Nucleolar Localization of the RNA Helicase DDX21 Predicts Survival Outcomes in Gynecologic Cancers.

Cancer cells with DNA repair defects (e.g., BRCA1/2 mutant cells) are vulnerable to PARP inhibitors (PARPi) due to induction of synthetic lethality. However, recent clinical evidence has shown that PARPi can prevent the growth of some cancers irrespective of their BRCA1/2 status, suggesting alternative mechanisms of action. We previously discovered one such mechanism in breast cancer involving DDX21, an RNA helicase that localizes to the nucleoli of cells and is a target of PARP1. We have now extended this observation in endometrial and ovarian cancers and provided links to patient outcomes. When PARP1-mediated ADPRylation of DDX21 is inhibited by niraparib, DDX21 is mislocalized to the nucleoplasm resulting in decreased rDNA transcription, which leads to a reduction in ribosome biogenesis, protein translation, and ultimately endometrial and ovarian cancer cell growth. High PARP1 expression was associated with high nucleolar localization of DDX21 in both cancers. High nucleolar DDX21 negatively correlated with calculated IC50s for niraparib. By studying endometrial cancer patient samples, we were able to show that high DDX21 nucleolar localization was significantly associated with decreased survival. Our study suggests that the use of PARPi as a cancer therapeutic can be expanded to further types of cancers and that DDX21 localization can potentially be used as a prognostic factor and as a biomarker for response to PARPi. SIGNIFICANCE: Currently, there are no reliable biomarkers for response to PARPi outside of homologous recombination deficiency. Herein we present a unique potential biomarker, with clear functional understanding of the molecular mechanism by which DDX21 nucleolar localization can predict response to PARPi.

Contemporary outcomes of surgical aortic valve replacement in patients referred for a transcatheter approach.

OBJECTIVES: The purpose of this study is to examine which patients referred to our structural valve clinic for potential transcatheter aortic valve replacement (TAVR) are receiving surgical aortic valve replacement (SAVR) whether due to unsuitable anatomy for TAVR versus other reasons. METHODS: Individuals referred for TAVR from January 2019 to March 2022, who ultimately underwent SAVR were examined, retrospectively. Patients were divided into 2 surgical groups: TAVR was technically unsuitable (SAVR-TU) and those in which TAVR was technically feasible (SAVR-TF). RESULTS: 215 patients referred for TAVR underwent SAVR with 61 (28.4%) patients in the SAVR-TU group and 154 (71.6%) in the SAVR-TF group. The SAVR-TU group were more commonly female (52.5% vs 23.4%, p < 0.0001), had a higher incidence of stroke at baseline (9.8% vs 2.0%, p = 0.017) were frailer (5-m gait 5.2 s vs 4.7 s, p = 0.0035), and had a higher Society of Thoracic Surgery risk score (2.2 vs 1.7, p = 0.04). In the SAVR-TU group, unsuitability for TAVR was due to inadequate aortic root anatomy (86.9%), and poor peripheral access (6.6%). In the SAVR-TF group, the most common reasons for SAVR referral were concomitant coronary artery disease (42.9%), bicuspid aortic valve disease (16.9%), and concomitant aortic aneurysm (10.4%). Overall, in-hospital mortality was 1.4% with no difference between both groups. One-year survival was 96.7%. CONCLUSION: Despite a higher trend of aortic stenosis being treated with TAVR, higher risk patients unsuitable for TAVR can have SAVR with excellent outcomes. Moreover, patients with AS and concomitant other pathology should be evaluated for cardiac surgery.

Neoadjuvant Chemotherapy and Radiation Improves Recurrence-free and Overall Survival in Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: The objective of this study is to analyze the outcomes of patients with resectable/borderline resectable PDAC who receive total neoadjuvant therapy vs upfront surgery. METHODS AND ANALYSIS: Patients who were treated at a single institution from 2006 to 2021 were included. The primary outcome was overall survival (OS). Secondary outcomes included disease free survival (DFS), rates of lymph node positivity, and R0 resection. All survival analyses were performed with intention-to-treat. RESULTS: 26 patients received neoadjuvant chemotherapy and radiation (TNT), 28 received neoadjuvant chemotherapy only (NAC), and 168 received upfront surgery. Demographics were comparable across all three groups. Patients who received TNT or NAC had longer OS and DFS compared to the surgery first patients (P < .01). Patients who received TNT had a lymph node positivity rate of 0% at time of surgery compared to 5.3% and 13.3% in the NAC and surgery-first groups, respectively (P < .01). The rate of R0 resection did not differ between groups (P = .17). CONCLUSION: Patients with resectable/borderline resectable PDAC who receive neoadjuvant therapy have longer OS and RFS relative to those who receive upfront surgery.

Social histories of public health misinformation and infodemics: case studies of four pandemics.

Recognition of misinformation as a public health threat and interest in infodemics, defined as an inundation of information accompanying an epidemic or acute health event, have increased worldwide. However, scientists have no consensus on how to best define and identify misinformation and other essential characteristics of infodemics. We conducted a narrative review of secondary historical sources to examine previous infodemics in relation to four infectious diseases associated with pandemics (ie, smallpox, cholera, 1918 influenza, and HIV) and challenge the assumption that misinformation is a new phenomenon associated with increased use of social media or with the COVID-19 pandemic. On the contrary, we found that the spread of health misinformation has always been a public health challenge that has necessitated innovative solutions from medical and public health communities. We suggest expanding beyond the narrow scope of addressing misinformation to manage information ecosystems, defined as how people consume, produce, interact with, and behave around information, which include factors such as trust, stigma, and scientific literacy. Although misinformation can spread on a global scale, this holistic approach advocates for community-level interventions that improve relationships and trust between medical or public health entities and local populations.

Comparison of Low Dose Recombinant Factor VIIa and 4-Factor Prothrombin Complex Concentrate for Treatment of Bleeding Related to Cardiac Surgery.

Background: Recombinant factor VIIa (rFVIIa) and prothrombin concentrate complex (PCC) are used for uncontrolled bleeding in cardiac surgery (CS), however, there are limited direct comparisons of these agents. Objective: To evaluate the efficacy and safety of rFVIIa and PCC in CS related bleeding. Methods: This retrospective study included adult CS patients who received either low dose rFVIIa (<30 mcg/kg) or 4-factor PCC. The primary outcome was transfusion requirements of packed red blood cells (pRBC) within 6 hours of factor administration. Secondary efficacy outcomes included transfusion requirements 0-18 hours, doses of additional factor product, thrombotic events, and acute kidney injury (AKI). Results: A total of 179 patients were included (n = 78 rFVIIa; n = 101 PCC). Of patients who received blood products, there was no difference in the requirement of pRBCs within 6 hours (73.8 vs 68.9%, P = .5359) or in the median amount of pRBC transfused (500 mL vs 640 mL, P = .0723) in the rFVIIa and PCC groups respectively. Patients in the PCC group were more likely to require additional factor products (24.4% vs 47.5%, P = .0015), develop AKI (12.8% vs 25.7%, P = .0325), have longer ICU lengths of stay [2 (IQR 1-5) vs 4 (IQR 2-6), P = .0487] and greater in-hospital mortality (2.6% vs 10.9%, P = .033). There was no difference in thrombotic events. Conclusion: Although, there was no difference in pRBC transfusion requirements between PCC and rFVIIa, more patients in the PCC group required additional factor products and had increased adverse effects. Further comparisons of PCC and rFVIIa are warranted.

Low-Dose Rivaroxaban as Extended Prophylaxis Reduces Postdischarge Venous Thromboembolism in Patients With Malignancy and IBD.

BACKGROUND: Despite guidelines suggesting the use of extended prophylaxis for prevention of venous thromboembolism in patients with colorectal cancer and perhaps IBD, routine use is low and scant data exist regarding oral forms of therapy. OBJECTIVE: The purpose was to compare the incidence of postdischarge venous thromboembolism in patients given extended prophylaxis with low-dose rivaroxaban. DESIGN: We used propensity matching to compare pre- and postintervention analyses from a 2-year period before instituting extended prophylaxis. SETTING: All colorectal patients at a single institution were prospectively considered for extended prophylaxis. PATIENTS: Patients with a diagnosis of IBD or colorectal cancer who underwent operative resection were included. INTERVENTIONS: Those considered for extended prophylaxis were prescribed 10 mg of rivaroxaban for 30 days postsurgery. MAIN OUTCOME MEASURES: The primary outcome was venous thromboembolism incidence 30 days postdischarge. The secondary outcome was bleeding rates, major or minor. RESULTS: Of the 498 patients considered for extended prophylaxis, 363 were discharged with rivaroxaban, 81 on baseline anticoagulation, and 54 without anticoagulation. Propensity-matched cohorts based on stoma creation, operative approach, procedure type, and BMI were made to 174 historical controls. After excluding cases of inpatient venous thromboembolism, postoperative rates were lower in the prospective cohort (4.8% vs 0.6%, p = 0.019). In the prospective group, 36 episodes of bleeding occurred, 26 (7.2%) were discharged with rivaroxaban, 8 (9.9%) discharged on other anticoagulants, and 2 (3.7%) with no postoperative anticoagulation. Cases of major bleeding were 1.1% (4/363) in the rivaroxaban group, and each required intervention. LIMITATIONS: The study was limited to a single institution and did not include a placebo arm. CONCLUSIONS: Among patients with IBD and colorectal cancer, extended prophylaxis with low-dose rivaroxaban led to a significant decrease in postdischarge thromboembolic events with a low bleeding risk profile. See Video Abstract . RIVAROXABN EN DOSIS BAJAS COMO PROFILAXIS PROLONGADA REDUCE LA TROMBOEMBOLIA VENOSA POSTERIOR AL ALTA, EN PACIENTES CON NEOPLASIAS MALIGNAS Y ENFERMEDAD INFLAMATORIA INTESTINAL: ANTECEDENTES:A pesar de las normas que sugieren el uso de profilaxis extendida para la prevención del tromboembolismo venoso en pacientes con cáncer colorrectal y tal vez enfermedad inflamatoria intestinal, el uso rutinario es bajo y existen escasos datos sobre las formas orales de terapia.OBJETIVO:Comparar la incidencia de tromboembolismo venoso posterior al alta, en pacientes que recibieron profilaxis prolongada con dosis bajas de rivaroxabán.DISEÑO:Utilizamos el emparejamiento de propensión para comparar un análisis previo y posterior a la intervención de un período de 2 años antes de instituir la profilaxis extendida.AJUSTE:Todos los pacientes colorrectales en una sola institución fueron considerados prospectivamente para profilaxis extendida.PACIENTES:Incluidos pacientes con diagnóstico de enfermedad inflamatoria intestinal o cáncer colorrectal sometidos a resección quirúrgica.INTERVENCIONES:A los considerados para profilaxis extendida se les prescribió 10 mg de rivaroxabán durante 30 días postoperatorios.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la incidencia de tromboembolismo venoso 30 días después del alta. El resultado secundario fueron las tasas de hemorragia, mayor o menor.RESULTADOS:De los 498 pacientes considerados para profilaxis extendida, 363 fueron dados de alta con rivaroxabán, 81 con anticoagulación inicial y 54 sin anticoagulación. Se realizaron cohortes emparejadas por propensión basadas en la creación de la estoma, abordaje quirúrgico, tipo de procedimiento y el índice de masa corporal en 174 controles históricos. Después de excluir los casos de tromboembolismo venoso hospitalizado, las tasas posoperatorias fueron más bajas en la cohorte prospectiva (4,8% frente a 0,6%, p = 0,019). En el grupo prospectivo ocurrieron 36 episodios de hemorragia, 26 (7,2%) fueron dados de alta con rivaroxaban, 8 (9,9%) fueron dados de alta con otros anticoagulantes y 2 (3,7%) sin anticoagulación posoperatoria. Los casos de hemorragia mayor fueron del 1,1% (4/363) en el grupo de rivaroxabán y cada uno requirió intervención.LIMITACIONES:Limitado a una sola institución y no incluyó un grupo de placebo.CONCLUSIONES:Entre los pacientes con enfermedad inflamatoria intestinal y cáncer colorrectal, la profilaxis extendida con dosis bajas de rivaroxabán condujo a una disminución significativa de los eventos tromboembólicos posteriores al alta, con un perfil de riesgo de hemorragia bajo. (Traducción-Dr. Fidel Ruiz Healy).

Clinical Predictors of Major Intrathoracic Injury in Pediatric Blunt Trauma.

OBJECTIVES: Blunt trauma in pediatric patients accounts for a significant proportion of pediatric death from traumatic injury. Currently, there are no clinical decision-making tools available to guide imaging choice in the evaluation of pediatric patients with blunt thoracic trauma (BTT). This study aimed to analyze the rates of missed major intrathoracic injuries on chest x-ray (CXR) and identify clinical risk factors associated with major intrathoracic injuries to formulate a clinical decision-making tool for computed tomography (CT) use in pediatric patients with BTT. METHODS: We performed a retrospective single-center study using an institutional trauma database of pediatric patients. Inclusion criteria included age, blunt trauma, and patients who received a CXR and thoracic CT within 24 hours of presentation. Thoracic CT findings were graded as major, minor, or none, and comparison CXR was used to determine the rate of missed thoracic injuries. Eighty-four patient variables were then collected, and clinically relevant variables associated with major intrathoracic injuries were placed in a logistic regression model to determine the best predictors of major injury in pediatric BTT patients. RESULTS: A total of 180 patients (48.3%) had CXR that missed an injury that was seen on thoracic CT. In our cohort, 20 patients (5.4%) had major injuries that were missed on CXR. Characteristics correlating with major thoracic injuries were older age (odds ratio [OR], 1.125; 95% confidence interval [CI], 1.015-1.247), chest pain (OR, 4.907; 95% CI, 2.173-11.083), abnormal chest auscultation (OR, 3.564; 95% CI, 1.406-9.035), and tachycardia (OR, 2.876; 95% CI, 1.256-6.586). Using these 4 variables, receiver operating characteristic analysis revealed an area under the curve of 0.7903. CONCLUSIONS: Pediatric BTT patients older than 15 years with tachycardia, chest pain, or abnormal chest auscultation are at increased risk for major intrathoracic injuries and may benefit from thoracic CT.

Vulvar cancer management and wrangling recurrent disease: A report from the society of gynecologic oncology journal club.

The Society of Gynecologic Oncology (SGO) Journal Club webinar series is an open forum that invites national experts to discuss the literature pertaining to important topics in the management of gynecologic cancers. On August 14th, 2023, SGO hosted a journal club focused on the management of upfront and recurrent vulvar cancer. Our discussants included Dr. Brian M Slomovitz from Mount Sinai Medical Center in Miami Beach, Dr. Emi Yoshida from the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, and Dr. Lilian Gien from the University of Toronto Sunnybrook Odette Cancer Center. During the discussion,we reviewed the progression of vulvar cancer surgery from en bloc resection of the vulva and groins, to partial radical vulvectomy and sentinel lymph nodes. We also reviewed the management of node positive vulvar cancer including published and accruing Groningen International Study on Sentinel Nodes in Vulvar Cancer (GROINSS) trials and other sentinel trials from the Gynecologic Oncology Group (GOG). Here we will also review the literature on the management of recurrent vulvar cancer, highlighting current treatment options and ongoing clinical trials. The following is a report of the journal club presentation.

ChatGPT for Automated Writing Evaluation in Scholarly Writing Instruction.

BACKGROUND: Effective strategies for developing scholarly writing skills in postsecondary nursing students are needed. Generative artificial intelligence (GAI) tools, such as ChatGPT, for automated writing evaluation (AWE) hold promise for mitigating challenges associated with scholarly writing instruction in nursing education. This article explores the suitability of ChatGPT for AWE in writing instruction. METHOD: ChatGPT feedback on 42 nursing student texts from the Michigan Corpus of Upper-Level Student Papers was assessed. Assessment criteria were derived from recent AWE research. RESULTS: ChatGPT demonstrated utility as an AWE tool. Its scoring performance demonstrated stricter grading than human raters, related feedback to macro-level writing features, and supported multiple submissions and learner autonomy. CONCLUSION: Despite concerns surrounding GAI in academia, educators can accelerate the feedback process without increasing their workload, and students can receive individualized feedback by incorporating AWE provided by ChatGPT into the writing process. [J Nurs Educ. 2023;62(12):721-727.].

Does Hispanic ethnicity play a role in outcomes for diverticular surgery in the USA?

OBJECTIVE: The aim of this study is to investigate whether origins of ethnicity affect the outcomes of surgery for diverticulitis in the USA. DESIGN: The American College of Surgeons National Surgical Quality Improvement Programme database from 2008 to 2017 was used to identify patients undergoing colectomy for diverticulitis. Patient demographics, comorbidities, procedural details and outcomes were captured and compared by ethnicity status. RESULTS: A total of 375 311 surgeries for diverticulitis were included in the final analysis. The average age of patients undergoing surgery for diverticulitis remained consistent over the time frame of the study (62 years), although the percentage of younger patients (age 18-39 years) rose slightly from 7.8% in 2008 to 8.6% in 2017. The percentage of surgical patients with Hispanic ethnicity increased from 3.7% in 2008 to 6.6% of patients in 2017. Hispanic patients were younger than their non-Hispanic counterparts (57 years vs 62 years, p<0.01) at time of surgery. There were statistically significant differences in the proportion of laparoscopic cases (51% vs 49%, p<0.01), elective cases (62% vs 66%, p<0.01) and the unadjusted rate of postoperative mortality (2.8% vs 3.4%, p<0.01) between Hispanic patients compared with non-Hispanic patients, respectively. Multivariable logistic regression models did not identify Hispanic ethnicity as a significant predictor for increased morbidity (p=0.13) or mortality (p=0.80). CONCLUSION: Despite a significant younger population undergoing surgery for diverticulitis, Hispanic ethnicity was not associated with increased rates of emergent surgery, open surgery or postoperative complications compared with a similar non-Hispanic population.

Incidence and clinical relevance of paraneoplastic syndromes in patients with renal cell carcinoma.

BACKGROUND: Paraneoplastic syndromes (PNS) are defined as the signs and symptoms attributed to cytokines or hormones released from a tumor or a patient's immune system. PNS have been reported with many cancers for decades and data supporting their relevance in renal cell carcinoma (RCC) are largely historical. The widespread use of electronic medical record (EMR) systems provides a more robust method to capture data. The objective of this study was to establish contemporary data regarding the incidence and relevance of PNS in patients undergoing nephrectomy for suspected RCC. METHODS: In this retrospective single-institution study, 851 patients undergoing nephrectomy for suspected RCC between 2011 and 2018 were assessed for the presence or absence of PNS as defined by laboratory abnormalities. Factors associated with PNS and with all-cause mortality were examined. RESULTS: The incidence of PNS was 33.1% among 851 patients prior to nephrectomy. The most prevalent PNS were anemia (22.4%), thrombocytosis (7.5%), and elevated C-reactive protein (CRP) (7.4%). PNS were more common in women (39.2% vs. 29.4%, p = 0.0032) and higher stage RCC (31.1% of stage I vs. 54.2% of stage IV, p = 0.0036). Factors associated with the presence of PNS in multivariable analysis included female gender, high comorbidity, and stage IV RCC. Prenephrectomy PNS were associated with poorer survival in multivariable analysis (HR: 2.12, p = 0.0002). Resolution of PNS occurred in 52.1% of patients after nephrectomy, including 55.2% with stage I to III and 38.5% with stage IV RCC (p = 0.10). CONCLUSIONS: Using EMR data, laboratory evidence of PNS was present in one-third of a contemporary cohort of patients undergoing nephrectomy, with >50% of PNS resolving after surgery. Consistent with prior reports, PNS are more common in higher-stage RCC and are associated with poorer survival in RCC patients.

The role of color in transsaccadic object correspondence.

With each saccade, visual information is disrupted, and the visual system is tasked with establishing object correspondence between the presaccadic and postsaccadic representations of the saccade target. There is substantial evidence that the visual system consults spatiotemporal continuity when determining object correspondence across saccades. The evidence for surface feature continuity, however, is mixed. Surface features that are integral to the saccade target object's identity (e.g., shape and contrast polarity) are informative of object continuity, but features that may only imply the state of the object (e.g., orientation) are ignored. The present study tested whether color information is consulted to determine transsaccadic object continuity. We used two variations of the intrasaccadic target displacement task. In Experiments 1 and 2, participants reported the direction of the target displacement. In Experiments 3 and 4, they instead reported whether they detected any target movement. In all experiments, we manipulated the saccade target's continuity by removing it briefly (i.e., blanking) and by changing its color. We found that large color changes can disrupt stability and increase sensitivity to displacements for both direction and movement reports, although not as strongly as long blank durations (250 ms). Interestingly, even smaller color changes, but not blanking, reduced response biases. These results indicate that disrupting surface feature continuity may impact the process of transsaccadic object correspondence more strongly than spatiotemporal disruptions by both increasing the sensitivity and decreasing the response bias.

Daily Nutritional Intake of Pediatric Patients (N = 64) on Extracorporeal Membrane Oxygenation from 2018 to 2022: A Single-Center Report.

Nutrition in pediatric populations who require life-saving extracorporeal membrane oxygenation (ECMO) remains a debate. We sought to identify if nutritional needs were met in a patient cohort. A retrospective chart review of patients (N = 64) requiring ECMO at Helen DeVos Children's Hospital between 2018 and 2022 was evaluated for demographics, daily nutritional data, laboratory values, ECMO complications, and outcome data, with primary outcome measures of percent protein and percent caloric intake. Secondary outcome measures included the intensive care unit length of stay, time on ECMO, mortality, and day 1 severity of illness scores (Pediatric Logistic Organ Dysfunction). The timeline partially overlapped with the COVID-19 pandemic. Data were collected for 467 ECMO days with a median age of 2.6 months; 57.8% of patients were male and 65.6% were with one pre-existing comorbidity. Venoarterial (VA) ECMO was utilized in 84.4% of patients; the ECMO indication was cardiac in 53.1% of patients. The 28-day mortality was 43.8%. The proportion of days in which the caloric goal was met was 0%; the proportion of days in which protein goals were met was 33.3%. Non-cardiac ECMO patients had a greater number of days where caloric goals were met (p-value = 0.04). Mortality at 28 days was not statistically significant (p-value = 0.28) for calories or protein administered. The patient cohort struggled to meet calorie and protein goals while on ECMO.

Targeting N-cadherin (CDH2) and the malignant bone marrow microenvironment in acute leukaemia.

This review discusses current research on acute paediatric leukaemia, the leukaemic bone marrow (BM) microenvironment and recently discovered therapeutic opportunities to target leukaemia-niche interactions. The tumour microenvironment plays an integral role in conferring treatment resistance to leukaemia cells, this poses as a key clinical challenge that hinders management of this disease. Here we focus on the role of the cell adhesion molecule N-cadherin (CDH2) within the malignant BM microenvironment and associated signalling pathways that may bear promise as therapeutic targets. Additionally, we discuss microenvironment-driven treatment resistance and relapse, and elaborate the role of CDH2-mediated cancer cell protection from chemotherapy. Finally, we review emerging therapeutic approaches that directly target CDH2-mediated adhesive interactions between the BM cells and leukaemia cells.

Correction of Breast Ptosis in Immediate Breast Reconstruction.

Nipple-sparing mastectomy is psychologically advantageous and can result in superior cosmetic outcomes. However, nipple position adjustment is challenging, and ischemic complications may arise. For patients who require timely mastectomies and reconstructions, concurrent mastopexy may prevent nipple malposition and reduce the risk for future corrections. Methods: A retrospective chart review of all patients undergoing immediate prosthetic reconstruction after nipple-sparing mastectomy were analyzed. Data regarding patient characteristics; surgical indications; reconstructive modality, including presence or absence of simultaneous nipple lift; and early and late complications were examined. Results: In total, 142 patients underwent 228 nipple-sparing mastectomies and prosthetic reconstructions. Correction of ptosis (lift) was performed in 22 patients and 34 breasts. The remaining 122 patients and 194 breasts did not receive mastopexy (no-lift). Two patients received bilateral reconstructions involving both lift and no-lift. Comparing the lift and no-lift cohorts demonstrated no differences in major complications (47.1% versus 57.7%; P = 0.25) and minor complications (76.5% versus 74.7%; P = 0.83). Control for plane of implant placement also did not show differences in major (P = 0.31) or minor (P = 0.97) complications. Similarly, control of application of acellular dermal matrix found major (P = 0.25) and minor (P = 0.83) complications uniform and not affected by lift status. Nipple lift distance was not associated with increased major (P = 0.10) complications. Conclusion: Simultaneous correction of nipple position in immediate prosthetic breast reconstruction seem safe with uniform complications rates that are unaffected by acellular dermal matrix use or plane of implant placement.

Outcomes of simultaneous versus staged intramedullary nailing fixation of multiple long bone lower extremity fractures.

INTRODUCTION: Repair of multiple lower extremity long bone fractures with intramedullary nail (IMN) fixation is associated with significant cardiopulmonary burden and may result in mortality. These patients are at an increased risk for fat embolism syndrome, pulmonary embolism, Acute Respiratory Distress Syndrome (ARDS), and pneumonia. No standardized guidelines exist to guide treatment of these patients. Further, there is a paucity of data regarding the risk of simultaneous versus staged fixation of multiple long bone fractures that includes both tibial and femoral injuries, as patients with multiple concomitant fractures are often excluded from relevant analyses. Our level one trauma center aimed to identify whether simultaneous fixation, defined by definitive fixation of multiple lower extremity long bone fractures during one operative event, led to increased cardiopulmonary complications as compared to a staged approach, defined as multiple operations to reach definitive fixation. PATIENTS AND METHODS: The Michigan Trauma Quality Improvement Program (MTQIP) database from 35 Level I and II trauma centers was queried to identify patients from January 2016 - December 2019. The primary outcome was incidence of cardiopulmonary complications for staged and simultaneous IMN fixation. RESULTS: We identified 11,427 patients with tibial and/or femoral fractures during the study period. 146 patients met the inclusion criteria of two or more fractures treated with IMN fixation. 118 patients underwent simultaneous IMN fixation, and 28 patients received staged IMN fixation. There were no significant differences in injury severity score (ISS), demographics, pre-existing conditions, and cardiopulmonary complications between the two groups. There was a statistically significant difference in hospital length of stay (LOS) (p = 0.0012). The median hospital LOS for simultaneous fixation was 8.3 days versus 15.8 days for the staged cohort, a difference of 7.5 days. CONCLUSION: This is the largest retrospective study to date examining simultaneous versus staged IMN fixation in patients with multiple long bone lower extremity fractures. In contrast to previous studies, we found no difference in cardiopulmonary complications. Given these findings, patients with multiple long bone lower extremity fractures should be considered for simultaneous IMN, an approach which may decrease hospital LOS.

Next generation organoid engineering to replace animals in cancer drug testing.

Cancer therapies have several clinical challenges associated with them, namely treatment toxicity, treatment resistance and relapse. Due to factors ranging from patient profiles to the tumour microenvironment (TME), there are several hurdles to overcome in developing effective treatments that have low toxicity that can mitigate emergence of resistance and occurrence of relapse. De novo cancer development has the highest drug attrition rates with only 1 in 10,000 preclinical candidates reaching the market. To alleviate this high attrition rate, more mimetic and sustainable preclinical models that can capture the disease biology as in the patient, are required. Organoids and next generation 3D tissue engineering is an emerging area that aims to address this problem. Advancement of three-dimensional (3D) in vitro cultures into complex organoid models incorporating multiple cell types alongside acellular aspects of tissue microenvironments can provide a system for therapeutic testing. Development of microfluidic technologies have furthermore increased the biomimetic nature of these models. Additionally, 3D bio-printing facilitates generation of tractable ex vivo models in a controlled, scalable and reproducible manner. In this review we highlight some of the traditional preclinical models used in cancer drug testing and debate how next generation organoids are being used to replace not only animal models, but also some of the more elementary in vitro approaches, such as cell lines. Examples of applications of the various models will be appraised alongside the future challenges that still need to be overcome.

Preoperative Immuno-Nutrition and Complications After Colorectal Surgery: Results of a 2-Year Prospective Study.

INTRODUCTION: Preoperative immuno-nutrition has been associated with reductions in infectious complications and length of stay, but remains unstudied in the setting of an enhanced recovery protocol. The objective was to evaluate outcomes after elective colorectal surgery with the addition of a preoperative immuno-nutrition supplement. METHODS: In October 2017, all major colorectal surgeries were given an arginine-based supplement prior to surgery. The control group consisted of cases within the same enhanced recovery protocol from three years prior. The primary outcome was a composite of overall morbidity. Secondary outcomes were infectious complications and length of stay with subgroup analysis based on degrees of malnutrition. RESULTS: Of 826 patients, 514 were given immuno-nutrition prospectively and no differences in complication rates (21.5% versus 23.9%, P = 0.416) or surgical site infections (SSIs) (6.4% versus 6.9%, P = 0.801) were observed. Hospitalization was slightly shorter in the immuno-nutrition cohort (5.0 [3.0, 7.0], versus 5.5 days [3.6, 7.9], P = 0.002). There was a clinically insignificant difference in prognostic nutrition index scores between cohorts (35.2 ± 5.6 versus 36.1 ± 5.0, P = 0.021); however, subgroup analysis (< 33, 34-38 and > 38) failed to demonstrate an association with complications (P = 0.275) or SSIs (P = 0.640) and immuno-nutrition use. CONCLUSIONS: Complication rates and SSIs were unchanged with the addition of immuno-nutrition before elective colorectal surgery. The association with length of stay is small and without clinical significance; therefore, the routine use of immuno-nutrition in this setting is of questionable benefit.

Long-term durability of self-expanding and balloon-expandable transcatheter aortic valve prostheses: UK TAVI registry.

BACKGROUND: With expansion of transcatheter aortic valve implantation (TAVI) into younger patients, valve durability is critically important. AIMS: We aimed to evaluate long-term valve function and incidence of severe structural valve deterioration (SVD) among patients ≥ 10-years post-TAVI and with echocardiographic follow-up at least 5-years postprocedure. METHODS: Data on patients who underwent TAVI from 2007 to 2011 were obtained from the UK TAVI registry. Patients with paired echocardiograms postprocedure and ≥5-years post-TAVI were included. Severe SVD was determined according to European task force guidelines. RESULTS: 221 patients (79.4 ± 7.3 years; 53% male) were included with median echocardiographic follow-up 7.0 years (range 5-13 years). Follow-up exceeded 10 years in 43 patients (19.5%). Valve types were the supra-annular self-expanding CoreValve (SEV; n = 143, 67%), balloon-expandable SAPIEN/XT (BEV; n = 67, 31%), Portico (n = 4, 5%) and unknown (n = 7, 3%). There was no difference between postprocedure and follow-up peak gradient in the overall cohort (19.3 vs. 18.4 mmHg; p = NS) or in those with ≥10-years follow-up (21.1 vs. 21.1 mmHg; p = NS). Severe SVD occurred in 13 patients (5.9%; median 7.8-years post-TAVI). Three cases (23.1%) were due to regurgitation and 10 (76.9%) to stenosis. Valve-related reintervention/death occurred in 5 patients (2.3%). Severe SVD was more frequent with BEV than SEV (11.9% vs. 3.5%; p = 0.02), driven by a difference in patients treated with small valves (BEV 28.6% vs. SEV 3.0%; p < 0.01). CONCLUSIONS: Hemodynamic function of transcatheter heart valves remains stable up to more than 10 years post-TAVI. Severe SVD occurred in 5.9%, and valve-related death/reintervention in 2.3%. Severe SVD was more common with BEV than SEV.

Randomized Feasibility Trial of Prophylactic Radiofrequency Ablation to Prevent Atrial Fibrillation after Cardiac Surgery.

OBJECTIVE: Evaluate the feasibility of prophylactic radiofrequency isolation of the pulmonary veins, with left atrial appendage amputation, to reduce the incidence of postoperative atrial fibrillation (POAF) after cardiac surgery in patients aged 70 and older. METHODS: The Federal Food and Drug Administration granted an investigational device exemption to utilize a bipolar radiofrequency clamp for prophylactic pulmonary vein isolation in a limited, feasibility trial. Sixty-two patients without prior dysrhythmias, were prospectively randomized to undergo either their index cardiac surgical procedure, or bilateral pulmonary vein isolation and left atrial appendage amputation during their cardiac operation. The primary outcome was occurrence of in-hospital POAF. Subjects were on 24-hour telemetry until discharge. Dysrhythmias, any episode of atrial fibrillation > 30 seconds, were confirmed by electrophysiologists blinded to the study. RESULTS: Sixty patients, mean age 75 years and mean CHA2DS2-VASc score 4, were analyzed. Thirty-one patients randomized to control and twenty-nine to the treatment group. Majority of cases in each group were isolated CABG. No perioperative complications related to the treatment procedure, need for permanent pacemaker, or mortality occurred. The in-hospital incidence of POAF was 55% (17/31) in the control group and 7% (2/29) in the treatment group. (p<0.001) The control group had a significantly higher requirement for antiarrhythmic medications at discharge, 45% (14/31) vs 7% (2/29) in the treatment group (p<0.001). CONCLUSIONS: Prophylactic radiofrequency isolation of the pulmonary veins with left atrial appendage amputation, during the primary cardiac surgical operation, reduced the incidence of POAF in patients 70 years and older with no history of atrial arrhythmias.