Does A Hinged Operating Table Facilitate Sagittal Correction in Transforaminal Lumbar Interbody Fusion With Smith-Peterson Osteotomy? A Radiographic Analysis.

BACKGROUND: Osteotomies allow the restoration of appropriate sagittal alignment; however, closure of osteotomies can be challenging. Typical closure involves compressing pedicle screw heads across the rods, potentially causing screw loosening and failure. Motorized hinged operating tables are often used to assist with controlled closure of osteotomies without manual compression, but there is no published research quantifying the amount of correction provided solely by changes in the table angle. QUESTION/PURPOSE: What is the incremental amount of correction achieved by change in the table angle versus instrumented manipulation during osteotomy closure in transforaminal lumbar interbody fusion (TLIF) with Smith-Petersen osteotomy? METHODS: Sixty-one patients undergoing Smith-Peterson osteotomy and bilateral TLIF using a motorized hinged table from October 2019 to March 2022 were prospectively enrolled. Two patients did not undergo surgery, two did not have table extension, and seven did not have data collected intraoperatively because of disruptions in research protocols owing to the coronavirus-19 pandemic. Fifty patients (24 male, 26 female) who underwent a total of 73 osteotomies were included in the final analysis. The mean ± standard deviation age was 61 ±11 years, and the mean BMI was 31 ± 6 kg/m2. Patients were positioned prone on the table and flexed to 10° for decompression, Smith-Petersen osteotomy, and TLIF. The table was then extended in 5° increments, and radiographs were taken until 10° of extension was achieved or the osteotomy was fully closed. Changes in segmental lordosis across the operative site for each 5° increment were measured to the nearest degree by two reviewers. Intraclass correlation coefficients for segmental lordosis measurements at each table angle change were calculated as 0.97 to 0.98, with all p values < 0.001, indicating excellent agreement. RESULTS: Table change from 10° to 5° yielded a mean segmental lordosis change of 1.9° ± 1.5° (73 osteotomies), 5° to 0° yielded a change of 1.3° ± 0.9° (73 osteotomies), 0° to -5° yielded a change of 1.3° ± 1.0° (69 osteotomies), and -5° to -10° yielded a change of 1.1° ± 1.3° (61 osteotomies). Rod placement and compression yielded a mean 1.8° ± 2.0° of additional segmental lordosis. CONCLUSION: Using a motorized hinged table facilitated an average of 5.6° of total segmental lordosis correction during controlled Smith-Peterson osteotomy closure without the need for cantilevering forces across spinal instrumentation. Surgeons can use this technique to reduce the compression forces needed to close osteotomies, which could eliminate a potential source of complications.Level of Evidence Level II, therapeutic study.

Sacroiliac joint fusion navigation: how accurate is pin placement?

OBJECTIVE: Sacroiliac joint (SIJ) fusion utilizing intraoperative navigation requires a standard reference frame, which is often placed using a percutaneous pin. Proper placement ensures the correct positioning of SIJ fusion implants. There is currently no grading scheme for evaluation of pin placement into the pelvis. The purpose of this study was to evaluate the occurrence of ideal percutaneous pin placement into the posterior ilium during navigated SIJ fusion. METHODS: After IRB approval was obtained, electronic medical records and intraoperative computed tomography images of patients who underwent navigated SIJ fusion by the senior author between October 2013 and January 2020 were reviewed. A pin placement grading scheme and the definition of "ideal" placement were developed by the authors and deemed acceptable by fellow attending surgeons. Six attending surgeons completed two rounds of pin placement grading, and statistical analysis was conducted. RESULTS: Of 90 eligible patients, 73.3% had ideal pin placement, 17.8% medial/lateral breach, and 8.9% complete miss. Male patients were 3.7 times more likely to have ideal placement than females (p < 0.05). There was no relationship between BMI, SIJ fusion laterality, or pin placement laterality and ideal placement. Interobserver reliability was 0.72 and 0.70 in the first and second rounds, respectively, and defined as "substantial agreement." Intraobserver reliability ranged from 0.74 (substantial agreement) to 0.92 (almost perfect agreement). CONCLUSIONS: Nonideal pin placement occurred in 26.7% of cases, but a true "miss" into the sacrum was rare. Ideal pin placement was more likely in males and was not associated with BMI, SIJ fusion laterality, or pin placement laterality. The grading scheme developed has high intraobserver and interobserver reliability, indicating that it is reproducible and can be used for future studies. When placing percutaneous pins, surgeons must be aware of factors that can decrease placement accuracy, regardless of location.

Fluid Intake in the First Week of Life and the Duration of Hemodynamically Significant Patent Ductus Arteriosus in Extremely Preterm Infants.

OBJECTIVE: This study aimed to determine the association between daily fluid intake and the duration of hemodynamically significant patent ductus arteriosus (hsPDA). STUDY DESIGN: This is a retrospective cohort study of extremely preterm infants (<29 weeks) admitted in the Neonatal Intensive Care Unit of the Advent Health for Children from January 2013 to March 2016, if hsPDA was diagnosed in first week of life and serial echocardiograms were available. Diagnosis of hsPDA was based on a scoring system and its duration was estimated from serial echocardiograms. Cohort was divided into two groups based on duration of hsPDA (<1week, group A and ≥1 week, group B). Daily fluid intake was categorized as prescribed and actual. Prescribed volume was ordered by clinicians based on birth weight, not including trophic feeds, intravenous (IV) boluses or transfusions, etc. Actual intake was calculated by the electronic medical records based on daily weights and included all enteral or parenteral fluids. Multivariate analysis was performed to determine an association between total daily fluid intake over the first week of life and the duration of hsPDA. Two groups were compared to observe the difference between prescribed and actual daily fluid intakes. RESULTS: We enrolled 50 infants in group A and 76 in group B. Infants in group B were of significantly lower gestation and required prolonged ventilation and hospitalization. An association between higher fluid intake in the first 2 days of life and prolonged duration of hsPDA was confirmed by multivariate analysis. Actual fluid intake was significantly higher than prescribed total fluid intake in first 4 days of life for infants in both groups. CONCLUSION: In extremely preterm infants, higher fluid intake in first 2 days of life is associated with prolonged duration of hsPDA. Actual daily fluid intake can be significantly higher than prescribed daily fluids due to daily weight changes and additional fluid administration. KEY POINTS: · In preterm infants, actual daily fluid intake may be higher than prescribed volume.. · Higher daily fluid intake in first week of life is associated with prolonged duration of PDA.. · PDA scoring system can be helpful for objective assessment of PDA in preterm infants..

D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice.

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) have been discovered in several cancer types and cause the neurometabolic syndrome D2-hydroxyglutaric aciduria (D2HGA). The mutant enzymes exhibit neomorphic activity resulting in production of D2-hydroxyglutaric acid (D-2HG). To study the pathophysiological consequences of the accumulation of D-2HG, we generated transgenic mice with conditionally activated IDH2(R140Q) and IDH2(R172K) alleles. Global induction of mutant IDH2 expression in adults resulted in dilated cardiomyopathy, white matter abnormalities throughout the central nervous system (CNS), and muscular dystrophy. Embryonic activation of mutant IDH2 resulted in more pronounced phenotypes, including runting, hydrocephalus, and shortened life span, recapitulating the abnormalities observed in D2HGA patients. The diseased hearts exhibited mitochondrial damage and glycogen accumulation with a concordant up-regulation of genes involved in glycogen biosynthesis. Notably, mild cardiac hypertrophy was also observed in nude mice implanted with IDH2(R140Q)-expressing xenografts, suggesting that 2HG may potentially act in a paracrine fashion. Finally, we show that silencing of IDH2(R140Q) in mice with an inducible transgene restores heart function by lowering 2HG levels. Together, these findings indicate that inhibitors of mutant IDH2 may be beneficial in the treatment of D2HGA and suggest that 2HG produced by IDH mutant tumors has the potential to provoke a paraneoplastic condition.

Moral distress in public health practice: Case studies from nursing education.

Moral distress in critical care nursing has been well studied; however, there is a gap in the literature related to moral distress among nurses and nursing students practicing in the community. This paper describes moral distress experienced during participation in the Interprofessional Care Access Network, a community-based nurse-led education and practice program providing longitudinal care coordination for underserved individuals and families in rural communities and urban neighborhoods. Two case studies represent client situations resulting in moral distress for nursing faculty and students. Contributing factors include unaddressed social determinants creating barriers to health and health care; inexperience and discomfort with people living in extreme poverty; lack of access to critical services for the most vulnerable; and powerlessness to influence discriminatory systems. Strategies are described to reduce moral distress and build moral resilience among students and faculty practicing in the community. Research is needed to expand understanding of causes, interventions, and consequences of moral distress in public health nursing.

The unique histidine in OSCP subunit of F-ATP synthase mediates inhibition of the permeability transition pore by acidic pH.

The permeability transition pore (PTP) is a Ca2+-dependent mitochondrial channel whose opening causes a permeability increase in the inner membrane to ions and solutes. The most potent inhibitors are matrix protons, with channel block at pH 6.5. Inhibition is reversible, mediated by histidyl residue(s), and prevented by their carbethoxylation by diethylpyrocarbonate (DPC), but their assignment is unsolved. We show that PTP inhibition by H+ is mediated by the highly conserved histidyl residue (H112 in the human mature protein) of oligomycin sensitivity conferral protein (OSCP) subunit of mitochondrial F1FO (F)-ATP synthase, which we also show to undergo carbethoxylation after reaction of mitochondria with DPC. Mitochondrial PTP-dependent swelling cannot be inhibited by acidic pH in H112Q and H112Y OSCP mutants, and the corresponding megachannels (the electrophysiological counterpart of the PTP) are insensitive to inhibition by acidic pH in patch-clamp recordings of mitoplasts. Cells harboring the H112Q and H112Y mutations are sensitized to anoxic cell death at acidic pH. These results demonstrate that PTP channel formation and its inhibition by H+ are mediated by the F-ATP synthase.

The Vaping Epidemic in Adolescents.

Electronic cigarette (e-cigarette) use has recently risen to the forefront of medical discussions across the country. A significant increase in e-cigarette use by adolescents has been observed over the last decade. This article discusses the targeting of adolescents by e-cigarette companies. It looks at how teenagers are uniquely affected by nicotine and at risk for progressing to using combustible cigarettes and marijuana. Lastly, it discusses the role of physicians in combating the spread of e-cigarettes.

Incorporating Group Interviews Into Holistic Review in Baccalaureate Nursing School Admissions.

Holistic review in admissions considers an applicant's background and experience in combination with academic achievement. In order to evaluate baccalaureate nursing school applicants more holistically, a school of nursing added group interviews as part of the admissions process. The school's Admission and Progression Committee consulted with other schools, developed interview questions, and implemented a strategy to interview applicants. Results of this process were high levels of candidate and faculty satisfaction and enrollment of a diverse cohort of students with a high preadmission grade point average. Areas for improvement and further research are discussed.

Discovery of selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors with pain efficacy in mice.

The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain. Unfortunately, drugs thought to garner efficacy via Nav1 inhibition have undesirable side effect profiles due to their lack of selectivity over channel isoforms. Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization. This effort produced inhibitors such as compound 5 with excellent potency, selectivity, behavioral efficacy in a rodent pain model, and efficacy in a mouse itch model suggestive of target modulation.

Common questions about the initial management of hypertension.

Hypertension is the most common chronic condition treated by family physicians. Elevated blood pressure is associated with an increased risk of heart failure, myocardial infarction, cerebrovascular disease, and death. Treatment of hypertension reduces the risk of these events. Several lifestyle modifications are associated with improvements in blood pressure, including the Dietary Approaches to Stop Hypertension diet, sodium restriction, regular exercise, and moderate weight loss. There is strong evidence that reducing diastolic blood pressure to less than 90 mm Hg is beneficial in adults older than 30 years. Although there is good evidence to support reducing systolic blood pressure to less than 150 mm Hg in adults older than 60 years, the evidence in younger adults is insufficient to recommend a specific goal. Black patients with chronic kidney disease who are treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to a blood pressure of less than 140/90 mm Hg experience slower declines in glomerular filtration rates than patients treated with other medications. A blood pressure goal of less than 140/90 mm Hg is recommended in patients with chronic kidney disease and in those with diabetes mellitus. Thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers are the preferred medications in nonblack patients; thiazide diuretics and calcium channel blockers are preferred in black patients.

A Novel Surgical Indication for Scheuermann's Kyphosis.

Scheuermann kyphosis can be treated surgically to restore proper sagittal alignment. Thoracic curves >70° are typically indicated for surgical intervention. However, patients who have reached their natural limit of compensatory lumbar hyperlordosis are at risk of accelerated degeneration. This can be determined by comparing lumbar lordosis on standing neutral radiographs and supine extension radiographs. Minimal additional lordosis in extension compared with neutral, abutment of the spinous processes, or greater lumbar lordosis standing than with attempted extension suggest the patient is maximally compensated. We present a case of an adolescent boy with Scheuermann kyphosis who had reached the limit of his hyperlordosis compensation reserve. He subsequently underwent a T4 to L2 posterior spinal fusion with T7 to T11 Ponte Smith-Petersen grade two osteotomies. He tolerated the procedure well with no intraoperative complications or neuromonitoring changes. The patient has continued to do well and progressed to normal activity at 5-month follow-up.

Association Between Antibiotic Duration and Recurrence of Urinary Tract Infection in the Neonatal Critical Care Unit.

OBJECTIVES: Urinary tract infection (UTI) is the most common bacterial infection in infants. Current practice guidelines suggest a treatment duration of 7 to 14 days. Suboptimal therapy may increase the risk for recurrent UTIs leading to renal scarring and possibly chronic kidney disease. The primary objective is to evaluate the duration of therapy for UTIs and its association with the incidence of recurrent UTIs in a neonatal intensive care unit (NICU). The secondary objectives are to identify the risk factors and the most common organisms for recurrent UTIs. METHODS: Patients were identified via the diagnosis codes for UTIs and were included if admitted to the NICU and if they received antibiotics prior to hospital discharge. Patients were divided into 2 groups: antibiotic treatment for 7 days or fewer and antibiotic treatment for greater than 7 days. RESULTS: Eighty-six infants were included in the study. Twenty-six patients received antibiotics for 7 days or fewer, and 60 for more than 7 days. In the study, the median birth weight was 977 g and the median gestational age was 27.6 weeks. There was no significant difference in the rate of recurrent UTIs between the 2 groups (p = 0.66). However, in the subgroup analysis, the incidence was higher for patients receiving antibiotic therapy for fewer than 7 days versus 7 days (p = 0.03). CONCLUSION: There was no difference in recurrence of UTI between treatment groups (≤7 days versus >7 days), and recurrence was seen in a higher percentage of patients with a urinary tract anomaly.

TKI Type Switching Overcomes ROS1 L2086F in ROS1 Fusion-Positive Cancers.

Purpose: Despite the robust efficacy of ROS1 tyrosine kinase inhibitors (TKIs) in ROS1-positive non-small cell lung cancer, TKI resistance continues to hamper durability of the therapeutic response. The resistance liabilities of next-generation ROS1 TKI are sparsely characterized. Design: We compared the activity of type I TKIs (crizotinib, entrectinib, taletrectinib, lorlatinib, and repotrectinib) to the type II TKIs (cabozantinib and merestinib), and to the type I FLT3 inhibitor, gilteritinib, in CD74-ROS1 wildtype and F2004C, L2026M, G2032R, or L2086 mutant Ba/F3 cells. The findings from the Ba/F3 cell model were confirmed using NIH3T3 colony formation assays and in vivo tumor growth. CRISPR/Cas9 gene editing was used to generate isogenic wildtype and L2086F mutant TPM3-ROS1 expressing patient-derived cell lines. These lines were used to further evaluate TKI activity using cell viability and immunoblotting methods. Molecular modeling studies enabled the characterization of structural determinants of TKI sensitivity in wildtype and mutant ROS1 kinase domains. We also report clinical cases of ROS1 TKI resistance that were treated with cabozantinib. Results: ROS1 L2086F mutant kinase is resistant to type I TKI including crizotinib, entrectinib, lorlatinib, repotrectinib, taletrectinib, while the type II TKI cabozantinib and merestinib retain activity. Additionally, we found that gilteritinib, a type I FLT3 inhibitor, inhibited wildtype and L2086F mutant ROS1, however ROS1 G2032R solvent front mutation imposed resistance. The specific binding poses adopted by cabozantinib in the DFG-out kinase conformation and gilteritinib in the DFG-in kinase, provide rationale for their activity in the ROS1 mutants. Clinical cases demonstrated response to cabozantinib in tumors developing TKI resistance due to the ROS1 L2086F mutation. Conclusion: Cabozantinib and gilteritinib effectively inhibit ROS1 L2086F. Clinical activity of cabozantinib is confirmed in patients with TKI-resistant, ROS1 L2086F mutant NSCLC. Gilteritinib may offer an alternative with distinct off-target toxicities, however further studies are required. Since cabozantinib and gilteritinib are multi-kinase inhibitors, there is a persistent unmet need for more selective and better-tolerated TKI to overcome ROS1 L2086F kinase-intrinsic resistance. Translational relevance: ROS1 L2086F is an emerging recurrent resistance mutation to type I ROS1 TKIs, including later generation TKIs. Here, we show corroborating preclinical and clinical evidence for the activity of the quinolone-based type II TKI, cabozantinib, in ROS1 L2086F resistance setting. In addition, we show activity of the pyrazine carboxamide-based type I TKI, gilteritinib, in ROS1 L2086F resistance, suggesting that gilteritinib could be another option for ROS1 L2086F TKI-resistant patients. This study represents the first comprehensive report of ROS1 L2086F in the context of later-generation TKIs, including the macrocyclic inhibitors.

Sacropelvic Fixation with Porous Fusion/Fixation Screws: A Technical Note and Retrospective Review.

OBJECTIVE: The goal of this study was to analyze our initial experience using a novel porous fusion/fixation screw (PFFS) for pelvic fixation, and to determine our rate of screw malposition requiring intraoperative repositioning. METHODS: We reviewed 83 consecutive patients who underwent sacropelvic fixation with PFFS at our institution from 6/1/2022-6/30/2023 using intraoperative CT-based computer-assisted navigation (CAN) via an open posterior approach. Following PFFS insertion, intraoperative CT scans were obtained to assess screw positioning. Demographic data was collected, and operative reports and patient images were reviewed to determine what implants were used and if any PFFS required repositioning. RESULTS: 74 patients (26M:48F) were included, and 57 (77.0%) had a prior sacroiliac joint or lumbar spine surgery. A stacked screw configuration was used in 62/74 cases (83.8%). A total of 235 PFFS were used and six (2.6%) were malpositioned. Of 88 cephalic screws placed in stacked configuration, 4 were malpositioned (4.5%); and 1/123 caudal screws were malpositioned (0.8%). One of 24 SAI screws placed in a stand-alone configuration was malpositioned (4.2%). Malpositions included four medial, one lateral, and one inferior; and all were revised intraoperatively without major sequela. CONCLUSIONS: Although PFFS are larger than traditional sacropelvic fixation screws, stacked SAI instrumentation can be done safely with CAN. We found a low malposition rate in our initial series of patients, the majority being the cephalad screw in a stacked configuration. This isn't surprising, as these are placed after the caudal screws which reduces the available corridor size and increases the placement difficulty.

Academic career progression in AANS/CNS Spine Section award recipients.

OBJECTIVE: The American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Joint Spine Section awards highlight outstanding abstracts submitted to the AANS/CNS Section on Disorders of the Spine and Peripheral Nerves by trainees interested in spine surgery, although the academic trajectory of awardees has not been studied. The aim of this study was to assess the academic career progression of prior recipients of the Journalistic and Academic Neurosurgical Excellence (JANE), Mayfield, and Kuntz research awards. METHODS: Prior JANE, Mayfield, and Kuntz award recipients were identified using awardee records accrued between 1984 and February 2022. Awardee sex, country of residence, specialty, subspecialty focus, and current academic appointment status (if applicable) were searched online. Awardee h-indices and number of peer-reviewed publications were assessed via Google Scholar profiles (or Scopus if unavailable) and PubMed, respectively. Receipt of federal research funding as principal investigator (PI) was determined using the websites of the National Institutes of Health, the National Science Foundation, and the Department of Defense Congressionally Directed Medical Research Programs. The abstract-to-publication rate was assessed. RESULTS: A total of 7 JANE awards, 57 Mayfield awards, and 149 Kuntz awards were identified. Of the JANE awardees, all recipients were male. Of the 4 unique JANE awardees who completed training, 2 (50.0%) held academic appointments at the time of the study. All of the JANE abstracts were published in peer-reviewed journals. The mean h-index of all JANE awardees was 28 and the mean number of publications was 126. None of the awardees have received federal research funding. Of the Mayfield awards, 98.2% were awarded to males. Of the 43 unique Mayfield awardees who completed training, 20 (46.5%) held faculty appointments at academic medical centers. All of the Mayfield abstracts since 2011 were published in peer-reviewed journals. The mean h-index of all Mayfield awardees was 26 and the mean number of publications was 82. Five Mayfield awardees received National Institutes of Health funding as PI, and 7 awardees received Department of Defense funding as PI. Of the Kuntz awards, 95.3% were awarded to males. Most awards were given to current residents and fellows (46.3%). Of the 55 unique Kuntz awardees who completed training, 31 (56.4%) held faculty appointments at academic medical centers. The abstract-to-publication rate of the total Kuntz abstracts was 70.5%. The mean h-index of all Kuntz awardees was 15 and the mean number of publications was 58. Five Kuntz awardees (3.4%) received federal research funding as PI. CONCLUSIONS: Many recipients of the JANE, Mayfield, and Kuntz Joint Spine Section awards have successfully translated award abstracts into peer-reviewed publications. Furthermore, approximately one-third of the awardees are active in academic neurosurgery, with some having secured federal research funding.

How can healthcare organisations increase doctors' research engagement? A scoping review.

PURPOSE: Clinician engagement in research has positive impacts for healthcare, but is often difficult for healthcare organisations to support in light of limited resources. This scoping review aimed to describe the literature on health service-administered strategies for increasing research engagement by medical practitioners. DESIGN/METHODOLOGY/APPROACH: Medline, EMBASE and Web of Science databases were searched from 2000 to 2021 and two independent reviewers screened each record for inclusion. Inclusion criteria were that studies sampled medically qualified clinicians; reported empirical data; investigated effectiveness of an intervention in improving research engagement and addressed interventions implemented by an individual health service/hospital. FINDINGS: Of the 11,084 unique records, 257 studies were included. Most (78.2%) studies were conducted in the USA, and were targeted at residents (63.0%). Outcomes were measured in a variety of ways, most commonly publication-related outcomes (77.4%), though many studies used more than one outcome measure (70.4%). Pre-post (38.8%) and post-only (28.7%) study designs were the most common, while those using a contemporaneous control group were uncommon (11.5%). The most commonly reported interventions included Resident Research Programs (RRPs), protected time, mentorship and education programs. Many articles did not report key information needed for data extraction (e.g. sample size). ORIGINALITY/VALUE: This scoping review demonstrated that, despite a large volume of research, issues like poor reporting, infrequent use of robust study designs and heterogeneous outcome measures limited application. The most compelling available evidence pointed to RRPs, protected time and mentorship as effective interventions. Further high-quality evidence is needed to guide healthcare organisations on increasing medical research engagement.

Spine surgeon versus AI algorithm full-length radiographic measurements: a validation study of complex adult spinal deformity patients.

INTRODUCTION: Spinal measurements play an integral role in surgical planning for a variety of spine procedures. Full-length imaging eliminates distortions that can occur with stitched images. However, these images take radiologists significantly longer to read than conventional radiographs. Artificial intelligence (AI) image analysis software that can make such measurements quickly and reliably would be advantageous to surgeons, radiologists, and the entire health system. MATERIALS AND METHODS: Institutional Review Board approval was obtained for this study. Preoperative full-length standing anterior-posterior and lateral radiographs of patients that were previously measured by fellowship-trained spine surgeons at our institution were obtained. The measurements included lumbar lordosis (LL), greatest coronal Cobb angle (GCC), pelvic incidence (PI), coronal balance (CB), and T1-pelvic angle (T1PA). Inter-rater intra-class correlation (ICC) values were calculated based on an overlapping sample of 10 patients measured by surgeons. Full-length standing radiographs of an additional 100 patients were provided for AI software training. The AI algorithm then measured the radiographs and ICC values were calculated. RESULTS: ICC values for inter-rater reliability between surgeons were excellent and calculated to 0.97 for LL (95% CI 0.88-0.99), 0.78 (0.33-0.94) for GCC, 0.86 (0.55-0.96) for PI, 0.99 for CB (0.93-0.99), and 0.95 for T1PA (0.82-0.99). The algorithm computed the five selected parameters with ICC values between 0.70 and 0.94, indicating excellent reliability. Exemplary for the comparison of AI and surgeons, the ICC for LL was 0.88 (95% CI 0.83-0.92) and 0.93 for CB (0.90-0.95). GCC, PI, and T1PA could be determined with ICC values of 0.81 (0.69-0.87), 0.70 (0.60-0.78), and 0.94 (0.91-0.96) respectively. CONCLUSIONS: The AI algorithm presented here demonstrates excellent reliability for most of the parameters and good reliability for PI, with ICC values corresponding to measurements conducted by experienced surgeons. In future, it may facilitate the analysis of large data sets and aid physicians in diagnostics, pre-operative planning, and post-operative quality control.

Immune-restoring CAR-T cells display antitumor activity and reverse immunosuppressive TME in a humanized ccRCC mouse model.

One of the major barriers that have restricted successful use of chimeric antigen receptor (CAR) T cells in the treatment of solid tumors is an unfavorable tumor microenvironment (TME). We engineered CAR-T cells targeting carbonic anhydrase IX (CAIX) to secrete anti-PD-L1 monoclonal antibody (mAb), termed immune-restoring (IR) CAR G36-PDL1. We tested CAR-T cells in a humanized clear cell renal cell carcinoma (ccRCC) orthotopic mouse model with reconstituted human leukocyte antigen (HLA) partially matched human leukocytes derived from fetal CD34+ hematopoietic stem cells (HSCs) and bearing human ccRCC skrc-59 cells under the kidney capsule. G36-PDL1 CAR-T cells, haploidentical to the tumor cells, had a potent antitumor effect compared to those without immune-restoring effect. Analysis of the TME revealed that G36-PDL1 CAR-T cells restored active antitumor immunity by promoting tumor-killing cytotoxicity, reducing immunosuppressive cell components such as M2 macrophages and exhausted CD8+ T cells, and enhancing T follicular helper (Tfh)-B cell crosstalk.