and after surgery: visual analog scale (VAS) for pain evaluation, grip strength, range of motion (ROM), ulnar variance, carpal height index, lunate height index, and the scapholunate and scaphocapitate angles. The patients were evaluated in accordance with Modified Mayo Wrist Score (MMWS). RESULTS: The average follow-up period was 30.5 months (range, 26-36 months). The stage II group showed significant improvements in the mean VAS (58-5), ROM (57% to 73%), grip strength (54% to 75%), and MMWS (51-78). Patients in the stage IIIA group showed nonsignificant changes in mean VAS score (64-42.5), ROM (52.5% to 55.5%), grip strength (46.5% to 57.5%), and MMWS (36-50.5). Significant decreases in the carpal height index and scaphocapitate angle, and an increase in scapholunate angle in all stage IIIA patients were observed. CONCLUSIONS: Distal capitate shortening with capitometacarpal arthrodesis can alleviate pain and improve ROM and grip strength in patients with stage II Kienböck's disease, but not in those with stage IIIA. Moreover, it cannot prevent carpal collapse, especially in stage IIIA of the disease. We do not recommend this technique for treating stage IIIA patients. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Fully laparoscopic left-sided donor hepatectomy is safe and associated with shorter hospital stay and earlier return to work: A comparative study.

Living donor liver transplantation has failed to become a major means of transplantation in the United States, where <5% of the transplants are performed with living donors. At least 30% to 50% of the complications of donor hepatectomy appear to be related to abdominal wall trauma, including hernia, bowel obstruction, and chronic abdominal discomfort. We analyzed our experience with laparoscopically procured donor hepatectomy. We compared 22 full laparoscopic donor hepatectomies to 20 open/hybrid hepatectomies over an 11-year period. Donor and recipient demographics, complications, and graft and recipient outcomes were analyzed. All 22 laparoscopically procured liver allografts were transplanted successfully. The laparoscopically procured grafts took longer to procure (7 hours 58 minutes versus 6 hours 38 minutes; P < 0.001). The laparoscopically procured cases had lower blood loss (177.3 versus 3753 cc; P < 0.001), a shorter length of stay, and significantly reduced days off work (P = .01). The 1-year graft survival was not different (90% in the laparoscopic group and 85% in the open group; P = 0.70). The 1-year patient survival was not different (95% in the laparoscopic group and 85% in the open group; P = 0.32). There was a trend toward lower wound issues in the laparoscopic group, but this did not reach significance (the hybrid/open group had a 15% hernia rate versus 5% for the laparoscopic group). In experienced living donor centers, laparoscopic liver donation appears to be feasible for all pediatric recipients and some adult recipients. Outcomes for the recipients of laparoscopically procured grafts do not appear significantly different from outcomes with hybrid/open techniques.

CNS Demyelination Syndromes Following COVID-19 Vaccination: A Case Series.

Background and Objectives: Although immunization against coronavirus disease 2019 (COVID-19) is ongoing, adverse reactions to these vaccinations have been observed in isolated cases. We aimed to report different neurological complications developed after COVID-19 vaccination. Materials and Methods: In our case series study, we report all cases of CNS demyelination following COVID-19 immunization. Clinical evaluation, brain MRI, and CSF analysis for oligoclonal bands and IgG index were performed for all patients. Other investigations were performed for selected patients, including spine MRI, EEG, VEP, and aquaporin-4. Results: Eighteen patients (eight males and ten females) with no history of COVID-19 infection had neurological manifestations (vertigo, ataxia, recurrent attacks of loss of consciousness, optic neuritis, and myelitis) starting within 14 days after Pfizer (n = 12) and AstraZeneca (n = 6) vaccination. MRI was obtained during the acute stage of the disease. The most common presenting symptoms were optic neuritis and hemiparesis. Sixteen patients had altered signal intensity and multiple variable-sized, round to ill-defined oval lesions suggestive of MS. Two showed findings compatible with transverse myelitis. Conclusion: This study identified CNS demyelination complications after COVID-19 vaccination. The COVID-19 vaccination could result in CNS complications, possibly connected to a post-vaccination inflammatory process. We recommend continuous post-marketing monitoring for adverse reactions in individuals who received the vaccines to establish a connection and guarantee the long-term safety of COVID-19 vaccines.

Augmented Reality Registration System for Visualization of Skull Landmarks.

BACKGROUND: Augmented reality (AR) is an emerging technology in neurosurgery with the potential to become a strategic tool in the delivery of care and education for trainees. Advances in technology have demonstrated promising use for improving visualization and spatial awareness of critical neuroanatomic structures. In this report, we employ a novel AR registration system for the visualization and targeting of skull landmarks. METHODS: A markerless AR system was used to register 3-dimensional reconstructions of suture lines onto the head via a head-mounted display. Participants were required to identify craniometric points with and without AR assistance. Targeting error was measured as the Euclidian distance between the user-defined location and the true craniometric point on the subjects' heads. RESULTS: All participants successfully registered 3-dimensional reconstructions onto the subjects' heads. Targeting accuracy was significantly improved with AR (3.59 ± 1.29 mm). Across all target points, AR increased accuracy by an average of 19.96 ± 3.80 mm. Posttest surveys revealed that participants felt the technology increased their confidence in identifying landmarks (4.6/5) and that the technology will be useful for clinical care (4.2/5). CONCLUSIONS: While several areas of improvement and innovation can further enhance the use of AR in neurosurgery, this report demonstrates the feasibility of a markerless headset-based AR system for visualizing craniometric points on the skull. As the technology continues to advance, AR is expected to play an increasingly significant role in neurosurgery, transforming how surgeries are performed and improving patient care.

Does Tighter Glycemic Control Beyond Hemoglobin A1c of 8% Improve Outcome for Lumbar Spine Surgery? A MSSIC Study.

BACKGROUND AND OBJECTIVES: Diabetes mellitus is associated with increased risk of postoperative adverse outcomes. Previous studies have emphasized the role of glycemic control in postoperative complications. This study aims to ascertain whether controlling hemoglobin A1c (HbA1c) lower than 8% preoperatively results in meaningful risk reduction or improved outcomes. METHODS: We used patient-level data from the Michigan Spine Surgery Improvement Collaborative registry, focusing on patients who underwent elective lumbar spine surgery between 2018 and 2021. The primary outcomes were length of stay and the occurrence of postoperative adverse events. Secondary outcomes included patient satisfaction, achievement of a minimum clinically important difference (MCID) of Patient-Reported Outcomes Measurement Information System-Physical Function, the EuroQol-5D and NRS of leg and back pain, and return to work. RESULTS: A total of 11 348 patients were included in this analysis. Patients with HbA1c above the thresholds before surgery had significantly higher risks of urinary retention for all 3 possible threshold values (incidence rate ratio [IRR] = 1.30, P = .015; IRR = 1.35, P = .001; IRR = 1.25, P = .011 for the HbA1c cutoffs of 8%, 7.5%, and 7%, respectively). They also had longer hospital stay (IRR = 1.04, P = .002; IRR = 1.03, P = .001; IRR = 1.03, P < .001 for the HbA1c cutoffs of 8%, 7.5%, and 7%, respectively) and had higher risks of developing any complication with HbA1c cutoff of 7.5% (IRR = 1.09, P = .010) and 7% (IRR = 1.12, P = .001). Diabetics with preoperative HbA1c above all 3 thresholds were less likely to achieve Patient-Reported Outcomes Measurement Information System MCID at the 90-day follow-up (IRR = .81, P < .001; IRR = .86, P < .001; IRR = .90, P = .007 for the HbA1c cutoffs of 8%, 7.5%, and 7%, respectively) and less likely to achieve EuroQol-5D MCID at the 2-year follow-up (IRR = .87, P = .027; IRR = .84, P = .005 for the HbA1c cutoffs of 7.5% and 7%, respectively). CONCLUSION: Our study suggests that reducing HbA1c below 8% may have diminishing returns regarding reducing complications after spine surgery.

The impact of serum albumin levels on postoperative complications in lumbar and cervical spine surgery: an analysis of the Michigan Spine Surgery Improvement Collaborative registry.

OBJECTIVE: Patients with serum albumin levels < 3.5 g/dL are considered malnourished, but there is a paucity of data regarding the outcomes of patients with albumin levels > 3.5 g/dL. The objective of this study was to evaluate the effect of albumin on postoperative outcome in patients undergoing elective cervical and lumbar spine procedures. METHODS: The Michigan Spine Surgery Improvement Collaborative database was queried for lumbar and cervical fusion surgeries between January 2020 and December 2022. Patients were grouped by preoperative serum albumin levels: < 3.5 g/dL, 3.5-3.7 g/dL, 3.8-4.0 g/dL, and > 4.0 g/dL. Primary outcomes included urinary retention, ileus, dysphagia, surgical site infection (SSI), readmission within 30 and 90 days, return to the operating room, and length of stay (LOS) ≥ 4 days. Multivariate analysis was conducted to adjust for potential confounders. RESULTS: This study included 15,629 lumbar cases and 6889 cervical cases. Within the lumbar cohort, an albumin level of 3.5-3.7 g/dL was associated with an increased risk of readmission at 30 days (p = 0.048) and 90 days (p = 0.005) and an LOS ≥ 4 days (p < 0.001). An albumin level of 3.8-4.0 g/dL was associated with an increased risk of an LOS ≥ 4 days (p < 0.001). Within the cervical cohort, an albumin level of 3.5-3.7 g/dL was associated with an increased risk of SSI (p = 0.023), readmission at 30 days (p < 0.002) and 90 days (p < 0.001), return to the operating room (p = 0.002), and an LOS ≥ 4 days (p < 0.001). An albumin level of 3.8-4.0 g/dL was associated with an increased risk of readmission at 30 days (p = 0.012) and 90 days (p = 0.001) and an LOS ≥ 4 days (p < 0.001). CONCLUSIONS: This study maintains that patients with hypoalbunemia undergoing spine surgery are at risk for postoperative adverse events. However, there also exist significant associations between borderline serum albumin levels of 3.5-4.0 g/dL and increased risk of postoperative adverse events.

The impact of anxiety and depression on lumbar spine surgical outcomes: a Michigan Spine Surgery Improvement Collaborative study.

OBJECTIVE: The presence of depression and anxiety has been associated with negative outcomes in spine surgery patients. While it seems evident that a history of depression or anxiety can negatively influence outcome, the exact additive effect of both has not been extensively studied in a multicenter trial. The purpose of this study was to investigate the relationship between a patient's history of anxiety and depression and their patient-reported outcomes (PROs) after lumbar surgery. METHODS: Patients in the Michigan Spine Surgery Improvement Collaborative registry undergoing lumbar spine surgery between July 2016 and December 2021 were grouped into four cohorts: those with a history of anxiety only, those with a history of depression only, those with both, and those with neither. Primary outcomes were achieving the minimal clinically important difference (MCID) for the Patient-Reported Outcomes Measurement Information System Physical Function 4-item Short Form (PROMIS PF), EQ-5D, and numeric rating scale (NRS) back pain and leg pain, and North American Spine Society patient satisfaction. Secondary outcomes included surgical site infection, hospital readmission, and return to the operating room. Multivariate Poisson generalized estimating equation models were used to report incidence rate ratios (IRRs) from patient baseline variables. RESULTS: Of the 45,565 patients identified, 3941 reported a history of anxiety, 5017 reported a history of depression, 9570 reported both, and 27,037 reported neither. Compared with those who reported having neither, patients with both anxiety and depression had lower patient satisfaction at 90 days (p = 0.002) and 1 year (p = 0.021); PROMIS PF MCID at 90 days (p < 0.001), 1 year (p < 0.001), and 2 years (p = 0.006); EQ-5D MCID at 90 days (p < 0.001), 1 year (p < 0.001), and 2 years (p < 0.001); NRS back pain MCID at 90 days (p < 0.001) and 1 year (p < 0.001); and NRS leg pain MCID at 90 days (p < 0.001), 1 year (p = 0.024), and 2 years (p = 0.027). Patients with anxiety only (p < 0.001), depression only (p < 0.001), or both (p < 0.001) were more likely to be readmitted within 90 days. Additionally, patients with anxiety only (p = 0.015) and both anxiety and depression (p = 0.015) had higher rates of surgical site infection. Patients with anxiety only (p = 0.006) and depression only (p = 0.021) also had higher rates of return to the operating room. CONCLUSIONS: The authors observed an association between a history of anxiety and depression and negative outcome after lumbar spine surgery. In addition, they found an additive effect of a history of both anxiety and depression with an increased risk of negative outcome when compared with either anxiety or depression alone.

Bone Grafting Options for Single-Level TLIF: So Many Options, What Is the Evidence?

BACKGROUND: This review seeks to investigate the clinically relevant bone graft materials in single-level transforaminal lumbar interbody fusion (TLIF) procedures as defined by (1) primary outcomes (ie, fusion rates and complication rates) and (2) patient-reported outcomes (ie, visual analog scale [VAS] and Oswestry disability index [ODI]). Because of the advantages in stimulating bone growth, autologous bone grafts such as the iliac crest bone graft (ICBG) have been the gold standard. Numerous alternatives to ICBG have been introduced. Understanding the risks and benefits of bone graft options is vital to optimizing patient care. METHODS: A PubMed search was performed for all clinical studies published between January 2008 and March 2023 that referenced the single-level TLIF procedure as well as one of the following grafts: autograft, allograft, bone morphogenetic protein (BMP), demineralized bone matrix, or mesenchymal stem cells (MSCs). Case studies and reports were excluded. RESULTS: Twenty-eight studies met the inclusion criteria. Studies from the PubMed search demonstrated similarly high fusion rates across nearly all graft materials, the lone exception being MSCs, which showed lower fusion rates. ICBG grafts experienced higher rates of postoperative graft site pain. The BMP graft material had high rates of radiculitis, heterogeneous ossification, and vertebral osteolysis. Patients saw an overall improvement in VAS and ODI scores with all graft materials. CONCLUSION: Local autografts and ICBG have been the most studied. Fusion rates during single-level TLIF were similar across all graft materials except MSCs. Patient-reported pain levels improved after TLIF surgery regardless of the type of grafts used. While BMP implants have shown promising benefits, they have introduced a new array of complications not normally seen in ICBG implants. The study is limited by the lack of evidence of certain graft materials as well as nonuniformity in metrics evaluating the efficacy of graft materials.

Non-alcoholic fatty liver disease is associated with decreased bone mineral density in upper Egyptian patients.

Nonalcoholic fatty liver disease (NAFLD) has been linked with a number of extra hepatic diseases and could be a potential risk factor of decreasing bone mineral density. To determine whether Upper Egyptian patients with NAFLD are at risk of developing osteoporosis. Cross sectional study was done on a total 100 individuals; 50 patients diagnosed with NAFLD (based on ultrasound imaging) crossed-matched with 50 individuals without NAFLD based on age, sex and body mass index. Bone mineral density, serum calcium and phosphorus levels, serum parathyroid hormone, serum vitamin D and fasting insulin level were assessed. Osteoporosis was prevalent in NAFLD patients versus to controls (19/50 vs. 0/50; P < 0.001). There was significant decrease in bone mineral density in NAFLD patients than controls (- 2.29 ± 0.4 vs. - 1.53 ± 0.1; P < 0.001). There was a statistical significance decrease in serum vitamin D and calcium levels in NAFLD patients than controls. Furthermore, vitamin D levels in the NAFLD group was a predictor for osteoporosis (OR 0.614; 95% CI 0.348-0.825). Patients with NAFLD tend to have a significant decrease in bone density, vitamin D, and serum calcium levels than controls.

The Potential Negative Effects of Smoking on Cervical and Lumbar Surgery Beyond Pseudarthrosis: A Michigan Spine Surgery Improvement Collaborative Study.

OBJECTIVE: To review the Michigan Spine Surgery Improvement Collaborative registry to investigate the long-term associations between current smoking status and outcomes after elective cervical and lumbar spine surgery. METHODS: Using the Michigan Spine Surgery Improvement Collaborative, we captured all cases from January 1, 2017, to November 21, 2020, with outcomes data available; 19,251 lumbar cases and 7936 cervical cases were included. Multivariate regression analyses were performed to assess the relationship of smoking with the clinical outcomes. RESULTS: Current smoking status was associated with lower urinary retention and satisfaction for patients after lumbar surgery and was associated with less likelihood of achieving minimal clinically important difference in primary outcome measures including Patient-Reported Outcomes Measurement Information System, back pain, leg pain, and EuroQol-5D at 90 days and 1 year after surgery. Current smokers were also less likely to return to work at 90 days and 1 year after surgery. Among patients who underwent cervical surgery, current smokers were less likely to have urinary retention and dysphagia postoperatively. They were less likely to be satisfied with the surgery outcome at 1 year. Current smoking was associated with lower likelihood of achieving minimal clinically important difference in Patient-Reported Outcomes Measurement Information System, neck pain, arm pain, and EuroQol-5D at various time points. There was no difference in return-to-work status. CONCLUSIONS: Our analysis suggests that smoking is negatively associated with functional improvement, patient satisfaction, and return-to-work after elective spine surgery.

Postoperative opioid prescription and patient-reported outcomes after elective spine surgery: a Michigan Spine Surgery Improvement Collaborative study.

OBJECTIVE: This study was designed to assess how postoperative opioid prescription dosage could affect patient-reported outcomes after elective spine surgery. METHODS: Patients enrolled in the Michigan Spine Surgery Improvement Collaborative (MSSIC) from January 2020 to September 2021 were included in this study. Opioid prescriptions at discharge were converted to total morphine milligram equivalents (MME). A reference value of 225 MME per week was used as a cutoff. Patients were divided into two cohorts based on prescribed total MME: ≤ 225 MME and > 225 MME. Primary outcomes included patient satisfaction, return to work status after surgery, and whether improvement of the minimal clinically important difference (MCID) of the Patient-Reported Outcomes Measurement Information System 4-question short form for physical function (PROMIS PF) and EQ-5D was met. Generalized estimated equations were used for multivariate analysis. RESULTS: Regression analysis revealed that patients who had postoperative opioids prescribed with > 225 MME were less likely to be satisfied with surgery (adjusted OR [aOR] 0.81) and achieve PROMIS PF MCID (aOR 0.88). They were also more likely to be opioid dependent at 90 days after elective spine surgery (aOR 1.56). CONCLUSIONS: The opioid epidemic is a serious threat to national public health, and spine surgeons must practice conscientious postoperative opioid prescribing to achieve adequate pain control. The authors' analysis illustrates that a postoperative opioid prescription of 225 MME or less is associated with improved patient satisfaction, greater improvement in physical function, and decreased opioid dependence compared with those who had > 225 MME prescribed.

Genomic characterization of SARS-CoV-2 in Egypt: insights into spike protein thermodynamic stability.

The overall pattern of the SARS-CoV-2 pandemic so far has been a series of waves; surges in new cases followed by declines. The appearance of novel mutations and variants underlie the rises in infections, making surveillance of SARS-CoV-2 mutations and prediction of variant evolution of utmost importance. In this study, we sequenced 320 SARS-CoV-2 viral genomes isolated from patients from the outpatient COVID-19 clinic in the Children's Cancer Hospital Egypt 57357 (CCHE 57357) and the Egypt Center for Research and Regenerative Medicine (ECRRM). The samples were collected between March and December 2021, covering the third and fourth waves of the pandemic. The third wave was found to be dominated by Nextclade 20D in our samples, with a small number of alpha variants. The delta variant was found to dominate the fourth wave samples, with the appearance of omicron variants late in 2021. Phylogenetic analysis reveals that the omicron variants are closest genetically to early pandemic variants. Mutation analysis shows SNPs, stop codon mutation gain, and deletion/insertion mutations, with distinct patterns of mutations governed by Nextclade or WHO variant. Finally, we observed a large number of highly correlated mutations, and some negatively correlated mutations, and identified a general inclination toward mutations that lead to enhanced thermodynamic stability of the spike protein. Overall, this study contributes genetic and phylogenetic data, as well as provides insights into SARS-CoV-2 viral evolution that may eventually help in the prediction of evolving mutations for better vaccine development and drug targets.