Predicting the effort required to manually mend auto-segmentations.

Auto-segmentation is one of the critical and foundational steps for medical image analysis. The quality of auto-segmentation techniques influences the efficiency of precision radiology and radiation oncology since high- quality auto-segmentations usually require limited manual correction. Segmentation metrics are necessary and important to evaluate auto-segmentation results and guide the development of auto-segmentation techniques. Currently widely applied segmentation metrics usually compare the auto-segmentation with the ground truth in terms of the overlapping area (e.g., Dice Coefficient (DC)) or the distance between boundaries (e.g., Hausdorff Distance (HD)). However, these metrics may not well indicate the manual mending effort required when observing the auto-segmentation results in clinical practice. In this article, we study different segmentation metrics to explore the appropriate way of evaluating auto-segmentations with clinical demands. The mending time for correcting auto-segmentations by experts is recorded to indicate the required mending effort. Five well-defined metrics, the overlapping area-based metric DC, the segmentation boundary distance-based metric HD, the segmentation boundary length-based metrics surface DC (surDC) and added path length (APL), and a newly proposed hybrid metric Mendability Index (MI) are discussed in the correlation analysis experiment and regression experiment. In addition to these explicitly defined metrics, we also preliminarily explore the feasibility of using deep learning models to predict the mending effort, which takes segmentation masks and the original images as the input. Experiments are conducted using datasets of 7 objects from three different institutions, which contain the original computed tomography (CT) images, the ground truth segmentations, the auto-segmentations, the corrected segmentations, and the recorded mending time. According to the correlation analysis and regression experiments for the five well-defined metrics, the variety of MI shows the best performance to indicate the mending effort for sparse objects, while the variety of HD works best when assessing the mending effort for non-sparse objects. Moreover, the deep learning models could well predict efforts required to mend auto-segmentations, even without the need of ground truth segmentations, demonstrating the potential of a novel and easy way to evaluate and boost auto-segmentation techniques.

Optimal strategies for modeling anatomy in a hybrid intelligence framework for auto-segmentation of organs.

Organ segmentation is a fundamental requirement in medical image analysis. Many methods have been proposed over the past 6 decades for segmentation. A unique feature of medical images is the anatomical information hidden within the image itself. To bring natural intelligence (NI) in the form of anatomical information accumulated over centuries into deep learning (DL) AI methods effectively, we have recently introduced the idea of hybrid intelligence (HI) that combines NI and AI and a system based on HI to perform medical image segmentation. This HI system has shown remarkable robustness to image artifacts, pathology, deformations, etc. in segmenting organs in the Thorax body region in a multicenter clinical study. The HI system utilizes an anatomy modeling strategy to encode NI and to identify a rough container region in the shape of each object via a non-DL-based approach so that DL training and execution are applied only to the fuzzy container region. In this paper, we introduce several advances related to modeling of the NI component so that it becomes substantially more efficient computationally, and at the same time, is well integrated with the DL portion (AI component) of the system. We demonstrate a 9-40 fold computational improvement in the auto-segmentation task for radiation therapy (RT) planning via clinical studies obtained from 4 different RT centers, while retaining state-of-the-art accuracy of the previous system in segmenting 11 objects in the Thorax body region.

Predicting human effort needed to correct auto-segmentations.

Medical image auto-segmentation techniques are basic and critical for numerous image-based analysis applications that play an important role in developing advanced and personalized medicine. Compared with manual segmentations, auto-segmentations are expected to contribute to a more efficient clinical routine and workflow by requiring fewer human interventions or revisions to auto-segmentations. However, current auto-segmentation methods are usually developed with the help of some popular segmentation metrics that do not directly consider human correction behavior. Dice Coefficient (DC) focuses on the truly-segmented areas, while Hausdorff Distance (HD) only measures the maximal distance between the auto-segmentation boundary with the ground truth boundary. Boundary length-based metrics such as surface DC (surDC) and Added Path Length (APL) try to distinguish truly-predicted boundary pixels and wrong ones. It is uncertain if these metrics can reliably indicate the required manual mending effort for application in segmentation research. Therefore, in this paper, the potential use of the above four metrics, as well as a novel metric called Mendability Index (MI), to predict the human correction effort is studied with linear and support vector regression models. 265 3D computed tomography (CT) samples for 3 objects of interest from 3 institutions with corresponding auto-segmentations and ground truth segmentations are utilized to train and test the prediction models. The five-fold cross-validation experiments demonstrate that meaningful human effort prediction can be achieved using segmentation metrics with varying prediction errors for different objects. The improved variant of MI, called MIhd, generally shows the best prediction performance, suggesting its potential to indicate reliably the clinical value of auto-segmentations.

Targeted Degradation of CDK9 Potently Disrupts the MYC Transcriptional Network.

Cyclin-dependent kinase 9 (CDK9) coordinates signaling events that regulate RNA polymerase II (Pol II) pause-release states. It is an important co-factor for transcription factors, such as MYC, that drive aberrant cell proliferation when their expression is deregulated. CDK9 modulation offers an approach for attenuating dysregulation in such transcriptional programs. As a result, numerous drug development campaigns to inhibit CDK9 kinase activity have been pursued. More recently, targeted degradation has emerged as an attractive approach. However, comprehensive evaluation of degradation versus inhibition is still critically needed to assess the biological contexts in which degradation might offer superior therapeutic benefits. We validated that CDK9 inhibition triggers a compensatory mechanism that dampens its effect on MYC expression and found that this feedback mechanism was absent when the kinase is degraded. Importantly, CDK9 degradation is more effective than its inhibition for disrupting MYC transcriptional regulatory circuitry likely through the abrogation of both enzymatic and scaffolding functions of CDK9. Highlights: - KI-CDK9d-32 is a highly potent and selective CDK9 degrader. - KI-CDK9d-32 leads to rapid downregulation of MYC protein and mRNA transcripts levels. - KI-CDK9d-32 represses canonical MYC pathways and leads to a destabilization of nucleolar homeostasis. - Multidrug resistance ABCB1 gene emerged as the strongest resistance marker for the CDK9 PROTAC degrader.

DHODH inhibition enhances the efficacy of immune checkpoint blockade by increasing cancer cell antigen presentation.

Pyrimidine nucleotide biosynthesis is a druggable metabolic dependency of cancer cells, and chemotherapy agents targeting pyrimidine metabolism are the backbone of treatment for many cancers. Dihydroorotate dehydrogenase (DHODH) is an essential enzyme in the de novo pyrimidine biosynthesis pathway that can be targeted by clinically approved inhibitors. However, despite robust preclinical anticancer efficacy, DHODH inhibitors have shown limited single-agent activity in phase 1 and 2 clinical trials. Therefore, novel combination therapy strategies are necessary to realize the potential of these drugs. To search for therapeutic vulnerabilities induced by DHODH inhibition, we examined gene expression changes in cancer cells treated with the potent and selective DHODH inhibitor brequinar (BQ). This revealed that BQ treatment causes upregulation of antigen presentation pathway genes and cell surface MHC class I expression. Mechanistic studies showed that this effect is (1) strictly dependent on pyrimidine nucleotide depletion, (2) independent of canonical antigen presentation pathway transcriptional regulators, and (3) mediated by RNA polymerase II elongation control by positive transcription elongation factor B (P-TEFb). Furthermore, BQ showed impressive single-agent efficacy in the immunocompetent B16F10 melanoma model, and combination treatment with BQ and dual immune checkpoint blockade (anti-CTLA-4 plus anti-PD-1) significantly prolonged mouse survival compared to either therapy alone. Our results have important implications for the clinical development of DHODH inhibitors and provide a rationale for combination therapy with BQ and immune checkpoint blockade.

Impact of surgeon volume, experience, and training on outcomes after arthroscopic rotator cuff repair: a nationwide analysis of 1489 surgeons.

Background: Given the complexity of arthroscopic rotator cuff repair (ARCR) and increasing prevalence, there is a need for comprehensive, large-scale studies that investigate potential correlations between surgeon-specific factors and postoperative outcomes after ARCR. This study examines how surgeon-specific factors including case volume, career length, fellowship training, practice setting, and regional practice impact two-year reoperation rates, conversion to total shoulder arthroplasty (anatomic or reverse), and 90-day post-ARCR hospitalization. Methods: The PearlDiver Mariner database was used to collect surgeon-specific variables and query patients who underwent ARCR from 2015 to 2018. Patient outcomes were tracked for two years, including reoperations, hospitalizations, and International Classification of Diseases, Tenth Revision codes for revision rotator cuff repair (RCR) laterality. Hospitalizations were defined as any emergency department (ED) visit or hospital readmission within 90 days after primary ARCR. Surgeon-specific factors including surgeon case volume, career length, fellowship training, practice setting, and regional practice were analyzed in relation to postoperative outcomes using both univariate and multivariate logistic regression. Results: 94,150 patients underwent ARCR by 1489 surgeons. On multivariate analysis, high-volume surgeons demonstrated a higher risk for two-year total reoperation (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.01-1.12, P = .03) and revision RCR (OR = 1.06, 95% CI: 1.01-1.12, P = .02) compared to low-volume surgeons. Early-career surgeons showed higher rates of 90-day ED visits (mid-career surgeons: OR = 0.78, 95% CI: 0.73-0.83, P < .001; late-career surgeons: OR = 0.73, 95% CI: 0.68-0.78, P < .001) and hospital readmission (mid-career surgeons: OR = 0.74, 95% CI: 0.63-0.87, P < .001; late-career surgeons: OR = 0.73, 95% CI: 0.61-0.88, P = .006) compared to mid- and late-career surgeons. Sports medicine and/or shoulder and elbow fellowship-trained surgeons demonstrated lower two-year reoperation risk (OR = 0.95, CI: 0.91-0.99, P = .04) and fewer 90-day ED visits (OR = 0.93, 95% CI = 0.88-0.98, P = .002). Academic surgeons experienced higher readmission rates compared to community surgeons (OR = 1.16, 95% CI = 1.01-1.34, P = .03). Surgeons practicing in the Northeast demonstrated lower two-year reoperation (OR = 0.88, 95% CI: 0.83-0.93, P < .001) and revision (OR = 0.88, 95% CI: 0.83-0.94, P < .001) RCR risk compared to surgeons in the Southern United States. Conclusion: High-volume surgeons exhibit higher two-year reoperation rates after ARCR compared to low-volume surgeons. Early-career surgeons demonstrate increased hospitalizations. Sports medicine or shoulder and elbow surgery fellowships correlate with reduced two-year reoperation rates and 90-day ED visits.

Factors associated with PrEP-era HIV seroconversion in a 4-year U.S. national cohort of n = 6059 sexual and gender minority individuals who have sex with men, 2017-2022.

INTRODUCTION: Community-based cohort studies of HIV seroconversion can identify important avenues for enhancing HIV prevention efforts in the era of pre-exposure prophylaxis (PrEP). Within individuals, one can assess exposure and outcome variables repeatedly and with increased certainty regarding temporal ordering. This cohort study examined the association of several risk factors with subsequent HIV seroconversion. METHODS: We report data from a 4-year study (2017-2022) of 6059 HIV seronegative sexual and gender minority individuals who have sex with men who had indications for-, but were not using-, PrEP at enrolment. Participants completed repeat exposure assessments and self-collection of biospecimens for HIV testing. We examined the roles of race and ethnicity, socio-economic status, methamphetamine use and PrEP uptake over the course of follow-up in relation to HIV seroconversion. RESULTS: Over 4 years, 303 of the participants seroconverted across 18,421 person-years (incidence rate = 1.64 [95% CI: 1.59-1.70] per 100 person-years). In multivariable discrete-time survival analysis, factors independently associated with elevated HIV seroconversion risk included being Black/African American (adjusted risk ratio [aRR]: 2.44, 1.79-3.28), Hispanic/Latinx (1.53, 1.19-1.96), housing instability (1.58, 1.22-2.05) and past year methamphetamine use (3.82, 2.74-5.33). Conversely, time since study enrolment (24 vs. 12 months, 0.67, 0.51-0.87; 36 months, 0.60, 0.45-0.80; 48 months, 0.48, 0.35-0.66) and higher education (master's degree or higher vs. less than or equal to high school, 0.36, 0.17-0.66) were associated with reduced seroconversion risk. Compared to non-PrEP users in the past 2 years without a current clinical indication, those who started PrEP but then discontinued had higher seroconversion risk, irrespective of clinical indication (3.23, 1.74-6.46) or lack thereof (4.30, 1.85-9.88). However, those who initiated PrEP in the past year (0.14, 0.04-0.39) or persistently used PrEP in the past 2 years (0.33, 0.14-0.74) had a lower risk of seroconversion. Of all HIV seroconversions observed during follow-up assessments (12, 24, 36 and 48 months), methamphetamine was reported in the 12 months prior 128 (42.2%) times (overall). CONCLUSIONS: Interventions that acknowledge race and ethnicity, economic variables such as education and housing instability, and methamphetamine use are critically needed. Not only are interventions to engage individuals in PrEP care needed, but those that retain them, and re-engage those who may fall out of care are essential, given the exceptionally high risk of seroconversion in these groups.

Concomitant Medial Collateral Ligament Injury Increases the Risk of Revision Anterior Cruciate Ligament Reconstruction.

PURPOSE: To compare rates of revisions between patients with isolated ACL reconstruction to those who had concomitant MCL injuries managed either operatively or non-operatively at time of index ACL reconstruction (ACLR). METHODS: The PearlDiver-Mariner Database was queried for all patients who underwent ACLR between 2016-2020 using laterality-specific International Classification of Diseases, Tenth Revision (ICD-10) and Current Procedural Terminology (CPT) codes. Patients were included if they were ages 15 or higher and had a minimum of 2 years follow-up after index ACLR. Patients were then divided into cohorts by presence or absence of concomitant MCL injury. The cohort of concomitant MCL injuries was further subdivided into those with MCL injuries managed non-operatively, with MCL repair, or with MCL reconstruction at time of index ACLR. Multivariate regression was performed between cohorts to evaluate for factors associated with revision ACLR. RESULTS: We identified 47,306 patients with isolated ACL injuries and 10,846 with concomitant MCL and ACL injuries. 93% of patients with concomitant MCL injuries had their MCL treated non-operatively; however, the annual proportion of patients being surgically managed for their MCL injury increased by 70% from 2016-2020. Concomitant MCL injury patients had higher odds of undergoing revision ACLR compared to patients with isolated ACL injuries (OR:1.50, 95%CI: 1.36-1.66, p<0.001). Amongst patients with concomitant MCL injuries, surgically managed patients had higher risk of revision ACLR compared to non-operatively managed MCL injuries (OR:1.39, 95%CI:1.01-1.86, p=0.034). CONCLUSIONS: Despite an increase in operatively managed concomitant MCL injuries, the majority of concomitant MCL injuries are still managed non-operatively at time of ACLR. Patients with concomitant MCL injury, particularly those managed operatively, at the time of ACLR are at increased risk of requiring revision ACLR compared to those with isolated ACL injuries.

No Differences in 2-Year Reoperation Rates for Meniscus Allograft Transplant With Concomitant Cartilage Restoration or Osteotomy: A National Database Study.

PURPOSE: To investigate reoperation rates after meniscus allograft transplant (MAT), comparing rates with and without concomitant articular cartilage and osteotomy procedures using a national insurance claims database. METHODS: We performed a retrospective cohort study of patients who underwent MAT from 2010 to 2021 with minimum 2 year follow-up using the PearlDiver database. Using Current Procedural Terminology (CPT) and International Classification of Diseases (ICD) codes, we identified patients who underwent concomitant procedures including chondroplasty or microfracture, cartilage restoration defined as osteochondral graft or autologous chondrocyte implantation (ACI), or osteotomy. Univariate logistic regressions identified risk factors for reoperation. Reoperations were classified as knee arthroplasty, interventional procedures, or diagnostic or debridement procedures. RESULTS: 750 patients were included with an average age of 29.6 years (interquartile range 21.0-36.8) and average follow-up time was 5.41 years (SD: 2.51). 90-day, 2-year, and all-time reoperation rates were 1.33%, 14.4%, and 27.6% respectively. MAT with cartilage restoration was associated with increased reoperation rate at 90 days (OR: 4.88; 95% CI: 1.38-19.27; p=.015), however there was no significant difference in reoperation rates at 2 years or to the end of follow-up. ACI had increased reoperation rates at 90 days (OR: 6.95; 95% CI: 1.45-25.96; p=.006), with no difference in reoperation rates 2 years post-operatively or to the end of follow-up. Osteochondral autograft and allograft were not associated with increased reoperation rates. CONCLUSION: 14.4% of patients in our cohort had a reoperation within 2 years of MAT. Nearly one in four patients undergoing MAT had concomitant cartilage restoration, showing that it is commonly performed on patients with articular cartilage damage. Concomitant osteochondral autograft, osteochondral allograft, chondroplasty, microfracture and osteotomy were not associated with any significant difference in reoperation rates. ACI was associated with increased reoperation rates at 90 days, but not later.

Degenerative medial and lateral menisci root tears: demographics, clinical presentation, imaging features, and associated findings.

PURPOSE: (I) Characterize the demographics and clinical features of patients with meniscal root tears (MRT); (II) analyze the morphology, extent, and grade of MRT on MRI; (III) evaluate associated abnormalities on imaging; and (IV) evaluate the associations between imaging findings, demographics, clinical features, and joint structural abnormalities. MATERIAL AND METHODS: A search was performed to identify meniscal root tears. Age, sex, BMI, and pain were recorded. Knee radiographs and MRI were reviewed. Presence, grade and morphology of MRT, meniscal extrusion, insufficiency fractures, as well as joint structural abnormalities were scored. For goals (I), (II), and (III), tabulations for categorical variables and mean for continuous variables were computed. MRT findings variables were described using percentages. For goal (IV), adjusted linear and logistic regression were employed. RESULTS: Ninety-six patients with a mean age of 56.6 years (69 females) and mean BMI of 28.9 kg/m2 were included; 88 of the MRT were located at the posterior horn of the medial meniscus (PHMM), and 82% were radial tear. The mean tear diameter was 3.8 mm, and 78/96 tears presented with meniscal extrusion. Nineteen patients presented with subchondral insufficiency fracture (SIF), which was significantly associated with the gap of the tear (p = 0.001) and grade of the meniscal root lesion (p = 0.005). CONCLUSION: MRT typically found in middle-aged to older overweight and obese women. Lesions were mostly radial tears and located at PHMM and were frequently associated with meniscal extrusion and SIF. Moreover, the presence of SIF was significantly associated with the gap width and grade of root tear.

MRI-based radiomic features of the urinary bladder wall identify patients with moderate-to-severe international prostate symptom score.

BACKGROUND: The International Prostate Symptom Score (IPSS) is a patient-reported measurement to assess the lower urinary tract symptoms of bladder outlet obstruction. Bladder outlet obstruction induces molecular and morphological alterations in the urothelium, suburothelium, detrusor smooth muscle cells, detrusor extracellular matrix, and nerves. We sought to analyze MRI-based radiomics features of the urinary bladder wall and their association with IPSS. METHOD: In this retrospective study, 87 patients who had pelvic MRI scans were identified. A biomarker discovery approach based on the optimal biomarker (OBM) method was used to extract features of the bladder wall from MR images, including morphological, intensity-based, and texture-based features, along with clinical variables. Mathematical models were created using subsets of features and evaluated based on their ability to discriminate between low and moderate-to-severe IPSS (less than 8 vs. equal to or greater than 8). RESULTS: Of the 7,666 features per patient, four highest-ranking optimal features were derived (all texture-based features), which provided a classification accuracy of 0.80 with a sensitivity, specificity, and area under the receiver operating characteristic curve of 0.81, 0.81, and 0.87, respectively. CONCLUSION: A highly independent set of urinary bladder wall features derived from MRI scans were able to discriminate between patients with low vs. moderate-to-severe IPSS with accuracy of 80%. Such differences in MRI-based properties of the bladder wall in patients with varying IPSS's might reflect differences in underlying molecular and morphological alterations that occur in the setting of chronic bladder outlet obstruction.

Barriers and Facilitators to Administering Burn Pit Registry Exams in VHA Facilities.

INTRODUCTION: The Veterans Health Administration (VHA) established the Airborne Hazards and Open Burn Pit Registry (AHOBPR) in 2014 to address exposure concerns for veterans who have served in military operations in Southwest Asia and Afghanistan. By 2021, over 236,086 veterans completed the online questionnaire and 60% requested an AHOBPR examination. Of those requesting an exam, only 12% had an exam recorded in their medical record. This article summarizes barriers and facilitators to delivering AHOBPR exams and shares lessons learned from facilities who have successfully implemented burn pit exams for veterans. MATERIALS AND METHODS: We (I.C.C and J.H.) constructed a key performance measure of AHOBPR examination (the ratio of examinations performed in facility over examinations assigned to a facility) to identify top performing facilities and then used stratified purposeful sampling among high-performing sites to recruit a diverse set of facilities for participation. We (P.V.C. and A.A.) recruited and interviewed key personnel at these facilities about their process of administering burn pit exams. Rapid qualitative methods were used to analyze interviews. RESULTS: The ratio of exams performed to exams assigned ranged from 0.00 to 14.50 for the 129 facilities with available information. Twelve interviews were conducted with a total of 19 participants from 10 different facilities. We identified 3 barriers: Unclear responsibility, limited incentives and competing duties for personnel involved, and constrained resources. Facilitators included the presence of an internal facilitator, additional staff support, and coordination across a facility's departments to provide care. CONCLUSIONS: Gaps across many VHA facilities to provide AHOBPR exams may be understood as stemming from organizational issues related to clear delegation of responsibility and staffing issues. VHA facilities that wish to increase AHOBPR exams for veterans may need additional administrative and medical staff.

Perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP) as an STI-prevention strategy among gay and bisexual men (GBM) in the United States: Results from a qualitative study.

OBJECTIVE: To leverage qualitative data to explore gay and bisexual men's (GBM) perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP). Doxy-PEP is a novel biomedical STI-prevention strategy that helps reduce the risk of acquiring bacterial STIs. Little is known about Doxy-PEP's acceptability in the U.S., nor how best to engage those most vulnerable to STIs in taking up this nascent prevention strategy. METHOD: Between July and September of 2023, 24 GBM from across the U.S. completed qualitative interviews about their perceptions regarding Doxy-PEP. Interviews were analyzed using a codebook approach to thematic analysis. RESULTS: Participants were generally interested in using Doxy-PEP, but were concerned about the potential for antibiotic resistance, side-effects, medication interactions to occur, along with stigmatizing discourse around its use. Meanwhile, participants were motivated by the simplicity of Doxy-PEP and the protection it could confer on both an individual and community-level- as well as its potential to reduce STI-related anxiety. Finally, participants desired additional information on Doxy-PEP to address their concerns. CONCLUSIONS: There is a need for clear guidelines and expanded public health messaging on Doxy-PEP in the U.S.

Irritable Bowel Syndrome in Veterans with Gulf War Illness Evaluated at VA's War-Related Illness and Injury Study Center.

INTRODUCTION: Excess rates of Gulf War illness (GWI) and irritable bowel syndrome (IBS), two chronic multisymptom illnesses, have long been documented among nearly 700,000 veterans who served in the 1990-1991 Persian Gulf War. We sought to report the prevalence, characteristics, and association of GWI and IBS decades after the war in a clinical cohort of deployed Gulf War veterans (GWVs) who were evaluated at the Department of Veterans Affairs' War Related Illness and Injury Study Center (WRIISC) for unexplained chronic symptoms. MATERIALS AND METHODS: We analyzed data gathered from clinical intake questionnaires of deployed GWVs who were evaluated at WRIISC clinics between 2008 and 2020. We applied Centers for Disease Control (CDC) criteria to determine the prevalence of severe GWI. IBS was identified using Rome IV diagnostic criteria (current IBS) and veterans' self-reported "history of physician-diagnosed IBS." We examined associations between IBS and GWI using bivariate analyses and multivariable logistic regression. RESULTS: Among the N = 578 GWVs evaluated by the WRIISC, severe GWI (71.8%), history of physician-diagnosed IBS (50.3%) and current IBS (42.2%) were all highly prevalent. Nearly half of GWVs with severe GWI met Rome criteria for IBS (45.8%), and over half reported a history of physician-diagnosed IBS (56.1%). In multivariable models, severe GWI was significantly associated both with current IBS (adjusted odds ratio (aOR): 1.68, 95% CI: 1.11, 2.54) and with veteran-reported history of physician-diagnosed IBS (aOR: 2.15, 95% CI: 1.43, 2.23). IBS with diarrhea (IBS-D) was the most common subtype among GWVs with current IBS (61.1%). However, IBS-mixed affected a significantly greater proportion of veterans with severe GWI, compared to veterans who did not have severe GWI (P = .03). CONCLUSIONS: More than 20 years after the Persian Gulf War, our findings indicate a high degree of comorbidity between severe GWI and IBS among deployed GWVs seeking care for unexplained illnesses. Our results suggest GWVs with GWI should be screened for IBS for which evidence-based treatments are available and could potentially reduce symptom burden. Conversely, symptoms of IBS should trigger additional evaluation for non-gastrointestinal symptoms in deployed Gulf War veterans to identify possible GWI and ensure a comprehensive approach to care.

The Use of Intraperitoneal Ampicillin in a Patient With Enterococcus faecalis Peritonitis.

INTRODUCTION: Peritoneal dialysis (PD) - associated peritonitis is a serious complication of peritoneal dialysis (PD). The 2022 International Society of Peritoneal Dialysis (ISPD) guidelines do not recommend intraperitoneal (IP) ampicillin for treatment of Enterococcal PD - associated peritonitis. To date, there is no in vivo data to support use of IP ampicillin for the treatment of Enterococcus faecalis. CASE DESCRIPTION: A 69-year-old man with a past medical history of end stage kidney disease (ESKD) requiring continuous cycling peritoneal dialysis (CCPD) was admitted to the hospital and treated for peritonitis with E. faecalis. The patient's CCPD prescription was 2.5% Dianeal with 5 total exchanges. IP ampicillin was added to the first 4 exchanges and additional ampicillin was added to the last fill. The patient successfully completed the treatment course with clinical cure. DISCUSSION: The use of IP ampicillin for E. faecalis peritonitis is controversial and previously lacked compelling clinical evidence for or against its use. This case demonstrates treatment of peritonitis using a modified dosing strategy with ampicillin added to each CCPD exchange and last fill. The loss of ampicillin antimicrobial activity reported in vitro with E. faecalis was not supported by this case.

Do Rib-Based Anchors Impair Chest Wall Motion in Early Onset Scoliosis (EOS)?

Purpose: There is a concern in pediatric surgery practice that rib-based fixation may limit chest wall motion in early onset scoliosis (EOS). The purpose of this study is to address the above concern by assessing the contribution of chest wall excursion to respiration before and after surgery. Methods: Quantitative dynamic magnetic resonance imaging (QdMRI) is performed on EOS patients (before and after surgery) and normal children in this retrospective study. QdMRI is purely an image-based approach and allows free breathing image acquisition. Tidal volume parameters for chest walls (CWtv) and hemi-diaphragms (Dtv) were analyzed on concave and convex sides of the spinal curve. EOS patients (1-14 years) and normal children (5-18 years) were enrolled, with an average interval of two years for dMRI acquisition before and after surgery. Results: CWtv significantly increased after surgery in the global comparison including all EOS patients (p < 0.05). For main thoracic curve (MTC) EOS patients, CWtv significantly improved by 50.24% (concave side) and 35.17% (convex side) after age correction (p < 0.05) after surgery. The average ratio of Dtv to CWtv on the convex side in MTC EOS patients was not significantly different from that in normal children (p=0.78), although the concave side showed the difference to be significant. Conclusion: Chest wall component tidal volumes in EOS patients measured via QdMRI did not decrease after rib-based surgery, suggesting that rib-based fixation does not impair chest wall motion in pediatric patients with EOS.

Virtual Growing Child (VGC): A general normative comparative system via quantitative dynamic MRI for quantifying pediatric regional respiratory anomalies with application in thoracic insufficiency syndrome (TIS).

Background: A normative database of regional respiratory structure and function in healthy children does not exist. Methods: VGC provides a database with four categories of regional respiratory measurement parameters including morphological, architectural, dynamic, and developmental. The database has 3,820 3D segmentations (around 100,000 2D slices with segmentations). Age and gender group analysis and comparisons for healthy children were performed using those parameters via two-sided t-testing to compare mean measurements, for left and right sides at end-inspiration (EI) and end-expiration (EE), for different age and gender specific groups. We also apply VGC measurements for comparison with TIS patients via an extrapolation approach to estimate the association between measurement and age via a linear model and to predict measurements for TIS patients. Furthermore, we check the Mahalanobis distance between TIS patients and healthy children of corresponding age. Findings: The difference between male and female groups (10-12 years) behave differently from that in other age groups which is consistent with physiology/natural growth behavior related to adolescence with higher right lung and right diaphragm tidal volumes for females(p<0.05). The comparison of TIS patients before and after surgery show that the right and left components are not symmetrical, and the left side diaphragm height and tidal volume has been significantly improved after surgery (p <0.05). The left lung volume at EE, and left diaphragm height at EI of TIS patients after surgery are closer to the normal children with a significant smaller Mahalanobis distance (MD) after surgery (p<0.05). Interpretation: The VGC system can serve as a reference standard to quantify regional respiratory abnormalities on dMRI in young patients with various respiratory conditions and facilitate treatment planning and response assessment. Funding: The grant R01HL150147 from the National Institutes of Health (PI Udupa).