Polycystic ovary syndrome: associations with cardiovascular disease.

Polycystic ovary syndrome (PCOS), characterized by abnormal menstrual periods, elevated androgen levels and polycystic ovary morphology on ultrasound, is the most common endocrine disorder among females. PCOS is associated with cardiovascular disease (CVD) risk factors including diabetes, obesity, metabolic syndrome, adverse pregnancy outcomes such as pre-eclampsia and psychosocial distress including depression. Previous evidence on the association between PCOS and CVD is inconclusive but the latest 2023 International Evidence-Based PCOS Guideline identifies PCOS as a risk factor for CVD. This review will discuss the relationship between PCOS and CVD along with current direction for CVD screening and prevention among individuals with PCOS.

[The system of criteria and indicators of accessibility of laboratory diagnostic in the Subject of The Russian Federation].

The modern health care is characterized by constant increasing need in laboratory tests. The quality and accessibility of laboratory diagnostics becomes one of key determinants of social well-being in aspect of maintaining population health. The purpose of the study is in developing system of criteria and indicators of accessibility of laboratory diagnostics applicable in organization of health care at the level of the Subject of the Russian Federation. The methods. The study was carried out based on principles of system approach. The methodological approach developed by Professor O. Yu. Alexandrova was applied. The analytical research methods (analysis, synthesis) were implemented. The results and discussion. The set of criteria, including three groups of measurable indicators, applicable in the field of laboratory diagnostics was developed. The original approach to determine time indicators of laboratory tests accessibility was proposed. The system can be applied as organizational technology permitting to establish specific requirements for laboratory diagnostics accessibility at the level of the Subject of the Russian Federation. These requirements can be included in local normative legal acts. The conclusions. The developed system of criteria and indicators of laboratory diagnostics accessibility can be used in development of medical care system that meets the best of characteristics and needs of particular Subject of the Russian Federation.

[The strategic management of laboratory diagnostic service: analysis of organization models].

The modern trends in health care (strategies of optimizing costs, value-oriented medical care) require systematic development of laboratory services for administrative territories. The study was carried out to provide support for decision-making by systematizing models of laboratory services on the basis of principles of systematic approach. Four basic models (centralization, outsourcing, horizontal integration, point-of-care) were analyzed. The study applied such research methods as analytical and strategic SWOT-analysis. The SWOT-analysis was implemented using list of standard characteristics for each model of laboratory service organization. Each model is distinguished by complex combination of strengths, weaknesses, lines of functioning and development. The availability of implementing particular model depends on delicate balance of opportunities and risks against the background of local characteristics of administrative subject. The dynamics of the social economic and infrastructural development of administrative subject can significantly affect effectiveness of model implementation. The objective set of characteristics was obtained for each model of laboratory service organization. Actually it is impossible to select particular model for specific administrative subject. Hence, scientific substantiation of "flexible" model is needed to implement.

Responses of Blood System to Doxorubicin/Docetaxel Chemotherapy in Patients with Breast Cancer.

We studied the effects of combined chemotherapy with doxorubicin/docetaxel on erythroid and granulocytic hematopoietic lineages with particular attention focused on their recovery in patients with stages III-IV breast cancer. Intensification of differentiation of erythroid and granulocytic CFU (even under conditions of their suppressed proliferation) provided the increase in the content of mature and morphologically differentiated elements in the bone marrow and peripheral blood. High proliferative activity of erythroid and granulomonocytic precursors resulted from enhanced production of hematopoiesis-stimulating activities by microenvironment elements.

Mechanisms of Granulocytopoiesis Recovery Stimulation with Filgrastim in Breast Cancer Patients Receiving Chemotherapy.

We studied myelotoxicity of modern schemes of chemotherapy for breast cancer (docetaxel/doxorubicin and cyclophosphamide/doxorubicin/5-fluorouracil) towards granulocytopoiesis, the mechanisms determining the differences of hematological effects of these schemes, and the efficiency of correction of the observed changes with granulocyte CSF (filgrastim). Granulocytopoiesis stimulation with filgrastim during the treatment with docetaxel/doxorubicin combination was more pronounced than during cyclophosphamide/doxorubicin/5-fluorouracil therapy. The observed differences were found at all levels of granulocyte lineage organization (central and peripheral), which is related to different effects of the cytostatic substances used in the proposed protocols on the structures controlling hemopoiesis.

Evaluation of the 1st metatarso-sesamoid joint using standing CT - The Stanmore classification.

BACKGROUND: Little is understood about the role that relative sesamoid displacement and chondral wear have on outcome after hallux valgus (HV) surgery. All existing methods to evaluate relative sesamoid displacement have limitations and furthermore, there have been no radiographic studies evaluating metatarso-sesamoid joint wear. Standing CT scan circumvents many of the existing problems in evaluation of relative sesamoid displacement, and also enables the first radiographic study assessing metatarso-sesamoid joint wear. METHODS: Fifty feet (in 43 patients) with symptomatic HV (Group A) were compared with a control group of 50 feet (50 patients) (Group B). All images were standardised to enable reproducible measurements. The hallux valgus angle, Intermetatarsal angle, sesamoid rotation angle, sesamoid position and metatarso-sesamoid joint space were measured in all patients. RESULTS: The intra and inter-observer reliability correlation showed that the standing CT assessment of sesamoid position (1.000), rotation (0.991) and metatarso-sesamoid joint space (0.960) were highly reproducible. There was a highly significant difference (p<0.0001) in sesamoid position, sesamoid rotation and metatarso-sesamoid joint space between Group A and Group B. CONCLUSIONS: Standing CT has been shown to be a reproducible and accurate method of assessing the relative sesamoid displacement and metatarso-sesamoid joint space narrowing. The results have been used to propose a novel standing CT based classification of hallucal sesamoids, considering the degree of displacement and wear. This classification may ultimately facilitate research to provide new insight into the effect relative sesamoid displacement and chondral wear have on outcomes from hallux valgus surgery.

Evaluation of C1q Status and Titer of De Novo Donor-Specific Antibodies as Predictors of Allograft Survival.

De novo donor-specific antibodies (dnDSAs) that develop after renal transplantation are independent predictors of allograft loss. However, it is unknown if dnDSA C1q status or titer at the time of first detection can independently predict allograft loss. In a consecutive cohort of 508 renal transplant recipients, 70 developed dnDSAs. Histologic and clinical outcomes were correlated with the C1q assay or dnDSA titer. C1q positivity correlated with dnDSA titer (p < 0.01) and mean fluorescence intensity (p < 0.01) and was more common in class II versus class I dnDSAs (p < 0.01). C1q status correlated with tubulitis (p = 0.02) and C4d status (p = 0.03) in biopsies at the time of dnDSA development, but not T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR). De novo DSA titer correlated with Banff g, i, t, ptc, C4d scores, TCMR (p < 0.01) and ABMR (p < 0.01). Post-dnDSA graft loss was observed more frequently in recipients with C1q-positve dnDSA (p < 0.01) or dnDSA titer ≥ 1:1024 (p ≤ 0.01). However, after adjustment for clinical phenotype and nonadherence in multivariate models, neither C1q status nor dnDSA titer were independently associated with allograft loss, questioning the utility of these assays at the time of dnDSA development.

Use of an anaesthesia workstation barrier device to decrease contamination in a simulated operating room.

BACKGROUND.: Strategies to achieve reductions in perioperative infections have focused on hand hygiene among anaesthestists but have been of limited efficacy. We performed a study in a simulated operating room to determine whether a barrier covering the anaesthesia workstation during induction and intubation might reduce the risk of contamination of the area and possibly, by extension, the patient. METHODS.: Forty-two attending and resident anaesthetists unaware of the study design were enrolled in individual simulation sessions in which they were asked to induce and intubate a human simulator that had been prepared with fluorescent marker in its oropharynx as a marker of potentially pathogenic bacteria. Twenty-one participants were assigned to a control group, whereas the other 21 performed the simulation with a barrier device covering the anaesthesia workstation. After the simulation, an investigator examined 14 target sites with an ultraviolet light to assess spread of the fluorescent marker of contamination to those sites. RESULTS.: The difference in rates of contamination between the control group and the barrier group was highly significant, with 44.8% (2.5%) of sites contaminated in the control group vs 19.4% (2.6%) of sites in the barrier group ( P <0.001). Several key clinical sites showed significant differences in addition to this overall decrement. CONCLUSIONS.: The results of this study suggest that application of a barrier device to the anaesthesia workstation during induction and intubation might reduce contamination of the intraoperative environment.

Assessment of Erythroid and Granulocytic Hematopoietic Lineages in Patients with Non-Small-Cell Lung Carcinoma.

The toxic effects of combined cisplatin/docetaxel therapy cycles on erythroid and granulocytic hematopoietic lineages as well as their intercycle recovery were examined in patients with stage III-IV non-small-cell lung carcinoma. Responsiveness of the blood system to this therapy remained at a high level. Combined therapy pronouncedly activated the key elements of the erythroid and granulocytic hematopoietic lineages leading to accumulation of immature and mature myelokaryocytes in the bone marrow, enlargement of the medullary pool of mature neutrophils, and increase in the count of medullary erythroid and granulocytic precursor cells under conditions of their accelerated maturation.

Team-based model for non-operating room airway management: validation using a simulation-based study.

BACKGROUND: Non-operating room (non-OR) airway management has previously been identified as an area of concern because it carries a significant risk for complications. One reason for this could be attributed to the independent practice of residents in these situations. The aim of the present study was to ascertain whether differences in performance exist between residents working alone vs with a resident partner when encountering simulated non-OR airway management scenarios. METHODS: Thirty-six anaesthesia residents were randomized into two groups. Each group experienced three separate scenarios (two scenarios initially and then a third 6 weeks later). The scenarios consisted of one control scenario and two critical event scenarios [i.e. asystole during laryngoscopy and pulseless electrical activity (PEA) upon post-intubation institution of positive pressure ventilation]. One group experienced the simulated non-OR scenarios alone (Solo group). The other group consisted of resident pairs, participating in the same three scenarios (Team group). RESULTS: Although the time to intubation did not differ between the Solo and Team groups, there were several differences in performance. The Team group received better overall performance ratings for the asystole (8.5 vs 5.5 out of 10; P<0.001) and PEA (8.5 vs 5.8 out of 10; P<0.001) scenarios. The Team group was also able to recognize asystole and PEA conditions faster than the Solo group [10.1 vs 23.5 s (P<0.001) and 13.3 vs 36.0 s (P<0.001), respectively]. CONCLUSIONS: Residents who performed a simulated intubation with a second trained provider had better overall performance than those who practised independently. The residents who practised in a group were also faster to diagnose serious complications, including peri-intubation asystole and PEA. Given these data, it is reasonable that training programmes consider performing all non-OR airway management with a team-based method.

Simulation as a set-up for technical proficiency: can a virtual warm-up improve live fibre-optic intubation?

BACKGROUND: Fibre-optic intubation (FOI) is an advanced technical skill, which anaesthesia residents must frequently perform under pressure. In surgical subspecialties, a virtual 'warm-up' has been used to prime a practitioner's skill set immediately before performance of challenging procedures. This study examined whether a virtual warm-up improved the performance of elective live patient FOI by anaesthesia residents. METHODS: Clinical anaesthesia yr 1 and 2 (CA1 and CA2) residents were recruited to perform elective asleep oral FOI. Residents either underwent a 5 min, guided warm-up (using a bronchoscopy simulator) immediately before live FOI on patients with predicted normal airways or performed live FOI on similar patients without the warm-up. Subjects were timed performing FOI (from scope passing teeth to viewing the carina) and were graded on a 45-point skill scale by attending anaesthetists. After a washout period, all subjects were resampled as members of the opposite cohort. Multivariate analysis was performed to control for variations in previous FOI experience of the residents. RESULTS: Thirty-three anaesthesia residents were recruited, of whom 22 were CA1 and 11 were CA2. Virtual warm-up conferred a 37% reduction in time for CA1s (mean 35.8 (SD 3.2) s vs. 57 (SD 3.2) s, P<0.0002) and a 26% decrease for CA2s (mean 23 (SD 1.7) s vs. 31 (SD 1.7) s, P=0.0118). Global skill score increased with warm-up by 4.8 points for CA1s (mean 32.8 (SD 1.2) vs. 37.6 (SD 1.2), P=0.0079) and 5.1 points for CA2s (37.7 (SD 1.1) vs. 42.8 (SD 1.1), P=0.0125). Crossover period and sequence did not show a statistically significant association with performance. CONCLUSIONS: Virtual warm-up significantly improved performance by residents of FOI in live patients with normal airway anatomy, as measured both by speed and by a scaled evaluation of skills.

Rates and determinants of progression to graft failure in kidney allograft recipients with de novo donor-specific antibody.

Understanding rates and determinants of clinical pathologic progression for recipients with de novo donor-specific antibody (dnDSA), especially subclinical dnDSA, may identify surrogate endpoints and inform clinical trial design. A consecutive cohort of 508 renal transplant recipients (n = 64 with dnDSA) was studied. Recipients (n = 388) without dnDSA or dysfunction had an eGFR decline of -0.65 mL/min/1.73 m(2) /year. In recipients with dnDSA, the rate eGFR decline was significantly increased prior to dnDSA onset (-2.89 vs. -0.65 mL/min/1.73 m(2) /year, p < 0.0001) and accelerated post-dnDSA (-3.63 vs. -2.89 mL/min/1.73 m(2) /year, p < 0.0001), suggesting that dnDSA is both a marker and contributor to ongoing alloimmunity. Time to 50% post-dnDSA graft loss was longer in recipients with subclinical versus a clinical dnDSA phenotype (8.3 vs. 3.3 years, p < 0.0001). Analysis of 1091 allograft biopsies found that dnDSA and time independently predicted chronic glomerulopathy (cg), but not interstitial fibrosis and tubular atrophy (IFTA). Early T cell-mediated rejection, nonadherence, and time were multivariate predictors of IFTA. Independent risk factors for post-dnDSA graft survival available prior to, or at the time of, dnDSA detection were delayed graft function, nonadherence, dnDSA mean fluorescence intensity sum score, tubulitis, and cg. Ultimately, dnDSA is part of a continuum of mixed alloimmune-mediated injury, which requires solutions targeting T and B cells.

Female-partnered and single women's contact motivations and experiences with donor-linked families.

STUDY QUESTION: What are female-partnered and single mothers' motivations and experiences at one donor insemination (DI) program with regard to contacting other families who share the same sperm donor? SUMMARY ANSWER: By and large, women reported seeking contact to obtain (i) support for their children and/or themselves, and (ii) information about shared traits and medical problems, ultimately describing a range of contact experiences, both positive (e.g. special bond created) and negative (e.g. uncomfortable encounters). WHAT IS KNOWN ALREADY: There is a growing phenomenon of donor insemination families-parents and/or offspring-seeking others who share their donor (i.e. are 'donor-linked'). There is limited understanding about parental motivations and experiences-especially in the presence of a second parent-due to the methodological constraints of previous quantitative studies. STUDY DESIGN, SIZE, DURATION: Semi-structured telephone interviews were conducted with 50 donor insemination mothers (14 single, 36 female-partnered). Participants were recruited by email invitation to parent members of a family-matching service at one donor insemination program in the USA. The criterion for inclusion was having matched to at least one donor-linked family. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the 50 mothers interviewed, all had at least one child conceived via donor insemination, who was between ages 0 and 15 years at first contact. Families matched with a median of three donor-linked families (range 1-10). Interview data were analyzed through qualitative (i.e. thematic) analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Overarching themes emerged of seeking contact to obtain (i) support and (ii) information about children's shared physical and psychological traits. Some wanted to increase their child's family network, through adding a sibling, but more often as extended family. Data, from partnered parents especially, revealed the challenges of balancing the boundaries of family formed without the genetic link with the perceived benefits of exploring the child's donor origins. LIMITATIONS, REASONS FOR CAUTION: Interviews focused on openness and information-sharing were conducted with parents from one American donor insemination program. Findings are limited to individuals who were open enough to share their experiences and able to take the time to do so. WIDER IMPLICATIONS OF THE FINDINGS: As donor-linking services become established independently (e.g. donor insemination program registries) or by the government (e.g. Victoria, Australia's Voluntary Register), these findings provide evidence that linking services are valued by individuals affected by donor conception. Caution is warranted, however, in that some participants reported mismatched expectations, both across donor-linked families and within families (e.g. between partners), suggesting the need for information and guidance both during and after matching. Overall, the range and balance of reported positives and negatives indicate that donor-linking can provide individuals with support and donor origins information-which are particularly important when these are not available elsewhere. STUDY FUNDING/COMPETING INTERESTS: Clark University provided support. No competing interests.

Learning through simulated independent practice leads to better future performance in a simulated crisis than learning through simulated supervised practice.

BACKGROUND: Anaesthetists may fail to recognize and manage certain rare intraoperative events. Simulation has been shown to be an effective educational adjunct to typical operating room-based education to train for these events. It is yet unclear, however, why simulation has any benefit. We hypothesize that learners who are allowed to manage a scenario independently and allowed to fail, thus causing simulated morbidity, will consequently perform better when re-exposed to a similar scenario. METHODS: Using a randomized, controlled, observer-blinded design, 24 first-year residents were exposed to an oxygen pipeline contamination scenario, either where patient harm occurred (independent group, n=12) or where a simulated attending anaesthetist intervened to prevent harm (supervised group, n=12). Residents were brought back 6 months later and exposed to a different scenario (pipeline contamination) with the same end point. Participants' proper treatment, time to diagnosis, and non-technical skills (measured using the Anaesthetists' Non-Technical Skills Checklist, ANTS) were measured. RESULTS: No participants provided proper treatment in the initial exposure. In the repeat encounter 6 months later, 67% in the independent group vs 17% in the supervised group resumed adequate oxygen delivery (P=0.013). The independent group also had better ANTS scores [median (interquartile range): 42.3 (31.5-53.1) vs 31.3 (21.6-41), P=0.015]. There was no difference in time to treatment if proper management was provided [602 (490-820) vs 610 (420-800) s, P=0.79]. CONCLUSIONS: Allowing residents to practise independently in the simulation laboratory, and subsequently, allowing them to fail, can be an important part of simulation-based learning. This is not feasible in real clinical practice but appears to have improved resident performance in this study. The purposeful use of independent practice and its potentially negative outcomes thus sets simulation-based learning apart from traditional operating room learning.

Use of inertial measurement units to assess age-related changes in gait kinematics in an active population.

To study mobility in older populations it can be advantageous to use portable gait analysis systems, such as inertial measurement units (IMUs), which can be used in the community. To define a normal range, 136 active subjects were recruited with an age range of 18 to 97. Four IMUs were attached to the subjects, one on each thigh and shank. Subjects were asked to walk 10 m at their own self-selected speed. The ranges of motion of thigh, shank, and knee in both swing and stance phase were calculated, in addition to stride duration. Thigh, shank, and knee range of movement in swing and stance were significantly different only in the > 80 age group. Regressions of angle against age showed a cubic relationship. Stride duration showed a weak linear relationship with age, increasing by approximately 0.1% per year.

Ring-substituted analogs of 3,3'-diindolylmethane (DIM) induce apoptosis and necrosis in androgen-dependent and -independent prostate cancer cells.

We recently reported that novel ring-substituted analogs of 3,3'-diindolylmethane (ring-DIMs) have anti-androgenic and growth inhibitory effects in androgen-dependent prostate cancer cells. The objectives of this study were to confirm the ability of 4,4'- and 7,7'-dibromo- and dichloro-substituted ring-DIMs to inhibit androgen-stimulated proliferation of androgen-dependent LNCaP human prostate cancer cells using a non-invasive, real-time monitoring technique. In addition, their ability to induce apoptotic and necrotic cell death in androgen-dependent as well as -independent (PC-3) prostate cancer cells was studied. Prostate cancer cells were treated with increasing concentrations of DIM and ring-DIMs (0.3-30 µM) and effects on cell proliferation were measured in real-time using an xCELLigence cellular analysis system. Chromatin condensation and loss of membrane integrity were determined by Hoechst and propidium iodide staining, respectively. Apoptotic protein markers were measured by immunoblotting and activation of caspases determined using selective fluorogenic substrates. Intra- and extracellular concentrations of DIM and ring-DIMs were assessed by electrospray ionization tandem mass spectrometry. Ring-DIMs inhibited androgen-stimulated LNCaP cell proliferation and induced apoptosis and necrosis in LNCaP and PC-3 cells with 2-4 fold greater potencies than DIM. DIM and the ring-DIMs increased caspases -3, -8 and -9 activity, elevated expression of Fas, FasL, DR4 and DR5 protein, and induced PARP cleavage in both cell lines. The cytotoxicity of the most potent ring-DIM, 4,4'-dibromoDIM, but not the other compounds was decreased by an inhibitor of caspase -3. The 4,4'-dibromoDIM was primarily found in the extracellular medium, whereas all other compounds were present to a much larger extent in the cell. In conclusion, ring-DIMs inhibited prostate cancer cell growth and induced cell death in LNCaP and PC-3 cells with greater potencies than DIM; they also structure-dependently activated different cell death pathways suggesting that these compounds have clinical potential as chemopreventive and chemotherapeutic agents in prostate cancer, regardless of hormone-dependency.

Vitamin D, asthma prevalence and asthma exacerbations: a large adult population-based study.

BACKGROUND: The impact of low vitamin D status on asthma, asthma morbidity and control is unclear. We aimed to investigate in adults the associations between serum 25-hydroxyvitamin D level and prevalent asthma as well as asthma exacerbations. METHODS: A cohort of Israeli adults aged 22-50 years with documented vitamin D status were extracted from Clalit Health Services (HMO) between July 1, 2008 and July 1, 2012. Among this population, those with physician-diagnosed asthma and asthma exacerbations were identified. Asthma exacerbations were defined as any of the following: prescription for oral corticosteroids, >5 prescriptions for short acting beta agonists and more than four visits to a physician for asthma. Logistic regression models assessed the associations between vitamin D and both asthma and asthma exacerbations. RESULTS: Approximately 308 000 members with at least one vitamin D measurement were included in the cohort. Among them, 6.9% (21 237) had physician-diagnosed asthma vs 5.7% in the general population. Serum 25-OHD levels across both groups were similar. However, among those with vitamin D deficiency, the odds of having an exacerbation were 25% greater compared to those with levels in the normal range. This association remained significant after controlling for known confounders. CONCLUSION: While there was no significant association between vitamin D status and physician-diagnosed asthma, there was a strong association with asthma exacerbations. The presented evidence supports vitamin D screening in the subgroup of asthmatics that are uncontrolled and experience recurrent exacerbations.

Medical clowns ease anxiety and pain perceived by children undergoing allergy prick skin tests.

BACKGROUND: Intervention of medical clowns (MC) during various medical procedures performed in children has been used to relieve anxiety and pain. Their role in allergy skin testing has never been evaluated. OBJECTIVE: To evaluate whether MC can diminish pain and anxiety perceived by children undergoing allergy skin prick tests (SPT). METHODS: In a prospective, randomized, controlled, and blinded study, children undergoing SPT were or were not accompanied by MC. All parents and children ≥8 years completed the State-Trait Anxiety Inventory (STAI) before and after SPT. Videotapes recorded during the procedure were scored for anxiety (m-YPAS) for all children and for pain (FLACC) for children 2-7 years old by a psychologist who was unaware of the MC's presence. After SPT, children ≥8 years completed a visual analog score (VAS) for pain. RESULTS: Ninety-one children (mean age 8.2 years, M/F = 54/37) were recruited of whom 45 were accompanied by clowns. A significant reduction in state-STAI was found in the clowns group, in both parents and children, when compared with the regular group (26.9 ± 6.6 and 32.3 ± 10.0; P = 0.004, and 27.1 ± 4.2 and 34.3 ± 7.6; P = 0.002, respectively). Both m-YPAS and FLACC were reduced in the clowns group compared with the regular one. In the clowns group, m-YPAS positively correlated with both VAS and FLACC (P = 0.000 and 0.002, respectively). m-YPAS was positively correlated with FLACC in the regular group (P = 0.000). CONCLUSION: Medical clowns significantly decrease the level of anxiety perceived by both children undergoing allergy SPT and their parents, as well as the pain perceived by young children.

Pathogenesis and outcomes of traumatic injuries of the esophagus.

Traumatic injury of the esophagus is extremely uncommon. The aims of this study were to use the Pennsylvania Trauma Outcome Study (PTOS) database to identify clinical factors predictive of esophageal trauma, and to report the morbidity and mortality of this injury. A cross-sectional review of patients presenting to 20 Level I trauma centers in Pennsylvania from 2004 to 2010 was performed. We compared clinical and demographic variables between patients with and without esophageal trauma both prior to and after arrival in the emergency room (ER). Primary mechanism of injury and clinical outcomes were analyzed. There were 231 694 patients and 327 (0.14%) had esophageal trauma. Patients with esophageal trauma were considerably younger than those without this injury. The risk of esophageal trauma was markedly increased in males (odds ratio [OR] = 2.62 [CI 1.98-3.47]). The risk was also increased in African Americans (OR = 4.61 [CI 3.65-5.82]). Most cases were from penetrating gunshot and stab wounds. Only 34 (10.4%) of esophageal trauma patients underwent an upper endoscopy; diagnosis was usually made by CT, surgery, or autopsy. Esophageal trauma patients were more likely to require surgery (35.8% vs. 12.5%; P < 0.001). Patients with esophageal trauma had a substantially higher mortality than those without the injury (20.5% vs. 1.4%; P < 0.005). In logistic regression modeling, traumatic injury of the esophagus (OR = 3.43 [2.50-4.71]) and male gender (OR = 1.52 [1.46-1.59]) were independently associated with mortality. For those patients with esophageal trauma, there was an association between trauma severity and mortality (OR = 1.10 [1.07-1.12]) but not for undergoing surgery within the first 24 hours of hospitalization (OR = 0.84; 0.39-1.83). Our study on traumatic injury of the esophagus is in concordance with previous studies demonstrating that this injury is rare but carries considerable morbidity (∼46%) and mortality (∼20%). The injury has a higher morbidity and mortality when the thoracic esophagus is involved compared to the cervical esophagus alone. The injury most commonly occurs in younger, Black males suffering gunshot wounds. Efforts to control gun violence in Pennsylvania are of paramount importance.

Class II HLA epitope matching-A strategy to minimize de novo donor-specific antibody development and improve outcomes.

De novo donor-specific antibody (dnDSA) develops in 15-25% of renal transplant recipients within 5 years of transplantation and is associated with 40% lower graft survival at 10 years. HLA epitope matching is a novel strategy that may minimize dnDSA development. HLAMatchmaker software was used to characterize epitope mismatches at 395 potential HLA-DR/DQ/DP conformational epitopes for 286 donor-recipient pairs. Epitope specificities were assigned using single antigen HLA bead analysis and correlated with known monoclonal alloantibody epitope targets. Locus-specific epitope mismatches were more numerous in patients who developed HLA-DR dnDSA alone (21.4 vs. 13.2, p < 0.02) or HLA-DQ dnDSA alone (27.5 vs. 17.3, p < 0.001). An optimal threshold for epitope mismatches (10 for HLA-DR, 17 for HLA-DQ) was defined that was associated with minimal development of Class II dnDSA. Applying these thresholds, zero and 2.7% of patients developed dnDSA against HLA-DR and HLA-DQ, respectively, after a median of 6.9 years. Epitope specificity analysis revealed that 3 HLA-DR and 3 HLA-DQ epitopes were independent multivariate predictors of Class II dnDSA. HLA-DR and DQ epitope matching outperforms traditional low-resolution antigen-based matching and has the potential to minimize the risk of de novo Class II DSA development, thereby improving long-term graft outcome.