Anatomic and physiologic classification of adults with congenital heart disease to predict adverse outcomes: Use of administrative codes compared to clinical staging.

BACKGROUND: The 2018 anatomic physiologic (AP) classification American Heart Association/American College of Cardiology (AHA/ACC) Guidelines for Adults with Congenital Heart Disease (ACHD) encompasses both native and post-operative anatomy and physiology to guide care management. As some physiologic conditions and post-operative states lack specific International Classification of Diseases (ICD) 9- Clinical Modification (CM) and 10-CM codes, an ICD code-based classification approximating the ACHD AP classification is needed for population-based studies. METHODS: A total of 232 individuals, aged ≥ 18 years at the time of a health encounter between January 1, 2010 and December 31, 2019 and identified with at least one of 87 ICD codes for a congenital heart defect were validated through medical chart review. Individuals were assigned one of 4 mutually exclusive modified AP classification categories: (1) severe AB, (2) severe CD, (3) non-severe AB, or (4) non-severe CD, based on native anatomy "severe" or "non-severe" and physiology AB ("none" or "mild") or CD ("moderate" or "severe") by two methods: (1) medical record review, and (2) ICD and Current Procedural Terminology (CPT) code-based classification. The composite outcome was defined as a combination of a death, emergency department (ED) visits, or any hospitalizations that occurred at least 6 months after the index date and was assessed by each modified AP classification method. RESULTS: Of 232 cases (52.2% male, 71.1% White), 28.4% experienced a composite outcome a median of 1.6 years after the index encounter. No difference in prediction of the composite outcome was seen based on modified AP classification between chart review and ICD code-based methodology. CONCLUSION: Modified AP classification by chart review and ICD codes are comparable in predicting the composite outcome at least 6 months after classification. Modified AP classification using ICD code-based classification of CHD native anatomy and physiology is an important tool for population-based ACHD surveillance using administrative data.

Sugammadex Versus Neostigmine for Reversal of Neuromuscular Blockade in Patients With Severe Renal Impairment: A Randomized, Double-Blinded Study.

BACKGROUND: Sugammadex is not advised for patients with severe renal impairment, but has been shown in a variety of other populations to be superior to neostigmine for reversal of neuromuscular blockade. The objective of this study was to determine if reversal of rocuronium-induced neuromuscular blockade with sugammadex versus reversal of cisatracurium-induced neuromuscular blockade with neostigmine results in a faster return to a train-of-four ratio (TOFR) ≥90% in patients with severe renal impairment. METHODS: We conducted a prospective, randomized, blinded, controlled trial at a large county hospital. A total of 49 patients were enrolled. Inclusion criteria included patients age ≥18, American Society of Anesthesiologists (ASA) physical status III and IV, with a creatinine clearance <30 mL/min, undergoing general anesthesia with expected surgical duration ≥2 hours and necessitating neuromuscular blockade. Subjects received either cisatracurium 0.2 mg/kg or rocuronium 0.6 mg/kg for induction of anesthesia to facilitate tracheal intubation. Subjects were kept at moderate neuromuscular blockade during surgery and received either 2 mg/kg sugammadex or 50 µg/kg neostigmine with 10 µg/kg glycopyrrolate for reversal of neuromuscular blockade. Neuromuscular monitoring was performed with electromyography (TwitchView), and the TOFR was recorded every minute after administration of the reversal agent. The time from administration of neuromuscular reversal until the patient reached a TOFR ≥90% was recorded as the primary outcome. RESULTS: The mean time to recovery of TOFR ≥90% was significantly faster with sugammadex at 3.5 (±1.6) min compared with neostigmine at 14.8 (±6.1) min ( P < .0001; mean difference, 11.3 minutes; 95% confidence interval [CI], 9.0-13.5 minutes). There were no major adverse events in either group. CONCLUSIONS: In patients with severe renal impairment, neuromuscular blockade with rocuronium followed by reversal with sugammadex provides a significantly faster return of neuromuscular function compared to cisatracurium and neostigmine, without any major adverse effects.

Biofire pneumonia panel in lung donors: faster detection but limited pathogens.

BACKGROUND: Culture of bronchoalveolar lavage (BAL) specimens takes time to report. We tested whether a molecular diagnostic test could accelerate donor lung assessment and treatment. METHODS: We compared BioFire Film Array Pneumonia Panel (BFPP) with standard of care (SOC) tests on lung allograft samples at three time points: (1) donor BAL at organ recovery, (2) donor bronchial tissue and airway swab at implantation, and (3) first recipient BAL following lung implantation. Primary outcomes were the difference in time to result (Wilcoxon signed-ranked tests) and the agreement in results between BFPP and SOC assays (Gwet's agreement coefficient). RESULTS: We enrolled 50 subjects. In donor lung BAL specimens, BFPP detected 52 infections (14 out of 26 pathogens in the panel). Viral and bacterial BFPP results were reported 2.4 h (interquartile range, IQR 2.0-6.4) following BAL versus 4.6 h (IQR 1.9-6.0, p = 0.625) for OPO BAL viral SOC results and 66 h (IQR 47-87, p < .0001) for OPO BAL bacterial SOC results. Although there was high overall agreement of results between BAL-BFPP versus OPO BAL-SOC tests (Gwet's AC p < .001 for all), the level of agreement differed among 26 pathogens designed in BFPP and differed by types of specimens. BFPP could not detect many infections identified by SOC assays. CONCLUSIONS: BFPP decreased time to detection of lung pathogens among donated lungs, but it cannot replace SOC tests due to the limited number of pathogens in the panel.

Using the Patient Health Questionnaire-2 to improve depression screening in head and neck cancer patients.

PURPOSE: The purpose of this study is to examine the use of the Patient Health Questionnaire-2 (PHQ-2) to screen for depression in patients undergoing treatment for head and neck cancer and to evaluate potential patient-specific risk factors that may contribute to depression. MATERIALS AND METHODS: This is a retrospective study at a tertiary-level hospital of outpatient adult patients with head and neck cancer who completed the PHQ-2/9 from 2019 to 2020. Patients were given a PHQ-2 during a surveillance visit. A positive PHQ-2 screen (score ≥ 3) prompted further evaluation with a PHQ-9. Patients were stratified into either low risk (PHQ-2 score < 3) or high risk (PHQ-2 score ≥ 3) for depression. Univariate regression was performed on all variables, and a multivariate logistic regression was performed on statistically significant variables (P < 0.05). RESULTS: In total, 110 patients were included in this study. Fifteen (14 %) patients had a positive PHQ-2 screen with a score ≥ 3 and underwent evaluation with a PHQ-9. The median PHQ-9 score was 15 (6-26). The PHQ-2 ≥ 3 group were significantly younger (59 years vs. 67 years; P = 0.03) and had a greater number of patients with a psychiatric history (33 % vs. 8 %; P < 0.01). CONCLUSIONS: There is a strong association between a PHQ-2 score ≥ 3 and detection of depressive symptoms among patients with head and neck cancer. Younger age and pretreatment mental illness are significant risk factors for developing depression following treatment. Early screening and treatment should be considered for all patients to mitigate the burden of depression and suicide in this patient population. Further research is warranted to investigate utilization of the PHQ-2/9 to detect depression and barriers that exist for timely screening and interventions.

Prions induce an early Arc response and a subsequent reduction in mGluR5 in the hippocampus.

Synapse dysfunction and loss are central features of neurodegenerative diseases, caused in part by the accumulation of protein oligomers. Amyloid-ß, tau, prion, and α-synuclein oligomers bind to the cellular prion protein (PrPC), resulting in the activation of macromolecular complexes and signaling at the post-synapse, yet the early signaling events are unclear. Here we sought to determine the early transcript and protein alterations in the hippocampus during the pre-clinical stages of prion disease. We used a transcriptomic approach focused on the early-stage, prion-infected hippocampus of male wild-type mice, and identify immediate early genes, including the synaptic activity response gene, Arc/Arg3.1, as significantly upregulated. In a longitudinal study of male, prion-infected mice, Arc/Arg-3.1 protein was increased early (40% of the incubation period), and by mid-disease (pre-clinical), phosphorylated AMPA receptors (pGluA1-S845) were increased and metabotropic glutamate receptors (mGluR5 dimers) were markedly reduced in the hippocampus. Notably, sporadic Creutzfeldt-Jakob disease (sCJD) post-mortem cortical samples also showed low levels of mGluR5 dimers. Together, these findings suggest that prions trigger an early Arc response, followed by an increase in phosphorylated GluA1 and a reduction in mGluR5 receptors.

Total laryngectomy negatively impacts sinonasal and olfactory-specific quality of life.

PURPOSE: The purpose of this study is to characterize deficits in olfactory-specific and sinonasal-specific QoL after total laryngectomy (TL) with validated patient reported outcome measures. METHODS: Thirty patients who had a TL were prospectively enrolled. Patient demographics, as well as scores from the Questionnaire of Olfactory Disorders Negative Statements (QOD-NS) and the Sino-nasal Outcome Test-22 (SNOT-22) were collected. Univariate analysis was performed to assess associations between patient characteristics and QoL scores. RESULTS: The average QOD-NS score was 37.9 ± 11.4 (<38.5 is considered abnormal) and average SNOT-22 score was 32.0 ± 3.8 (>20 indicates a moderate/severe impact on QoL). The abnormal QOD-NS group had a greater percentage of former smokers compared to the normal group (77.8% vs. 58.1%; P = 0.56) and more median days from surgery compared to the normal group (904 vs. 477 days; P = 0.24). CONCLUSIONS: Olfactory dysfunction associated with TL results in blunting of olfactory-specific QoL.

Assessment for Different Neural Networks with FeatureSelection in Classification Issue.

In general, the investigation of NN (neural network) computing systems requires the management of a significant number of simultaneous distinct algorithms, such as parallel computing, fault tolerance, classification, and data optimization. Supervised learning for NN originally comes from certain parameters, such as self-revised learning, input learning datasets, and multiple second learning processes. Specifically, the operation continues to adjust the NN connection synapses' weight to achieve a self-learning computer system. The current article is aimed at developing the CC (correlation coefficient) assignment scheme adaptively joint with the FS (feature selection) categories to pursue the solutions utilized in solving the restrictions of NN computing. The NN computing system is expected to solve high-dimensional data, data overfitting, and strict FS problems. Hence, the Fruits-360 dataset is applied in the current article, that is, the variety of fruits, the sameness of color, and the differences in appearance features are utilized to examine the NN system accuracy, performance, and loss rate. Accordingly, there are 120 different kinds with a total of 20,860 fruit image datasets collected from AlexNet, GoogLeNet, and ResNet101, which were implemented in the CC assignment scheme proposed in this article. The results are employed to verify that the accuracy rate can be improved by reducing strict FS. Finally, the results of accuracy rate from the training held for the three NN frameworks are discussed. It was discovered that the GoogLeNet model presented the most significant FS performance. The demonstrated outcomes validate that the proposed CC assignment schemes are absolutely worthwhile in designing and choosing an NN training model for feature discrimination. From the simulation results, it has been observed that the FS-based CC assignment improves the accurate rate of recognition compared to the existing state-of-the-art approaches.

Lung transplantation from swimming pool drowning victims: A case series.

The use of donor lungs from victims of drowning remains a rare occurrence, given concerns over lung parenchymal injury and microbial contamination secondary to aspiration. Given this infrequency, there is a relative paucity of literature surrounding the use of organs from drowned donors, with the few that exist on this subject focusing primarily on cases of drowning in naturally occurring bodies of water (i.e., drowning at sea). Little is known regarding the outcomes of utilizing donor lungs from victims of drowning in artificial bodies of water (i.e., swimming pools). Here, we describe three cases of bilateral lung transplantation from donors who drowned in swimming pools, with good short- and long-term outcomes. These cases lend further evidence to the feasibility of using such organs that have traditionally been viewed with much trepidation. With continually growing demand for donor organs, the use of drowned donor lungs may serve as a means to expand the donor pool and lessen the burden of waitlist mortality.

Rapid molecular detection of airway pathogens in lung transplant recipients.

BACKGROUND: Airway infections are difficult to distinguish from acute rejection in lung transplant recipients. Traditional culture techniques take time that may delay treatment. We hypothesized that a rapid multiplex molecular assay could improve time to diagnosis and appropriate clinical decision making. METHODS: In a prospective observational study of recipients undergoing bronchoscopy, we assessed the BioFire® FilmArray® Pneumonia Panel (BFPP) in parallel to standard of care (SOC) diagnostics. Research clinicians performed shadow (research only) clinical decision making in real time. Time to report and interpretation were reported as median and interquartile ranges and compared by Wilcoxon signed-ranked test. Agreement was defined based on detection of any species targeted in the molecular assay. RESULTS: For the 150 enrolled subjects, BFPP results were available 3.8 hours (IQR 2.8-5.1) following bronchoscopy, compared to 13 hours for viral SOC (IQR 10-34, P < .001) results and 48 hours for bacterial SOC (IQR 46-70, P < .001) results. Positive BFPP results were interpreted in 9 hours (IQR 5-20) following bronchoscopy, compared to 74 hours for SOC (IQR 37-110, P < .001). Assays agreed for 138 (92%) of the 150 subjects. Of 22 BFPP diagnoses, five (23%) resulted in a shadow antibiotic recommendation. Notable BFPP deficiencies included fungal species and H parainfluenzae, accounting for 15 (27%) and 13 (23%) of the 56 actionable SOC results, respectively. CONCLUSIONS: This molecular diagnostic including bacterial targets has the potential to shorten time to diagnosis and augment current clinical decision making but cannot replace SOC culture methods.

A Positive Cocaine Urine Toxicology Test and the Effect on Intraoperative Hemodynamics Under General Anesthesia.

BACKGROUND: Cocaine has a short biological half-life, but inactive urine metabolites may be detectable for a week following use. It is unclear if patients who test positive for cocaine but have a normal electrocardiogram and vital signs have a greater percentage of hemodynamic events intraoperatively. METHODS: A total of 328 patients with a history of cocaine use who were scheduled for elective noncardiac surgery under general anesthesia were enrolled. Patients were categorized into cocaine-positive versus cocaine-negative groups based on the results of their urine cocaine toxicology test. The primary aim of this study was to evaluate whether asymptomatic cocaine-positive patients had similar percentages of intraoperative hemodynamic events, defined as (1) a mean arterial blood pressure (MAP) of <65 or >105 mm Hg and (2) a heart rate (HR) of <50 or >100 beats per minute (bpm) compared to cocaine-negative patients. The study was powered to assess if the 2 groups had an equivalent mean percent of intraoperative hemodynamic events within specific limits using an equivalence test of means consisting of 2 one-sided tests. RESULTS: The cocaine-positive group had a blood pressure (BP) that was outside the set limits 19.4% (standard deviation [SD] 17.7%) of the time versus 23.1% (SD 17.7%) in the cocaine-negative group (95% confidence interval [CI], 0.5-7.0). The cocaine-positive group had a HR outside the set limits 9.6% (SD 16.2%) of the time versus 8.2% (SD 14.9%) in the cocaine-negative group (95% CI, 4.3-1.5). Adjusted for age, sex, body mass index (BMI), smoking status, and the presence of comorbid hypertension, renal disease, and psychiatric illness, the cocaine-positive and cocaine-negative patients were similar within a 7.5% margin of equivalence for MAP data (ß coefficient = 2%, P = .003, CI, 2-6) and within a 5% margin of equivalence for HR data (ß coefficient = 0.2%, P < .001, CI, 4-3). CONCLUSIONS: Asymptomatic cocaine-positive patients undergoing elective noncardiac surgery under general anesthesia have similar percentages of intraoperative hemodynamic events compared to cocaine-negative patients.

Neuraxial anesthesia and pain control for pediatric burn patients receiving excision and split-thickness skin grafts-A retrospective case series.

BACKGROUND: Postoperative pain management in pediatric burn patients requiring excision and split-thickness skin grafts remains largely under-studied. ICU care is often necessary due to the level of sedation and amount of opioids required to achieve adequate pain control. AIMS: Our case series aimed to describe a pain management strategy using neuraxial anesthesia intraoperatively. Primary outcomes include pain scores, postoperative opioid consumption, and adverse events. METHODS: A retrospective chart review was performed on a total of 61 patients who received intraoperative neuraxial anesthesia for split-thickness skin grafting between January 1st, 2017 and June 1st, 2018. Patient demographics, operating room data, and subsequent hospital course was extracted from their electronic medical record and plotted using R Studio statistical software. RESULTS: The overwhelming majority of patients received single-shot spinals with both local anesthetic and either morphine or hydromorphone. Average pain scores were 1 out of 10 with standard deviation of 1.6 in the immediate postoperative period and decreased over the next 72 h. Oral morphine equivalents consumed did not exceed 0.61 ME/kg/day. The most common adverse reaction was pruritus. CONCLUSIONS: Spinal anesthesia was most commonly used for split-thickness skin grafting in the pediatric burn population and provides excellent analgesia for patients' immediate postoperative course, including their initial dressing changes, with minimal risk for complications. Pain was well-controlled in all subgroups indicating that this strategy can be used flexibly in a variety of pediatric burn patients.

Mitochondrial DNA Stimulates TLR9-Dependent Neutrophil Extracellular Trap Formation in Primary Graft Dysfunction.

The immune system is designed to robustly respond to pathogenic stimuli but to be tolerant to endogenous ligands to not trigger autoimmunity. Here, we studied an endogenous damage-associated molecular pattern, mitochondrial DNA (mtDNA), during primary graft dysfunction (PGD) after lung transplantation. We hypothesized that cell-free mtDNA released during lung ischemia-reperfusion triggers neutrophil extracellular trap (NET) formation via TLR9 signaling. We found that mtDNA increases in the BAL fluid of experimental PGD (prolonged cold ischemia followed by orthotopic lung transplantation) and not in control transplants with minimal warm ischemia. The adoptive transfer of mtDNA into the minimal warm ischemia graft immediately before lung anastomosis induces NET formation and lung injury. TLR9 deficiency in neutrophils prevents mtDNA-induced NETs, and TLR9 deficiency in either the lung donor or recipient decreases NET formation and lung injury in the PGD model. Compared with human lung transplant recipients without PGD, severe PGD was associated with high levels of BAL mtDNA and NETs, with evidence of relative deficiency in DNaseI. We conclude that mtDNA released during lung ischemia-reperfusion triggers TLR9-dependent NET formation and drives lung injury. In PGD, DNaseI therapy has a potential dual benefit of neutralizing a major NET trigger (mtDNA) in addition to dismantling pathogenic NETs.

Effect of initial infusion rates of fluid resuscitation on outcomes in patients with septic shock: a historical cohort study.

BACKGROUND: Fluid resuscitation has become the cornerstone of early septic shock management, but the optimal fluid rate is still not well studied. The goal of this investigation is to examine the relationship between fluid resuscitation rate and septic shock resolution. METHOD: We retrospectively studied adult (≥ 18 years) patients with septic shock, defined based on sepsis III definition, from January 1, 2006, through May 31, 2018, in the medical intensive care unit (MICU) of Mayo Clinic Rochester. The fluid resuscitation time was defined as the time required to infuse the initial fluid bolus of 30 ml/kg, based on the recommendations of the 2016 surviving sepsis campaign. The cohort was divided into four groups based on the average fluid rate (group 1 ≥ 0.5, group 2 0.25-0.49, group 3 0.17-0.24, and group 4 < 0.17 ml/kg/min). The primary outcome was the time to shock reversal. Multivariable regression analyses were conducted to account for potential confounders. RESULT: A total of 1052 patients met eligibility criteria and were included in the analysis. The time-to-shock reversal was significantly different among the groups (P < .001). Patients in group 1 who received fluid resuscitation at a faster rate had a shorter time to shock reversal (HR = 0.78; 95% CI 0.66-0.91; P = .01) when compared with group 4 with a median (IQR) time-to-shock reversal of 1.7 (1.5, 2.0) vs. 2.8 (2.6, 3.3) days, respectively. Using 0.25 ml/kg/min as cutoff, the higher fluid infusion rate was associated with a shorter time to shock reversal (HR = 1.22; 95% CI 1.06-1.41; P = .004) and with decreased odds of 28-day mortality (HR = 0.71; 95% CI 0.60-0.85; P < .001). CONCLUSION: In septic shock patients, initial fluid resuscitation rate of 0.25-0.50 ml/kg/min (i.e., completion of the initial 30 ml/kg IV fluid resuscitation within the first 2 h), may be associated with early shock reversal and lower 28-day mortality compared with slower rates of infusion.

Redefining marginality: donor lung criteria.

PURPOSE OF REVIEW: Despite an increase in lung transplantation globally, the waitlist mortality persists due to organ shortage. In order to keep up with the demand, the marginal lung donor criteria need to be revisited. The goal of this review is to redefine the lung donor criteria based on the most recent data. RECENT FINDINGS: Recent evidence indicates that lungs from donor with traditional extended criteria such as, age more than 55, PaO2/FiO2 threshold of less than 300, ischemia time more than 6 h, positive sputum microbiology, abnormal radiography no longer represent contraindications to lung transplantation by themselves. In addition, the introduction of new antiviral agents, organs from Hepatitis C positive donors, though not extended in the traditional sense, have shown positive outcomes. SUMMARY: The decision to use such organs, including those with smoking history, should be taken in totality weighing both donor and recipient characteristics. Hence, authors would advocate removing the term 'marginal' or 'extended' from lung donor criteria.

Lung transplant programs in developing countries: challenges, solutions, and outcomes.

PURPOSE OF REVIEW: The majority of lung transplants (LT) performed are in developed countries. In contrast, little is known about the status of LT in developing nations. The objective is to summarize the challenges, present solutions, and review outcomes of LT in developing countries. We hope this review will guide healthcare providers in such countries that are contemplating embarking on this journey. RECENT FINDINGS: The key challenges that programs in developing countries encountered included shortage and marginal quality of donated organs, lack of dedicated multi-disciplinary LT team, limited availability of advanced technology and high risk of post-transplant infections. Education and collaboration among government, public, and healthcare sectors was seen as fundamental to building and maintaining a successful program. Despite minimal resources and huge challenges, LT survival rates in developing countries improved and were comparable with outcomes reported by the International Society for Heart and Lung Transplantation (ISHLT) Registry. SUMMARY: Starting a new LT program is a daunting task that is complex and resource intensive, especially in developing countries. Improving outcomes indeed provide impetus to continue to persevere in this endeavor with support from all sectors. The findings presented here could help new programs to better anticipate and tackle challenges.

The Effect of Vertically Yoked Prisms on Binocular Vision and Accommodation.

SIGNIFICANCE: Vertically yoked prisms have been used in treatment of binocular vision dysfunction despite minimal supporting evidence. In people with normal binocular vision, the impact on phorias has been assessed but not the impact on accommodation, accommodation vergence interactions, or the horopter. We found that vertically yoked prisms have minor effects during short-term wear in young adults. PURPOSE: The purpose of this study was to determine effects of vertically yoked prisms on accommodative response and several binocular vision tasks. METHODS: There were 45 participants aged 18 to 24 years. The 23 myopes wore distance-corrected soft contact lenses. In a random arrangement, each person wore spectacles containing planopower lenses with either 8 Δ base-up, 4 Δ base-up, zero, 4 Δ base-down, and 8 Δ base-down prisms. Before spectacle wear, baseline measurements of near heterophoria, accommodation response, negative and positive relative accommodations, fusional vergence, and Nonius-horopter spatial perception were taken. Measurements were repeated after a 40-minute wear, spectacles were removed, and tests were performed 20 minutes later. On a 22-participant subset, on a separate occasion, measurements of heterophoria, accommodation response, and relative accommodation were made immediately after spectacles were fitted. RESULTS: Most changes relative to baseline were not significant. Where effects occurred, these were nearly all associated with prism presence rather than adaptation. There were significant effects on accommodation response, but these seem to be refraction effects produced by pantoscopic tilt-induced power changes rather than perceptual effects altering accommodation. There were statistically significant effects on negative relative accommodation (P < .01), with zero prism giving more negative relative accommodation than 8 Δ base-down prisms. Tendencies were noted for prisms to move horopter limits toward the observer. Effects were small and likely not of clinical relevance. CONCLUSIONS: Vertically yoked prisms have minor effects on accommodation and binocular vision, at least during short-term wear in young adults with normal binocular vision.

Why do patients receive care from a short-term medical mission? Survey study from rural Guatemala.

BACKGROUND: Hospital de la Familia was established to serve the indigent population in the western highlands of Guatemala and has a full-time staff of Guatemalan primary care providers supplemented by short-term missions of surgical specialists. The reasons for patients seeking surgical care in this setting, as opposed to more consistent care from local institutions, are unclear. We sought to better understand motivations of patients seeking mission-based surgical care. METHODS: Patients presenting to the obstetric and gynecologic, plastic, ophthalmologic, general, and pediatric surgical clinics at the Hospital de la Familia from July 27 to August 6, 2015 were surveyed. The surveys assessed patient demographics, surgical diagnosis, location of home, mode of travel, and reasons for seeking care at this facility. RESULTS: Of 252 patients surveyed, 144 (59.3%) were female. Most patients reported no other medical condition (67.9%, n = 169) and no consistent income (83.9%, n = 209). Almost half (44.9%, n = 109) traveled >50 km to receive care. The most common reasons for choosing care at this facility were reputation of high quality (51.8%, n = 130) and affordability (42.6%, n = 102); the least common reason was a lack of other options (6.4%, n = 16). CONCLUSIONS: Despite long travel distances and the availability of other options, reputation and affordability were primarily cited as the most common reasons for choosing to receive care at this short-term surgical mission site. Our results highlight that although other surgical options may be closer and more readily available, reputation and cost play a large role in choice of patients seeking care.

Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis.

KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with Kras(G12D) to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy.