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It is suggested that in addition to seismicity deep fluid injection may cause surface uplift and subsidence in oil and gas-producing regions. This study uses the Raton Basin as an example to investigate the hydromechanical processes of surface uplift and subsidence during wastewater injection. The Raton Basin, in southern central Colorado and northern central New Mexico, has experienced wastewater injection related to coalbed methane and gas production starting in 1994. In this study, we estimate the extent and magnitude of total vertical deformation in the Raton Basin from 1994 to 2020 and incremental deformation between the years 2017 to 2020. Results indicate a modeled uplift as much as 15 cm occurring between 1994 and 2020. Between 2017 and 2020, up to 3 cm of uplift occurred, largely near the northwestern injection wells. Most modeled uplift between 1994 and 2020 occurred near the southern wells, where the greatest cumulative volume of wastewater was injected. However, modeled subsidence occurred around the southern and eastern wells between 2017 and 2020, after the rate of injection decreased. Modeling indicates that while the magnitude of modeled uplift corresponds to cumulative injection volume and maximum rate in the long-term, short-term incremental deformation (uplift or subsidence) is controlled by changes in the rate of injection. The number of yearly earthquake events follows periods of rapid modeled uplifting throughout the Basin, suggesting that measurable surface deformation may be caused by the same injection-induced pore pressure perturbations that initiate seismicity., (© 2024 The Authors. Groundwater published by Wiley Periodicals LLC on behalf of National Ground Water Association.)

Women with germline pathogenic variants (PV) in the fumarate hydratase (FH) gene develop cutaneous and uterine leiomyomata and have an increased risk of developing aggressive renal cell carcinomas. Many of these women are unaware of their cancer predisposition until an atypical uterine leiomyoma is diagnosed during a myomectomy or hysterectomy, making a streamlined genetic counseling process after a pathology-based atypical uterine leiomyoma diagnosis critical. However, the prevalence of germline pathogenic/likely PVs in FH among atypical uterine leiomyomata cases is unknown. To better understand FH germline PV prevalence and current patterns of genetic counseling and germline genetic testing, we undertook a retrospective review of atypical uterine leiomyomata cases at a single large center. We compared clinical characteristics between the FH PV, FH wild-type (WT), and unknown genetic testing cohorts. Of the 144 cases with atypical uterine leiomyomata with evaluable clinical data, only 49 (34%) had documented genetic test results, and 12 (8.3%) had a germline FH PV. There were 48 IHC-defined FH-deficient cases, of which 41 (85%) had FH testing and nine had a germline FH PV, representing 22% of the tested cohort and 18.8% of the FH-deficient cohort. Germline FH PVs were present in 8.3% of evaluable patients, representing 24.5% of the cohort that completed genetic testing. These data highlight the disconnect between pathology and genetic counseling, and help to refine risk estimates that can be used when counseling patients with atypical uterine leiomyomata., Prevention Relevance: Women diagnosed with fumarate hydratase (FH)-deficient uterine leiomyomata are at increased risk of renal cancer. This work suggests a more standardized pathology-genetic counseling referral pathway for these patients, and that research on underlying causes of FH-deficient uterine leiomyomata in the absence of germline FH pathogenic/likely pathogenic variants is needed., (©2024 American Association for Cancer Research.)

Objective: Hepatobiliary tumors have evolving management guidelines. Patient educational needs and interest in community engagement are unknown. This study serves as a needs assessment., Methods: A prospective, needs assessment, survey study of hepatobiliary patients was performed (2016-2019). Surveys ( n  = 169) were distributed covering three domains of interest: informational needs, interest in outreach, and engagement preferences., Results: Seventy patients completed the survey (response rate = 41.4%). Most patients had completed surgical treatment (84.3%). C ancer treatment was ranked as their primary topic of interest ( n  = 39, 55.7bold%), followed by symptom management , nutrition , and survivorship . Most patients did not participate in screening ( n  = 57, 81.4%), though were interested in learning more about these programs. Thirty-nine patients (55.7%) stated they would want to receive more education. Only 17 (24.3%) were interested in attending in-person events. Patients preferred online methods for education ( n  = 49, 70%). While patients were aware of their case presentation at tumor board, only 38 (54.3%) felt well-informed about recommendations., Conclusion: Multidisciplinary care is complex and difficult for patients to navigate. Most patients have interest in educational resources and prefer online modalities. Patients understand multidisciplinary tumor boards, but communication could be improved., Innovation: These data inform a new, innovative, approach to outreach efforts in this population., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier B.V.)

Background: The familial aggregation of bladder cancers has been observed, but the incidence and association of familial bladder cancer with germline pathogenic and likely pathogenic (P/LP) variants is unknown., Patients and Methods: A retrospective analysis was conducted of patients with bladder cancer treated at the Dana-Farber Cancer Institute to identify those with a first-degree relative with bladder cancer. A second cohort of patients referred to DFCI for suspicion of a cancer predisposition syndrome was analyzed for candidate P/LP germline variants. Descriptive statistics were generated., Results: Among 885 patients with bladder cancer, 38 patients (4.3%) had a family history of bladder cancer in a first-degree relative. No significant association of age of diagnosis was observed between patients with and without a first-degree family history of bladder cancer (P = .3). In the second cohort, 27 of 80 (34%) patients with bladder cancer evaluated for cancer predisposition syndromes harbored a P/LP germline variant. P/LP variants were identified most commonly in the following genes: BRCA1 (n = 5), MSH2 (n = 5), MLH1 (n = 4), ATM (n = 3), and CHEK2 (n = 2). Of the 27 patients with identified germline P/LP variants, 20 (74%) had a family history of a tumor component syndrome in a first- or second-degree relative and 3 were subsequently diagnosed with another genetically-linked associated cancer., Conclusion: Familial bladder cancer defined as bladder cancer in the proband and a first-degree relative, was present in 4.3% of patients with bladder cancer and was not associated with age of diagnosis. Additionally, among patients suspected to have a familial cancer syndrome, one-third harbored a germline P/LP variant. Further study of germline variants in patients with familial bladder cancer including somatic testing for loss of heterozygosity may provide insights regarding disease pathogenesis and inform therapy., (Copyright © 2022. Published by Elsevier Inc.)

Background: Cancer family history is a vital part of cancer genetic counseling (GC) and genetic testing (GT), but increasing indications for germline cancer GT necessitate less labor-intensive models of collection. We evaluated the impact of GC on patient pedigrees generated by an electronic cancer family history questionnaire (eCFHQ)., Methods: An Institutional Review Board-approved review of pedigrees collected through an eCFHQ was conducted. Paired pre-GC and post-GC pedigrees (n=1,113 each group) were analyzed independently by cancer genetic counselors for changes in patient-reported clinical history and to determine whether the pedigrees met NCCN GT criteria. Discrepancy in meeting NCCN GT criteria between pre-GC and post-GC pedigrees was the outcome variable of logistic regressions, with patient and family history characteristics as covariates., Results: Overall, 780 (70%) patients had cancer (affected), 869 (78%) were female, and the median age was 57 years (interquartile range, 45-66 years; range, 21-91 years). Of the 1,113 pairs of pre-GC and post-GC pedigrees analyzed, 85 (8%) were blank, 933 (84%) were not discrepant, and 95 (9%) were discrepant in meeting any NCCN GT criteria. Of the discrepant pedigrees, n=79 (83%) became eligible for testing by at least one of the NCCN GT criteria after GC. Patients with discrepant pedigrees were more likely to report no or unknown history of GT (odds ratio [OR], 4.54; 95% CI, 1.66-18.70; P=.01, and OR, 18.47; 95% CI, 5.04-88.73; P<.0001, respectively) and belonged to racially and/or ethnically underrepresented groups (OR, 1.91; 95% CI, 1.08-3.25; P=.02)., Conclusions: For most patients (84%), a standalone eCFHQ was sufficient to determine whether NCCN GT criteria were met. More research is needed on the performance of the eCFHQ in diverse patient populations.

Objective: Surgical complications have substantial impact on healthcare costs. We propose an analysis of the financial impact of postoperative complications., Summary of Background Data: Both complications and preoperative patient risk have been shown to increase costs following surgery. The extent of cost increase due to specific complications has not been well described., Methods: A single institution's American College of Surgeons National Surgical Quality Improvement Program data was queried from 2012 to 2018 and merged with institutional cost data for each encounter. A mixed effects multivariable generalized linear model was used to estimate the mean relative increase in hospital cost due to each complication, adjusting for patient and procedure-level fixed effects clustered by procedure. Potential savings were calculated based on projected decreases in complication rates and theoretical hospital volume., Results: There were 11,897 patients linked between the 2 databases. The rate of any American College of Surgeons National Surgical Quality Improvement Program complication was 11.7%. The occurrence of any complication resulted in a 1.5-fold mean increase in direct hospital cost [95% confidence interval (CI) 1.49-1.58]. The top 6 most costly complications were postoperative septic shock (4.0-fold, 95% CI 3.58-4.43) renal insufficiency/failure (3.3-fold, 95% CI 2.91-3.65), any respiratory complication (3.1-fold, 95% CI 2.94-3.36), cardiac arrest (3.0-fold, 95% CI 2.64-3.46), myocardial infarction (2.9-fold, 95% CI 2.43-3.42) and mortality within 30 days (2.2-fold, 95% CI 2.01-2.48). Length of stay (6.5 versus 3.2 days, P < 0.01), readmission rate (29.1% vs 3.1%, P < 0.01), and discharge destination outside of home (20.5% vs 2.7%, P < 0.01) were significantly higher in the population who experienced complications., Conclusions: Decreasing complication rates through preoperative optimization will improve patient outcomes and lead to substantial cost savings., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The value of neoadjuvant treatment in combination with resection as multimodality therapy (MMT) for stage IIB non-small cell lung cancer remains controversial., Methods: This was a national cohort study of patients with clinical stage IIB non-small cell lung cancer (2006 to 2015) that used the National Cancer Database. Cohorts were defined on the basis of the MMT sequence and were categorized as follows: surgery plus adjuvant chemotherapy (AC), surgery plus adjuvant chemoradiation (ACRT), neoadjuvant therapy plus surgery (NA), surgery-alone, and definitive chemotherapy or chemoradiation (nonsurgical). The primary comparison was between the NA and AC cohorts. Propensity matching methods were used to match cohorts who had AC vs NA. Multivariable Cox regression was used to analyze the difference in risk of death between the NA and AC groups., Results: There were 10,841 patients with stage IIB lung cancer: 2476 in the AC, 854 with ACRT, 1195 with NA, 2019 with surgery alone, and 4297 with nonsurgical treatment. Of the 6544 patients who underwent surgery, 37.8% had AC, 13.1% had ACRT, 18.3% had NA, and 30.9% had surgery alone. Relative to those patients treated with AC, nonsurgical treatment (hazard ratio [HR], 2.92; 95% confidence interval [CI], 2.69 to 3.17) or surgery-alone (HR, 1.26; 95% CI, 1.14 to 1.38) was associated with a significantly higher risk of death. After propensity matching, there was no difference in the risk of death between the NA and AC cohorts (HR, 1.07; 95% CI, 0.88 to 1.31)., Conclusions: MMT, including surgical resection, is associated with improved OS, regardless of treatment sequence, with no difference in survival on the basis of an NA or AC approach. The potential benefits of NA over AC to ensure that patients complete MMT warrant further prospective investigation., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Multigene panel testing (MGPT) identifies TP53 pathogenic or likely pathogenic (P/LP) variants in patients with diverse phenotypes, of which only one is classic Li-Fraumeni syndrome. Low variant allelic fraction (VAF) in TP53 found on germline testing may suggest aberrant clonal expansion or constitutional mosaicism. We evaluated TP53 -positive probands seen in a cancer genetics program to determine germline versus somatic status., Methods: We reviewed TP53 -positive probands from 2012 to 2019 identified by MGPT on blood or saliva (N = 84). Available VAFs were collected. Probands with a familial variant, who met Li-Fraumeni syndrome testing criteria or who carried a founder variant, were considered germline. For those with uncertain germline status, TP53 variants were further examined using ancillary data of family members and somatic tissue., Results: Of the 84 probands, 54.7% had germline variants with 33.3% meeting criteria for germline status and 21.4% confirmed through ancillary testing. Aberrant clonal expansion comprised 13.1% with clonal hematopoiesis of indeterminate potential and 2.4% with a hematologic malignancy. Constitutional mosaicism was confirmed in 8.3% probands. Definitive status could not be determined in 3.6% despite ancillary assessment, and 17.9% did not have ancillary testing., Conclusion: A TP53 P/LP variant found on peripheral blood or saliva MGPT does not always originate in the germline. In a clinical cancer genetics cohort, approximately half of the patients had TP53 P/LP germline variants; these patients plus those with constitutional mosaicism require intensified surveillance. A framework of multiple strategies enables discernment of germline from constitutional mosaic and acquired variants, which is essential for appropriate management., Competing Interests: Alison N. SchwartzConsulting or Advisory Role: InVitae Nadine M. TungResearch Funding: AstraZeneca (Inst) Jeffrey N. WeitzelSpeakers' Bureau: AstraZeneca Huma Q. RanaResearch Funding: Ambry Genetics, InVitae Corp Judy E. GarberConsulting or Advisory Role: Novartis (I), GTx (I), Helix BioPharma, Konica Minolta, Aleta BioTherapeutics (I), H3 Biomedicine (I), Kronos Bio (I)Research Funding: Novartis (I), Ambry Genetics, InVitae, Myriad GeneticsOther Relationship: Susan G. Komen for the Cure (I), AACR, Diana Helis Henry Medical Foundation (I), James P. Wilmot Foundation (I), Adrienne Helis Malvin Medical Research Foundation (I), Breast Cancer Research Foundation, Facing our Risk of Cancer EmpoweredNo other potential conflicts of interest were reported.

Background: Procedure-based opioid-prescribing guidelines have reduced the amount of opioids prescribed after surgery; however, many patients are still overprescribed opioids. The 24-h predischarge opioid consumption (PDOC) metric has been proposed to guide patient-centered prescribing., Materials and Methods: This is a single-institution, retrospective study of patients who underwent major abdominal surgery. We assessed the correlation between inpatient opioid use and discharge prescriptions using morphine milligram equivalents (MMEs). The adequacy of discharge prescriptions for individual patients was assessed using 2 models, one assuming constant opioid use (based on 24-h PDOC) and the other assuming a linear taper., Results: Of 596 included patients, gastric bypass and colectomy were the most common operations. Median length of stay was 3.5 d. Inpatient opioid use and discharge prescriptions were weakly correlated (r = 0.35). Patients with no opioid use 24 h before discharge (n = 133, 22.3%) were frequently discharged with opioid prescriptions. Patients with high opioid use (24-h PDOC >60 MME) were often discharged with prescriptions that would have lasted <48 h (164/200, 82%). Assuming constant opioid use, discharge prescriptions would have lasted patients a median of 5.1 d. With linear opioid tapering, 440 (72.9%) patients would have had leftover pills. A theoretical discharge prescription of 4 times 24-h PDOC would reduce the median prescription by 130 MMEs and allow a linear taper for 97.6% of patients., Conclusions: At our institution, opioid prescribing was rarely patient-centered, with little correlation between patient's inpatient opioid use and discharge prescriptions. This leads to overprescribing for most patients and underprescribing for others., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Endocrinopathic laminitis develops in association with insulin dysregulation, but the role of insulin in the pathogenesis remains unclear. Hyperinsulinemia can cause hypoaminoacidemia, which is associated with integumentary lesions in other species and therefore warrants investigation as a potential mechanism in laminitis., Objective: Evaluate plasma amino acid concentrations in the euglycemic-hyperinsulinemic clamp (EHC) and prolonged glucose infusion (PGI) laminitis models., Animals: Sixteen Standardbred horses., Methods: Prospective experimental study. Plasma amino acid concentrations were measured in samples collected every 6 hours from horses that underwent a 48-hour EHC (n = 8) or 66-hour PGI (n = 8) after a 24- or 6-hour baseline period in EHC and PGI groups, respectively., Results: Fifteen of the 20 measured amino acid concentrations decreased over time in both EHC and PGI horses (P < 0.001). The median percentage change from baseline for these amino acids was: histidine (EHC: 41.5%; PGI: 43.9%), glutamine (EHC: 51.8%; PGI: 35.3%), arginine (EHC: 51.4%; PGI: 41%), glutamic acid (EHC: 52.4%; PGI: 31.7%), threonine (EHC: 62.8%; PGI: 25.2%), alanine (EHC: 48.9%; PGI: 19.5%), proline (EHC: 56.2%; PGI: 30.3%), cystine (EHC: 34.9%; PGI: 31.2%), lysine (EHC: 46.4%; PGI: 27.8%), tyrosine (EHC: 27.5%; PGI: 16.9%), methionine (EHC: 69.3%; PGI: 50.8%), valine (EHC: 50.8%; PGI: 34.4%), isoleucine (EHC: 60.8%; PGI: 38.7%), leucine (EHC: 48.2%; PGI: 36.6%), and phenylalanine (EHC: 16.6%; PGI: 12.1%)., Conclusions and Clinical Importance: Hypoaminoacidemia develops in EHC and PGI laminitis models. The role of hypoaminoacidemia in the development of hyperinsulinemia-associated laminitis warrants further investigation., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Breast cancer is the most common malignancy in female patients with Li-Fraumeni syndrome (LFS), a rare autosomal dominant hereditary syndrome characterized by germline TP53 mutations. Recent studies have shown that the majority of these tumors are estrogen receptor (ER) positive with frequent HER2 co-expression. However, the morphologic features of these tumors have not been as well studied as other germline-associated breast cancers. We evaluated the pathologic features of 27 invasive and in situ carcinomas from patients with known germline TP53 mutations collected through the Li-Fraumeni Consortium. Overall, 60% of cases were HER2 positive and 44% showed ER co-expression. Most DCIS was high nuclear grade with central necrosis and associated periductal fibrosis and lymphocytic response. Invasive carcinomas were mostly of ductal type (NOS), modified Scarff-Bloom-Richardson (mSBR) high grade, with marked nuclear atypia and high mitotic rate. Prominent tumor infiltrating lymphocytes, syncytial growth pattern, or pushing borders were not seen in these tumors. High p53 IHC expression was seen in tumors from individuals with germline TP53 missense mutations whereas little or no protein expression (<1% nuclear expression, null pattern) was seen in tumors from carriers of non-missense mutations. In this study, we report in detail the morphologic features of invasive and in situ carcinomas in LFS. We found that these tumors share features with cancers harboring somatic TP53 mutations but are distinct from BRCA-associated breast cancers.

Objective: Germline genetic testing is crucial to the care of ovarian cancer patients, and as part of the guideline-based care for ovarian cancer patient's adherence to this recommendation has been low. We sought to determine whether embedding a genetic counselor (GC) within a medical and gynecologic oncology clinic would increase testing rates and improve the timeliness of testing., Methods: Prospective cohort study of 358 ovarian cancer patients seen by medical and gynecologic oncologists between 2013 and 2015. Rates of referrals, completion of counseling, and genetic testing and timeliness of counseling were abstracted before and after a GC was embedded in the clinic in 2014. An additional year of data (2015) was collected to evaluate sustainability of the intervention., Results: Between 2013 and 2015, 88-92% of women were referred for genetic testing, but in 2013 only 66% completed counseling and 61% were tested. After a GC was embedded in the clinic in 2014, more than 80% of referred women completed counseling and germline genetic testing. Time to genetic counseling also decreased from a median of 107 to 40 days, irrespective of age and cancer family history (p < 0.01)., Conclusions: Embedding a GC into the workflow for ovarian cancer patients is an effective way of improving access to genetic counseling, testing rates, and the timeliness of testing., Competing Interests: Declaration of Competing Interest Dr. Judy E. Garber has the following COI: personal fees from Helix Genetics, Novartis Oncology, GTx, Aleta BioTherepeutics, H3 Biomedicine, Inc., Kronos Bio, American Society of Clinical Oncology (ASCO), James P. Wilmot Foundation, Inc., Diane Helis Henry Medical Research Foundation, and Adrienne Helis Melvin Medical Research Foundation, and other from Myriad Genetics, Astrazeneca, Ambry Genetics, Invitae Genetics, GV20 Therapeutics, American Association for Cancer Research, Breast Cancer Research Foundation, Konica Minolta, and Facing Our Risk of Cancer Empowered, outside the submitted work. Dr. Ursula Matulonis has the following COI: personal fees from Astrazeneca, Myriad Genetics, Clovis, Merck, Eli Lilly, Mersana, Geneos, Fuji Film, Cerulean, Immunogen, Novartis, and 2× Oncology, outside the submitted work. Ms. Kipnis reports personal fees from Invitae outside the submitted work. All other authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

BACKGROUND RET p.V804M is a known activating oncogenic variant that confers an increased risk for medullary thyroid carcinoma (MTC). Based on age-specific penetrance, the American Thyroid Association (ATA) categorizes this variant as posing moderate risk. Therefore, ATA guidelines endorse prophylactic thyroidectomy for carriers in childhood (by age 5-10 years) or adulthood, or when the serum calcitonin level becomes elevated. The recommendation for thyroidectomy is increasingly controversial due to the recently reported low penetrance of the RET p.V804M variant in a large unbiased ascertainment cohort. CASE REPORT We describe the unexpected identification of this variant in a 62-year-old woman undergoing broad, multigene cancer panel testing for her personal and family history of breast cancer. There was no known family history of MTC. Biochemical screening prompted by the RET p.V804M result revealed a mildly elevated serum calcitonin. Pathology examination of her thyroidectomy specimen revealed multifocal medullary thyroid microcarcinoma; her sibling's prophylactic thyroidectomy after a RET p.V840M-positive result similarly revealed early-stage MTC. CONCLUSIONS This report demonstrates the value of genetic counseling, shared decision-making, cascade testing, and timely thyroidectomy in the management of a patient with an unexpected RET p.V804M result.

Background: A majority of surgical patients are prescribed opioids for pain management. Many patients have pre-existing chronic pain managed with opioids and/or opioid use disorders (OUDs), which can complicate perioperative management. Patients who use opioids prior to surgery are at increased risk of developing OUD after surgery. To date, no studies have examined the prevalence of opioid screening and electronic medical record (EMR) documentation prior to surgery., Materials and Methods: A 40-item survey was administered to 268 patients at their first postoperative care visit at a single tertiary academic center from October 2017 to July 2018. A chart review of a random sample of 100 patients was performed to determine provider opioid screening prevalence in the presurgical setting. Log-binomial models were used to calculate prevalence ratios (PRs) to determine the provider role (surgeon, advanced practice clinicians [APC], surgical trainee) association with opioid screening documentation. Exploratory qualitative interviews were conducted with surgical providers to identify barriers to screening and screening documentation., Results: Only 7% of patients were screened preoperatively for opioid use. A total of 38% of patients self-reported that they had used opioids in the past year. Of that group, only 3% had screening by a surgical provider prior to surgery documented in their EMR. Provider role was not associated with likelihood of opioid screening (surgeon versus trainee, PR = 1.2, 95% CI 0.2-8.5) (surgeons versus APCs, PR = 1.05, 95% CI 0.17-8.53). EMRs were discordant with patient survey results for patients with no ICD-10 codes for opioid use. The most common perceived barriers to preoperative screening were insufficient clinic time; logistics of who should screen/not required as part of their clinical workflow; not perceiving screening as a priority; and lack of expertise in the area of chronic opioid use and OUD., Conclusions: Preoperative screening for opioid use is uncommon, and EMRs are often discordant with patient self-reported use. Efforts to increase preoperative screening will need to address barriers screening practices and increasing health system support by incorporating screening into the clinical workflow and adding it to documentation templates., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Continuous digital hypothermia (CDH) prevents lamellar failure in the euglycaemic hyperinsulinaemic clamp (EHC) and oligofructose (OF) laminitis models, but the mechanisms remain unclear., Objectives: To evaluate the effects of CDH on lamellar energy metabolism and perfusion in healthy horses and during EHC and OF laminitis models., Study Design: In vivo experiment., Methods: Archived samples were used from Standardbred geldings that received no treatment (CON) (n = 8) or underwent EHC (n = 8) or OF (n = 6) laminitis models. Both forelimbs were instrumented with a lamellar microdialysis system, and one forelimb was cooled (CDH) with the other maintained at ambient temperature (AMB). Microdialysate was collected every 6 hours and analysed for glucose, lactate and pyruvate concentrations and lactate to pyruvate ratio (L:P). Microdialysis urea clearance was used to estimate lamellar tissue perfusion. Data were analysed using a mixed-effects linear regression model., Results: Glucose did not change in CDH limbs relative to AMB in CON (P = .3), EHC (P = .3) or OF (P = .6) groups. There was a decrease in lactate (P < .001) and pyruvate (P < .01) in CDH limbs relative to AMB in all groups. L:P decreased in CON CDH relative to CON AMB (P < .001) but was not different in EHC (P = .6) and OF (P = .07) groups. Urea clearance decreased in CDH limbs relative to AMB in CON (P = .002) and EHC (P < .001), but not in OF (P = .4)., Main Limitations: The EHC model may not mimic natural endocrinopathic laminitis., Conclusions: CDH caused a marked decrease in lamellar glucose metabolism (CON, EHC and OF) and perfusion (CON and EHC) without affecting lamellar glucose concentration. Although cellular energy failure is not a primary pathophysiological event in EHC and OF laminitis models, CDH may act by limiting energy supply to pathologic cellular processes whilst preserving those critical to lamellar homoeostasis., (© 2019 EVJ Ltd.)

Background: Hyperinsulinaemia is associated with the development of endocrinopathic laminitis; however, the mechanisms remain unclear., Objectives: Evaluate the effects of hyperinsulinaemia on lamellar energy metabolism and perfusion during laminitis development., Study Design: In vivo experiment., Methods: Eight Standardbred horses were instrumented with a microdialysis probe in the lamellae of a forelimb. A 24 hours baseline period (BASELINE) was followed by 48 hours of a continuous euglycaemic hyperinsulinaemic clamp (EHC) from 24 to 72 hours (CLAMP). Microdialysate was collected every 6 hours and analysed for glucose, lactate and pyruvate concentrations and lactate-to-pyruvate ratio (L:P). Microdialysis urea clearance was used to estimate lamellar tissue perfusion. Archived microdialysis samples from six identically instrumented Standardbred horses served as controls (CON). Variables were compared over time and between EHC and CON horses using a mixed-effects linear regression model., Results: Glucose concentration decreased during the CLAMP period in CON and EHC horses (P < .001), but there was no difference between CON and EHC (P > .9). Lactate concentration increased during the CLAMP period in CON and EHC horses (P < .001), however, the rate of increase was significantly higher in EHC horses relative to CON (P = .014). There was a relative increase in pyruvate concentration in EHC horses compared with CON during the CLAMP period (P = .03). L:P increased significantly in CON horses during the CLAMP period (P < .001) but not in EHC (P = .1). Urea clearance did not change in CON (P = .9) or EHC (P = .05) during the CLAMP, but did increase in EHC relative to CON (P = .02)., Main Limitations: The effects of microdialysis probe implantation on perfusion and metabolism remain unclear. The EHC model may not mimic natural endocrinopathic laminitis., Conclusions: Laminitis developed without evidence of lamellar hypoperfusion or energy stress. Therapies to improve perfusion are unlikely to affect the initial development of endocrinopathic laminitis., (© 2019 EVJ Ltd.)

Background: Continuous digital hypothermia (CDH) prevents lamellar failure in the euglycemic hyperinsulinemic clamp (EHC) model of laminitis, but the protective mechanisms are unclear., Hypothesis/objectives: To determine if CDH inhibits lamellar inflammatory signaling in the EHC model of laminitis., Animals: Eight Standardbred horses., Methods: Prospective experimental study. Horses underwent an EHC, with 1 forelimb treated with CDH and the other kept at ambient temperature (AMB). Horses were euthanized 48 hours after initiation of the EHC and lamellar tissue was analyzed via polymerase chain reaction (pro-inflammatory cytokine and chemokine genes-CXCL1, CXCL6, CXCL8, IL-6, MCP-1, MCP-2, IL-1β, IL-11, cyclooxygenase 1 and 2, tumour necrosis factor-alpha [TNF-α], E-selectin, and intercellular adhesion molecule-1 [ICAM-1]) and immunoblotting (phosphorylated and total signal transducer and activator of transcription 1 [STAT1] and STAT3)., Results: Compared to AMB, lamellar messenger ribonucleic acid (mRNA) concentrations of CXCL6 (P =.02), CXCL8 (P = .008), IL-6 (P = .008), IL-1β (P = .008), IL-11 (P = .008), and cyclooxygenase-2 (P = .008) were decreased in CDH. Cyclooxygenase-1 (P = .008) was increased in CDH, while CXCL1 (P = .15), MCP-1 (P = .05), MCP-2 (P = .46), TNF-α (P = .05), E-selectin (P = .15), and ICAM-1 (P = .15) mRNA were not significantly different. Compared to AMB, lamellar concentration of total STAT3 protein was decreased in CDH (P < .001), but there was no change in phosphorylated STAT3 (P-STAT3 [S727] P = .19; P-STAT3 [Y705] P = .05). There was no change in lamellar concentrations of total STAT1 (P = .75) or phosphorylated STAT1 (P-STAT1 [S727], P = .25; P-STAT1 [Y701], P = .64)., Conclusions and Clinical Importance: These data add further support for the use of CDH as a first aid treatment for severe acute laminitis associated with hyperinsulinemia in horses., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

We describe a novel esophagogastric anastomotic technique ("side-to-side: staple line-on-staple line", STS) for intrathoracic anastomoses designed to create a large diameter anastomosis while simultaneously maintaining conduit blood supply. This technique aims to minimize the incidence of anastomotic leaks and strictures, which is a frequent source of morbidity and occasional mortality after esophagectomy. We analyze the results of this STS technique on 368 patients and compared outcomes to 112 patients who underwent esophagogastric anastomoses using an end-to-end stapler (EEA) over an 8-year time interval at our institution. The STS technique involves aligning the remaining intrathoracic esophagus over the tip of the lesser curve staple line of a stomach tube, created as a replacement conduit for the esophagus. A linear stapling device cuts through and restaples the conduit staple line to the lateral wall of the esophagus in a side-to-side fashion. The open common lumen is then closed in two layers of sutures. There was a total of 12 (3.8%) anastomotic leaks in patients who underwent STS esophagogastric anastomosis. Two of eight patients (25%) had anastomotic leaks after esophagectomy for end-stage achalasia as compared to a 2.8% leak rate (10/336) after esophagectomy for other conditions. Eighteen (5.2%) patients required a median of 2 dilatations for anastomotic stricture after STS anastomosis. Supplemental jejunostomy feedings were required in only 11.1% of patients undergoing STS anastomoses following hospital discharge. In contrast, patients undergoing EEA anastomoses demonstrated anastomotic leak and stricture rates of 16.1% and 14.3% respectively (p<0.01). Time analysis of postoperative contrast studies following the STS technique typically demonstrated a straight/uniform diameter conduit with essentially complete contrast emptying into the small bowel within 3 minutes in 88.4% of patients. The incidence of esophagogastric anastomotic leaks and strictures were extremely low using this novel anastomotic technique. Additionally we believe that based on time and qualitative analyses of postoperative contrast studies, this technique appears to optimize postoperative upper gastrointestinal tract function; however, further comparative studies are needed.

Background: Postoperative overprescribing is common, and many patients will have excess medications. An effective method to encourage disposal is lacking. We hypothesized that a convenient home disposal kit will result in more appropriate disposal of excess opioids., Materials and Methods: We conducted a single-center prospective observational pilot study to evaluate the effectiveness of a postoperative opioid disposal kit. Patients in the intervention group received an opioid disposal kit and educational handout before discharge from the hospital. At the first follow-up visit, patients completed a survey in which they reported the remaining amount of pain medications from their original prescription and their plan for the excess medication. Patients were asked about risk factors for chronic opioid use. We used multivariable Poisson regression to identify independent factors associated with an increased likelihood of appropriate opioid disposal., Results: The survey was offered to 904 patients with a response rate of 91.7%. After excluding those with missing data, 571 patients were included in the study. Overall, 83 (14.5%) patients never filled an opioid prescription, and 286 (60.0%) patients had tablets remaining at the time of the follow-up visit. Among those with tablets remaining, 52 received a home disposal kit, whereas 234 patients with tablets remaining did not. Patients who received the kit were more likely to dispose of opioid medications (54.9% versus 34.8%, relative risk = 1.8, 95% CI 1.3-2.5). No confounders were identified during multivariable analysis that increased a patient's likelihood of disposing excess medications., Conclusions: The provision of a convenient home disposal kit postoperatively increased patient-reported opioid disposal., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Continuous digital hypothermia can prevent the development and progression of laminitis associated with sepsis but its effects on laminitis due to hyperinsulinaemia are unknown., Objectives: To determine the effects of continuous digital hypothermia on laminitis development in the euglycaemic hyperinsulinaemic clamp model., Study Design: Randomised, controlled (within subject), blinded, experiment., Methods: Eight clinically normal Standardbred horses underwent laminitis induction using the euglycaemic hyperinsulinaemic clamp model (EHC). At initiation of the EHC, one forelimb was continuously cooled (ICE), with the other maintained at ambient temperature (AMB). Dorsal lamellar sections (proximal, middle, distal) were harvested 48 h after initiation of the EHC and were analysed using histological scoring (0-3) and histomorphometry. Cellular proliferation was quantified by counting epidermal cell nuclei staining positive with an immunohistochemical proliferation marker (TPX2)., Results: Severe elongation and disruption of SEL with dermo-epidermal separation (score of 3) was observed in all AMB feet at one or more section locations, but was not observed in any ICE sections. Overall 92% of the AMB sections received the most severe histological score (grade 3) and 8% were grade 2, whereas ICE sections were classified as either grade 1 (50%) or grade 2 (50%). Relative to AMB feet, ICE sections were 98% less likely to exhibit grades 2 or 3 (OR: 0.02, 95% CI 0.001, 0.365; P<0.01). Histomorphometry measurements of total and nonkeratinised primary epidermal lamellar length were significantly increased (P<0.01) in AMB limbs compared with ICE. TPX2 positive cell counts were significantly increased (P<0.01) in AMB limbs compared with ICE., Main Limitations: Continuous digital hypothermia was initiated before recognition of laminitis and therefore the clinical applicability requires further investigation., Conclusions: Continuous digital hypothermia reduced the severity of laminitis in the EHC model and prevented histological lesions compatible with lamellar structural failure., (© 2019 EVJ Ltd.)

Background: Accurate staging of non-small cell lung cancer (NSCLC) is critical for identifying patients who will benefit from multimodality therapy. This study evaluated clinical-pathologic correlation and its effects on receipt of guideline-concordant therapy in a national cohort., Methods: A retrospective cohort study of patients with surgically resected NSCLC in the National Cancer Database (NCDB) between 2004 and 2014 was conducted. Primary tumor and nodal staging information was analyzed in patients who underwent upfront surgery and neoadjuvant therapy to calculate correlation between clinical and pathologic stages and estimate downstaging rate. Staging accuracy and Spearman's rank correlation coefficients were calculated. Multivariable Cox regression was used to evaluate the association between receipt of guideline-concordant therapy and overall risk of death., Results: Among 82,999 patients, correlation between clinical and pathologic stages was strong (r = 0.69). Correlation of primary tumor staging was high (71.2%-84.5%). The positive predictive value of nodal staging was 78.2%. Neoadjuvant therapy was associated with downstaging in tumor stage (T1, 1.5%; T2, 22.6%; T3, 28%; T4, 42%) and 17.3% of positive nodes. Patients with stage I disease had high rates of guideline-concordant treatment (IA, 97.4%; and IB, 97.9%). Patients with stage IIA to IIIA disease had lower rates of guideline concordance. Receipt of guideline-concordant care was associated with a significantly lower risk of death (hazard ratio, 0.84; 95% confidence interval, 0.80-0.87)., Conclusions: Clinical staging modalities are reasonably accurate. However, less than one half of patients with stage IIA to IIIA NSCLC receive guideline-concordant therapy, and this deficiency is associated with inferior survival. Identifying factors contributing to these differences is crucial to improve outcomes., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Aims: A quality improvement project was conducted in a General Dental Practice environment. The aim was to reduce the rate of Acute Alveolar Osteitis, which was locally found to be at 19.4%., Methods: A range of quality improvement tools were utilised to determine and measure potential interventions, and the results from the initial Plan-Do-Study-Act cycle utilising perioperative 0.2% Chlorhexidine as a preventative method are presented., Results: The use of perioperative 0.2% Chlorhexidine mouthwash showed an absolute risk reduction of 6.2%., Discussion: Generalisation from the results is highly dependent on local factors, although the favourable reduction in acute alveolar osteitis and cost savings found supported the project., Conclusions: This project highlights the strengths of Quality Improvement methodologies in implementing and assessing changes to improve service provision and patient outcomes., Competing Interests: Competing interestsThe authors declare no competing interests.

Despite progress in many different domains of surgical care, we are still striving toward practices which will consistently lead to the best care for an increasingly complex surgical population. Thoracic surgical patients, as a group, have multiple medical co-morbidities and are at increased risk for developing complications after surgical intervention. Our healthcare systems have been focused on treating complications as they occur in the hopes of minimizing their impact, as well as aiding in recovery. In recent years there has emerged a body of evidence outlining opportunities to optimize patients and likely prevent or decrease the impact of many complications. The purpose of this review article is to summarize four major domains-optimal pain control, nutritional status, functional fitness, and smoking cessation-all of which can have a substantial impact on the thoracic surgical patient's course in the hospital-as well as to describe opportunities for improvement, and areas for future research efforts., Competing Interests: Conflicts of Interest: TK Varghese Jr: National Cancer Institute RO1 funding (1R01CA211705-01A1) for Precision Exercise Prescription (PEP) Clinical Trial for patients undergoing Lung Cancer Resection; Medical Director, American College of Surgeons Strong for Surgery program (https://www.facs.org/quality-programs/strong-for-surgery). The other authors have no conflicts of interest to declare.

Background: The impact of insurance on outcomes in the modern era of evidence-based guidelines is unclear. We sought to examine differences in receipt of therapy and outcomes for early stage, non-small cell lung cancer patients by insurance coverage., Method: Clinical T1-3 N0-1 non-small cell lung cancer cases were identified in the 2004 to 2014 National Cancer Database and compared across 4 groups: private, Medicare, Medicaid, and uninsured. A multivariable, linear regression model was used to examine the effects of insurance status on time to curative surgical therapy, adjusting for patient and facility characteristics. Receipt of different therapies was examined with multivariable logistic regression. Survival analysis was conducted with Cox regression., Results: A total of 240,361 patients presented with early stage non-small cell lung cancer (60,532 private, 164,377 Medicare, 11,001 Medicaid, and 4,451 uninsured). After adjustment, Medicaid and uninsured patients received surgical therapy later than privately insured patients (9.5 days and 7.0 days, respectively, P < .001), were more likely to be delayed > 8 weeks (odds ratio 1.64, 95% confidence interval 1.55-1.73 and odds ratio 1.46, 95% confidence interval 1.34-1.58), and were significantly less likely to receive surgery (odds ratio 0.53, 95% confidence interval 0.50-0.56 and odds ratio 0.50, 95% confidence interval 0.47-0.55). Uninsured patients were more likely to receive no treatment (odds ratio 2.15, 95% confidence interval 1.92-2.41), followed by Medicaid patients (odds ratio 1.66, 95% confidence interval 1.53-1.80). The 5-year overall survival was significantly worse in the Medicaid and uninsured populations., Conclusion: Even in the modern era, uninsured and Medicaid early stage non-small cell lung cancer patients have decreased odds of receiving a potentially curative operation and experience inferior outcomes. Given substantial expenditures on the Medicaid program, strategies for increasing utilization of curative surgery in Medicaid patients with lung cancer are needed., (Published by Elsevier Inc.)

Background: The treatment of injured children contributes substantially to the financial burden of a health care system. The purpose of this study was to characterize these charges at a level-1 pediatric trauma center., Methods: Financial data for children (<14 years) admitted for traumatic injury from 1/2009 to 12/2014 were analyzed. The charges of the index admission and first two years following discharge were evaluated., Results: 5853 trauma patients were included with average annual charges of $11,128,730. The most common mechanisms of injury were fall (44%), sports (12%), and bike (9%). The median ISS was 6 (IQR 4-10) with a mortality rate of 1.8% and Z-score of 13.04 (p<0.001). The overall total charges per patient during the index admission were $9513. Spinal cord and major abdominal injuries had the greatest charges per patient ($55,560 and $23,618 respectively) primarily owing to hospital LOS. During the first year after discharge, the total charges per patient were $1733, of which spinal cord injury resulted in highest overall ($19,426), owing to inpatient rehabilitation. For all other injury patterns, mean total charges per patient were $2376 (range $791-$3573)., Conclusions: The value proposition in health care requires us to define outcomes relative to costs. Injury severity, major injury location, and hospital length of stay are the highest contributors for the financial burden of pediatric traumatic injury, while inpatient readmissions and inpatient rehabilitation drove higher charges in the years following discharge., Type of Study: Clinical Research Paper., Level of Evidence: II - Cohort Study., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Anastomotic complications represent a significant source of morbidity and occasionally mortality after esophagectomy. Since 2009, we have used a novel "side-to-side: staple line-on-staple line" (STS) technique for intrathoracic esophagogastric anastomoses, designed to create a wide-diameter esophagogastric anastomosis while preserving stomach conduit blood supply. In this study, we describe the technique and review outcomes of our institution's initial 6-year experience., Methods: An institutional database query identified 278 consecutive patients who underwent Ivor Lewis esophagogastrectomy using an STS esophagogastric anastomotic technique from 2009 through 2015. A retrospective review was conducted to assess outcomes with a focus on anastomotic complications., Results: There were a total of 8 (2.9%) anastomotic leaks in patients who underwent STS esophagogastric anastomosis, 3 of which were grade I/II leaks and required no intervention. There was a leak rate of 6.3% (2 of 32) after esophagectomy for benign conditions (both leaks occurring in 8 total patients (25%) who received surgery for end-stage achalasia) compared with a 2.4% leak rate (6 of 246) in whom esophagectomy was performed for malignancy (P = .22). Fourteen patients (5.0%) required a median of 2 dilatations for anastomotic stricture after STS anastomosis. Supplemental jejunostomy feedings were required in only 11.1% of these patients after hospital discharge., Conclusions: We believe this novel STS technique provides excellent results with respect to the incidence of intrathoracic esophagogastric anastomotic leak and stricture after esophagectomy. Additionally this technique has significantly reduced the need for enteral feeding after hospital discharge., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Several hemodynamic parameters have been promoted to help establish a rapid diagnosis of hemorrhagic shock, but they have not been well validated in the pregnant population. In this study, we examined the association between three measures of shock and early blood transfusion requirements among pregnant trauma patients., Methods: This study included 81 pregnant trauma patients admitted to a level 1 trauma center (2010-2015). In separate logistic regression models, we tested the relationship between exposure variables-initial systolic blood pressure (SBP), shock index (SI), and rate over pressure evaluation (ROPE)-and the outcome of transfusion of blood products within 24 hours of admission. To test the predictive ability of each measure, we used receiver operating characteristic (ROC) curves., Results: A total of 10% of patients received blood products in the patient cohort. No patients had an initial SBP≤90, so the SBP measure was excluded from analysis. We found that patients with SI>1 were significantly more likely to receive blood transfusions compared with patients with SI<1 (OR 10.35; 95% CI 1.80 to 59.62), whereas ROPE>3 was not associated with blood transfusion compared with ROPE≤3 (OR 2.92; 95% CI 0.28 to 30.42). Furthermore, comparison of area under the ROC curve for SI (0.68) and ROPE (0.54) suggested that SI was more predictive than ROPE of blood transfusion., Conclusion: We found that an elevated SI was more closely associated with early blood product transfusion than SBP and ROPE in injured pregnant patients., Level of Evidence: Prognostic, level III., Competing Interests: Competing interests: None declared.

Background: Level 1 programs have improved outcomes by expediting the multidisciplinary care of critically ill patients. We established a novel level 1 program for the management of esophageal emergencies., Methods: After institutional review board approval, we performed a retrospective analysis of patients referred to our level 1 esophageal emergency program from April 2013 through November 2015. A historical comparison group of patients treated for the same diagnosis in the previous 2 years was used., Results: Eighty patients were referred and transported an average distance of 56 miles (range, 1-163 miles). Median time from referral to arrival was 2.4 hours (range, 0.4-12.9 hours). Referrals included 6 (7%) patients with esophageal obstruction and 71 (89%) patients with suspected esophageal perforation. Of the patients with suspected esophageal perforation, causes included iatrogenic (n = 26), Boerhaave's syndrome (n = 32), and other (n = 13). Forty-six percent (n = 33) of patients were referred because of pneumomediastinum, but perforation could not be subsequently demonstrated. Initial management of patients with documented esophageal perforation included operative treatment (n = 25), endoscopic intervention (n = 8), and supportive care (n = 5). Retrospective analysis demonstrated a statistically significant difference in mean Pittsburgh severity index score (PSS) between esophageal perforation treatment groups (p < 0.01). In patients with confirmed perforations, there were 3 (8%) mortalities within 30 days. More patients in the esophageal level 1 program were transferred to our institution in less than 24 hours after diagnosis than in the historical comparison group (p < 0.01)., Conclusions: Development of an esophageal emergency referral program has facilitated multidisciplinary care at a high-volume institution, and early outcomes appear favorable., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: The rate of feeding advancement following surgery for hypertrophic pyloric stenosis (HPS) affects length of stay. We hypothesized that: 1) a relaxed feeding regimen following pyloromyotomy would allow infants to achieve feeding goals more quickly without affecting postoperative emesis, and 2) preoperative metabolic derangements would impair the ability to advance feedings following pyloromyotomy., Methods: A prospective, randomized trial compared two postoperative feeding methods. The primary outcome was length of time to tolerate two consecutive goal feeds (GFs). Infants were randomized into the Incremental-arm (N=74), in which infants were gradually advanced on enteral formula, or the Relaxed-arm (N=69), in which infants were allowed to consume up to GF immediately. Preoperative variables, time to GF, preoperative laboratory values, and postoperative emesis were recorded. A p-value less than 0.05 was significant., Results: Patient demographics, pyloric ultrasound measurements, and episodes of postoperative emesis were similar between groups. Infants in the Relaxed-arm reached GF more quickly than those in the Incremental-arm and had a shorter length of stay (p<0.001). Infants with preoperative serum chloride less than 100mmol/L reached GF more slowly than those with normal labs (p<0.03)., Conclusion: Following surgery for HPS, surgeons can safely utilize a relaxed, nonstructured feeding regimen, which may allow infants to reach feeding goals more quickly without untoward vomiting., Level of Evidence: Level 1-therapeutic., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Obesity is a public health concern in the United States due to its increasing prevalence, especially in younger age groups. Trauma is the most common cause of death for people under aged 40 y. The purpose of this study is to determine the association between obesity and specific infectious complications after traumatic injury., Materials and Methods: A retrospective analysis was conducted using data from the 2012 National Trauma Data Bank. The National Trauma Data Bank defined obesity as having a body mass index of 30 or greater. Descriptive statistics were calculated and stratified by obesity status. A hierarchical regression model was used to determine the odds of experiencing an infectious complication in patients with obesity while controlling for age, gender, diabetes, number of comorbidities, injury severity, injury mechanism, head injury, and surgical procedure., Results: Patients with a body mass index of 30 or greater compared with nonobese patients had increased odds of having an infectious complication (Odds Ratio, 1.59; 1.49-1.69). In addition to obesity, injury severity score greater than 29, age 40 y or older, diabetes, comorbid conditions, and having a surgical procedure were also predictive of an infectious complication., Conclusions: Our results indicate that trauma patients with obesity are nearly 60% more likely to develop an infectious complication in the hospital. Infection prevention and control measures should be implemented soon after hospital arrival for patients with obesity, particularly those with operative trauma., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Intestinal ischemia can quickly escalate to bowel necrosis and perforation. Transplantation of stem cells presents a novel treatment modality for this problem. We hypothesized that: human adipose-derived stromal cells (hASCs) would increase survival and mesenteric perfusion to a greater degree compared with differentiated cellular controls following ischemic intestinal injury, and improved outcomes with hASC therapy would be associated with preservation of intestinal histological and tight junction architecture, and lower levels of systemic inflammation following intestinal injury., Methods: hASCs and keratinocytes (differentiated cellular control) were cultured on polystyrene flasks at 37°C in 5% CO2 in air. Adult male C57Bl6J mice were anesthetized and a midline laparotomy performed. The intestines were eviscerated, the small bowel mesenteric root identified, and intestinal ischemia was established by temporarily occluding the superior mesenteric artery for 60 min with a noncrushing vascular clamp. Following ischemia, the clamp was removed, and the intestines were returned to the abdominal cavity. Before abdominal closure, 2 million hASCs or keratinocytes in 250 μL of phosphate-buffered saline (carrier for cells and control solution) were infused into the peritoneum. Animals were allowed to recover for 12 or 24 h (perfusion, histology, cytokine, and immunofluoresence studies), or 7 days (survival studies). Intestinal perfusion was assessed by laser Doppler imaging. Intestinal tissue segments were stained with hematoxylin and eosin, as well as antibodies for the tight junction protein claudin-1. Separate aliquots of intestine, liver, and lung tissue were homogenized and assessed for inflammatory cytokines via multiplex beaded assay., Results: Animals administered hASCs following intestinal ischemia and reperfusion (I/R) injury had significantly greater 7-day survival and better postischemic recovery of mesenteric perfusion compared with vehicle or keratinocyte therapy. hASCs also abated intestinal mucosal destruction, facilitated preservation of intestinal tight junctions, and decreased the systemic inflammatory response to injury., Conclusions: Human adipose-derived stromal cells improved survival and mesenteric perfusion and attenuated the mucosal damage associated with intestinal I/R injury. hASCs should be considered as a plausible cell source for novel cellular treatment plans following intestinal ischemia.

A 43-year-old female presented with persistent nasal congestion with intermittent epistaxis without resolution for the preceding 5 years. Clinical examination revealed a large pink rubbery mass, medial to the middle turbinate in the right nasal cavity extending to the choana. Radiographic images demonstrated a heterogeneously enhancing lobular soft tissue mass filling the right nasal cavity, causing lateral bowing of the right medial orbital wall and extending posteriorly to the right anterior ethmoid sinus. The clinical, radiographic, histologic, and immunohistochemical features of olfactory neuroblastoma are discussed.

We discuss 3 popular misconceptions about Cronbach α or coefficient α, traditionally used in public health and the behavioral sciences as an index of test score reliability. We also review several other indices of test score reliability. We encourage researchers to thoughtfully consider the nature of their data and the options when choosing an index of reliability, and to clearly communicate this choice and its implications to their audiences.

Therapeutic reduction of intussusception by air or contrast enema may require surgery if the bowel is irreducible or perforates. There is no standard for the involvement of a pediatric surgeon in the workup of the condition. A regional survey of clinical practices was therefore undertaken to attempt to establish a consensus as to when the presence of a pediatric surgeon is required. Distributed to pediatric surgeons at 32 institutions, a questionnaire asked the process of imaging and reduction of infants with intussusception and the extent of pediatric surgical involvement. Surgeons at 29 institutions responded (91%). Ultrasound was used in diagnosis in 16 (55%), 13 (45%) requiring a positive ultrasound diagnosis of intussusception before attempting reduction. Three-fourths (22 [76%]) required surgeon notification that enema reduction was taking place, and one-fourth (seven [24%]) required prior surgical consultation. Only three (10%) required the presence of a surgery team member. Most (21 [72%]) did not demand one, and five (18%) indicated that surgical presence was desirable but not a necessity. There is no consensus for pediatric surgical involvement before and during reduction of an intussusception.

Complicated necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are major causes of mortality. We hypothesized that peritoneal drainage (PD) is more efficacious in SIP. Newborn infants with intestinal perforation treated with PD at our institution between 2007 and 2012 were divided into two groups: Group 1, infants with complicated NEC (n = 19), and Group 2, infants with SIP (n = 15). In Group 1, median birth weight was 705 g; median gestational age was 25.9 weeks. Median age at PD was 24 days. Six required laparotomy. Median time from PD to enteral feeds was 22.5 days. In Group 2, median birth weight was 685 g; median gestational age was 25.3 weeks. Median age at PD was 5 days. Two required laparotomy. Median time from PD to enteral feeds was 16 days. In Group 1, eight patients survived to discharge; median length of hospital stay (LOS) was 104.5 days. In Group 2, eight survived; median LOS was 109.5 days. Neither outcome was statistically significant (P = 0.73 and 0.878, respectively). Management of premature infants with intestinal perforation remains challenging. Mortality is high. Between our cohorts, there were no differences in regard to PD as definitive therapy, survival, and LOS.

A rapid, reproducible and sensitive reversed phase liquid chromatography-mass spectrometry method was developed and validated for the identification and semi-quantitative confirmation of stimulants in urine. The method is capable of separating compounds such as cocaine and metabolites, amphetamines, substituted cathinones and other designer drugs, with a total run time of 11 min. The method was subsequently used to confirm the presence of these stimulants in the urine of patients attending the Drug Treatment Centre Board Ireland over the period in which legislation banning some named cathinones was introduced in Ireland. Substituted cathinones were the predominant drug of choice, outside of cocaine use. Mephedrone was the most widely detected cathinone in 2010, whereas 3,4-methylenedioxypyrrolidinobutyrophenone featured more prevalently in screenings in 2011. The appearance of adverse effects increases during multi-stimulant use related to synergistic pharmacological combinations, and this method has benefits in identifying multi-drug use between next generation designer drugs and commonly used stimulants.

Surgeons may be confronted with providing periodontal plastic or implant therapy for patients with gingival manifestations of systemic conditions. These conditions (often referred to as mucocutaneous disorders) commonly present with features of desquamative gingivitis, which was once believed to represent a disease entity. However, today, the term desquamative gingivitis is used to describe clinical features of various local or systemic diseases or disorders that result in chronic gingival lesions characterized by epithelial desquamation, erythema, ulceration, and/or vesiculobullous lesions of the gingiva. Often, other oral tissues also are involved. Mucocutaneous disorders include such disease entities as lichen planus, graft-versus-host disease, pemphigoid, pemphigus vulgaris, lupus erythematosus, erythema multiforme, and linear IgA disease. Surgeons should be able to recognize these disorders and have the tools necessary to treat these conditions so that they can render the appropriate surgical care. This article describes the diagnosis, etiology, and clinical manifestation of these disease entities, as well as the surgical considerations and management in providing care to these patients.