The Effect of the Adoption of the National Accreditation Program for Rectal Cancer Process on Compliance Standards at a Single Institution.

Background: The National Accreditation Program for Rectal Cancer (NAPRC) was developed to enhance the quality of rectal cancer care in the United States. This project compared NAPRC compliance at a single tertiary care academic hospital before and after the institution adopted these standards in 2019. Methods: Rectal cancer patients from 2016 to 2023 who met NAPRC eligibility criteria were retrospectively reviewed for compliance with pre-selected patient care standards. Patients diagnosed prior to August 1, 2019 (pre-NAPRC) were compared with those diagnosed afterward (post-NAPRC) to determine whether compliance with these standards differed following the institution's adoption of new guidelines. Results: This study included 353 patients, 146 pre-NAPRC and 207 post-NAPRC. The post-NAPRC group demonstrated significantly higher compliance with pretreatment standards compared to the pre-NAPRC group, including attaining magnetic resonance imaging (MRI) (P = .015), computed tomography (CT) (P < .001), and a carcinoembryonic antigen (CEA) level (P < .001). Postoperative standards were more frequently met in the post-NAPRC group regarding the photographing of surgical specimens (P < .001). No significant differences were observed in confirming a tissue diagnosis, starting treatment within a 60-day timeframe, or completing surgical pathology reports. Prior to initiation of the NAPRC process, the institution had achieved accreditation-level compliance in 2 of the 7 standards. Within 2 years of adopting NAPRC standards, complete compliance was met in 6 of the 7 measures. Conclusions: A single institution's adoption of NAPRC standards improved compliance with multiple rectal cancer care standards, achieving near-complete accreditation level compliance within 2 years.

Fueling the heartbeat: Dynamic regulation of intracellular ATP during excitation-contraction coupling in ventricular myocytes.

The heart beats approximately 100,000 times per day in humans, imposing substantial energetic demands on cardiac muscle. Adenosine triphosphate (ATP) is an essential energy source for normal function of cardiac muscle during each beat, as it powers ion transport, intracellular Ca2+ handling, and actin-myosin cross-bridge cycling. Despite this, the impact of excitation-contraction coupling on the intracellular ATP concentration ([ATP]i) in myocytes is poorly understood. Here, we conducted real-time measurements of [ATP]i in ventricular myocytes using a genetically encoded ATP fluorescent reporter. Our data reveal rapid beat-to-beat variations in [ATP]i. Notably, diastolic [ATP]i was <1 mM, which is eightfold to 10-fold lower than previously estimated. Accordingly, ATP-sensitive K+ (KATP) channels were active at physiological [ATP]i. Cells exhibited two distinct types of ATP fluctuations during an action potential: net increases (Mode 1) or decreases (Mode 2) in [ATP]i. Mode 1 [ATP]i increases necessitated Ca2+ entry and release from the sarcoplasmic reticulum (SR) and were associated with increases in mitochondrial Ca2+. By contrast, decreases in mitochondrial Ca2+ accompanied Mode 2 [ATP]i decreases. Down-regulation of the protein mitofusin 2 reduced the magnitude of [ATP]i fluctuations, indicating that SR-mitochondrial coupling plays a crucial role in the dynamic control of ATP levels. Activation of ß-adrenergic receptors decreased [ATP]i, underscoring the energetic impact of this signaling pathway. Finally, our work suggests that cross-bridge cycling is the largest consumer of ATP in a ventricular myocyte during an action potential. These findings provide insights into the energetic demands of EC coupling and highlight the dynamic nature of ATP concentrations in cardiac muscle.

Retrospective evaluation of the effects of a single intraoperative dose of dexamethasone in horses undergoing exploratory laparotomy for small intestinal lesions (2008-2019): 240 cases.

OBJECTIVE: To determine the effect of a single intraoperative dose of dexamethasone on the risk of postoperative reflux (POR) in horses undergoing small intestinal surgery and to investigate its association with incisional complications and short-term survival. DESIGN: Retrospective cohort study over an 11-year period (2008-2019). SETTING: UK-based private referral center. ANIMALS: Two hundred and forty client-owned horses >6 months of age undergoing exploratory laparotomy for treatment of a small intestinal lesion. INTERVENTIONS: Ninety-seven horses received a single intraoperative dose of dexamethasone (0.1 mg/kg, IV). MEASUREMENTS AND MAIN RESULTS: Of 97 horses that received dexamethasone, 52 (53.6%) required small intestinal resection. Of 143 horses that did not receive dexamethasone, small intestinal resection was performed in 78 (54.5%). A total of 70 horses (29%) developed POR. There was no difference in the risk of POR between horses that received dexamethasone (25/97; 26%) and those that did not (45/143; 31%, P = 0.34). Risk factors associated with the development of POR included small intestinal resection (odds ratio [OR]: 4.55, 95% confidence interval [CI]: 2.27-9.11, P < 0.001), a PCV >40% 24 hours postoperatively (OR: 4.11, 95% CI: 2-8.45, P < 0.001), and a WBC count >10 × 109/L on admission (OR: 3.29, 95% CI: 1.47-7.41, P = 0.004). Dexamethasone was not associated with the odds of POR. Horses undergoing repeat laparotomy had a higher risk of incisional infection (OR: 8.07, 95% CI: 1.98-32.81, P = 0.004). Dexamethasone administration was not associated with incisional infection. The development of POR was negatively associated with short-term survival (OR: 0.07, 95% CI: 0.03-0.17, P ≤ 0.001). Dexamethasone administration was not retained in the final multivariable model for survival. CONCLUSIONS: Intraoperative dexamethasone was not associated with the development of POR in this study population, nor did it have an effect on postoperative survival or incisional infection in horses undergoing surgical management of small intestinal disease.

BIN1 knockdown rescues systolic dysfunction in aging male mouse hearts.

Cardiac dysfunction is a hallmark of aging in humans and mice. Here we report that a two-week treatment to restore youthful Bridging Integrator 1 (BIN1) levels in the hearts of 24-month-old mice rejuvenates cardiac function and substantially reverses the aging phenotype. Our data indicate that age-associated overexpression of BIN1 occurs alongside dysregulated endosomal recycling and disrupted trafficking of cardiac CaV1.2 and type 2 ryanodine receptors. These deficiencies affect channel function at rest and their upregulation during acute stress. In vivo echocardiography reveals reduced systolic function in old mice. BIN1 knockdown using an adeno-associated virus serotype 9 packaged shRNA-mBIN1 restores the nanoscale distribution and clustering plasticity of ryanodine receptors and recovers Ca2+ transient amplitudes and cardiac systolic function toward youthful levels. Enhanced systolic function correlates with increased phosphorylation of the myofilament protein cardiac myosin binding protein-C. These results reveal BIN1 knockdown as a novel therapeutic strategy to rejuvenate the aging myocardium.

Sleeve Gastrectomy Reduces the Need for Liver Transplantation in Patients with Obesity and Non-Alcoholic Steatohepatitis: a Predictive Model.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is one of the leading indications for liver transplantation (LT) in the United States. As with the current obesity epidemic, the incidence of NASH continues to rise. However, the impact of broad utilization of bariatric surgery (BS) for patients with NASH is unknown, particularly in regard to mitigating the need for LT. METHODS: Markov decision analysis was performed to simulate the lives of 20,000 patients with obesity and concomitant NASH who were deemed ineligible to be waitlisted for LT unless they achieved a body mass index (BMI) < 35 kg/m2. Life expectancy following medical weight management (MWM) and sleeve gastrectomy (SG) were estimated. Base case patients were defined as having NASH without fibrosis and a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. RESULTS: Simulated base case analysis patients who underwent SG gained 14.3 years of life compared to patients who underwent MWM. One year after weight loss intervention, 9% of simulated MWM patients required LT compared to only 5% of SG patients. Survival benefit for SG was observed above a BMI of 32.2 kg/m2. CONCLUSION: In this predictive model of 20,000 patients with obesity and concomitant NASH, surgical weight loss is associated with a reduction in the progression of NASH, thereby reducing the need for LT. A reduced BMI threshold of 32 kg/m2 for BS may offer survival benefit for patients with obesity and NASH.

2-Aminoethyl Dihydrogen Phosphate (2-AEH2P) Associated with Cell Metabolism-Modulating Drugs Presents a Synergistic and Pro-Apoptotic Effect in an In Vitro Model of the Ascitic Ehrlich Tumor.

The progression and maintenance of cancer characteristics are associated with cellular components linked to the tumor and non-cellular components with pro-tumoral properties. Pharmacological association with antagonists of the cellular components of the tumor, such as anti- and pro-apoptotic drugs, represents a novel adjuvant strategy. In this study, the antiproliferative, pro-apoptotic, and pharmacological effects of the combination of monophosphoester 2-AEH2P with Simvastatin, Coenzyme Q10, the chemotherapeutic drug paclitaxel, and colony-stimulating factor (GM-CSF) were evaluated. Tests were conducted to determine cytotoxic activity using the MTT method, cell cycle phases, and fragmented DNA by flow cytometry, mitochondrial membrane potential, expression of cell markers Bcl2, TNF-α/DR-4, Cytochrome c, caspase 3, and P53, and analysis of drug combination profiles using Synergy Finder 2.0 Software. The results showed a synergistic effect among the combinations, compared to individual treatments with the monophosphoester and other drugs. In addition, there was modulation of marker expression, indicating a pro-apoptotic and immunomodulatory effect of 2-AEH2P. Pharmacological analysis revealed that tumor cells treated with GM-CSF + 2-AEH2P exhibited a synergistic effect, while groups of tumor cells treated with paclitaxel, Coenzyme Q10, and Simvastatin showed additive effects. Furthermore, treatment with the paclitaxel + 2-AEH2P combination (12 h) resulted in a significant reduction in mitochondrial membrane potential. Pharmacological combinations for normal cells did not exhibit deleterious effects compared to mammary carcinomatosis tumor (EAT) cells.

Food Insecurity in the Elective Enhanced Recovery After Surgery Colorectal Surgical Population: Prevalence and Implications for Surgical Outcomes.

BACKGROUND: Food insecurity is defined as having limited or uncertain availability of nutritionally adequate food. Approximately 10.5% of U.S. households are food-insecure. Our study aimed to determine the prevalence and postoperative implications of food insecurity in a diverse group of colorectal surgery patients admitted to a hospital in an area with a higher-than-average median income. METHODS: The 6-question Household Food Security Survey was added to the colorectal surgery ERAS program preoperative paperwork. Patient demographics, comorbidities, operative parameters, length of stay, and postoperative outcomes were collected by review of electronic medical records. RESULTS: A total of 294 ERAS patients (88.8%) completed the survey over an 11-month period. Thirty-three patients (11.2%) were identified as food-insecure. Food-insecure patients were more likely to be non-white (P = .003), younger (P = .009), smokers (P = .004), chronic narcotic users (P < .001), unmarried (P = .007), and have more comorbidities (P = .004). The food-insecure population had more frequent postoperative ileus (P = .044). Hospital length of stay was significantly longer in food-insecure patients (8.6 days vs 5.4 days, P < .001). Food-insecure patients also had higher rates of >30-day mortality (P = .049). DISCUSSION: Food insecurity was found to occur in patients that lived in communities deemed both affluent and distressed. These patients had longer hospital stays and higher mortality. A food insecurity questionnaire can easily identify patients at risk. Further investigations to mitigate these complications are warranted.

Effort-related effects of chronic administration of the DA D2 receptor antagonist haloperidol via subcutaneous programmable minipumps: Reversal by co-administration of the adenosine A2A antagonist istradefylline.

RATIONALE: Long-acting antipsychotics such as haloperidol decanoate are becoming more commonly used. Long-acting depot formulations have several advantages, but secondary negative effects of prolonged delivery, including motivational dysfunctions, could have debilitating effects. Assessing the behavioral changes that emerge during chronic antipsychotic administration in rats could provide insight regarding the development of motivational dysfunctions and drug tolerance. OBJECTIVES: Acute administration of dopamine D2 antagonists such as haloperidol induce motivational deficits in rats, as marked by a shift towards a low-effort bias during effort-based choice tasks. In the present studies, programmable subcutaneous infusion pumps provided continuous and controlled drug delivery of haloperidol. Animals were assessed using a fixed ratio (FR) 5 lever pressing schedule and the FR5/chow feeding test of effort-based choice. The adenosine A2A antagonist istradefylline was studied for its ability to reverse the effects of chronic haloperidol. RESULTS: Continuous chronic infusions of haloperidol produced significant reductions in FR5 performance and a shift from lever pressing to chow intake in rats tested on FR5/chow feeding choice, with no evidence of tolerance over the 4-week infusion period. Behavior returned to baseline during the vehicle-infusion washout period. Istradefylline significantly reversed the effects of haloperidol, increasing lever pressing and decreasing chow intake in haloperidol-treated rats. CONCLUSIONS: These studies provide an important behavioral characterization of the effects of chronically infused haloperidol, and demonstrate that A2A antagonism reverses the effects of chronic haloperidol. This research could contribute to the understanding and treatment of motivational dysfunctions seen in schizophrenia, Parkinson's disease, and other disorders involving dopamine.

Effects of the atypical antipsychotic and D3/D2 dopamine partial agonist cariprazine on effort-based choice behavior: implications for modeling avolition.

RATIONALE: Cariprazine is an atypical antipsychotic that acts as a D3/D2 receptor partial agonist. In addition to treating positive symptoms of schizophrenia, cariprazine may have utility for treating negative symptoms. Rodent studies have focused on the effects of cariprazine on cognitive functions and behaviors thought to be related to anhedonia. Avolition, which is characterized by reduced initiation and persistence of goal-directed behavior, is another important negative symptom. OBJECTIVES: Effort-related choice tasks have been used as animal models of avolition. In these studies, cariprazine was assessed for its effects on effort-based choice in both rats and mice. Previous work has shown that D2 antagonists such as haloperidol and eticlopride produce a low-effort bias in rodents tested on effort-based choice tasks. RESULTS: Low doses of cariprazine produced a low-effort bias in rats tested on the fixed ratio 5/chow feeding choice task, decreasing lever pressing for high carbohydrate pellets but increasing chow intake. Cariprazine did not alter preference or intake of these foods in free-feeding tests. The effort-related effects of cariprazine were reversed by co-administration of the adenosine A2A antagonist istradefylline, and cariprazine failed to reverse the effort-related effects of the dopamine-depleting agent tetrabenazine. In mouse touchscreen choice tests, low doses of cariprazine also produced a low-effort bias, shifting behavior away from panel pressing. CONCLUSIONS: These results demonstrate that with these rodent models of avolition, cariprazine appears to act like a D2-family antagonist even at very low doses. Furthermore, the pharmacological regulation of avolition may differ from that of other negative symptoms.

Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model.

BACKGROUND: Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. In contrast, CAR-T cell efficacy against solid tumors has been difficult to achieve. METHODS: To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc. The efficacy of four Tn-dependent CARs with varying affinity to Tn antigen, and each containing CD28/CD3ζ cytoplasmic domains, were compared in vitro and in vivo in this study. RESULTS: In line with many observations about the impact of aberrant O-linked glycosylation, the ID8Cosmc knock-out (ID8Cosmc-KO) exhibited more rapid tumor progression compared with wild-type ID8. Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8Cosmc-KO tumors. Tumor regression could be achieved with a single intravenous dose of the CARs, but intraperitoneal administration was even more effective. The CAR-T cells persisted over a period of months, allowing CAR-treated mice to delay tumor growth in a re-challenge setting. The most effective CARs exhibited the highest affinity for antigen. Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10. CONCLUSION: The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. Importantly, the most potent Tn-dependent CAR-T cells showed no evidence of toxicity in tumor-bearing mice in a syngeneic, immunocompetent system.

Indications for a "Surgery-First" Approach for the Treatment of Lower Extremity Arterial Disease.

BACKGROUND: In recent years, there has been a tendency toward an "endovascular-first" approach for the treatment for femoropopliteal arterial disease. The purpose of this study is to determine if there are patients that are better served with an initial femoropopliteal bypass (FPB) rather than an endovascular attempt at revascularization. METHODS: A retrospective analysis of all patients undergoing FPB between June 2006 - December 2014 was performed. Our primary endpoint was primary graft patency, defined as patent using ultrasound or angiography without secondary intervention. Patients with <1-year follow-up were excluded. Univariate analysis of factors significant for 5-year patency was performed using χ2 tests for binary variables. A binary logistic regression analysis incorporating all factors identified as significant by univariate analysis was used to identify independent risk factors for 5-year patency. Event-free graft survival was evaluated using Kaplan-Meier models. RESULTS: We identified 241 patients undergoing FPB on 272 limbs. FPB indication was disabling claudication in 95 limbs, chronic limb-threatening ischemia (CLTI) in 148, and popliteal aneurysm in 29. In total, 134 FPB were saphenous vein grafts (SVG), 126 were prosthetic grafts, 8 were arm vein grafts, and 4 were cadaveric/xenografts. There were 97 bypasses with primary patency at 5 or more years of follow-up. Grafts patent at 5 years by Kaplan-Meier analysis were more likely to have been performed for claudication or popliteal aneurysm (63% 5-year patency) as compared with CLTI (38%, P < 0.001). Statistically significant predictors (using log rank test) of patency over time were use of SVG (P = 0.015), surgical indication of claudication or popliteal aneurysm (P < 0.001), Caucasian race (P = 0.019) and no history of COPD (P = 0.026). Multivariable regression analysis confirmed these 4 factors as significant independent predictors of 5-year patency. Of note, there was no statistical correlation between FPB configuration (above or below knee anastomosis, in-situ versus reversed saphenous vein) and 5-year patency. There were 40 FPBs in Caucasian patients without a history of COPD receiving SVG for claudication or popliteal aneurysm that had a 92% estimated 5-year patency by Kaplan-Meier survival analysis. CONCLUSIONS: Long-term primary patency that was substantial enough to consider open surgery as a first intervention was demonstrated in Caucasian patients without COPD, having good quality saphenous vein, and who underwent FPB for claudication or popliteal artery aneurysm.

Incidence of venous thromboembolism in patients with sickle cell disease undergoing noncardiovascular surgery.

OBJECTIVE: Patients with sickle cell disease (SCD) will have a baseline hypercoagulable state and an increased risk of venous thromboembolism (VTE). Few data are available regarding the efficacy of standard prophylaxis in preventing VTE after noncardiovascular surgery for patients with SCD. Our objective was to investigate the incidence of VTE in patients with SCD who had undergone noncardiovascular surgery. METHODS: We performed a retrospective medical record review of 352 patients with SCD who had undergone noncardiovascular surgery from August 2009 to August 2019 at Beaumont Hospitals. An equal number of control patients without SCD were propensity matched for age, sex, race, body mass index, and specific surgery. The data collected included demographics, comorbidities, VTE prophylaxis used, occurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE), hospital length of stay, and 30-day mortality. RESULTS: We found no differences in age, race, sex, ethnicity, operative time, or hospital length of stay between the SCD and propensity-matched control patients. DVT prophylaxis was used more frequently for the SCD patients than for the controls (96.0% vs 88.6%; P < .001). Four SCD patients (1.1%) had developed DVT vs five control patients (1.4%; P > .999). One patient in each group had developed PE (0.3%; P > .999). No difference was found in 30-day mortality between the SCD group and the control group (1 [0.3%] vs 3 [0.9%]; P = .312). Of those with a diagnosis of VTE ≤30 days postoperatively, no differences were present in age, sex, race, BMI, or procedure type. DVT had been diagnosed significantly later in the SCD patients than in the controls (median, postoperative day 12 vs 5; P = .014). None of the five SCD patients with VTE was a smoker compared with four of the six non-SCD patients with VTE, who were current or former tobacco users (P = .061). All the patients who had developed VTE had received DVT prophylaxis at surgery. CONCLUSIONS: We found no differences in the perioperative rates of DVT, PE, or mortality between the SCD patients and matched control patients after noncardiovascular surgery. Vigilant attention to routine VTE prophylaxis seemed to effectively reduce the VTE risk for these hypercoagulable patients. SCD patients might need VTE prophylaxis for a longer period postoperatively compared with those without SCD.

Teaching veterinary surgical skills: Comparison of massed versus spaced instruction.

OBJECTIVE: To determine the effect of massed instruction (MI) versus spaced instruction (SI) of veterinary surgical skills on students' cognitive load and skill retention. STUDY DESIGN: Prospective randomized cohort study STUDY POPULATION: First-year veterinary students from Louisiana State University (LSU; n = 47) and Lincoln Memorial University (LMU; n = 101). METHODS: Students were randomized to MI (two skills in a single session of twice the duration) or SI (one skill per session on two consecutive days). Instructors, instructional ratio, and total educational time was equivalent. Following instruction, students completed a cognitive load questionnaire and underwent a structured assessment immediately after (LMU only), 1 day after, and 3-4 weeks after learning the second skill. Students completed two supervised practice sessions one and 2 weeks after the initial laboratory session(s). RESULTS: Overall cognitive load did not differ between groups (p > .05), although LMUs MI group reported higher physical and time demands, effort, and frustration. At initial assessment, SI students scored higher than MI students for the first skill at both LSU (mean checklist score = 27.7 vs. mean = 24; p = .004) and LMU (mean global rating score = 4.76 vs. mean = 4.55; p = .029). Differences between groups were no longer evident by 3-4 weeks after instruction. CONCLUSION: SI may lead to improved immediate performance; however, supervised practice was sufficient to overcome the initial disparity. CLINICAL SIGNIFICANCE: SI may be beneficial for initial skill performance. However, SI and MI students had similar performance after 3 weeks, suggesting the more convenient curricular design of MI may be sufficient as long as practice sessions are incorporated.

Loss of TAF8 causes TFIID dysfunction and p53-mediated apoptotic neuronal cell death.

Mutations in genes encoding general transcription factors cause neurological disorders. Despite clinical prominence, the consequences of defects in the basal transcription machinery during brain development are unclear. We found that loss of the TATA-box binding protein-associated factor TAF8, a component of the general transcription factor TFIID, in the developing central nervous system affected the expression of many, but notably not all genes. Taf8 deletion caused apoptosis, unexpectedly restricted to forebrain regions. Nuclear levels of the transcription factor p53 were elevated in the absence of TAF8, as were the mRNAs of the pro-apoptotic p53 target genes Noxa, Puma and Bax. The cell death in Taf8 forebrain regions was completely rescued by additional loss of p53, but Taf8 and p53 brains failed to initiate a neuronal expression program. Taf8 deletion caused aberrant transcription of promoter regions and splicing anomalies. We propose that TAF8 supports the directionality of transcription and co-transcriptional splicing, and that failure of these processes causes p53-induced apoptosis of neuronal cells in the developing mouse embryo.

Intramural hematoma of the thoracic aorta: A single-institution, 12-year experience.

OBJECTIVE: The natural history and management of intramural hematoma (IMH) has varied significantly worldwide. From the present retrospective analysis of our institutional database, we have reported the long-term results from medical and surgical management of types A and B IMH. METHODS: Computed tomography reports completed at our tertiary care hospital from July 2007 to July 2020 were used to identify patients with IMH with a thickness of ≥7 mm. Those with IMH directly related to trauma, previous aortic surgery, penetrating atheromatous ulcer, dissection flap, or an iatrogenic source and those who had never received any treatment of IMH at presentation were excluded. RESULTS: A total of 54 patients with IMH had met the inclusion and exclusion criteria. Of the 54 patients, 24 had presented with Stanford type A. Of these 24 patients, 10 had initially undergone surgery and 14 had initially received medical treatment. Two patients in the medical group had subsequently undergone surgery. In addition, 30 patients had presented with type B IMH and had initially received medical treatment, with 3 eventually requiring surgical intervention. In-hospital survival was 90% for type A IMH treated surgically, 93% for type A IMH treated medically, and 97% for type B IMH treated medically. At the last follow-up imaging study of the medically treated patients, 36% of those with type A IMH and 31% of those with type B IMH had experienced complete resolution of IMH at 3.7 and 31.5 months respectively, without surgical intervention. The development of an aortic aneurysm at the site of a previous IMH had occurred in 18% (2 of 11) and 12% (3 of 26) of the type A medical and type B medical cohorts. The overall rate of aortic aneurysm formation in the region of IMH or in another segment was 50%. No difference was found in long-term survival between the three cohorts at a mean follow-up of 22.8 months. CONCLUSIONS: A role appears to exist for medical treatment with anti-impulse therapy for appropriately selected patients with type A IMH. These patients must be followed up closely clinically and radiographically for signs of deterioration in the short- and long-term phases of their care. They can achieve long-term survival similar to that of surgically treated type A IMH and medically treated type B IMH patients using this algorithm. However, they might require late surgical intervention, especially for aneurysmal disease.

Arabidopsis thaliana CYCLIC NUCLEOTIDE-GATED CHANNEL2 mediates extracellular ATP signal transduction in root epidermis.

Damage can be signalled by extracellular ATP (eATP) using plasma membrane (PM) receptors to effect cytosolic free calcium ion ([Ca2+ ]cyt ) increase as a second messenger. The downstream PM Ca2+ channels remain enigmatic. Here, the Arabidopsis thaliana Ca2+ channel subunit CYCLIC NUCLEOTIDE-GATED CHANNEL2 (CNGC2) was identified as a critical component linking eATP receptors to downstream [Ca2+ ]cyt signalling in roots. Extracellular ATP-induced changes in single epidermal cell PM voltage and conductance were measured electrophysiologically, changes in root [Ca2+ ]cyt were measured with aequorin, and root transcriptional changes were determined by quantitative real-time PCR. Two cngc2 loss-of-function mutants were used: cngc2-3 and defence not death1 (which expresses cytosolic aequorin). Extracellular ATP-induced transient depolarization of Arabidopsis root elongation zone epidermal PM voltage was Ca2+ dependent, requiring CNGC2 but not CNGC4 (its channel co-subunit in immunity signalling). Activation of PM Ca2+ influx currents also required CNGC2. The eATP-induced [Ca2+ ]cyt increase and transcriptional response in cngc2 roots were significantly impaired. CYCLIC NUCLEOTIDE-GATED CHANNEL2 is required for eATP-induced epidermal Ca2+ influx, causing depolarization leading to [Ca2+ ]cyt increase and damage-related transcriptional response.

Predictors of mortality in nonagenarians undergoing abdominal aortic aneurysm repair: Analysis of the National Surgical Quality Improvement Program dataset.

BACKGROUND: The present study used the American College of Surgeons National Surgical Quality Improvement Program dataset to identify the predictors of 30-day mortality for nonagenarians undergoing endovascular aortic aneurysm repair (EVAR) or open surgical repair (OSR). METHODS: Patients aged >90 years who had undergone abdominal aortic aneurysm repair from 2005 to 2017 were identified using procedure codes. Those with operative times <15 minutes were excluded. The demographics, preoperative comorbidities, and postoperative complications of those who had died by 30 days were compared with those of the patients alive at 30 days. RESULTS: A total of 1356 nonagenarians met the criteria: 1229 (90.6%) had undergone EVAR and 127 (9.4%) had undergone OSR. The overall 30-day mortality was 10.4%. The patients who had died within 30 days were significantly more likely to have undergone OSR than EVAR (40.9% vs 7.2%; P < .001). They also had a greater incidence of dependent functional status (22.0% for those who had died vs 8.1% for those alive at 30 days; P < .001), American Society of Anesthesiology (ASA) classification of ≥4 (81.2% vs 18.8%; P < .001), perioperative blood transfusion (59.6% vs 20.3%; P < .001), postoperative pneumonia (12.1% vs 2.9%; P = .001), mechanical ventilation >48 hours (22.7% vs 2.6%; P < .001), and acute renal failure (12.1% vs 0.5%; P < .001). The EVAR group had a 30-day mortality rate of 2.6% in 1008 elective cases and 28.6% in 221 emergent cases. The OSR group had a 30-day mortality rate of 19.1% in 47 elective cases and 53.7% in 80 emergent cases. In the EVAR cohort, the 30-day mortality group had had a significantly greater incidence of dependent functional status (17% for those who had died vs 8% for those alive at 30 days; P = .004), ASA classification of ≥4 (76.4% vs 40.3%; P < .001), perioperative blood transfusion (57% vs 19%; P < .001), emergency surgery (71% vs 14%; P < .001), and longer operative times (150 vs 128 minutes; P = .001). CONCLUSIONS: Nonagenarians had an incrementally increased, but acceptable, risk of 30-day mortality with EVAR in elective and emergent cases compared with that reported for octogenarians and cohorts of patients not selected for age. We found greater mortality for patients with dependent status, a higher ASA classification, emergent repair, and OSR. These preoperative risk factors could help identify the best surgical candidates. Given these results, consideration for EVAR or OSR might be reasonable for highly selected patients, especially for elective patients with a larger abdominal aortic aneurysm diameter for whom the risk of rupture is higher.

Vascular invasion predicts advanced tumor characteristics in papillary thyroid carcinoma.

BACKGROUND: The clinical impact of vascular invasion in Papillary Thyroid Carcinoma (PTC) is not well understood. Our aim was to determine if there was an association between vascular invasion and other tumor characteristics and patient outcomes in PTC. METHODS: A retrospective chart review was performed of 536 patients with PTC between January 2007-December 2011. Patient demographics, comorbidities, tumor characteristics, and outcomes were collected. RESULTS: Vascular invasion was associated with lymphatic invasion, capsular invasion, extrathyroidal extension, and the presence of positive lymph nodes. Logistic regression revealed that tumor size was a predictor of vascular invasion. Vascular invasion in PTC tumors was associated with higher tumor recurrence rates, but there were no differences in mortality. CONCLUSION: This study indicates that vascular invasion in PTC is associated with other aggressive pathologic features and an increased recurrence rate. For these reasons, vascular invasion should be an important tumor characteristic when determining extent of treatment.