Hypobaria During Aeromedical Evacuation and Systemic Inflammation after Porcine Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI)-related morbidity is caused largely by secondary injury resulting from hypoxia, excessive sympathetic drive, and uncontrolled inflammation. Aeromedical evacuation (AE) is utilized by the military for transport of wounded soldiers to higher levels of care. We hypothesized that the hypobaric, hypoxic conditions of AE may exacerbate uncontrolled inflammation following TBI that could contribute to more severe TBI-related secondary injury. STUDY DESIGN: Thirty-six female pigs were used to test TBI vs. TBI sham, hypoxia vs. normoxia, and hypobaria vs. ground conditions. TBI was induced by controlled cortical injury, hypobaric conditions of 12,000 feet were established in an altitude chamber, and hypoxic exposure was titrated to 85% SpO2 while at altitude. Serum cytokines, UCH-L1 and TBI biomarkers were analyzed via ELISA. Gross analysis and staining of cortex and hippocampus tissue was completed for glial fibrillary acidic protein (GFAP) and phosphorylated tau (p-tau). RESULTS: Serum IL-1b, IL-6, and TNFα were significantly elevated following TBI in pigs exposed to altitude-induced hypobaria/hypoxia, as well as hypobaria alone, compared to ground level/normoxia. No difference in TBI biomarkers following TBI or hypobaric, hypoxic exposure was noted. No difference in brain tissue GFAP or p-tau when comparing the most different conditions of sham TBI+ground/normoxia to the TBI+hypobaria/hypoxia group was noted. CONCLUSION: The hypobaric environment of AE induces systemic inflammation following TBI. Severe inflammation may play a role in exacerbating secondary injury associated with TBI and contribute to worse neurocognitive outcomes. Measures should be taken to minimize barometric and oxygenation changes during AE following TBI.

Re-Evaluating the Use of High Sensitivity Troponin to Diagnose Blunt Cardiac Injury.

INTRODUCTION: Blunt cardiac injury (BCI) can be challenging diagnostically, and if misdiagnosed, can lead to life-threatening complications. Our institution previously evaluated BCI screening with troponin and electrocardiogram (EKG) during a transition from troponin I to high sensitivity troponin (hsTnI), a more sensitive troponin I assay. The previous study found an hsTnI of 76 ng/L had the highest capability of accurately diagnosing a clinically significant BCI. The aim of this study was to determine the efficacy of the newly implemented protocol. METHODS: Patients diagnosed with a sternal fracture from March 2022 to April 2023 at our urban level-1 trauma center were retrospectively reviewed for EKG findings, hsTnI trend, echocardiogram changes, and clinical outcomes. The BCI cohort and non-BCI cohort ordinal measures were compared using Wilcoxon's two-tailed rank sum test and categorical measures were compared with Fisher's exact test. Youden indices were used to evaluate hsTnI sensitivity and specificity. RESULTS: Sternal fractures were identified in 206 patients, of which 183 underwent BCI screening. Of those screened, 103 underwent echocardiogram, 28 were diagnosed with clinically significant BCIs, and 15 received intervention. The peak hsTnI threshold of 76 ng/L was found to have a Youden index of 0.31. Rather, the Youden index was highest at 0.50 at 40 ng/L (sensitivity 0.79 and specificity 0.71) for clinically significant BCI. CONCLUSIONS: Screening patients with sternal fractures for BCI using hsTnI and EKG remains effective. To optimize the hsTnI threshold, this study determined the hsTnI threshold should be lowered to 40 ng/L. Further improvements to the institutional protocol may be derived from multicenter analysis.

Direct red blood cell effect on thrombosis is dependent on the interaction of tissue factor and calcium with membrane phosphatidylserine.

BACKGROUND: Prior literature has implicated Red Blood Cells (RBCs) in the initiation of thrombosis and suggests that post-transfusion hypercoagulability may occur secondary to the effects of RBCs. Elevated serum tissue factor is a known sequelae of acute trauma. Phosphatidylserine is a pro-thrombotic phospholipid present within the RBC cell membrane. We hypothesized that RBC aggregation is dependent on the interaction between RBC membrane bound (exposed) PS, extracellular calcium, and tissue factor. METHODS: Human whole blood (WB) was separated into components including red blood cells (RBC) and platelet-rich plasma (PRP). WB, PRP, and RBCs underwent impedance aggregometry utilizing arachidonic acid (AA), ADP, collagen, calcium, and tissue factor (TF)-based agonists. RBCs then underwent impedance aggregometry utilizing combined calcium and TF agonists. RBCs were pre-treated with Annexin V, a known PS blocking agent, and underwent impedance aggregometry with combined calcium and TF agonists to determine if the mechanism of calcium/TF-induced RBC aggregability is dependent on PS. RBCs treated with calcium, TF, calcium+TF, and pre-treated with Annexin V followed by calcium+TF were perfused through an in vitro model of pulmonary microcirculatory flow. RESULTS: RBC aggregation was significantly higher than that of WB and PRP when utilizing a TF agonist, an effect unique to TF. The combination of calcium and TF demonstrated significantly higher RBC aggregation than either agonist alone. Pre-treatment with Annexin V resulted in a significantly reduced aggregability of RBC following treatment with TF + calcium. RBCs aged to 42 days did not exhibit significant change in aggregation. Exposure to calcium and TF significantly reduced time to thrombosis of RBCs perfused through a pulmonary microcirculatory model. CONCLUSION: Treatment with both TF and calcium synergistically induces RBC aggregation. PS appears to play an integral role in the TF/calcium-based, age-independent RBC aggregation response. RBCs treated with TF + calcium exhibit more rapid thrombus formation in an in vitro model of pulmonary microcirculatory perfusion.Study Type: human sample-based study. LEVEL OF EVIDENCE: basic science paper.

Just Say NO: Inhaled Nitric Oxide Effect on Respiratory Parameters Following Traumatic Brain Injury in Humans and a Porcine Model.

INTRODUCTION: The mechanism of post-traumatic brain injury (TBI) hypoxemia involves ventilation/perfusion mismatch and loss of pulmonary hypoxic vasoconstriction. Inhaled nitric oxide (iNO) has been studied as an adjunct treatment to avoid the use of high positive end-expiratory pressure and inspired oxygen in treatment-refractory hypoxia. We hypothesized that iNO treatment following TBI would improve systemic and cerebral oxygenation via improved matching of pulmonary perfusion and ventilation. METHODS: Thirteen human patients with isolated TBI were enrolled and randomized to receive either placebo or iNO with measured outcomes including pulmonary parameters, blood gas data, and intracranial pressure (ICP) /perfusion. To complement this study, a porcine model of TBI (including 10 swine) was utilized with measured outcomes of brain tissue blood flow and oxygenation, ventilator parameters, and blood gas data both after administration and following drug removal and clearance. RESULTS: There were no clinically significant changes in pulmonary parameters in either the human or porcine arm following administration of iNO when compared to either the placebo group (human arm) or the internal control (porcine arm). Analysis of pooled human data demonstrated the preservation of alveolar recruitment in TBI patients. There were no clinically significant changes in human ICP or cerebral perfusion pressure following iNO administration compared to controls. CONCLUSIONS: iNO had no significant effect on clinically relevant pulmonary parameters or ICPs following TBI in both human patients and a porcine model. The pressure-based recruitment of the human lungs following TBI was preserved. Further investigation will be needed to determine the degree of utility of iNO in the setting of hypoxia after polytrauma.

Desmopressin, Misoprostol, nor Carboprost Affect Platelet Aggregability Following Traumatic Brain Injury and Aspirin.

INTRODUCTION: Desmopressin (DDAVP) has been utilized clinically in patients taking aspirin (ASA) to improve drug-induced platelet dysfunction. Misoprostol and carboprost, prostaglandin analogs commonly used for postpartum hemorrhage, may also induce platelet aggregation. The aim of this study was to determine the effects of DDAVP, misoprostol, and carboprost administration on platelet aggregability following traumatic brain injury (TBI) in mice treated with ASA. METHODS: Male C57BL/6 mice were randomized into seven groups (n = 5 each): untouched, ASA only, Saline/TBI, ASA/TBI, ASA/TBI/DDAVP 0.4 µg/kg, ASA/TBI/misoprostol 1 mg/kg, and ASA/TBI/carboprost 100 µg/kg. TBI was induced via a weight drop model 4-h after ASA (50 mg/kg) gavage. Mice were given an intraperitoneal injection of DDAVP, misoprostol, or carboprost 10 minutes after TBI. In vivo testing was completed utilizing tail vein bleed. Mice were sacrificed 30-min posttreatment and blood was collected via cardiac puncture. Whole blood was analyzed via Multiplate impedance aggregometry, rotational thromboelastometry, and TEG6s. RESULTS: Mice receiving misoprostol after ASA/TBI demonstrated decreased tail vein bleeding times compared to ASA only treated mice. However, mice treated with misoprostol following ASA and TBI demonstrated decreased platelet aggregability compared to untouched mice and TBI only mice within the arachidonic acid agonist pathway. By contrast, DDAVP and carboprost did not significantly change platelet aggregability via adenosine diphosphate or arachidonic acid following ASA and TBI. However, DDAVP did decrease the platelet contribution to clot via rotational thromboelastometry. CONCLUSIONS: Reversal of medication-induced platelet inhibition has become increasingly controversial after TBI. Based on these results, DDAVP, misoprostol, nor carboprost consistently improve platelet aggregability following TBI in those also treated with ASA.

Murine Traumatic Brain Injury Model Comparison: Closed Head Injury Versus Controlled Cortical Impact.

INTRODUCTION: Various murine models have been utilized to study TBI, including closed head injury (CHI) and controlled cortical impact (CCI), without direct comparison. The aim of our study was to evaluate these models to determine differences in neurological and behavioral outcomes postinjury. METHODS: Male C57B/6 mice (9-10 wk) were separated into six groups including: untouched, sham craniotomy (4 mm), CCI 0.9 mm depth of impact, CCI 1.6 mm, CCI 2.2 mm, and CHI. CCI was performed using a 3 mm impact tip at a velocity of 5 m/s, dwell time of 250 ms, and depth as noted above. CHI was completed with a centered 400 g weight drop from 1 cm height. Mice were survived to 14-d (n = 5 per group) and 30-d (n = 5 per group) respectively for histological analysis of p-tau within the hippocampus. These mice underwent Morris Water Maze memory testing and Rotarod motor testing. Serum was collected from a separate cohort of mice (n = 5 per group) including untouched, isoflurane only, CCI 1.6 mm, CHI at 1, 4, 6, and 24 h for analysis of neuron specific enolase and glial fibrillary acidic protein (GFAP) via ELISA. Laser speckle contrast imaging was analyzed prior to and after impact in the CHI and CCI 1.6 mm groups. RESULTS: There were no significant differences in Morris Water Maze or Rotarod testing times between groups at 14- or 30-d. P-tau was significantly elevated in all groups except CCI 1.6 mm contralateral and CCI 2.2 mm ipsilateral compared to untouched mice at 30-d. P-tau was also significantly elevated in the CHI group at 30 d compared to CCI 1.6 mm contralateral and CCI 2.2 mm on both sides. GFAP was significantly increased in mice undergoing CHI (9959 ± 91 pg/mL) compared to CCI (2299 ± 1288 pg/mL), isoflurane only (133 ± 75 pg/mL), and sham (86 ± 58 pg/mL) at 1-h post TBI (P < 0.0001). There were no differences in serum neuron specific enolase levels between groups. Laser doppler imaging demonstrated similar decreases in cerebral blood flow between CHI and CCI; however, CCI mice had a reduction in blood flow with craniotomy only that did not significantly decrease further with impact. CONCLUSIONS: Based on our findings, CHI leads to increased serum GFAP levels and increased p-tau within the hippocampus at 30-d postinjury. While CCI allows the comparison of one cerebral hemisphere to the other, CHI may be a better model of TBI as it requires less technical expertise and has similar neurological outcomes in these murine models.

Syndecan-1 as the Effect or Effector of the Endothelial Inflammatory Response?

INTRODUCTION: Syndecan-1 is a heparan sulfate proteoglycan found in the glycocalyx of vascular endothelial cells. Serum levels of syndecan-1 have repeatedly been demonstrated to increase following traumatic injury and shock, but it is unclear whether syndecan-1 plays an active role in the inflammatory response or is simply a biomarker of a state of hypoperfusion. The aim of this study was to identify the role of syndecan-1 role in the inflammatory process in the absence of trauma. METHODS: Male mice were randomized into five groups (n = 3). Four groups received increasing concentrations of syndecan-1 (1, 10, 100, and 1000pg/mL per blood volume) and a fifth group was given normal saline as a control via intravenous injection. These concentrations were selected based on previous syndecan-1 enzyme-linked immunosorbent assay data acquired following induced hemorrhagic shock in mice resulting in serum levels of 10-6000 pg/mL. Mice from each group were sacrificed at 1-, 4-, and 24-h time points for serum biomarker evaluation. A multiplex enzyme-linked immunosorbent assay was performed to analyze proinflammatory cytokines and chemokines including interleukin (IL)-1a, IL-1b, IL-2, IL-3, IL-4, IL-6, IL-10, IL-12, IL-17, monocyte chemoattractant protein-1, TNF-α, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor, and normal T cell expressed and presumably secreted levels. Whole blood was analyzed via rotational thromboelastometry in a separate group of mice dosed with syndecan-1 at 1000 pg/mL and compared to sham mice at 1 h. RESULTS: Tumor necrosis factor-α was significantly elevated in the 1000 pg/mL group compared to sham animals. There were no significant changes in IL-1a, IL-1b, IL-2, IL-3, IL-4, IL-6, IL-10, IL-12, monocyte chemoattractant protein--1, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor, or normal T cell expressed and presumably secretedat 1, 4, and 24 h for any group when compared to mice receiving saline alone. No significant differences were noted in coagulability between the 1000 pg/mL syndecan-1 group and shams at 1 h CONCLUSIONS: Inflammatory cytokine concentrations did not change with increasing dosage of syndecan-1 within mice at any timepoint, except for an acute change in tumor necrosis factor-α which was transient. Based on our results, syndecan-1 appears to be a biomarker for inflammation rather than an active participant in eliciting an inflammatory response. Further research will focus on the role of syndecan-1 following hemorrhagic shock.

Validation of Preload Assessment Technologies at Altitude in a Porcine Model of Hemorrhage.

INTRODUCTION: Dynamic preload assessment measures including pulse pressure variation (PPV), stroke volume variation (SVV), pleth variability index (PVI), and hypotension prediction index (HPI) have been utilized clinically to guide fluid management decisions in critically ill patients. These values aid in the balance of correcting hypotension while avoiding over-resuscitation leading to respiratory failure and increased mortality. However, these measures have not been previously validated at altitude or in those with temporary abdominal closure (TAC). METHODS: Forty-eight female swine (39 ± 2 kg) were separated into eight groups (n = 6) including all combinations of flight versus ground, hemorrhage versus no hemorrhage, and TAC versus no TAC. Flight animals underwent simulated aeromedical evacuation via an altitude chamber at 8000 ft. Hemorrhagic shock was induced via stepwise hemorrhage removing 10% blood volume in 15-min increments to a total blood loss of 40% or a mean arterial pressure of 35 mmHg. Animals were then stepwise transfused with citrated shed blood with 10% volume every 15 min back to full blood volume. PPV, SVV, PVI, and HPI were monitored every 15 min throughout the simulated aeromedical evacuation or ground control. Blood samples were collected and analyzed for serum levels of serum IL-1ß, IL-6, IL-8, and TNF-α. RESULTS: Hemorrhage groups demonstrated significant increases in PPV, SVV, PVI, and HPI at each step compared to nonhemorrhage groups. Flight increased PPV (P = 0.004) and SVV (P = 0.003) in hemorrhaged animals. TAC at ground level increased PPV (P < 0.0001), SVV (P = 0.0003), and PVI (P < 0.0001). When TAC was present during flight, PPV (P = 0.004), SVV (P = 0.003), and PVI (P < 0.0001) values were decreased suggesting a dependent effect between altitude and TAC. There were no significant differences in serum IL-1ß, IL-6, IL-8, or TNF-α concentration between injury groups. CONCLUSIONS: Based on our study, PPV and SVV are increased during flight and in the presence of TAC. Pleth variability index is slightly increased with TAC at ground level. Hypotension prediction index demonstrated no significant changes regardless of altitude or TAC status, however this measure was less reliable once the resuscitation phase was initiated. Pleth variability index may be the most useful predictor of preload during aeromedical evacuation as it is a noninvasive modality.

Defining the Disparity: A Multi-Institutional Analysis of Factors Associated With Decreased Resident Operative Experience.

INTRODUCTION: Technical learning in surgical training is multifaceted and existing literature suggests a positive relationship between case volume and proficiency. Little is known about factors associated with a decreased volume of operative experience. This study aimed to identify resident and program factors associated with general surgery residents (GSR) in the bottom quartile of logged case volume upon program completion. METHODS: A post hoc analysis of a multicenter study was used to examine case logs for categorical GSR. Participants included graduates between 2010 and 2020 from 20 programs. Residents below and above the 25th percentile for total operative volume were compared. RESULTS: The present study includes 1343 GSR who graduated over the 11-y period. In total, 336 residents were below the 25th percentile and 1007 residents were above the 25th percentile. Those below the 25th percentile were more likely to be female (41% versus 34%, P = 0.02), identify as underrepresented in medicine (22% versus 14%, P < 0.01), and pursue fellowship (86% versus 80%, P = 0.01) compared to those above the 25th percentile. Residents below the 25th percentile were more likely to have graduated from a low volume program (55% versus 25%, P < 0.01) and from top National Institutes of Health funded institutions (57% versus 52%, P = 0.01). CONCLUSIONS: This study identified individual and program characteristics associated with lower operative volume of GSR. Understanding such characteristics will aid surgical educators to achieve better equity in training.

A multi-institutional study from the US ROPE consortium examining factors associated with endocrine surgery exposure for general surgery residents.

BACKGROUND: Prior analyses of general surgery resident case logs have indicated a decline in the number of endocrine procedures performed during residency. This study aimed to identify factors contributing to the endocrine operative experience of general surgery residents and compare those who matched in endocrine surgery fellowship with those who did not. METHODS: We analyzed the case log data of graduates from 18 general surgery residency programs in the US Resident Operative Experience Consortium over an 11-year period. RESULTS: Of the 1,240 residents we included, 17 (1%) matched into endocrine surgery fellowships. Those who matched treated more total endocrine cases, including more thyroid, parathyroid, and adrenal cases, than those who did not (81 vs 37, respectively, P < .01). Program-level factors associated with increased endocrine volume included endocrine-specific rotations (+10, confidence interval 8-12, P < .01), endocrine-trained faculty (+8, confidence interval 7-10, P < .01), and program co-location with otolaryngology residency (+5, confidence interval 2 -8, P < .01) or endocrine surgery fellowship (+4, confidence interval 2-6, P < .01). Factors associated with decreased endocrine volume included bottom 50th percentile in National Institute of Health funding (-10, confidence interval -12 to -8, P < .01) and endocrine-focused otolaryngologists (-3, confidence interval -4 to -1, P < .01). CONCLUSION: Several characteristics are associated with a robust endocrine experience and pursuit of an endocrine surgery fellowship. Modifiable factors include optimizing the recruitment of dedicated endocrine surgeons and the inclusion of endocrine surgery rotations in general surgery residency.

Long-term follow-up of temporary abdominal closure in complex abdomens during liver transplant.

BACKGROUND: Temporary abdominal closure is commonly employed in liver transplantation when patient factors make primary fascial closure challenging. However, there is minimal data evaluating long-term survival and patient outcomes after temporary abdominal closure. METHODS: A single-center, retrospective review of patients undergoing liver transplantation from January 2013 through December 2017 was performed with a 5-year follow-up. Patients were characterized as either requiring temporary abdominal closure or immediate primary fascial closure at the time of liver transplantation. RESULTS: Of 422 patients who underwent 436 liver transplantations, 17.2% (n = 75) required temporary abdominal closure, whereas 82.8% (n = 361) underwent primary fascial closure. Patients requiring temporary abdominal closure had higher Model for End-Stage Liver Disease scores preoperatively (27 [22-36] vs 23 [20-28], P = .0002), had higher rates of dialysis preoperatively (28.0% vs 12.5%, P = .0007), and were more likely to be hospitalized within 90 days of liver transplantation (64.0% vs 47.5%, P = .0093). On univariable analysis, survival at 1 year was different between the groups (90.9% surviving at 1 year for primary fascial closure versus 82.7% for temporary abdominal closure, P = .0356); however, there was no significant difference in survival at 5 years (83.7% vs 76.0%, P = .11). On multivariable analysis, there was no difference in survival after adjusting for multiple factors. Patients requiring temporary abdominal closure were more likely to have longer hospital stays (median 16 days [9.75-29.5] vs 8 days [6-14], P < .0001), more likely to be readmitted within 30 days (45.3% vs 32.2%, P = .03), and less likely to be discharged home (36.5% vs 74.2%, P < .0001). CONCLUSIONS: Temporary abdominal closure after liver transplantation appears safe and has similar outcomes to primary fascial closure, though it is used more commonly in complex patients.

Predictive Value of Early Inflammatory Markers in Trauma Patients Based on Transfusion Status.

INTRODUCTION: Seven key inflammatory biomarkers were recently found to be associated with the risk of mortality in a multicenter study of massively transfused patients. The aim of this prospective single-center study was to determine which of these early inflammatory markers could predict 30-d mortality among all critically injured trauma patients. METHODS: Serum samples were collected at 6, 24, and 72 h from 238 consecutive patients admitted to the intensive care unit following traumatic injury. Inflammatory markers syndecan-1, eotaxin, IL-1ra, IL-6, IL-8, IL-10, IP-10, and MCP-1 were analyzed via multiplex enzyme-linked immunosorbent assay. Subgroup analysis was performed for patients undergoing massive transfusion (≥5 red blood cells), submassive transfusion (1-4 red blood cells), or no transfusion during the first 4 h postinjury. The primary outcome of 30-d survival was modeled as a function of each biomarker and confounders using repeat measures logistic regression. RESULTS: Patients had a median age of 51.3 y [33.7, 70.2], 70.6% were male, 17.4% experienced penetrating trauma, and had a median injury severity score of 22 [14, 33]. IL-1ra, IL-8, IL-10, and MCP-1 were significantly increased during the first 72 h in nonsurvivors (n = 31). Elevated IL-1ra, IL-8, IL-10, and MCP-1 at 6 h postinjury were associated with 30-d mortality. By contrast, serum syndecan-1 and eotaxin levels were not associated with mortality at any time point. IL-8 and lactate were increased at 6 h in 30-d nonsurvivors for patients receiving submassive transfusion (n = 78). CONCLUSIONS: Early evaluations of IL-1ra, IL-8, IL-10, and IP-10 within 6 h of injury are useful predictors of 30-d mortality. Subgroup analysis suggests that transfusion status does not significantly affect early inflammatory markers. LEVEL OF EVIDENCE: Level III, prognostic/epidemiological.

Social media and academic surgical research dissemination.

Academic research dissemination has evolved tremendously throughout the 20th and early 21st centuries. With the advent of new technology and remote communication, the fast and efficient sharing of ideas has spread worldwide and has been appropriately embraced by academic surgical researchers. The use of social media by surgeons has expanded our ability to share hypotheses and published works that lead to higher degrees of collaboration than previously possible. The strengths of social media use for research dissemination in surgery include immediate collaboration on a global scale, faster dissemination of results previously hindered by the publishing process, open peer review from a wider audience, and enhancing the experience of academic meetings. However, social media use for research dissemination is not perfect and is hindered by lack of author verification, public misinterpretation, and lack of standardized enforceable professional guidelines. To combat these potential pitfalls, surgical societies should prioritize specific and intervenable guidelines for surgeons regarding the appropriate use of social media for research dissemination.

Selective MAP1LC3C (LC3C) autophagy requires noncanonical regulators and the C-terminal peptide.

LC3s are canonical proteins necessary for the formation of autophagosomes. We have previously established that two paralogs, LC3B and LC3C, have opposite activities in renal cancer, with LC3B playing an oncogenic role and LC3C a tumor-suppressing role. LC3C is an evolutionary late gene present only in higher primates and humans. Its most distinct feature is a C-terminal 20-amino acid peptide cleaved in the process of glycine 126 lipidation. Here, we investigated mechanisms of LC3C-selective autophagy. LC3C autophagy requires noncanonical upstream regulatory complexes that include ULK3, UVRAG, RUBCN, PIK3C2A, and a member of ESCRT, TSG101. We established that postdivision midbody rings (PDMBs) implicated in cancer stem-cell regulation are direct targets of LC3C autophagy. LC3C C-terminal peptide is necessary and sufficient to mediate LC3C-dependent selective degradation of PDMBs. This work establishes a new noncanonical human-specific selective autophagic program relevant to cancer stem cells.

An Update on the Energy Sources and Catheter Technology for the Ablation of Atrial Fibrillation.

The ablation of atrial fibrillation (AF) is an area of intense research in cardiac electrophysiology. In this review, we discuss the development of catheter-based interventions for AF ablation. We outline the pathophysiologic and anatomic bases for ablative lesion sets and the evolution of various catheter designs for the delivery of radiofrequency (RF), cryothermal, and other ablative energy sources. The strengths and weaknesses of various specialized RF catheters and alternative energy systems are delineated, with respect to efficacy and patient safety.