Clinicopathologic characteristics and treatment outcomes of pancreatic cancer patients at a tertiary referral hospital in Kenya.

The global incidence of pancreatic cancer (PC) continues to steadily increase whereas its prognosis remains poor. Previous studies have suggested worse outcomes among individuals of African descent. The characteristics of patients with PC in Kenya, and their contemporary management and survival outcomes remain largely unknown. This study aimed to describe the clinical and pathologic characteristics, management, and outcomes of patients diagnosed with PC at Kenyatta National Hospital (KNH), a tertiary referral hospital in Kenya. Records of 242 patients diagnosed with PC at KNH between 1st January 2014 and 30th September 2021 were assessed in this retrospective cohort study. Data on their clinical, histopathologic, and treatment characteristics was presented as mean (± standard deviation) and/or median (interquartile range) for continuous variables and frequency (percentage) for categorical variables. Kaplan-Meier and Cox proportional hazard ratios were used for survival analysis. PC occurred in a young population, the median age being 58.5 years (inter-quartile range 35-88). The majority of tumours (54%) were metastatic at diagnosis, while 28% and 14% were stage III and stage I/II, respectively. Surgical resections with curative intent were performed on 7% overall and 44% of stage I/II cases. The majority of patients with stage I/II disease (52.9%) received chemotherapy whereas the majority with stage III and IV disease received the best supportive care only (62.7% and 64.9%, respectively). Patients who underwent surgical resection (HR for mortality 0.20, 95% CI 0.05-0.83, p = 0.021) and chemotherapy (HR for mortality 0.15, 95% CI 0.08-0.29, p < 0.001) had significantly improved survival, reflecting a more favourable stage of the disease more amenable to aggressive therapies. The median survival time was 3 months and the 1-year survival rate was 32%.

Three-dimensional vertebral shape changes confirm growth modulation after anterior vertebral body tethering for idiopathic scoliosis.

PURPOSE: To evaluate three-dimensional (3D) vertebra and disk shape changes over 2 years following anterior vertebral body tether (AVBT) placement in patients with idiopathic scoliosis (IS). METHODS: Patients with right thoracic IS treated with AVBT were retrospectively evaluated. 3D reconstructions were created from biplanar radiographs. Vertebral body and disk height (anterior, posterior, left and right) and shape (wedging angle) were recorded over the three apical segments in the local vertebral reference planes. Changes in height and wedging were measured through 2 years postoperatively. Change in patient height was correlated with changes in the spine dimensions. RESULTS: Forty-nine patients (Risser 0-3, Sanders 2-4) were included. The mean age was 12.2 ± 1.4 years (range 8-14). The mean coronal curve was 51 ± 10° preoperatively, 31 ± 9° at first postoperative time point and 27 ± 11° at 2-year follow-up (p < 0.001). The mean patient height increased 8 cm by 2 years (p < 0.001). The left side of the spine (vertebra + disc) grew in height by 2.2 mm/level versus 0.7 mm/level on the right side (p < 0.001). This differential growth was composed of 0.5 mm/vertebral level and 1.0 mm/disk level. Evaluation of the change in disk heights showed significantly decreased height anteriorly (- 0.4 mm), posteriorly (- 0.3 mm) and on the right (- 0.5 mm) from FE to 2 years. Coronal wedging reduced 2.3°/level with 1.1°/vertebral level change and 1.2°/disk level. There was no differential growth in the sagittal plane (anterior/posterior height). Patient height change moderately correlated with 3D measures of vertebra + disk shape changes. CONCLUSIONS: Three-dimensional analysis confirms AVBT in skeletally immature patients results in asymmetric growth of the apical spine segments. The left (untethered) side length increased more than 3 × than the right (tethered) side length with differential effects observed within the vertebral bodies and disks, each correlating with overall patient height change.

Disparities in Indications and Outcomes Reporting for Spinal Column Shortening for Tethered Cord Syndrome: The Need for a Standardized Approach.

STUDY DESIGN: Systematic review. OBJECTIVE: To identify commonly reported indications and outcomes in spinal column shortening (SCS) procedures. SUMMARY OF BACKGROUND DATA: SCS is a surgical procedure used in patients with tethered cord syndrome (TCS)-characterized by abnormal attachment of neural components to surrounding tissues-to shorten the vertebral column, release tension on the spinal cord/neural elements, and alleviate associated symptoms. METHODS: PubMed and EMBASE searches captured SCS literature published between 1950 and 2023. Prospective/retrospective cohort studies and case series were included without age limit or required follow-up period. Review articles without new patient presentations, meta-analyses, systematic reviews, conference abstracts, and letters were excluded. Studies included adult and pediatric patients. RESULTS: The 29 identified studies represented 278 patients (age 5-76 y). In 24.1% of studies, patients underwent primary TCS intervention via SCS. In 41.4% of studies, patients underwent SCS after failed previous primary detethering (24.1% of studies were mixed and 10.3% were unspecified). The most commonly reported non-genitourinary/bowel surgical indications were back pain (55.2%), lower-extremity pain (48.3%), lower-extremity weakness (48.3%), lower-extremity numbness (34.5%), and lower-extremity motor dysfunction (34.5%). Genitourinary/bowel symptoms were most often described as nonspecific bladder dysfunction (58.6%), bladder incontinence (34.5%), and bowel dysfunction (31.0%). After SCS, non-genitourinary/bowel outcomes included lower-extremity pain (44.8%), back pain (31.0%), and lower-extremity sensory and motor function (both 31.0%). Bladder dysfunction (79.3%), bowel dysfunction (34.5%), and bladder incontinence (13.8%) were commonly reported genitourinary/bowel outcomes. In total, 40 presenting surgical indication categories and 33 unique outcome measures were reported across studies. Seventeen of the 278 patients (6.1%) experienced a complication. CONCLUSION: The SCS surgical literature displays variability in operative indications and postoperative outcomes. The lack of common reporting mechanisms impedes higher-level analysis. A standardized outcomes measurement tool, encompassing both patient-reported outcome measures and objective metrics, is necessary. LEVEL OF EVIDENCE: Level 4.

Association of maternal insulin resistance with neonatal insulin resistance and body composition/size: a prospective cohort study in a sub-Saharan African population.

PURPOSE: We prospectively evaluated the association of the insulin resistance of third-trimester Nigerian pregnant women with their newborn infants' insulin resistance and birth size. Pregnancy-associated insulin resistance (IR), often assessed with homeostatic model assessment of IR (HOMA-IR), is associated, especially among women with gestational diabetes (GDM), with abnormal neonatal birth size and body composition, predisposing the baby to metabolic disorders like diabetes and obesity. The associations of maternal IR with neonatal IR, birth size and body composition are less studied in nondiabetic pregnant women, especially in sub-Saharan settings like Nigeria. METHODS: We originally recruited 401 third trimester, nondiabetic pregnant women to a prospective cohort study, followed up until birth. Blood samples of mothers and babies were obtained, respectively, at recruitment and within 24 hours postbirth for fasting serum glucose (FSG) and insulin (FSI) assays, and HOMA-IR was calculated as [(FSI × FSG)/22.5)]. RESULTS: Complete data for 150 mother-baby dyads was analysed: the mothers, with a mean (standard deviation [SD]) age of 31.6 (4.5) years, had live births at a mean (SD) gestational age of 39.2 weeks. The proportions of infants with wasting, stunting, impaired fetal growth (either wasting or stunted), small-for-gestation-age, large-for-gestational-age, low birthweight, and macrosomia were 4.2% (95% confidence interval, 1.1-10.3), 19.7% (12.9-28.0), 23.1% (15.8-31.8), 10.1% (5.3-17.0), 12.6% (7.2-19.9), 0.8% (0.02-4.5), and 5.0% (1.8-10.5), respectively. Maternal HOMA-IR was not associated with neonatal HOMA-IR (p=0.837), birth weight (p=0.416) or body composition measured with weight-length ratio (p=0.524), but birth weight was independently predicted by maternal weight (p=0.006), body mass index (p=0.001), and parity (p=0.012). CONCLUSION: In this nondiabetic/non-GDM cohort, maternal HOMA-IR was not associated with neonatal IR, body size or body composition. Larger studies are required to confirm these findings, with addi-tional inclusion of mothers with hyperglycaemia for comparison.

GC Content Across Insect Genomes: Phylogenetic Patterns, Causes and Consequences.

The proportions of A:T and G:C nucleotide pairs are often unequal and can vary greatly between animal species and along chromosomes. The causes and consequences of this variation are incompletely understood. The recent release of high-quality genome sequences from the Darwin Tree of Life and other large-scale genome projects provides an opportunity for GC heterogeneity to be compared across a large number of insect species. Here we analyse GC content along chromosomes, and within protein-coding genes and codons, of 150 insect species from four holometabolous orders: Coleoptera, Diptera, Hymenoptera, and Lepidoptera. We find that protein-coding sequences have higher GC content than the genome average, and that Lepidoptera generally have higher GC content than the other three insect orders examined. GC content is higher in small chromosomes in most Lepidoptera species, but this pattern is less consistent in other orders. GC content also increases towards subtelomeric regions within protein-coding genes in Diptera, Coleoptera and Lepidoptera. Two species of Diptera, Bombylius major and B. discolor, have very atypical genomes with ubiquitous increase in AT content, especially at third codon positions. Despite dramatic AT-biased codon usage, we find no evidence that this has driven divergent protein evolution. We argue that the GC landscape of Lepidoptera, Diptera and Coleoptera genomes is influenced by GC-biased gene conversion, strongest in Lepidoptera, with some outlier taxa affected drastically by counteracting processes.

Scoliosis Research Society-22r and Ceiling Effects: Limited Capabilities for Precision-Medicine with Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective registry analysis. OBJECTIVE: To examine predictions of individual Scoliosis Research Society-22r (SRS-22r) questions one year after surgery for adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: A precision-medicine approach to AIS surgery will inform patients of the likelihood of achieving particular results from surgery, specifically individual responses to the SRS-22r questionnaire. METHODS: A multi-center AIS registry was queried for surgical AIS patients treated between 2002-2020. Preoperative data collected included standard demographic data, deformity descriptive data, and SRS-22r scores. Postoperative 1yr SRS-22r scores were modeled using ordinal logistic regression. . The highest probability was the most likely response. Model performance was examined by c-statistics, where c>.8 was considered excellent. Ceiling effects were measured by the proportion of patients reporting "5" to each question. RESULTS: 3251 patients contributed data to the study; mean age 14.4 (±2.2) yrs, female 2631 (81%), major thoracic coronal curve 53°, mean lumbar 41°. C-statistic values ranged from .6 (poor) to .8 (excellent) evidence of varied predictive capabilities. Q17 ("days off work/school", c = .84, ceiling achieved 75%) and Q15 ("financial difficulties", c = .86, ceiling achieved 82%) had the greatest predictive capabilities while Q11 ("pain medication", c=.73, ceiling achieved 67%), Q10 ("appearance", c=.72, ceiling achieved 35%), and Q19 ("attractive", c=.69, ceiling achieved 37%) performed poorly. CONCLUSION: Prediction of individual SRS-22r item responses perhaps most germane to AIS treatment was poor. Prediction of less relevant outcomes, where ceiling effects are present, was greater as the models chose "5" for all responses. These ceiling effects may limit discrimination and hamper efforts at personalized outcome predictions. LEVEL OF EVIDENCE: 3.

Intrawound Vancomycin Powder Reduces Delayed Deep Surgical Site Infections Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective. OBJECTIVE: Evaluate whether the use of vancomycin powder (VP) placed in the surgical site prior to wound closure prevents delayed deep surgical site infections (DDI). SUMMARY OF BACKGROUND DATA: DDI after posterior spinal fusion (PSF) in adolescent idiopathic scoliosis (AIS) patients remains a significant major complication. The use of VP to prevent acute surgical site infection has been reported but the impact on DDI is unknown. METHODS: AIS patients treated over the past 20 years with PSF/instrumentation from a large muti-center registry were reviewed. Patients were divided into two groups: intraoperative vancomycin powder placed in the wound (VP) or no antibiotics placed in the wound (NVP). DDI was defined as an infection that occurred >90 days after surgery and required surgical intervention in the operating room. Patients who developed a DDI had secondary verification of VP use or not. Chi square and Kaplan-Meier (K-M) survivorship analyses were used to compare demographics and incident rate of DDI between groups. RESULTS: 4145 cases met inclusion for this study. A total of 43 DDI cases were identified (1.0%). The incidence of DDI for the VP group was 0.2% (4/2111), and 1.9% (39/2034) in the NVP group (P<0.001). Given the difference in follow-up for the 2 groups a Cumulative Survival and Kaplan-Meier analysis revealed the VP group had significantly better "survival" (no DDI) than the NVP group (P<0.001). CONCLUSION: DDIs are significant, adverse events that can greatly complicate patient recovery after PSF for AIS, including rehospitalization. This study found that patients who received VP intraoperatively were 10 times less likely to develop a DDI than those who did not receive VP. Although other advances/changes in surgical techniques may contribute to the significant decrease in infections found in the more recent VP cohort, VP should be considered as a prophylactic measure.

3D analysis of the preoperative deformity in AIS can be used to guide surgical treatment decisions for selective thoracic fusion.

PURPOSE: To identify 3D measures of scoliosis from preoperative imaging that are associated with optimal radiographic outcomes after selective thoracic fusion (STF) for adolescent idiopathic scoliosis (AIS). METHODS: Subjects with primary thoracic curves (Lenke 1-4, B or C modifiers) fused selectively (L1 or above) who had preoperative 3D reconstructions and minimum 2 years of follow-up were included. An optimal outcome at 2 years was defined as having 4 of 5 parameters previously defined in the literature: (1) lumbar curve < 26º, (2) deformity flexibility quotient < 4, (3) C7-CSVL < 2 cm, (4) lumbar prominence < 5º and (5) trunk shift < 1.5 cm. Univariate and CART analyses were performed to identify preoperative variables associated with achieving an optimal outcome 2 years postoperatively. RESULTS: Ninety-nine (88F, 11 M) patients met inclusion. Mean age was 15 ± 2 years. Fifty-one subjects (52%) had an optimal outcome. Seven preoperative deformity measures representing smaller thoracolumbar/lumbar deformity in the optimal group were found to be significant on univariate analysis. CART analysis identified the following variables associated with optimal outcomes: difference in apical rotation > 30° = 27% optimal outcomes, difference in apical rotation ≤ 30° and coronal vertebral wedging of lumbar apex > 3° = 46% optimal outcomes, and difference in apical rotation ≤ 30° and coronal vertebral wedging of lumbar apex ≤ 3° = 80% optimal outcomes (p < 0.05). CONCLUSION: Optimal outcomes after STF were associated with a preoperative difference in apical vertebral rotation in the axial plane less than 30° between thoracic and lumbar curves as well as coronal plane vertebral wedging of the lumbar apical vertebra less than 3°.

Depression Screening in Pediatric Orthopedic Surgery Clinics and Identifying Patients At-Risk.

BACKGROUND: Up to 25% of youth experience a depressive episode by 18 years of age, leading the US Preventive Services Task Force to recommend depression screening within this population. This study aimed to understand the prevalence of depression identified within pediatric orthopedic clinics compared with primary care clinics after the implementation of a screening program and present data on the prevalence of moderate-severe depression across specific pediatric orthopedic clinics, characterizing and identifying specific populations at higher risk. METHODS: A retrospective review was performed to identify all patients screened using the 2-item and 9-item versions of the Patient Health Questionnaire (PHQ-2/PHQ-9) and the Columbia-Suicide Severity Rating Scale over a 2-year period (October 2018 to January 2021) within pediatric primary care and orthopaedic clinics. Demographic and clinical characteristics were collected. Statistical analysis was performed to compare scores between orthopedic and primary care clinics, as well as between the different pediatric orthopedic subspecialties and included χ 2 test, ANOVA, and logistic regression. RESULTS: There were 32,787 unique adolescent patients screened in primary care clinics, with an additional 14,078 unique adolescent patients screened in orthopaedic clinics, leading to a 30% increase in the overall number of patients receiving depression screening. 5.2% of patients in primary care pediatric clinics screened positive for moderate-severe depression versus 2.0% in pediatric orthopaedic clinics ( P <0.001). 2.7% of primary care patients were at risk of self-harm compared with 0.8% of orthopedic patients ( P <0.001). Within orthopaedic subspecialty clinics, the spine patients were at the highest risk of moderate-severe depression (3.5%), significantly higher than both the sports (1.4%, P =0.006) and patients with acute fracture (1.3%, P <0.001). CONCLUSIONS: This study demonstrates the high incidence of patients screening positive for depression in pediatric and adolescent orthopaedic clinics. By identifying high-risk clinics and patient groups, health care systems can apply a more practical approach and appropriately deploy behavioral health specialists for timely counseling and treatment discussions. LEVEL OF EVIDENCE: Level-III.

Prospectively Collected Comparison of Outcomes Between Surgically and Conservatively Treated Patients with Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective review of a prospectively collected multicenter registry. OBJECTIVE: To evaluate health-related quality of life (HRQOL) measures in an operative cohort of patients (OP) and compare them with a matched nonoperative cohort (NON). SUMMARY OF BACKGROUND DATA: Historically, the surgical outcomes of adolescent idiopathic scoliosis (AIS) have been radiographically evaluated. However, the importance of HRQOL measures and their impact on surgical outcomes are increasingly being understood. METHODS: We identified 90 NON patients with curves in the operative range who were observed for at least 2 years. These patients were matched with an OP cohort of 689 patients. All patients completed the Scoliosis Research Society-22 (SRS-22) questionnaire at the initial evaluation and at a minimum of 2-year follow-up. Subgroup comparisons were based on curve type: primary thoracic (Th), primary thoracolumbar/lumbar (TL/L), and double major (DM) curves. RESULTS: The preoperative major curves in the Th, TL/L, and DM OP subgroups averaged 50.4°, 45.4°, and 51.5°, respectively, and 49.4°, 43.7°, and 48.9° in the NON cohort (P > 0.05). At 2 years postoperatively, the major curve in the Th, TL/L, and DM OP subgroups improved to 19.0°, 19.2°, and 19.3°, respectively, compared to the progression to 51.3°, 44.5°, and 49.7° in the NON group at 2-year follow-up (P < 0.05). The SRS-22 self-image, mental health, satisfaction, and total scores at the 2-year follow-up were significantly better in all OP subgroups (P < 0.001) but remained largely unchanged in the NON group. A significant percentage of patients (P < 0.001) in the OP cohort reported better SRS-22 scores at the 2-year follow-up in the self-image, mental health, and satisfaction domains than the NON group at 2 years. CONCLUSIONS: Surgically treated patients with AIS have improved HRQOL outcomes in several domains compared to age- and curve magnitude-matched nonoperatively treated patients at 2-year follow-up.

Vertebral body tethering for Lenke 1A curves: the lumbar modifier predicts less optimal outcomes.

INTRODUCTION: The addition of the L4 "AR" and "AL" lumbar modifier for Lenke 1A idiopathic scoliosis (IS) has been shown to direct treatment in posterior spinal fusion; however, its utility in vertebral body tethering (VBT) has yet to be evaluated. METHODS: A review of a prospective, multicenter database for VBT in IS was performed for patients with Lenke 1A deformities and a minimum of 2 years follow-up. Patients were categorized by their lumbar modifier (AR vs AL). Less optimal VBT outcome (LOVO) was defined as a final coronal curve > 35°, lumbar adding-on, or revision surgery for deformity progression or adding-on. RESULTS: Ninety-nine patients met inclusion criteria (81% female, mean 12.6 years), with 55.6% being AL curves. Overall, there were 23 instances of tether breakage (23.3%) and 20 instances of LOVO (20.2%). There was a higher rate of LOVO in AR curves (31.8% vs 10.9%, P = 0.01). Patients with LOVO had greater preoperative deformity, greater apical translation, larger coronal deformity on first erect radiographs, and less coronal deformity correction. Failure to correct the deformity < 30° on first erect was associated with LOVO, as was LIV selection short of the last touch vertebra (TV). Independent risk factors for LOVO included AR curves (OR 3.4; P = 0.04) and first erect curve magnitudes > 30 degrees (OR 6.0; P = 0.002). DISCUSSION: There is a 20.2% rate of less optimal VBT following VBT for Lenke 1A curves. AR curves are independently predictive of less optimal outcomes following VBT and require close attention to LIV selection. Surgeons should consider achieving an initial coronal correction < 30 degrees and extending the LIV to at least the TV to minimize the risk of LOVO.

Validation of biomarkers of aging.

The search for biomarkers that quantify biological aging (particularly 'omic'-based biomarkers) has intensified in recent years. Such biomarkers could predict aging-related outcomes and could serve as surrogate endpoints for the evaluation of interventions promoting healthy aging and longevity. However, no consensus exists on how biomarkers of aging should be validated before their translation to the clinic. Here, we review current efforts to evaluate the predictive validity of omic biomarkers of aging in population studies, discuss challenges in comparability and generalizability and provide recommendations to facilitate future validation of biomarkers of aging. Finally, we discuss how systematic validation can accelerate clinical translation of biomarkers of aging and their use in gerotherapeutic clinical trials.

The effects of TGF-ß1 and IFN-α2b on decorin, decorin isoforms and type I collagen in hypertrophic scar dermal fibroblasts.

Hypertrophic scars (HTS) develop from an excessive synthesis of structural proteins like collagen and a decreased expression of proteoglycans such as decorin. Previous research has demonstrated that decorin expression is significantly down-regulated in HTS, deep dermal tissue, and thermally injured tissue, reducing its ability to regulate pro-fibrotic transforming growth factor-beta 1 (TGF-ß1) and normal fibrillogenesis. However, treatment of HTS fibroblasts with interferon-alpha 2b (IFN-α2b) has been shown to reduce excessive collagen synthesis and improve HTS by reducing serum TGF-ß1 levels. The expression of decorin isoforms in HTS is currently unknown and the effects of TGF-ß1 and IFN-α2b on decorin, decorin isoform expression and type 1 collagen are of great interest to our group. Dermal fibroblasts were treated with TGF-ß1 and/or IFN-α2b, for 48 h. The expression and secretion of decorin, decorin isoforms and type 1 collagen were quantified with reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining and enzyme-linked immunosorbent assays. The mRNA expression of decorin and each isoform was significantly reduced in HTS fibroblasts relative to normal skin. TGF-ß1 decreased the mRNA expression of decorin and decorin isoforms, whereas IFN-α2b showed the opposite effect. IFN-α2b significantly inhibited TGF-ß1's effect on the mRNA expression of type I collagen alpha 1 in papillary dermal fibroblasts and overall showed relative effects of inhibiting TGF-ß1. These data support that a further investigation into the structural and functional roles of decorin isoforms in HTS pathogenesis is warranted and that IFN-α2b is an important agent in reducing fibrotic outcomes.

A novel smartphone application for early detection of habanero disease.

Habanero plant diseases can significantly reduce crop yield and quality, making early detection and treatment crucial for farmers. In this study, we discuss the creation of a modified VGG16 (MVGG16) Deep Transfer Learning (DTL) model-based smartphone app for identifying habanero plant diseases. With the help of the smartphone application, growers can quickly diagnose the health of a habanero plant by taking a photo of one of its leaves. We trained the DTL model on a dataset of labelled images of healthy and infected habanero plants and evaluated its performance on a separate test dataset. The MVGG16 DTL algorithm had an accuracy, precision, f1-score, recall and AUC of 98.79%, 97.93%, 98.44%, 98.95 and 98.63%, respectively, on the testing dataset. The MVGG16 DTL model was then integrated into a smartphone app that enables users to upload photographs, get diagnosed, and explore a history of earlier diagnoses. We tested the software on a collection of photos of habanero plant leaves and discovered that it was highly accurate at spotting infected plants. The smartphone software can boost early identification and treatment of habanero plant diseases, resulting in higher crop output and higher-quality harvests.

Performance of MIL-101(Cr) and MIL-101(Cr)-Pore Expanded as Drug Carriers for Ibuprofen and 5-Fluorouracil Delivery.

Metal-organic frameworks (MOFs) have been extensively investigated as nanocarriers for drug delivery applications owing to their remarkable surface area and porosity, which allow for impregnation of large quantities of drugs with fast pharmacokinetics. In this work, we developed a pore-expanded version of MIL-101(Cr), MIL-101(Cr)-P, and assessed its potential as a carrier for ibuprofen and 5-fluorouracil drugs along with its regular MIL-101(Cr) analogue. The pore expansion strategy gave rise to a higher surface area and mesopore volume for MIL-101(Cr)-P relative to regular MIL-101(Cr). The characterization results revealed successful incorporation of 30, 50, and 80 wt % of both drugs within the MOF structure. Upon incorporation of species, the surface area and porosity of the two MOF carriers decreased drastically; however, the drug-loaded MOFs still retained some degree of porosity, even at high drug loadings. For both drugs, the delivery experiments conducted in phosphate-buffered saline (PBS) showed that MIL-101(Cr)-P possessed better pharmacokinetic behavior than MIL-101(Cr) by delivering higher amounts of drug at all three loadings and exhibiting much faster release rates. Such behavior was originated from large mesopores that were created during pore expansion, providing diffusional pathways for efficient delivery of the drugs. The highest rate constant obtained by fitting the release kinetics to the Higuchi model was found to be 0.44 h-1/2 for the release of 30 wt % 5-fluorouracil from MIL-101(Cr)-P. The findings of this study highlight the role of tuning physiochemical properties of MOFs in improving their pharmacokinetic behavior as drug carriers.

Incidence of Tether Breakage in Anterior Vertebral Body Tethering.

BACKGROUND: Thoracic anterior vertebral body tethering (TAVBT) is an emerging treatment for adolescent idiopathic scoliosis. Tether breakage is a known complication of TAVBT with incompletely known incidence. We aim to define the incidence of tether breakage in patients with adolescent idiopathic scoliosis who undergo TAVBT. The incidence of tether breakage in TAVBT is hypothesized to be high and increase with time postoperatively. METHODS: All patients with right-sided, thoracic curves who underwent TAVBT with at least 2 and up to 3 years of radiographic follow-up were included. Tether breakage between 2 vertebrae was defined a priori as any increase in adjacent screw angle >5 degrees from the minimum over the follow-up period. The presence and timing of tether breakage were noted for each patient. A Kaplan-Meier survival analysis was performed to calculate expected tether breakage up to 36 months. χ 2 analysis was performed to examine the relationship between tether breakage and reoperations. Independent t test was used to compare the average final Cobb angle between cohorts. RESULTS: In total, 208 patients from 10 centers were included in our review. Radiographically identified tether breakage occurred in 75 patients (36%). The initial break occurred at or beyond 24 months in 66 patients (88%). Kaplan-Meier survival analysis estimated the cumulative rate of expected tether breakage to be 19% at 24 months, increasing to 50% at 36 months. Twenty-one patients (28%) with a radiographically identified tether breakage went on to require reoperation, with 9 patients (12%) requiring conversion to posterior spinal fusion. Patients with a radiographically identified tether breakage went on to require conversion to posterior spinal fusion more often than those patients without identified tether breakage (12% vs. 2%; P =0.004). The average major coronal curve angle at final follow-up was significantly larger for patients with radiographically identified tether breakage than for those without tether breakage (31 deg±12 deg vs. 26 deg±12 deg; P =0.002). CONCLUSIONS: The incidence of tether breakage in TAVBT is high, and it is expected to occur in 50% of patients by 36 months postoperatively. LEVEL OF EVIDENCE: Level IV.

Breaking the Rules in Three Dimensions: What to Expect After a Thoracic-only Fusion With Structural Thoracic and Thoracolumbar Curves.

OBJECTIVE: Despite guidelines to fuse both thoracic and thoracolumbar/lumbar (TH/L) curves in patients with structural curves in both regions, a thoracic-only fusion allows preservation of lumbar motion segments. The purpose of this study was to assess the 2-year postoperative three-dimensional (3D) radiographic and clinical outcomes of patients with double or triple major (thoracic curves >TH/L curves) structural curves who underwent a thoracic-only fusion. METHODS: A prospective adolescent idiopathic scoliosis registry was queried for double or triple major curves undergoing thoracic-only posterior fusion and a minimum 2-year follow-up. 3D reconstructions were generated from bi-planar radiographs. Paired sample t tests were used to assess differences in the coronal, sagittal, and axial planes pre and postoperatively, as well as Scoliosis Research Society Questionnaire-22 scores. Pearson correlations were utilized to identify variables related to spontaneous lumbar derotation. RESULTS: Twenty-two patients met the inclusion criteria. Both thoracic [61 ± 10 degrees to 20 ± 9 degrees ( P < 0.001)] and lumbar curves [41 ± 7 degrees to 22±7 degrees ( P < 0.001)] had significant coronal improvement and T5 to T12 kyphosis improved from 7 ± 14 degrees to 23 ± 8 degrees ( P < 0.001). The thoracic apical translation was significantly improved postoperatively (4.7 ± 1.5 to 0.5 ± 1 cm, P < 0.001), but the lumbar apical translation was unchanged (-1.7 ± 0.6 to -1.7±0.8 cm, P = 0.94). Scoliosis Research Society Questionnaire-22 scores significantly improved by 2 years postoperative. CONCLUSIONS: Unlike the 3D correction observed in nonstructural TH/L curves after thoracic-only fusion, patients with double or triple major curves demonstrated only spontaneous coronal correction of the lumbar curve, whereas the sagittal and axial planes were not significantly improved. These radiographic parameters did not negatively affect subjective or clinical outcomes at minimum 2-year follow-up. LEVEL OF EVIDENCE: Level IV-therapeutic.

Radiation risk assessment of quarry pit soil as construction material in Abeokuta, Nigeria: implications for environmental and public health.

ABSTRACTEnvironmental and health risks posed by radionuclides in quarry pit soils are of great concern in environmental health monitoring. The current investigation was aimed at determining the natural radionuclide activity concentration (in Bq kg-1) of the understudied quarry pit granules used as construction materials. The collection and preparation of pit soil samples from Abeokuta quarry sites were done using standard methods, analysis of radiological parameters was carried out using hyperpure germanium (HPGe) spectrometer. Specific activity concentrations of 226Ra, 232Th, and 40K were measured. The values obtained were greater than the world weighted average of 35, 30, and 400 Bq kg-1 for 226Ra, 232Th, and 40K, respectively. The absorbed dose, the annual effective dose, and the radium equivalent were calculated and demonstrated significant values. The radionuclide content of the samples is relatively high and the use of pit soils as a building material, therefore, raises radiological concerns for dwellers in this area and requires periodic monitoring and undergoing a radiation protection program.

BrAIST-Calc: Prediction of Individualized Benefit From Bracing for Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Prospective multicenter study data were used for model derivation and externally validated using retrospective cohort data. OBJECTIVE: Derive and validate a prognostic model of benefit from bracing for adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: The Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) demonstrated the superiority of bracing over observation to prevent curve progression to the surgical threshold; 42% of untreated subjects had a good outcome, and 28% progressed to the surgical threshold despite bracing, likely due to poor adherence. To avoid over-treatment and to promote patient goal setting and adherence, bracing decisions (who and how much) should be based on physician and patient discussions informed by individual-level data from high-quality predictive models. MATERIALS AND METHODS: Logistic regression was used to predict curve progression to <45° at skeletal maturity (good prognosis) in 269 BrAIST subjects who were observed or braced. Predictors included age, sex, body mass index, Risser stage, Cobb angle, curve pattern, and treatment characteristics (hours of brace wear and in-brace correction). Internal and external validity were evaluated using jackknifed samples of the BrAIST data set and an independent cohort (n=299) through estimates of discrimination and calibration. RESULTS: The final model included age, sex, body mass index, Risser stage, Cobb angle, and hours of brace wear per day. The model demonstrated strong discrimination ( c -statistics 0.83-0.87) and calibration in all data sets. Classifying patients as low risk (high probability of a good prognosis) at the probability cut point of 70% resulted in a specificity of 92% and a positive predictive value of 89%. CONCLUSION: This externally validated model can be used by clinicians and families to make informed, individualized decisions about when and how much to brace to avoid progression to surgery. If widely adopted, this model could decrease overbracing of AIS, improve adherence, and, most importantly, decrease the likelihood of spinal fusion in this population.

Non-Fusion Versus Fusion Surgery in Pediatric Idiopathic Scoliosis: What Trade-Offs in Outcomes Are Acceptable for the Patient and Family?

BACKGROUND: Vertebral body tethering and other non-fusion techniques for the treatment of pediatric idiopathic scoliosis are increasing in popularity. There is limited physician consensus on this topic as the result of a paucity of published data regarding which patients most benefit from non-fusion strategies. Thus, much of the decision-making is left to patients and parents, who must select a treatment based on their goals and values and the information available from health-care providers, the internet, and social media. We sought to understand patient and family preferences regarding the attributes of fusion versus non-fusion surgery that drive these choices. METHODS: Patients and families were recruited from 7 pediatric spine centers and were asked to complete a survey-based choice experiment that had been jointly developed with the U.S. Food and Drug Administration (FDA) to evaluate patient preferences. Choices between experimentally designed alternatives were analyzed to estimate the relative importance of outcomes and requirements associated with the choice options (attributes). The attributes included appearance, confidence in the planned correction, spinal motion, device failure, reoperation, and recovery period. The inclusion criteria were (1) an age of 10 to 21 years and (2) a diagnosis of adolescent idiopathic scoliosis in patients who were considering, or who had already undergone, treatment with fusion or non-fusion surgery. Preference weights were estimated from the expected changes in choice given changes in the attributes. RESULTS: A total of 344 respondents (124 patients, 92 parents, and 128 parent/patient dyads) completed the survey. One hundred and seventy-three patients were enrolled prior to surgery, and 171 were enrolled after surgery. Appearance and motion were found to be the most important drivers of choice. For the entire cohort, fusion was preferred over non-fusion. For patients who were considering surgery, the most important attributes were preservation of spinal motion and appearance. CONCLUSIONS: Patients and families seeking treatment for idiopathic scoliosis value appearance and preservation of spinal motion and, to a lesser extent, reoperation rates when considering fusion versus non-fusion surgery.