Identification of HEPACAM2 as a novel and specific marker of small cell carcinoma.

BACKGROUND: Small cell lung cancer (SCLC) is the most aggressive neuroendocrine lung cancer, with a dismal 5-year survival rate. No reliable biomarkers or imaging are available for early SCLC detection. In a search for a specific marker of SCLC, this study identified that hepatocyte cell adhesion molecule 2 (HEPACAM2), a member of the immunoglobulin-like superfamily, is highly and specifically expressed in SCLC. METHODS: This study investigated HEPACAM2 expression in patients with SCLC via RNA sequencing and evaluated its relationship to progression-free survival (PFS) and overall survival (OS). Immunofluorescence microscopy was used to assess the cellular location of HEPACAM2 and to conduct in vitro and in vivo studies to understand its expression and functional significance. These findings were integrated with databases of patients with SCLC. RESULTS: HEPACAM2 is highly expressed and specific to SCLC. HEPACAM2 levels are inversely correlated with PFS and OS in patients with SCLC and are expressed at all stages. Moreover, HEPACAM2 messenger RNA and its peptides can be detected in the secretomes in cell lines. Positively correlated with ASCL1 expression in SCLC tumors, HEPACAM2 is localized primarily to the plasma membrane and linked to extracellular matrix signaling and cellular migration. A loss of HEPACAM2 in SCLC cells attenuated ASCL1 and MYC expression. Consistent with clinical data, in vitro and in vivo studies suggested that HEPACAM2 promotes cancer cell growth. CONCLUSIONS: With its remarkable specificity, high expression, presence in early disease, and extracellular secretion, HEPACAM2 could be a potential diagnostic cell surface biomarker for early SCLC detection. These findings warrant further investigation into its role in the pathobiology of SCLC.

Maternal Minocycline as Fetal Therapy in a Rat Model of Myelomeningocele.

INTRODUCTION: This study aimed to investigate whether the maternal administration of minocycline, a tetracycline antibiotic known to have anti-inflammatory and neuroprotective properties in models of neural injury, reduces inflammation and neural cell death in a fetal rat model of myelomeningocele (MMC). METHODS: E10 pregnant rats were gavaged with olive oil or olive oil + retinoic acid to induce fetal MMC. At E12, the dams were exposed to regular drinking water or water containing minocycline (range, 40-140 mg/kg/day). At E21, fetal lumbosacral spinal cords were isolated for immunohistochemistry and quantitative gene expression studies focused on microglia activity, inflammation, and apoptosis (P < 0.05). RESULTS: There was a trend toward decreased activated Iba1+ microglial cells within the dorsal spinal cord of MMC pups following minocycline exposure when compared to water (H2O) alone (P = 0.052). Prenatal minocycline exposure was correlated with significantly reduced expression of the proinflammatory cytokine, IL-6 (minocycline: 1.75 versus H2O: 3.52, P = 0.04) and apoptosis gene, Bax (minocycline: 0.71 versus H2O: 1.04, P < 0.001) among MMC pups. CONCLUSIONS: This study found evidence that the maternal administration of minocycline reduces selected markers of inflammation and apoptosis within the exposed dorsal spinal cords of fetal MMC rats. Further study of minocycline as a novel prenatal treatment strategy to mitigate spinal cord damage in MMC is warranted.

Recalcitrant Lateral Epicondylitis: A Systematic Review on Current Nonoperative and Operative Treatment Modalities.

BACKGROUND: Lateral epicondylitis is a common cause of elbow pain that is generally self-limiting. For patients who have persistent symptoms refractory to conservative treatment, there is still no clear consensus on the most favorable treatment modality. The purpose of this systematic review was to synthesize the available literature regarding both nonoperative and operative treatment modalities for recalcitrant lateral epicondylitis (RLE) to provide insight into the efficacy of treatment options. METHODS: A systematic review was performed in accordance with the 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, where the PubMed, MEDLINE/Ovid, CINAHL, Cochrane, and Scopus databases were queried to identify studies evaluating treatment options for RLE. RESULTS: A total of 27 studies with 1,958 patients were included. Of the reviewed studies, there were a wide variety of treatments including platelet-rich plasma injections, percutaneous tenotomies, and various arthroscopic and open procedures. CONCLUSION: There are a wide variety of treatment modalities available for RLE that have promising efficacy in the short, medium, and long terms. A comprehensive approach combining evidence-based and patient-centered care is critical for effective management of refractory symptoms. LEVEL OF EVIDENCE: Level IV. See Instructions for Authors for a complete description of levels of evidence.

Convenience and price drive online pharmacy usage by veterinary clients.

OBJECTIVE: To evaluate factors that influence client selection of a veterinary pharmacy and assess client perception of the impact of online pharmacies on veterinary clinics. METHODS: Survey data and satisfaction metrics were compared between online pharmacies, a teaching hospital pharmacy (UW Veterinary Care), and primary care veterinary clinics between March and April 2023. Online pharmacy users were asked about perceived impact of online pharmacies on veterinary clinics. Personal values were correlated with the likelihood of using a pharmacy. RESULTS: 158 surveys were analyzed; 32.9% of respondents used an online pharmacy. Of those, 20% used a veterinary-affiliated online pharmacy. Convenience was the value most liked by online pharmacy and primary care clinic users. Online users reported liking price most, whereas veterinary clinic pharmacy users (UW Veterinary Care and primary care clinics) reported liking communication and trust. Online users ranked price as more important, whereas veterinary clinic users ranked personalized experience (caring, explanations, veterinary recommended) as more important. Regardless of pharmacy type, satisfaction scores were high. Most online users perceived a negative impact of online pharmacies on veterinary clinics; this did not change reported usage. CONCLUSIONS: Online and veterinary clinic users prioritized different values. Online users prioritized price and veterinary clinic users prioritized personalized experience. Online usage was not influenced by perceived impact. CLINICAL RELEVANCE: For veterinary clinics attempting to increase revenue, appealing to these 2 distinct driving values is essential. Offering practice-directed online pharmacies with competitive and transparent pricing could procure online consumers, while maintaining a personalized experience remains important for consumers purchasing prescriptions in-house.

Comparative Transcriptome Analysis of Human and Mouse Canalicular Lungs in Fetal Diaphragmatic Hernia.

BACKGROUND: The nitrofen model of congenital diaphragmatic hernia (CDH) is widely used in translational research. However, the molecular pathways associated with pulmonary hypoplasia in this model compared to the human CDH phenotype have not been well described. The aim of this study was to investigate differentially expressed genes (DEG) and signaling pathways in early stage fetal lungs in mouse and human CDH. METHODS: CDH lung tissue was obtained from human fetuses (21-23 weeks gestation) and nitrofen mouse pups (E15.5). NovaSeq Flowcell RNA-seq was performed to evaluate differentially expressed transcriptional and molecular pathways (DEGs) in fetal mice with CDH, compared with age-matched normal mouse lungs and human CDH samples. RESULTS: There were thirteen overlapping DEGs in human and mouse CDH lung samples compared to controls. These genes were involved in extracellular matrix, myogenesis, cilia, and immune modulation pathways. Human CDH was associated with an upregulation of collagen formation and extracellular matrix reorganization whereas mouse CDH was associated with an increase in muscular contraction. The most common cell types upregulated in human and mouse CDH samples were ciliated airway cells. CONCLUSIONS: This study highlights the unique gene transcriptional patterns in early fetal mouse and human lungs with CDH. These data have implications when determining the translational potential of novel therapies in CDH using nitrofen-based animal models. LEVEL OF EVIDENCE: Level IV. STUDY TYPE: Basic science/case series.

Pain hypersensitivity, sensorimotor impairment, and decreased muscle force in a novel rat model of radiation-induced peripheral neuropathy.

INTRODUCTION: Radiation-induced peripheral neuropathy is a rare, but serious complication often resulting in profound morbidity, life-long disability, and chronic debilitating pain. Unfortunately, this type of peripheral neuropathy is usually progressive, and almost always irreversible. To date, a standardized rat model of radiation-induced peripheral neuropathy has not been established. The purpose of the present study was to examine neuropathic pain, sensorimotor impairment, and muscle force parameters following the administration of a clinically relevant radiation dose in a rat model. METHODS: Ten rats were randomly assigned to one of two experimental groups: (1) radiation and (2) sham-radiated controls. Radiated animals were given a clinically relevant dose of 35 Gray (Gy) divided into five daily doses of 7 Gy/day. This regimen represents a human equivalent dose of 70 Gy, approximating the same dosage utilized for radiotherapy in oncologic patients. Sham-radiated controls were anesthetized and placed in the radiation apparatus but were not given radiation. All animals were tested for baseline values in both sensorimotor and pain behavioral tests. Sensorimotor testing consisted of the evaluation of walking tracks with the calculation of the Sciatic Functional Index (SFI). Pain-related behavioral measures consisted of mechanical allodynia (von Frey test), cold allodynia (Acetone test), and thermal allodynia (Hargreaves test). Animals were tested serially over an 8-week period. At the study endpoint, electrophysiological and muscle force assessments were completed, and histomorphometric analysis was performed on all sciatic nerves. RESULTS: Animals that underwent radiation treatment displayed significantly greater pain hypersensitivity to mechanical stimulation as compared to sham radiated controls from weeks 4 to 8 of testing. SFI values indicated sensorimotor impairments in the overground gait of radiated animals as compared to non-radiated animals. Furthermore, radiated animals displayed reduced twitch and tetanic muscle force when compared to sham radiated controls. CONCLUSIONS: A clinically relevant human equivalent dose of fractionated 35 Gy in rats established significant pain hypersensitivity, impairments in sensorimotor locomotion, and decreased muscle force capacity. This novel rodent model of radiation-induced peripheral neuropathy can be utilized to assess the potential efficacy of therapeutic treatments to either prevent or remediate this clinically debilitating condition.

Writing Groups for Healthcare Professionals in Academic Medicine.

Within the Department of Medicine (DOM) in a large tertiary academic health care facility in midwestern United States, we have developed an educational offering that incorporates an academic writing program (AWP) blending the approaches of a writing accountability work group, a writing workshop, and didactic writing courses. The purpose of this AWP was to assist healthcare professionals (HCP) with their manuscript writing skills to enhance academic productivity. We report our evolving journey and experiences with this AWP. To date, it has been offered 3 times to 25 HCP over the course of 3 years. Among those responding to a post program follow up survey (N = 11), 8 (73%) indicated that they completed the project that they were working on during the AWP and went on to publish the manuscript (N = 5) or were in the process of submission (N = 2). Some indicated they has also gone on to present posters (N = 2) or were in the process of presenting posters (N = 2) or had received grants (N = 1) or were awaiting grant notice (N = 1). A number of attendees have continued to use and share the tools presented during the AWP. Based on input from attendees and increased requests for this AWP, this educational program has been deemed a success and expansion of this program is currently underway.

Concurrent Prescription Fills of Opioids and Benzodiazepines Among Postpartum Women During COVID-19.

Introduction: Concurrent prescribing of opioids and benzodiazepines is associated with increased risk of emergency department visits and overdose. Postpartum women commonly receive opioids for pain after delivery and are at risk for postpartum depression/anxiety. Although prior research finds increases in opioid prescribing and symptoms of depression/anxiety during COVID-19, concurrent prescribing among postpartum women has not been examined in the context of COVID-19. Methods: Using data from a large sample of privately insured postpartum women (N=514,120), the authors compared concurrent prescription fills of opioids and benzodiazepines before March 1, 2020, and after March 1, 2020. Primary outcome variables measured whether a patient ever filled concurrent opioid and benzodiazepine prescriptions and the number of concurrent prescription fills per patient in the 6 months after delivery. Results: Roughly 46.4% of postpartum women filled an opioid prescription, 2.4% filled a benzodiazepine prescription, and 1.2% of women filled a concurrent prescription. Among postpartum women filling a benzodiazepine prescription, 50.7% filled a concurrent opioid prescription. The number of concurrent fills among postpartum women significantly increased during the early period of COVID-19. On average, postpartum women filled 0.009 more concurrent prescriptions than expected on the basis of the preexisting trend, representing a 22.0% increase in the number of concurrent prescriptions relative to the sample mean. Conclusions: Concurrent prescribing of opioids and benzodiazepines places postpartum women at higher risk of emergency department visits and overdose. To reduce the harms associated with concurrent prescribing, clinicians should carefully consider whether opioids and/or benzodiazepines are clinically necessary for treatment and consult their state prescription drug monitoring program prior to prescribing these medications.

Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in Pseudomonas aeruginosa of clinical origin.

The siderophore-cephalosporin cefiderocol (FDC) presents a promising treatment option for carbapenem-resistant (CR) P. aeruginosa (PA). FDC circumvents traditional porin and efflux-mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression. Further, difficulties with antimicrobial susceptibility testing (AST) and unexpected negative clinical treatment outcomes have prompted concerns for heteroresistance, where a single lineage isolate contains resistant subpopulations not detectable by standard AST. This study aimed to evaluate the prevalence of TBDR mutations among clinical isolates of P. aeruginosa and the phenotypic effect on FDC susceptibility and heteroresistance. We evaluated the sequence of pirR, pirS, pirA, piuA, or piuD from 498 unique isolates collected before the introduction of FDC from four clinical sites in Portland, OR (1), Houston, TX (2), and Santiago, Chile (1). At some clinical sites, TBDR mutations were seen in up to 25% of isolates, and insertion, deletion, or frameshift mutations were predicted to impair protein function were seen in 3% of all isolates (n = 15). Using population analysis profile testing, we found that P. aeruginosa with major TBDR mutations were enriched for a heteroresistant phenotype and undergo a shift in the susceptibility distribution of the population as compared to susceptible strains with wild-type TBDR genes. Our results indicate that mutations in TBDR genes predate the clinical introduction of FDC, and these mutations may predispose to the emergence of FDC resistance.

Outcomes of upper extremity sensory neuromas treated with excision and burial.

Background: Upper extremity sensory neuromas can be extremely debilitating leading to pain and dysfunction. Surgical management of neuromas can either be ablative or reconstructive. The primary aim of this study was to examine the outcomes of surgically treated sensory neuromas within the forearm, wrist, and hand with exclusion of digital neuromas. Methods: A retrospective review was conducted of patients surgically treated for an upper extremity sensory neuroma from a multi-surgeon, single institution database. The types of neuroma, mechanism of injury and the surgical technique utilized for treatment were documented. Patient reported outcomes were collected including resolution of symptoms, pain scores, complications, and need for revision surgery. Averages and proportions were used for analysis. Results: 79 patients were included with mean age of 42.3 years and an average follow-up of 6.7 months. The types of sensory neuromas included 23 dorsal radial sensory, 21 medial antebrachial cutaneous, 15 palmar cutaneous, and 14 dorsal ulnar sensory. Single isolated cases of neuromas were more common (94.9%) than multiple neuromas (5.1%). 67.1% (53/79) of patients experienced pain or hypersensitivity with a mean improvement of 2.0 in the visual analog scale (VAS) following surgery. 6.3% (5/79) required revision surgery, and 82% returned to work in some capacity. Conclusion: Surgical excision of neuroma and burial into local surrounding tissue can be safely performed with a relatively low reoperation rate. 80% of patients had full resolution or improvement in their symptoms.

Data-driven mathematical modeling of sleep consolidation in early childhood.

Across early childhood development, sleep behavior transitions from a biphasic pattern (a daytime nap and nighttime sleep) to a monophasic pattern (only nighttime sleep). The transition to consolidated nighttime sleep, which occurs in most children between 2- and 5-years-old, is a major developmental milestone and reflects interactions between the developing homeostatic sleep drive and circadian system. Using a physiologically-based mathematical model of the sleep-wake regulatory network constrained by observational and experimental data from preschool-aged participants, we analyze how developmentally-mediated changes in the homeostatic sleep drive may contribute to the transition from napping to non-napping sleep patterns. We establish baseline behavior by identifying parameter sets that model typical 2-year-old napping behavior and 5-year-old non-napping behavior. Then we vary six model parameters associated with the dynamics of and sensitivity to the homeostatic sleep drive between the 2-year-old and 5-year-old parameter values to induce the transition from biphasic to monophasic sleep. We analyze the individual contributions of these parameters to sleep patterning by independently varying their age-dependent developmental trajectories. Parameters vary according to distinct evolution curves and produce bifurcation sequences representing various ages of transition onset, transition durations, and transitional sleep patterns. Finally, we consider the ability of napping and non-napping light schedules to reinforce napping or promote a transition to consolidated sleep, respectively. These modeling results provide insight into the role of the homeostatic sleep drive in promoting interindividual variability in developmentally-mediated transitions in sleep behavior and lay foundations for the identification of light- or behavior-based interventions that promote healthy sleep consolidation in early childhood.

Clinical Features and Genomic Epidemiology of Bloodstream Infections due to Enterococcal Species Other Than Enterococcus faecalis or E. faecium in Patients With Cancer.

Background: Non-Enterococcus faecium, non-E. faecalis (NFF) enterococci are a heterogeneous group of clinically pathogenic enterococci that include species with intrinsic low-level vancomycin resistance. Patients with cancer are at increased risk for bacteremia with NFF enterococci, but their clinical and molecular epidemiology have not been extensively described. Methods: We conducted a retrospective review of all patients (n = 70) with NFF bacteremia from 2016 to 2022 at a major cancer center. The main outcomes assessed were 30-day mortality, microbiological failure (positive blood cultures for ≥4 days), and recurrence of bacteremia (positive blood culture <14 days after clearance). Whole-genome sequencing was performed on all available NFF (n = 65). Results: Patients with hematological malignancies made up 56% of the cohort (77% had leukemia). The majority of solid malignancies (87%) were gastrointestinal in origin. The majority of infections (83%) originated from an intra-abdominal source. The most common NFF species were E. gallinarum (50%) and E. casseliflavus (30%). Most (61%) patients received combination therapy. Bacteremia recurred in 4.3% of patients, there was a 30-day mortality of 23%, and 4.3% had microbiological failure. E. gallinarum and E. casseliflavus isolates were genetically diverse with no spatiotemporal clustering to suggest a single strain. Frequencies of ampicillin resistance (4.3%) and daptomycin resistance (1.9%) were low. Patients with hematologic malignancy had infections with NFF enterococci that harbored more resistance genes than patients with solid malignancy (P = .005). Conclusions: NFF bacteremia is caused by a heterogeneous population of isolates and is associated with significant mortality. Hematological malignancy is an important risk factor for infection with NFF resistant to multiple antibiotics.

Quality and Reliability Analysis of YouTube as a Source for Patient Education on Dupuytren's Contracture.

Purpose: This study seeks to assess the quality and reliability of YouTube videos on Dupuytren's contracture. Methods: The first 50 unique videos on Dupuytren's contracture were evaluated by searching YouTube for Dupuytren's contracture. Video metrics, source, and content type were recorded. Video reliability was assessed using the Journal of American Medical Association (JAMA) Benchmark criteria. Video educational quality was assessed using the Global Quality Score (GQS) and a Dupuytren's Contracture-Specific Score (DC-SS). Results: The total number of views for all 50 videos evaluated was 1,908,608 (mean, 38,172.16 ± 5,502.45 views). The mean reliability (JAMA) score was 2.21 ± 0.69 (range 0-4), the mean educational quality (GQS) score was 2.80 ± 1.28 (range 1-5), and the mean disease-specific (DC-SS) score was 6.05 ± 2.17 (range 0-15). Nonphysician health care professionals had the most popular videos, but the lowest DC-SS. GQS varied based on the video source, with physician-uploaded videos having the highest average quality scores. Physician source was an independent positive predictor of higher quality (GQS) (ß = 0.477). Conclusions: Videos on Dupuytren's contracture were frequently viewed on YouTube but had overall low educational quality and reliability. Of the videos that discussed collagenase as a treatment option, 40% failed to mention percutaneous needle aponeurotomy. Patients may be exposed to an incomplete set of treatment options. Educational content on YouTube should be interpreted cautiously and proper in-office education and high-quality resources for Dupuytren's contracture should be provided by physicians. Type of Study/Level of Evidence: Therapeutic IV.

Analysis of variability and trends in medical school clerkship grades.

Background: Medical school clerkship grades are used to evaluate orthopedic surgery residency applicants, however, high interinstitutional variability in grade distribution calls into question the utility of clerkship grades when evaluating applicants from different medical schools. This study aims to evaluate the variability in grade distribution among medical schools and look for trends in grade distribution over recent years. Methods: Applications submitted to Rush University's orthopedic surgery residency program from 2015, 2019, and 2022 were collected from the Electronic Residency Application Service. Applications from the top 100 schools according to the 2023-2024 U.S. News and World Report Research Rankings were reviewed. The percentage of "honors" grades awarded by medical schools for the surgery and internal medicine clerkships were extracted from applicants' Medical Student Performance Evaluation letters. Results: The median percentage of honors given in 2022 was 36.0 % (range 10.0-82.0) for the surgery clerkship and 33.0 % (range 6.7-80.0) for the internal medicine clerkship. Honors were given 6.6 % more in the surgery clerkship in 2022 compared to 2015. There was a negative correlation between a higher (worse) U.S. News and World Report research ranking and the percentage of honors awarded in 2022 for the surgery and internal medicine clerkships. Conclusion: There is substantial interinstitutional variability in the rate that medical schools award an "honors" grade with evidence of grade inflation in the surgery clerkship. Residency programs using clerkship grades to compare applicants should do so cautiously provided the variability demonstrated in this study.

Patient Characteristics, Treatment, and Survival in Pleuropulmonary Blastoma: An Analysis from the National Cancer Database.

Pleuropulmonary blastoma (PPB) is a rare childhood tumor originating from the lung or pleura, typically treated with surgery, chemotherapy (CTx), and/or radiation therapy (RTx). This study aimed to assess patient and tumor features, treatment methods, and survival rates in PPB. We retrospectively analyzed PPB patients under 18 from 2004 to 2019, using the National Cancer Database (NCDB). We assessed 5-year overall survival (OS) rates based on disease presentation and treatment regimens, using Kaplan-Meier curves and Cox proportional regression. Among 144 cases identified, 45.9% were female, with a median age of 2 years (interquartile range 1-3). In all, 62.5% of tumors originated from the lung, and 10.4% from the pleura. Moreover, 6.9% were bilateral, and the median tumor size was 8.9 cm, with 4.2% presenting with metastases. The 5-year OS rate was 79.6%, with no significant change over time (2004-2009, 77.6%; 2010-2014, 90.8%; 2015-2019, OS 75.3%; p = 0.08). In all, 5.6% received CTx alone, 31.3% surgery alone, 45.8% surgery/CTx, and 17.4% surgery/CTx/RTx. The OS rates were comparable between the surgery/CTx/RTx (80.0%) and surgery/CTx (76.5%) groups (adjusted Hazard Ratio, 1.72; 95% CI, 0.57-5.19; p = 0.34). Therefore, due to the unchanged survival rates over time, further prospective multicenter studies are needed to determine the optimal multimodal treatment regimens for this rare pediatric tumor.

Neurodevelopmental Outcomes in Children After Fetoscopic Endoluminal Tracheal Occlusion for Severe Congenital Diaphragmatic Hernia: Results From a Multidisciplinary Clinic.

BACKGROUND: We compared early neurodevelopmental morbidity in young children with severe CDH who underwent FETO to those without fetal therapy. METHODS: We conducted a prospective study of severe CDH patients undergoing FETO (n = 18) at a single North American center from 2015 to 2021 (NCT02710968). Outpatient survivors (n = 12) were evaluated by a multidisciplinary team and compared to expectantly managed CDH patients. Neurodevelopmental outcomes were assessed using the Capute Scales [Clinical Linguistic and Auditory Milestone Scales (CLAMS) and Cognitive Adaptive Test (CAT)], with a developmental quotient (DQ) < 85 indicative of at-risk for delay. RESULTS: At one year, 58% (n = 7) of FETO patients underwent evaluation, with notable concern for language delay (CLAMS median DQ, 80.1 [interquartile range, 67.6-86.7]). FETO scores improved by 24-months, whereas high severity/non-FETO scores declined [CLAMS median DQ (Difference in DQ), 92.3 (+12.2) vs. 77.1 (-13.4), respectively; p = 0.049]. On the initial CAT, FETO patients had concern for visual motor and problem-solving delays, with a median DQ of 81.3 (62.1-89.4). At 24-months, FETO patients had improving scores [Median CAT DQ, 90.8 (+9.5)], whereas high severity/non-FETO [87.5 (-3.0), p = 0.28] had declining scores. CONCLUSION: These initial data suggest that FETO is associated with favorable neurodevelopmental outcomes at 24-months compared to severe CDH under expectant management. LEVEL OF EVIDENCE: III.

Association of Gabapentinoids With Opioid-Related Overdose in the Inpatient Setting: A Single Center Retrospective Case-Control Study.

Objectives: Recent data suggest concomitant gabapentinoid use increases opioid-related overdose (ORO) risk; however, this association has not been well studied in the hospital setting. The primary objective of this study was to compare ORO risk, indicated by naloxone administration, in patients receiving opioids plus gabapentinoids versus opioids alone. Methods: In this retrospective case-control study of adults admitted to a large community hospital from 1/1/20 to 12/31/21, all cases (defined as patients who received naloxone more than 24 hours after admission) identified were matched 1:1 to randomly selected controls (defined as patients on opioids who did not receive naloxone). The primary outcome was the percentage of cases and controls with concomitant inpatient gabapentinoid use. Logistic regression was performed to determine the independent association between gabapentinoids and ORO (as evidenced by inpatient naloxone administration). Results: Baseline characteristics were similar between the 144 cases and 144 controls. Gabapentinoid exposure was greater for cases than controls (34.0%vs 20.8%, P = .0118). Median hospital length of stay (11vs 4 days, P < .0001) and mortality (19%vs 5%; P = .0018) were also higher for cases. In logistic regression analysis, ORO (adjusted OR 4.91; 95% CI 1.86-12.96) and serotonergic medication exposure (adjusted OR 4.31; 95% CI 1.50-12.38) were significantly associated with gabapentinoid use. Conclusions: Concomitant gabapentinoid use with opioids was associated with increased ORO risk in the inpatient setting. When considering prescribing gabapentinoids in conjunction with opioids in the hospital setting, potential benefits should be weighed against increased overdose risk.

Operative Volumes and Postoperative Outcomes After Elective Resection of Congenital Lung Malformations in Infants.

OBJECTIVE: To determine whether hospital- and surgeon-level operative volumes are associated with differences in postoperative outcomes among infants undergoing elective lung surgery for a congenital lung malformation (CLM). SUMMARY BACKGROUND DATA: Infant lung surgery is a relatively uncommon procedure performed by pediatric surgeons nationwide. The relationship between surgical volume and postoperative outcomes remains unknown. METHODS: A retrospective cohort study of asymptomatic infants who underwent elective lung resection of a CLM was conducted using the Pediatric Health Information System database (2016-2020). Multivariable linear and poisson regressions were performed based on annual lung resection tertiles. RESULTS: There were 1420 infants managed by 48 hospitals and 309 primary surgeons. Institutions that performed seven or fewer CLM resections per year (56%) were associated with significantly higher postoperative complication rates compared to medium- and high-volume hospitals (low: 134 [34%], medium: 110 [21%], high: 144 [29%]; P<0.001). Surgeons who performed one or fewer CLM resections per year (82%) were associated with significantly higher complication rates compared to medium- and high-volume surgeons (low: 171 [31%], medium: 75 [26%], high: 119 [24%]; P=0.02). Multivariable analyses confirmed that low-volume hospitals were associated with higher complications (OR 1.81, CI 1.38-2.37; P<0.001), and low-volume surgeons had an increased risk of complications (overall: OR 1.37, CI 1.01-1.84; P=0.04). CONCLUSIONS: In this cohort study of infants undergoing elective lung resection for a CLM, lower volume providers were associated with higher postoperative patient morbidity. These findings represent an opportunity to inform quality improvement initiatives on pediatric lung resection and the debate on surgical subspecialization for this unique patient population.

The impact of undergoing elective pediatric lung resection during respiratory syncytial virus peak season on patient outcomes: A nationwide retrospective analysis.

OBJECTIVES: Observational data to support delaying elective pediatric thoracic surgery during peak respiratory viral illness season is lacking. This study evaluated whether lung surgery during peak viral season is associated with differences in postoperative outcomes and resource utilization. METHODS: A retrospective observational cohort study was performed using the Pediatric Health Information System (PHIS). Patients with a congenital lung malformation (CLM) who underwent elective lung resection between 1 January 2016 and 29 February 2020 were included. Respiratory syncytial virus (RSV) incidence was used as a proxy for respiratory viral illness circulation. Monthly hospital-specific RSV incidence was calculated from PHIS data, and peak RSV season was defined by Centers for Disease Control data. Multivariable regression models were built to identify predictors of postoperative mechanical ventilation, which was the main outcome measure, as well as secondary outcomes including 30-day readmission after lung resection, postoperative length of stay (LOS) and hospital billing charges. RESULTS: Of 1542 CLM patients identified, 344 (22.3%) underwent lung resection during peak RSV season. 38% fewer operations were performed per month during peak RSV season than during off-peak months (p < .001). Children who underwent surgery during peak RSV season did not differ from the off-peak group in terms of age at operation, race, or comorbid conditions (i.e., congenital heart disease, newborn respiratory distress, and preoperative pneumonia). There was no association between hospital-specific RSV incidence at the time of surgery and postoperative mechanical ventilation, postoperative LOS, 30-day readmission rate or hospital billing charges. DISCUSSION: Performing elective lung surgery in children with CLMs during peak viral season is not associated with adverse surgical outcomes or increased utilization of healthcare resources.

Modifiable Preoperative Risk Factors to Mitigate Postoperative Site Infection Following Pediatric Gastrostomy.

PURPOSE: There are limited studies assessing modifiable preoperative risk factors for pediatric laparoscopic gastrostomy tubes (LGT) and percutaneous endoscopic gastrostomy (PEG) tubes. We sought to evaluate the effect of demographics and surgical/infectious history on the superficial infection rate following gastrostomy tube (GT) placement. METHODS: After IRB approval, we conducted a single-institution retrospective cohort study from 2015 to 2021 of pediatric patients undergoing LGT or PEG tube. The primary outcome was cellulitis or abscess formation within 30-days and 90-days postoperatively. Statistical analyses were performed with t-tests, Chi-squared, and logistic regression(p ≤ 0.05). RESULTS: There were 382 patients, with 181 (47%) LGT and 201 (53%) PEGs. LGT patients were younger (5.9 vs. 12.3 months, p < 0.001) and more likely to be admitted to the neonatal or cardiac intensive care unit prior to their GT. There were similar rates of prior surgical intervention (58% vs. 66%, p = 0.29) and previous infection (37% vs. 38%, p = 0.87) in both LGT and PEG patients. Within 30-days postoperatively, LGT patients had a higher superficial infection rate (12% vs. 6%, p = 0.04). On multivariate regression, Black race (Odds Ratio 0.10, p = 0.03) was protective and prior Staphylococcus colonization (OR 2.35, p = 0.04) increased the odds of infection. In those patients colonized with Staphylococcus, 21% developed a superficial site infection compared to 9% in those not colonized (p = 0.01). CONCLUSION: These data suggest prior Staphylococcus colonization is a significant risk factor for superficial infection following GT. Further work into preoperative decolonization strategies may provide an avenue to decrease the high infection rate in this common pediatric procedure. LEVEL OF EVIDENCE: Level III.