Defining blood hematology reference values in female pig-tailed macaques (Macaca nemestrina) using the Isolation Forest algorithm.

BACKGROUND: Pig-tailed macaques (PTMs) are commonly used as preclinical models to assess antiretroviral drugs for HIV prevention research. Drug toxicities and disease pathologies are often preceded by changes in blood hematology. To better assess the safety profile of pharmaceuticals, we defined normal ranges of hematological values in PTMs using an Isolation Forest (iForest) algorithm. METHODS: Eighteen female PTMs were evaluated. Blood was collected 1-24 times per animal for a total of 159 samples. Complete blood counts were performed, and iForest was used to analyze the hematology data to detect outliers. RESULTS: Median, IQR, and ranges were calculated for 13 hematology parameters. From all samples, 22 outliers were detected. These outliers were excluded from the reference index. CONCLUSIONS: Using iForest, we defined a normal range for hematology parameters in female PTMs. This reference index can be a valuable tool for future studies evaluating drug toxicities in PTMs.

Treatment modalities for lymphocytic and neutrophilic scarring alopecia.

Primary cicatricial alopecia can result in permanent hair loss from the destruction of hair follicles. Early intervention is key in controlling disease progression, reducing symptoms, and optimizing hair density. Treatment modalities range from topical and intralesional therapies to oral medications and light therapy.

Generation of a new mouse line with conditionally activated signaling through the BMP receptor, ACVR1: A tool to characterize pleiotropic roles of BMP functions.

BMP signaling plays pleiotropic roles in various tissues during embryogenesis and after birth. We have previously generated a constitutively activated Acvr1(ca-Acvr1) transgenic mouse line (line L35) through pronuclei injection to investigate impacts of enhanced BMP signaling in a tissue specific manner. However, line L35 shows a restricted expression pattern of the transgene. Here, we generated another ca-Acvr1 transgenic line, line A11, using embryonic stem (ES) transgenesis. The generated line A11 shows distinctive phenotypes from line L35, along with very limited expression levels of the transgene. When the transgene is activated in the neural crest cells in a Cre-dependent manner, line A11 exhibits cleft palate and shorter jaws, while line L35 develops ectopic cartilages and highly hypomorphic facial structures. When activated in limb buds, line A11 develops organized but smaller limb skeletal structures, while line L35 forms disorganized limbs with little mineralization. Additionally, no heterotopic ossification (HO) is identified in line A11 when bred with NFATc1-Cre mice even after induction of tissue injury, which is an established protocol for HO for line L35. Therefore, the newly generated conditional ca-Acvr1 mouse line A11 provides an additional resource to dissect highly context dependent functions of BMP signaling in development and disease.

A Phase 1 dose-escalation study of disulfiram and copper gluconate in patients with advanced solid tumors involving the liver using S-glutathionylation as a biomarker.

BACKGROUND: Disulfiram and metals inactivate key oncoproteins resulting in anti-neoplastic activity. The goal of this study was to determine the maximum tolerated dose of copper when administered with disulfiram in patients with advanced solid tumors and liver involvement. METHODS: Disulfiram 250 mg was administered daily in 28-day cycles. Four doses of copper gluconate were tested (2, 4, 6, and 8 mg of elemental copper) in a standard 3 + 3 dose escalation design. Patients were evaluated for dose limiting toxicities and response. Protein S-glutathionylation was evaluated as a pharmacodynamic marker. RESULTS: Twenty-one patients were enrolled and 16 patients were evaluable for dose limiting toxicities. Among the 21 patients, there was a median of 4 lines of prior chemotherapy. Five Grade 3 toxicities were observed (anorexia, elevated aspartate aminotransferase or AST, elevated alkaline phosphatase, fever, and fatigue). Response data was available for 15 patients. Four patients had stable disease with the longest duration of disease control being 116 days. The median duration of treatment for evaluable patients was 55 days (range 28-124). Reasons for discontinuation included functional decline, disease progression, and disease-associated death. Increased S-glutathionylation of serum proteins was observed with treatment. CONCLUSION: Disulfiram 250 mg daily with copper gluconate (8 mg of elemental copper) was well-tolerated in patients with solid tumors involving the liver and was not associated with dose limiting toxicities. While temporary disease stabilization was noted in some patients, no objective responses were observed. Treatment was associated with an increase in S-glutathionylation suggesting that this combination could exert a suppressive effect on cellular growth and protein function. TRIAL REGISTRATION: NCT00742911 , first posted 28/08/2008.

Insurance Type and Marital Status Impact Hospital Length of Stay After Pancreatoduodenectomy.

BACKGROUND: Recognition of the impact of social determinants on health care and surgical outcomes is imperative to improve patient care. This study aims to examine the impact social determinants have on hospital length of stay (LOS) after pancreatoduodenectomy (PD). METHODS: Retrospective review of a prospective American College of Surgeons-National Surgical Quality Improvement Program database identified patients who underwent PD from 2013 to 2018. Patients were categorized by insurance type (public/private/multiple), and electronic medical record review was performed to obtain distance from home, marital status, and race. Public insurance included Medicare and Medicaid; multiple types were defined as public insurance supplemented by a private insurance. Univariable analysis was used to identify potential confounders. Significant differences (P < 0.05) were controlled for using multivariable regression models to examine the effect of variables on LOS. RESULTS: About 813 PDs were included (n = 341 public; n = 238 private; and n = 234 multiple). Patients with public insurance had significantly longer LOS than patients with private on univariate (P < 0.001) and multivariable analyses (P = 0.021) (8 versus 7 d). Patients with multiple insurance types showed significantly increased LOS compared with patients with private on univariable (P < 0.001) and multivariable analyses (P = 0.006) (8 versus 7 d). Single patients had significantly longer LOS compared with married patients on univariable (P = 0.012) and multivariable analyses (P = 0.005) (8 versus 7 d). Distance from home, race, gender, or age did not have a significant impact on LOS. CONCLUSIONS: Single patients and patients with public or multiple insurance types are more likely to have longer hospital LOS after PD. These findings will enable physicians to identify patients at risk and target them for enhanced recovery programming.

Impact of a Novel Preoperative Patient-centered Surgical Wellness Program.

OBJECTIVE: The objective of this study was to evaluate if a preoperative wellness bundle significantly decreases the risk of hospital acquired infections (HAI). BACKGROUND: HAI threaten patient outcomes and are a significant burden to the healthcare system. Preoperative wellness efforts may significantly decrease the risk of infections. METHODS: A group of 12,396 surgical patients received a wellness bundle in a roller bag during preoperative screening at an urban academic medical center. The wellness bundle consisted of a chlorhexidine bath solution, immuno-nutrition supplements, incentive spirometer, topical mupirocin for the nostrils, and smoking cessation information. Study staff performed structured patient interviews, observations, and standardized surveys at key intervals throughout the perioperative period. Statistics compare HAI outcomes of patients in the wellness program to a nonintervention group using the Fisher's exact test, logistic regression, and Poisson regression. RESULTS: Patients in the nonintervention and intervention groups were similar in demographics, comorbidity, and type of operations. Compliance with each element was high (80% mupirocin, 72% immuno-nutrition, 71% chlorhexidine bath, 67% spirometer). The intervention group had statistically significant reductions in surgical site infections, Clostridium difficile, catheter associated urinary tract infections, and patient safety indicator 90. CONCLUSIONS: A novel, preoperative, patient-centered wellness program dramatically reduced HAI in surgical patients at an urban academic medical center.

Description of Mexican Cleft Surgeons' Experience With Foreign Surgical Volunteer Missions in Mexico.

BACKGROUND AND PURPOSE: Mexican cleft surgeons provide multidisciplinary comprehensive cleft lip and palate care to children in Mexico. Many Mexican cleft surgeons have extensive experience with foreign, visiting surgeons. The purpose of this study was to characterize Mexican cleft surgeons' domestic and volunteer practice and to learn more about Mexican cleft surgeons' experience with visiting surgeons. METHODS: A cross-sectional validated e-mail survey tool was sent to Mexican cleft surgeons through 2 Mexican plastic surgery societies and the Asociación Mexicana de Labio y Paladar Hendido y Anomalías Craneofaciales, the national cleft palate society that includes plastic and maxillofacial surgeons who specialize in cleft surgery. We utilized validated survey methodology, including neutral fact-based questions and repeated e-mails to survey nonresponders to maximize validity of statistical data; response rate was 30.6% (n = 81). RESULTS: Mexican cleft surgeons performed, on average, 37.7 primary palate repairs per year with an overall complication rate of 2.5%; 34.6% (n = 28) of respondents had direct experience with patients operated on by visiting surgeons; 53.6% of these respondents performed corrective surgery because of complications from visiting surgeons. Respondents rated 48% of the functional outcomes of visiting surgeons as "acceptable," whereas 43% rated aesthetic outcomes of visiting surgeons as "poor"; 73.3% of respondents were never paid for the corrective surgeries they performed. Thirty-three percent of Mexican cleft surgeons believe that there is a role for educational collaboration with visiting surgeons. CONCLUSIONS: Mexican cleft surgeons have a high volume of primary cleft palate repairs in their domestic practice with good outcomes. Visiting surgeons may play an important role in Mexican cleft care through educational collaborations that complement the strengths of Mexican cleft surgeons.

A Macaque Model for Rectal Lymphogranuloma Venereum and Non-Lymphogranuloma Venereum Chlamydia trachomatis: Impact on Rectal Simian/Human Immunodeficiency Virus Acquisition.

BACKGROUND: Sustained genital tract inflammation caused by sexually transmitted infections (STIs) is known to increase risk of vaginal human immunodeficiency virus (HIV) infections but, to our knowledge, there are no nonhuman primate studies that have evaluated its link to rectal HIV acquisition. METHODS: Rhesus macaques inoculated with Chlamydia trachomatis (CT) (serovars LGV-L2 and CT-E; n = 7) or saline (n = 7) received up to 20 rectal challenges twice a week of simian/HIV immunodeficiency virus (SHIVSF162p3). SHIV viremia was determined by real-time PCR and Chlamydia infection by APTIMA Combo 2 testing. The rectal cytokine-chemokine levels were evaluated by multiplex bead assays. RESULTS: Rectal Chlamydia infection was maintained throughout the study. We did not observe significant differences (P = 1.0) in frequency of SHIV acquisition between the STI and control arms. It took fewer SHIV challenges to infect the STI animals although the difference was not significant (P = 0.59). There were no significant differences in peak plasma viremia between STI and control arms (P = 0.63). The association of plasma viremia with rectal shedding was significantly different by arm (P = 0.038). CONCLUSIONS: In the first such study in a macaque model, we did not observe an increased risk of SHIV acquisition due to rectal Chlamydia coinfection. This macaque model can be further developed and expanded to better investigate the impact of different rectal STIs on HIV acquisition.

Against the Odds: Syringe Exchange Policy Implementation in Indiana.

Indiana recently passed legislation allowing local governments to establish syringe exchanges. While the effectiveness of syringe exchange programming is established, there is a dearth of studies about associated policy adoption and implementation. This study documents the experiences of 24 Indiana counties engaged in the process of establishing syringe exchange programming under new state law. A mixed method, qualitative, exploratory case study was conducted from May 2015 to April 2016. We observed rapid and widespread policy adoption interest, and yet counties reported significant policy ambiguity, epidemiologic and resource capacity issues. The emergence of health commons involving information and tangible resource sharing networks allowed institutional rearrangement in the midst of resource scarcity; however, such rearrangement appeared to be a central threat to policy adoption and implementation given state structural barriers. The emerging commons could be a critical policy success factor, as it would achieve efficiencies not possible in the current resource environment, and can help achieve institutional rearrangement for the improvement of population health. Several recommendations for improvement are offered.

Development of a rectal sexually transmitted infection (STI) Model in Rhesus macaques using Chlamydia trachomatis serovars E and L2.

BACKGROUND: Rectal STI coinfection models enhance the understanding of rectal HIV transmission risk factors. MATERIALS AND METHODS: Rhesus macaques (n=9) were exposed to one of three rectal Chlamydia trachomatis (CT) challenges: C. trachomatis L2 (CT-L2 ); C. trachomatis serovar E (CT-E), followed by CT-L2 ; or CT-E, treatment/clearance, then CT-L2 . Infections were monitored by PCR. Weekly blood and rectal secretion/lavage samples were collected for cytokine analyzes and/or epithelial sloughing, occult, and overt blood determinations. RESULTS: Chlamydial infections were successfully established in each animal, with varying degrees of persistence. Mucosal IL-1beta was upregulated in animals consecutively infected with CT-E then CT-L2 (P=.05). Epithelial sloughing was also significantly increased post-infection in this group (P=.0003). CONCLUSIONS: This study demonstrates successful rectal infection of rhesus macaques with CT-E and CT-L2 and describes measures of assessing rectal inflammation and pathology. Different infection strategies yield varying inflammatory and pathologic outcomes, providing well-described models for future SIV/SHIV susceptibility studies.

Do Gestational Age Dating Criteria Matter in Medically Indicated Late Preterm, Early-Term, and Full-Term Inductions of Labor?

OBJECTIVES: To assess short-term neonatal respiratory morbidity from inductions of labor (IOL) in well-dated (WD) pregnancies (dating ultrasound [US] <20 0/7 weeks) versus non-well-dated (NWD) pregnancies when applying National Institutes of Health/Society for Maternal-Fetal Medicine/American College of Obstetricians and Gynecologists delivery recommendations at ≥34 0/7 weeks. METHODS: Ours was a 1-year retrospective cohort of women with medically indicated IOL between 34 0/7 and 40 6/7 weeks with a live, cephalic, singleton gestation and no lethal anomaly. The primary outcome was a composite of neonatal respiratory morbidity (respiratory distress syndrome, transient tachypnea of the newborn, ventilator support, oxygen administration, and pneumonia). RESULTS: A total of 476 WD and 231 NWD women underwent IOL during the study period. The groups had similar maternal characteristics, indications for IOL, and mode of delivery. There was no difference in the rate of primary outcome (8.7% in NWD group vs 8.8% in WD group; P = 0.95). This finding persisted after control for parity, gestational age (GA) at first US, operator of the dating US, and exposure to antenatal corticosteroids and magnesium sulfate. When stratified by GA at delivery and GA at first US, these findings persisted even when the dating US was performed at >35 weeks. There were no differences in maternal or other neonatal outcomes between the WD and NWD pregnancies. CONCLUSIONS: In our cohort of medically indicated IOL, a dating US before 20 weeks was not associated with a difference in neonatal respiratory morbidity.

Time and Note Characteristic Effects of an Electronic Health Record Template for Internal Medicine Resident Notes.

Background Inpatient internal medicine (IM) residents spend most of their time on indirect patient care activities such as clinical documentation. Objective We developed optimized electronic health record (EHR) templates for IM resident admission and progress notes, with the objective to reduce note-writing time, shorten note length, and decrease the percentage of progress note text that was copy-forwarded from prior notes. Methods In 2022, a multidisciplinary team created, over an 8-month period, optimized EHR templates for IM resident admission and progress notes. A retrospective analysis was performed to assess differences in resident time spent writing notes, note length in characters, and percentage of progress note text that was copy-forwarded. All 94 residents in the IM residency program had the opportunity to use the novel templates. Results Following implementation of the novel templates, residents spent on average 3.6 minutes less per progress note compared to pre-intervention (P=.008; 95% CI of the difference: 1.1-6.0 minutes). Notes in the post-intervention period were shorter for admission notes (mean reduction of 1041 characters; P<.001; 95% CI of the difference: 448-1634 characters) and progress notes (mean reduction of 764 characters; P<.001; 95% CI of the difference: 103-1426 characters). Progress notes also saw an average 22% decrease of copy-forwarded text (P<.001, 95% CI of the difference: 18.7%-25.4%). Conclusions The optimized note templates led to a reduction in resident progress note-writing time, shortened note length, and a lower percentage of copy-forwarded text.