An Alternatively Spliced Gain-of-Function NT5C2 Isoform Contributes to Chemoresistance in Acute Lymphoblastic Leukemia.

Relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) is a major cause of pediatric cancer-related deaths. Relapse-specific mutations do not account for all chemotherapy failures in B-ALL patients, suggesting additional mechanisms of resistance. By mining RNA-seq datasets of paired diagnostic/relapse pediatric B-ALL samples, we discovered pervasive alternative splicing (AS) patterns linked to relapse and affecting drivers of resistance to glucocorticoids, anti-folates, and thiopurines. Most splicing variations represented cassette exon skipping, "poison" exon inclusion, and intron retention, phenocopying well-documented loss-of-function mutations. In contrast, relapse-associated AS of NT5C2 mRNA yielded an isoform with the functionally uncharacterized in-frame exon 6a. Incorporation of the 8-amino acid sequence SQVAVQKR into this enzyme created a putative phosphorylation site and resulted in elevated nucleosidase activity, which is a known consequence of gain-of-function mutations in NT5C2 and a common determinant of 6-mercaptopurine (6-MP) resistance. Consistent with this finding, NT5C2ex6a and the R238W hotspot variant conferred comparable levels of resistance to 6-MP in B-ALL cells both in vitro and in vivo. Furthermore, both the NT5C2ex6a and R238W variants induced collateral sensitivity to the inosine monophosphate dehydrogenase (IMPDH) inhibitor mizoribine. These results ascribe an important role for splicing perturbations in chemotherapy resistance in relapsed B-ALL and suggest that IMPDH inhibitors, including the commonly used immunosuppressive agent mycophenolate mofetil, could be a valuable therapeutic option for treating thiopurine-resistant leukemias.

An Alternatively Spliced Gain-of-Function NT5C2 Isoform Contributes to Chemoresistance in Acute Lymphoblastic Leukemia.

Relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) is a major cause of pediatric cancer-related deaths. Relapse-specific mutations do not account for all chemotherapy failures in B- ALL patients, suggesting additional mechanisms of resistance. By mining RNA-seq datasets of paired diagnostic/relapse pediatric B-ALL samples, we discovered pervasive alternative splicing (AS) patterns linked to relapse and affecting drivers of resistance to glucocorticoids, anti-folates, and thiopurines. Most splicing variations represented cassette exon skipping, "poison" exon inclusion, and intron retention, phenocopying well-documented loss-of-function mutations. In contrast, relapse-associated AS of NT5C2 mRNA yielded an isoform with the functionally uncharacterized in-frame exon 6a. Incorporation of the 8-amino acid sequence SQVAVQKR into this enzyme created a putative phosphorylation site and resulted in elevated nucleosidase activity, which is a known consequence of gain-of-function mutations in NT5C2 and a common determinant of 6-mercaptopurine (6-MP) resistance. Consistent with this finding, NT5C2ex6a and the R238W hotspot variant conferred comparable levels of resistance to 6-MP in B-ALL cells both in vitro and in vivo. Furthermore, both the NT5C2ex6a and R238W variants induced collateral sensitivity to the inosine monophosphate dehydrogenase (IMPDH) inhibitor mizoribine. These results ascribe an important role for splicing perturbations in chemotherapy resistance in relapsed B-ALL and suggest that IMPDH inhibitors, including the commonly used immunosuppressive agent mycophenolate mofetil, could be a valuable therapeutic option for treating thiopurine-resistant leukemias.

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.

A Multiomics, Molecular Atlas of Breast Cancer Survivors.

Breast cancer imposes a significant burden globally. While the survival rate is steadily improving, much remains to be elucidated. This observational, single time point, multiomic study utilizing genomics, proteomics, targeted and untargeted metabolomics, and metagenomics in a breast cancer survivor (BCS) and age-matched healthy control cohort (N = 100) provides deep molecular phenotyping of breast cancer survivors. In this study, the BCS cohort had significantly higher polygenic risk scores for breast cancer than the control group. Carnitine and hexanoyl carnitine were significantly different. Several bile acid and fatty acid metabolites were significantly dissimilar, most notably the Omega-3 Index (O3I) (significantly lower in BCS). Proteomic and metagenomic analyses identified group and pathway differences, which warrant further investigation. The database built from this study contributes a wealth of data on breast cancer survivorship where there has been a paucity, affording the ability to identify patterns and novel insights that can drive new hypotheses and inform future research. Expansion of this database in the treatment-naïve, newly diagnosed, controlling for treatment confounders, and through the disease progression, can be leveraged to profile and contextualize breast cancer and breast cancer survivorship, potentially leading to the development of new strategies to combat this disease and improve the quality of life for its victims.

Distraction Osteogenesis Reconstruction Following Resection of Bone Sarcomas: Surgical, Functional, and Oncological Outcomes from a Prospective Trial Analysis.

BACKGROUND: While sustainable long-term function has been established for biological reconstruction with distraction osteogenesis (DO) following osseous resections, there is a paucity of published data informing surgeons and patients on important milestones in the reconstructive process. The objectives of this study were to determine when to expect complete bone healing and full weight-bearing as well as to quantify the influence of chemotherapy on the osseous regeneration process. METHODS: Prospectively, pathological and clinical data were collected for 30 consecutive patients who underwent primary or secondary DO-based reconstruction following osseous resection from 2018 to 2021. Serial radiographs indicated the times to cortex formation and full union. An unpaired t test was used to compare the time required for full bone remodeling of segments transported with and without concurrent chemotherapy. RESULTS: The average resection length was 13.6 cm (range, 4 to 22 cm). Patients underwent an average of 6.1 procedures (range, 1 to 14 procedures). Half (50%) of all procedures were planned, while half were unplanned procedures. All patients achieved full, independent weight-bearing at a median of 12 months (interquartile range [IQR], 9 to 16 months). For the 34 segments transported concurrently with chemotherapy, the mean bone healing index (BHI) was 2.3 ± 0.7, and the mean BHI was 1.2 ± 0.4 for the 25 segments without chemotherapy at any point during their transport (p < 0.0001). CONCLUSIONS: All 30 patients achieved full bone healing and independent weight-bearing at a median of 1 year postoperatively and continued to show functional improvement afterward. Surgeons and patients can expect bone healing to be nearly twice as fast for segments transported after completion of systemic chemotherapy compared with segments transported concurrently with adjuvant chemotherapy. LEVEL OF EVIDENCE: Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.

The effect of cannabinoids on single-level lumbar arthrodesis outcomes in a rat model.

BACKGROUND CONTEXT: The opioid epidemic is a public health crisis affecting spine care and pain management. Medical marijuana is a potential non-opioid analgesic yet to be studied in the surgical setting since its effects on bone healing are not fully understood. Studies have demonstrated analgesic and potentially osteoinductive properties of cannabinoids with endocannabinoid receptor expression in bone tissue. PURPOSE: We hypothesize that tetrahydrocannabinol (THC) and cannabidiol (CBD) will not decrease bone healing in spinal fusion. STUDY DESIGN: Seventy-eight adult Sprague-Dawley rats were used for this study. Utilizing allogenic bone grafts (6 donor rats), posterolateral inter-transverse lumbar fusion at the L4-L5 level was performed. The animals were equally divided into four treatment groups, each receiving 0.1 ml intraperitoneal injections weekly as follows: placebo (saline), 5 mg/kg THC, 5 mg/kg CBD, and a combination of 5 mg/kg THC and 5mg/kg CBD (Combo). METHODS: Callus tissue was harvested 2- and 8-weeks post-surgery for qPCR assessment to quantify changes in the expression of osteogenic genes. Manual palpation was done to assess the strength of the L4-L5 arthrodesis on all rats. µCT image-based callus analysis and histology were performed. One-way ANOVA followed by post hoc comparisons was performed. RESULTS: µCT demonstrated no significant differences. Treatment groups had slightly increased bone volume and density compared to control. qPCR at two weeks indicated downregulated RANKL/OPG ratios skewing towards osteogenesis in the CBD group, with the THC and CBD+THC groups demonstrating a downward trend (p>.05). ALPL, BMP4, and SOST were significantly higher in the CBD group, with CTNNB1 and RUNX2 also showing an upregulating trend. The CBD group showed elevation in Col1A1 and MMP13. Data at eight weeks showed ALPL, RUNX2, BMP4, and SOST were downregulated for all treatment groups. In the CBD+THC group, RANK, RANKL, and OPG were downregulated. OPG downregulation reached significance for the THC and CBD+THC group compared to saline. Interestingly, the RANKL/OPG ratio showed upregulation in the CBD and CBD+THC groups. RANKL showed upregulation in the CBD group. At 2 and 8 weeks, the CBD treatment group showed superior histological progression, increasing between time points. CONCLUSION: This study demonstrates that CBD and THC have no adverse effect on bone healing and the rate of spinal fusion in rats. Osteogenic factors were upregulated in the CBD-treated groups at two weeks, which indicates a potential for bone regeneration. In this group, compared to control, the RANKL/OPG ratio at the early healing phase demonstrates the inhibition of osteoclast differentiation, enhancing bone formation. Interestingly, it shows promoted osteoclast differentiation at the later healing phase, enhancing bone remodeling. This aligns with the physiological expectation of a lower ratio in the early phases and a higher ratio in the later remodeling phases. CLINICAL SIGNIFICANCE: CBD and THC showed no inhibitory effects on bone healing in a spinal fusion model. Moreover, histologic and gene expression analysis demonstrated that CBD may, in fact, enhance bone healing. Further research is needed to confirm the safe usage of THC and CBD in the post-operative setting following spinal fusions.

International Knee Documentation Committee Subjective Knee Form Latent Growth Model Analysis: Assessing Recovery Trajectories.

Patient-Reported Outcome Measures (PROMs), such as the six-item International Knee Documentation Committee Subjective Knee Form (IKDC-6), play a crucial role in assessing health conditions and guiding clinical decisions. Latent Growth Modeling (LGM) can be employed to understand recovery trajectories in patients post-operatively. Therefore, the purpose of this study was to assess LGM properties of the IKDC-6 in patients with knee pathologies that require surgical intervention and to assess differences between subgroups (i.e., sex and age). A cross-sectional study was conducted using the Surgical Outcome System (SOS) database with patients who had undergone knee arthroscopy. Our results found that preoperative scores did not influence the rate of change overtime. Perceived knee health improved over time, with varying rates among individuals. The adolescent age subgroup and male subgroup exhibited faster recovery rates compared to the older age subgroup and female subgroup. While initial hypotheses suggested IKDC-6 could serve as a prognostic tool, results did not support this. However, results indicated favorable outcomes irrespective of preoperative perceived knee impairment levels. This study provides valuable insights into recovery dynamics following knee surgery, emphasizing the need for personalized rehabilitation strategies tailored to individual patient characteristics.

Standardized In-harness Ultrasound Protocol Improves Success Rate of Brace Treatment for Dislocated Hips.

OBJECTIVE: Infant hip dislocations benefit from early detection and treatment for optimal outcomes. Prior studies have identified that there remains wide variability in the success rate of bracing between institutions. Although there are standardized methods to screen infants for hip dysplasia, there are no clear guidelines regarding how to image a child being treated for a hip dislocation with a Pavlik harness. As a result, there is substantial variability in how treatment success or failure is monitored between and within institutions. The goal of our study is to determine whether a standardized in-harness imaging protocol improves outcomes and the likelihood of successful treatment for dislocated hips being treated with the Pavlik harness. METHODS: All patients with hip dislocations and pretreatment ultrasound (US) were included from July 2018 to July 2022. A new institutional US protocol was implemented in July 2020, during which standardized in-harness imaging was obtained for patients with hip dislocations. Patients treated before the implementation of standardized in-harness imaging were categorized as nonstandardized and after implementation as a standardized group. Outcomes were compared between standardized and nonstandardized groups. P <0.05 determined the statistical significance. RESULTS: One hundred twenty-eight hips met the inclusion criteria (n = 97 patients). The mean age at diagnosis was 41.6 ± 23.4 days and was predominantly female (85.6%). There was no significant difference between the patients' demographics and baseline clinical characteristics between the standardized and nonstandardized groups. Pavlik harness success rate was significantly higher in the standardized group (85% vs 60%, P = 0.0024). Twenty-eight hips in the nonstandardized group remained dislocated and were indicated for surgical treatment, whereas only 8 hips remained dislocated in the standardized group and necessitated closed or open reduction. CONCLUSIONS: Standardization of in-harness imaging for patients undergoing treatment for developmental hip dislocations can significantly improve the Pavlik harness success rate. These findings emphasize the importance of obtaining images with the hip in flexion and abduction to prevent inadvertent stress during US evaluation for hips that have not yet stabilized, which may lead to premature cessation of the Pavlik harness. LEVEL OF EVIDENCE: Level III.

Heterogeneous PSMA ligand uptake inside parotid glands.

The purpose of this investigation is to quantify the spatial heterogeneity of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) uptake within parotid glands. We aim to quantify patterns in well-defined regions to facilitate further investigations. Furthermore, we investigate whether uptake is correlated with computed tomography (CT) texture features. METHODS: Parotid glands from [18F]DCFPyL PSMA PET/CT images of 30 prostate cancer patients were analyzed. Uptake patterns were assessed with various segmentation schemes. Spearman's rank correlation coefficient was calculated between PSMA PET uptake and feature values of a Grey Level Run Length Matrix using a long and short run length emphasis (GLRLML and GLRLMS) in subregions of the parotid gland. RESULTS: PSMA PET uptake was significantly higher (p < 0.001) in lateral/posterior regions of the glands than anterior/medial regions. Maximum uptake was found in the lateral half of parotid glands in 50 out of 60 glands. The difference in SUVmean between parotid halves is greatest when parotids are divided by a plane separating the anterior/medial and posterior/lateral halves symmetrically (out of 120 bisections tested). PSMA PET uptake was significantly correlated with CT GLRLML (p < 0.001), and anti-correlated with CT GLRLMS (p < 0.001). CONCLUSION: Uptake of PSMA PET is heterogeneous within parotid glands, with uptake biased towards lateral/posterior regions. Uptake within parotid glands was strongly correlated with CT texture feature maps.

Effect of an Outbound Scheduling Team on the Timeliness of Scheduling Referrals to Pediatric Otolaryngology.

OBJECTIVE: Families preferring to receive care in a language-other-than-English have disparities in access to care. We studied the effect of implementing an ambulatory outbound scheduling team on the timeliness of scheduling referrals to pediatric otolaryngology. We hypothesized this intervention could increase access to care. STUDY DESIGN: Retrospective cohort analysis. SETTING: Tertiary care academic center. METHODS: Data were abstracted from the hospital's enterprise database for patients referred to Otolaryngology over 3 years (October 2019-August 2022; 7675 referrals). An outbound scheduling team was created April 2021 and tasked with calling out to schedule referrals within one business day of receipt. Referral lag was compared across patient cohorts before and after the scheduling intervention. Log-transformed linear regression models were used to assess the impact of the scheduling intervention on referral lag for language cohorts. RESULTS: The median preintervention referral lag was 6 days (interquartile range [IQR] 2-18), which was reduced to 1 day postintervention (IQR 0-5; P < .001). Preintervention language-other-than-English families had a median referral lag of 8 days (IQR 2-23), which was 1.27 times higher than for patients speaking English (P < .001). With implementation of the scheduling intervention, language-other-than-English families were scheduled in a median of 1 day (IQR 0-6), and the disparity in timeliness of scheduling was eliminated (P = .131). Postintervention, referral lag was reduced by 58% in the English and 64% in the language other than English cohorts. CONCLUSION: Implementation of an outbound ambulatory scheduling process reduces referral lag for all patients and eliminated a disparity in referral lag for language-other-than-English families.

The Burden of Back and Neck Strains and Sprains in Professional Baseball Players.

STUDY DESIGN: A retrospective case series study. OBJECTIVE: To analyze the epidemiology of diagnoses of back and neck strains and sprains among Major League (MLB) and Minor League (MiLB) Baseball players. BACKGROUND: Baseball players perform unique sets of repetitive movements that may predispose to neck and back strains and sprains. Data are lacking concerning the epidemiology of these diagnoses in this population. MATERIALS AND METHODS: De-identified data on neck/back strains and sprains were collected from all MLB and MiLB teams from 2011 to 2016 using the MLB-commissioned Health and Injury Tracking System database. Diagnosis rates of conditions related to cervical, thoracic, and lumbar musculature and their impact on days missed due to injury, player participation, and season or career-ending status were assessed. Injury rates were reported as injuries per 1000 athlete exposures (AEs). RESULTS: There were 3447 cases of neck/back strains and sprains in professional baseball players from 2011 to 2016. Seven hundred twenty-one of these occurred in MLB versus 2726 in MiLB. Of injuries 136 were season-ending (26 in MLB, 110 in MiLB); 22 were career-ending (2 in MLB, 20 in MiLB). The total days missed were 39,118 (8838 from MLB and 30,280 from MiLB). Excluding season or career-ending injuries, the mean days missed were 11.8 (12.7 and 11.6 in MLB and MiLB, respectively). The median days missed were 4 (3 and 5 in MLB and MiLB, respectively). Combining MLB and MiLB, the pitcher injury rate was 1.893 per 1000 AEs versus 0.743 per 1000 Aes for other position players ( P < 0.0001). CONCLUSION: There was a high incidence of neck/back strains and sprains in MLB and MiLB players, with nearly 40,000 aggregate days missed in our 6-year study period. The median days missed were lower than the mean days missed, indicating rightward outliers. Pitchers had over double the rates of injuries compared with other position players. LEVEL OF EVIDENCE: Level III.

Factors affecting risk of recurrence with periprosthetic infection in shoulder arthroplasty.

BACKGROUND: The goal of treating periprosthetic infection, besides its eradication, is to avoid recurrence. The purpose of this study was to evaluate the impact of increasing Infection Severity (IS) score (based on the 2018 International Consensus Meeting on Orthopedic Infections statement), single-stage revision, and pathogenicity of the infective organism on the risk of infection recurrence. METHODS: A database of 790 revisions performed by a single surgeon from 2004-2020 was reviewed for patients with minimum 2-year follow-up and ≥1 positive culture finding and/or pathology result from the revision surgical procedure. In total, 157 cases performed in 144 patients met the inclusion criteria. These cases were then categorized by infection probability (IS score) according to the 2018 consensus statement. Of 157 cases, 46 (29%) were classified as definitely or probably infected; 25 (16%), possibly infected; and 86 (55%), unlikely to be infected. Additionally, patients were grouped by single-stage surgery and pathogenicity of the infective organism. RESULTS: A recurrence in this study was classified as the growth of the same organism in any patient requiring revision surgery. The 86 cases in the group with unlikely infection showed a recurrence rate of 2.3%. The 25 cases in the group with possible infection showed a recurrence rate of 12%. The 46 cases in the group with definite or probable infection showed a recurrence rate of 17.4%. Patients in the definite/probable infection group had a higher rate of recurrence than those in the groups with possible infection and unlikely infection (P = .009). The IS score was higher in the recurrence group than the non-recurrence group (7.5 ± 4.3 vs. 3.9 ± 3.4, P < .001). Overall, patients who underwent 1-stage revision had a 5.0% recurrence rate, but among the 34 patients with an infection classification of definite or probable who underwent 1-stage revision, the recurrence rate was 5.9%. Cases of highly virulent methicillin-resistant Staphylococcus aureus also showed a recurrence rate of 30.8% compared with 4.0% and 5.9% for Cutibacterium acnes and coagulase-negative staphylococci, respectively (P = .005). CONCLUSION: Recurrent infection after treatment of a periprosthetic infection is associated with increasing severity scores, as defined in the 2018 consensus statement, and more aggressive microorganisms. However, a single-stage surgical procedure, even in patients with higher IS scores, did not impart a significantly increased risk of recurrence.

Do preoperative scapular fractures affect long-term outcomes after reverse shoulder arthroplasty?

BACKGROUND: Postoperative scapular stress fractures (SSFs) are a formidable problem after reverse shoulder arthroplasty (RSA). Less is known about patients who have these fractures preoperatively. The primary aim of this study was to examine postoperative satisfaction in patients undergoing primary RSA who have preoperative SSF and compared to a matched cohort without preoperative fracture. The secondary aim was to examine the differences in patient-reported outcomes between and within study cohorts. METHODS: A retrospective chart review of primary RSAs performed by a single surgeon from 2000 to 2020 was conducted. Patients diagnosed with cuff tear arthropathy (CTA), massive cuff tear (MCT), or rheumatoid arthritis (RA) were included. Five hundred twenty-five shoulders met inclusion criteria. Fractures identified on preoperative computed tomography scans were divided into 3 groups: (1) os acromiale, (2) multifragments (MFs), and (3) Levy types. Seventy-two shoulders had an occurrence of SSF. The remaining 453 shoulders were separated into a nonfractured cohort. American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) and visual analog scale (VAS) scores were compared pre- and postoperatively in the total fracture group and the nonfractured group cohort. The multifragment subgroup was also compared to the pooled Os/Levy subgroup. RESULTS: The total incidence of SSF in all shoulders was 13.7%. There was a difference in satisfaction scores at all time points between the nonfracture (7.9 ± 2.8) and total fracture group (5.4 ± 3.6, P < .001, at last visit). There was also a greater ASES total score in the nonfractured group vs the total fracture group at the final visit (69.4 ± 23.4 and 62.1 ± 24.2; P = .02). The MF group had worse ASES functional or VAS functional scores than the Os/Levy group at all time points: at 1 year, ASES function: MF 24.2 ± 14.5 and Os/Levy 30.7 ± 14.2 (P = .045); at 2 years, ASES function: MF 21.4 ± 14.4 and Os/Levy 35.5 ± 10.6 (P < .001); and at last follow-up, VAS function: MF 4.8 ± 2.8 and Os/Levy 6.4 ± 3.2 (P = .023). DISCUSSION: Scapular fractures were proportionally most common in patients diagnosed with CTA (16.3%) compared with a 9.2% and 8.6% incidence in patients diagnosed with MCT and RA, respectively. Patients with preoperative SSF still see an improvement in ASES scores after RSA but do have lower satisfaction scores compared with the nonfractured cohort. The multifragment fracture group has lower functional and satisfaction scores at all postoperative time points compared with both the nonfracture and the Os/Levy fracture group.

Outcomes of Long Bones Treated With Carbon-Fiber Nails for Oncologic Indications: International Multi-institutional Study.

BACKGROUND: Intramedullary nail fixation is commonly used for prophylactic stabilization of impending and fixation of complete pathological fractures of the long bones. However, metallic artifacts complicate imaging evaluation for bone healing or tumor progression and postoperative radiation planning. Carbon-fiber implants have gained popularity as an alternative, given their radiolucency and superior axial bending. This study evaluates incidences of mechanical and nonmechanical complications. METHODS: Adult patients (age 18 years and older) treated with carbon-fiber nails for impending/complete pathological long bone fractures secondary to metastases from 2013 to 2020 were analyzed for incidences and risk factors of mechanical and nonmechanical complications. Mechanical complications included aseptic screw loosening and structural failures of host bone and carbon-fiber implants. Deep infection and tumor progression were considered nonmechanical. Other complications/adverse events were also reported. RESULTS: A total of 239 patients were included; 47% were male, and 53% were female, with a median age of 68 (IQR, 59 to 75) years. Most common secondary metastases were related to breast cancer (19%), lung cancer (19%), multiple myeloma (18%), and sarcoma (13%). In total, 17 of 30 patients with metastatic sarcoma received palliative intramedullary nail fixation for impending/complete pathological fractures, and 13 of 30 received prophylactic nail stabilization of bone radiated preoperatively to manage juxta-osseous soft-tissue sarcomas, where partial resection of the periosteum or bone was necessary for negative margin resection. 33 (14%) patients had complications. Mechanical failures included 4 (1.7%) structural host bone failures, 7 (2.9%) implant structural failures, and 1 (0.4%) aseptic loosening of distal locking screws. Nonmechanical failures included 8 (3.3%) peri-implant infections and 15 (6.3%) tumor progressions with implant contamination. The 90-day and 1-year mortalities were 28% (61/239) and 53% (53/102), respectively. The literature reported comparable failure and mortality rates with conventional titanium treatment. CONCLUSIONS: Carbon-fiber implants might be an alternative for treating impending and sustained pathological fractures secondary to metastatic bone disease. The seemingly comparable complication profile warrants further cohort studies comparing carbon-fiber and titanium nail complications.

National health insurance scheme improves access and optimization of antimicrobial use in the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria.

BACKGROUND: Nigeria instituted the National Health Insurance Scheme (NHIS) for universal health coverage. This study compared the NHIS and out-of-pocket (OOP) antibiotic prescribing with the World Health Organization (WHO) optimal values. METHODS: A total of 2190 prescription forms from the NHIS and OOP were included in this study conducted at Obafemi Awolowo University Teaching Hospitals Complex, Nigeria from January 2021 to December 2022 and analysed using WHO drug prescribing guidelines. RESULTS: The average number of drugs per encounter was higher in the NHIS prescribing (χ2=58.956, p=0.00) than in OOP prescribing. The percentage of encounters with an antibiotic prescribed is higher in NHIS prescribing (χ2=46.034, p=0.000) than in OOP prescribing. The percentage of parenteral antibiotic prescribing is higher in OOP prescribing (χ2=25.413, p=0.000) than in NHIS prescribing. The percentage of antibiotic prescribed from the National Essential Medicine List is higher in NHIS prescribing (χ2=8.227, p=0.000) as well as the antibiotics prescribed from the Access category of the WHO Access, Watch and Reserve (AWaRe) Classification of antibiotics (χ2=23.946, p=0.000) when compared with OOP prescribing. CONCLUSIONS: Prescribing indicators show better performances with NHIS antibiotic prescribing and are closer to the WHO-recommended optimal values than in OPP prescribing. Hence NHIS prescribing can be an easy target for hospital antibiotic stewardship intervention for optimal antibiotic prescribing.

Why Start Now? Retrospective Study Evaluating Baseline Screening Mammography in Patients Age 60 and Older.

PURPOSE: Extensive data exist regarding the importance of baseline mammography and screening recommendations in the age range of 40-50 years old, however, less is known about women who start screening at age 60. The purpose of this retrospective study is to assess the characteristics and outcomes of women aged 60 years and older presenting for baseline mammographic screening. METHODS: This is an IRB-approved single institution retrospective review of data from patients aged 60+ receiving baseline screening mammograms between 2010 and 2022 was obtained. Information regarding patient demographics, breast density, and BI-RADS assessment was acquired from Cerner EHR. Of patients with a BI-RADS 0 assessment, imaging, and chart review was performed. Family history, gynecologic history, prior breast biopsy or surgery, and hormone use was reviewed. For those with a category 4 or 5 assessment after diagnostic work-up, biopsy outcomes were reported. Cancer detection rate (CDR), recall rate (RR), positive predictive value 1 (PPV1), PPV2, and PPV3 were calculated. RESULTS: Data was analyzed from 1409 women over age 60 who underwent breast cancer screening. The recall rate was 29.3% (413/1409). The CDR, PPV1, PPV2, and PPV3 were calculated as 15/1000, 5.2% (21/405), 29.2% (21/72), and 31.8% (21/66), respectively. After work-up, 224 diagnostic patients had a 1-year follow-up and none were diagnosed with breast cancer. One (1.4%, 1/71) of the BI-RADS 3 lesions was malignant at 2-year follow-up. Of the patients recalled from screening, 29.6% had a family history of breast cancer, and the majority of both recalled and nonrecalled patients had Category B breast density. There was no statistically significant difference in breast density or race of patients recalled vs not recalled. 93.2% of recalled cases were given BI-RADS descriptors, with mass and focal asymmetry being the most common lesions, and 22.1% of recalled cases included more than one lesion. CONCLUSION: Initiating screening mammography for patients over 60 years old may result in higher recall rates, but also leads to a high CDR of potentially clinically relevant invasive cancers. After a diagnostic work-up, BI-RADS 3 assessments are within standard guidelines. This study provides guidance for radiologists reading baseline mammograms and clinicians making screening recommendations in patients over age 60.

Glass shards masquerading as calcifications in the breast: A case report.

Noniatrogenically acquired foreign bodies in the nipple-areola complex or breast skin are rare and can have variable imaging features, depending on the nature of the foreign material. We present the case of a 41-year-old female who had numerous apparent round and punctate calcifications in the right periareolar breast, predominantly within the skin. The biopsy showed multiple glass shards on a background of scar tissue. Further discussion with the patient confirmed that the glass shards were acquired during a motor vehicle accident several years earlier. We also review the types of foreign body material observed in the breast, the imaging appearance of glass foreign bodies in soft tissue, and methods of removal.

The Role of En Bloc Resection in the Modern Era for Primary Spine Tumors.

STUDY DESIGN: A literature review. OBJECTIVE: The aim of this review is to provide an overview of benign and malignant primary spine tumors and a balanced analysis of the benefits and limitations of (and alternatives to) surgical treatment with en bloc resection. SUMMARY OF BACKGROUND DATA: Primary spine tumors are rare but have the potential to cause severe morbidity, either from the disease itself or as a result of treatment. The prognosis, goals, and treatment options vary significantly with the specific disease entity. Appropriate initial management is critical; inappropriate surgery before definitive treatment can lead to recurrence and may render the patient incurable, as salvage options are often inferior. METHODS: We performed a comprehensive search of the PubMed database for articles relevant to primary spine neoplasms and en bloc spine surgery. Institutional review board approval was not needed. RESULTS: Although Enneking-appropriate en bloc surgery can be highly morbid, it often provides the greatest chance for local control and/or patient survival. However, there is growing data to support modern radiotherapy as a feasible and less morbid approach to certain primary neoplasms that historically were considered radioresistant. CONCLUSIONS: Choosing the optimal approach to primary spine tumors is complex. A comprehensive and up-to-date assessment of the evidence is required to guide patient care and to balance the often-competing goals of prolonging life and preserving quality of life.

Validation of Biomechanical Computed Tomography for Fracture Risk Classification in Metastatic Hormone-sensitive Prostate Cancer.

BACKGROUND: Guidelines recommend dual-energy x-ray absorptiometry (DXA) screening to assess fracture risk and benefit from antiresorptive therapy in men with metastatic hormone-sensitive prostate cancer (mHSPC) on androgen deprivation therapy (ADT). However, <30% of eligible patients undergo DXA screening. Biomechanical computed tomography (BCT) is a radiomic technique that measures bone mineral density (BMD) and bone strength from computed tomography (CT) scans. OBJECTIVE: To evaluate the (1) correlations between BCT- and DXA-assessed BMD, and (2) associations between BCT-assessed metrics and subsequent fracture. DESIGN, SETTING, AND PARTICIPANTS: A multicenter retrospective cohort study was conducted among patients with mHSPC between 2013 and 2020 who received CT abdomen/pelvis or positron emission tomography/CT within 48 wk before ADT initiation and during follow-up (48-96 wk after ADT initiation). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used univariate logistic regression to assess the associations between BCT measurements and the primary outcomes of subsequent pathologic and nonpathologic fractures. RESULTS AND LIMITATIONS: Among 91 eligible patients, the median ([interquartile range) age was 67 yr (62-75), 44 (48.4%) were White, and 41 (45.1%) were Black. During the median follow-up of 82 wk, 17 men (18.6%) developed a pathologic and 15 (16.5%) a nonpathologic fracture. BCT- and DXA-assessed femoral-neck BMD T scores were strongly correlated (R2 = 0.93). On baseline CT, lower BCT-assessed BMD (odds ratio [OR] 1.80, 95% confidence interval or CI [1.10, 3.25], p = 0.03) was associated with an increased risk of a pathologic fracture. Lower femoral strength (OR 1.63, 95% CI [0.99, 2.71], p = 0.06) was marginally associated with an increased risk of a pathologic fracture. Neither BMD (OR 1.52, 95% CI [0.95, 2.63], p = 0.11) nor strength (OR 1.14, 95% CI [0.75, 1.80], p = 0.57) was associated with a nonpathologic fracture. BCT identified nine (9.9%) men eligible for antiresorptive therapy, of whom four (44%) were not treated. Limitations include low fracture numbers resulting in lower power to detect fracture associations. CONCLUSIONS: Among men diagnosed with mHSPC, BCT assessments were strongly correlated with DXA, predicted subsequent pathologic fracture, and identified additional men indicated for antiresorptive therapy. PATIENT SUMMARY: We assess whether biomechanical computer tomography (BCT) from routine computer tomography (CT) scans can identify fracture risk among patients recently diagnosed with metastatic prostate cancer. We find that BCT and dual-energy x-ray absorptiometry-derived bone mineral density are strongly correlated and that BCT accurately identifies the risk for future fracture. BCT may enable broader fracture risk assessment and facilitate timely interventions to reduce fracture risk in metastatic prostate cancer patients.

Disseminated Cryptococcus infection presenting as lytic skeletal lesions suggesting bony metastatic disease.

A 76-year-old male diagnosed with sarcoidosis presented with atraumatic left anterior knee pain. Initial imaging of the left lower extremity revealed an eccentrically-based lytic lesion in the mid-distal femur with cortical erosion and an additional lytic lesion in the proximal tibia. Magnetic resonance imaging (MRI) demonstrated an aggressive lesion in the proximal tibia with surrounding marrow edema, cortical breach, and erosion into the distal patellar tendon. Given concern for metastatic bone lesions, a18-fluorodeoxyglucose positron emission tomography/computed tomography scan (FDG PET/CT) was performed which demonstrated concordant hypermetabolic lytic lesions at the left mid-distal femur and the left proximal tibia, as well as hypermetabolic diffuse lymphadenopathy. The patient was presumed to have metastatic lung cancer based on the presence of lung nodules. Due to concern for impending pathologic fracture, the patient underwent open biopsy with a plan for prophylactic fixation of both lesions. Intra-operatively, however, both lesions were found to contain pus, from which cultures ultimately grew Cryptococcus neoformans. This is a case of disseminated skeletal cryptococcosis masquerading as metastatic cancer in a patient without classic risk factors for disseminated cryptococcosis (defined as extrapulmonary evidence of infection). Classically, disseminated cryptococcosis is thought to occur in severely immunocompromised patients, such as those with human immunodeficiency virus (HIV) or organ transplant recipients. This case highlights the need to maintain a high index of suspicion in patients with underlying immunocompromising conditions, including less common conditions such as sarcoid, who present with bony lesions. This case report then discusses the diagnostic evaluation and treatment of disseminated skeletal cryptococcosis.