Two Decades Using Stentless Porcine Aortic Root in Right Ventricular Outflow Tract Reconstruction.

BACKGROUND: The stentless porcine aortic root prosthesis (SPAR) has been described as a suitable valve for right ventricular outflow tract reconstruction (RVOTR). Indiana University Methodist Hospital in Indianapolis, Indiana began using this valve for RVOTR in 1998. This study reports medium-term to late- term outcomes of the valve in the pulmonary position. METHODS: A retrospective chart review was conducted of patients older than 18 years of age who underwent RVOTR with a SPAR between April 2000 and October 2019. Primary outcomes included survival and freedom from any valvular reintervention. Secondary outcomes included endocarditis and conduit dysfunction detected by routine echocardiography or cardiac magnetic resonance imaging. RESULTS: A total of 135 patients underwent RVOTR with a SPAR at a median age of 32.4 years (range, 18 to 71 years). Of these patients, 129 had previous surgery. Indications included pulmonary insufficiency (90.4%), stenosis (34.8%), endocarditis (7.4%), and carcinoid (4.4%). Median follow-up was 2.97 years (interquartile range, 0.6 to 8.0 years). Overall survival was 93.3%, with 3 perioperative death and 6 late deaths. Endocarditis developed in 4 patients (2.9%), 2 of whom required reoperation. Progressive conduit degradation was evident at 10 years, with 22.2% and 7.7% having moderate stenosis and insufficiency, respectively. Eight (5.9%) reinterventions included 2 surgical replacements, 3 percutaneous replacements, and 3 balloon valvuloplasties at means of 8.5, 7.4, and 2.2 years, respectively. Overall freedom from reintervention at 1, 5, and 10 years was 99.1%, 94.7% and 90.7%, respectively. CONCLUSIONS: In this large, single-institution experience with a long follow-up period, use of the SPAR demonstrated excellent midterm to long-term durability, low rates of endocarditis, and high freedom from reintervention.

Self-regulation of adult thalamocortical neurons.

The thalamus acts as a conduit for sensory and other information traveling to the cortex. In response to continuous sensory stimulation in vivo, the firing rate of thalamocortical neurons initially increases, but then within a minute firing rate decreases and T-type Ca(2+) channel-dependent action potential burst firing emerges. While neuromodulatory systems could play a role in this inhibitory response, we instead report a novel and cell-autonomous inhibitory mechanism intrinsic to the thalamic relay neuron. Direct intracellular stimulation of thalamocortical neuron firing initially triggered a continuous and high rate of action potential discharge, but within a minute membrane potential (Vm) was hyperpolarized and firing rate to the same stimulus was decreased. This self-inhibition was observed across a wide variety of thalamic nuclei, and in a subset firing mode switched from tonic to bursting. The self-inhibition resisted blockers of intracellular Ca(2+) signaling, Na(+)-K(+)-ATPases, and G protein-regulated inward rectifier (GIRK) channels as implicated in other neuron subtypes, but instead was in part inhibited by an ATP-sensitive K(+) channel blocker. The results identify a new homeostatic mechanism within the thalamus capable of gating excitatory signals at the single-cell level.

Proximal junctional kyphosis and failure after spinal deformity surgery: a systematic review of the literature as a background to classification development.

STUDY DESIGN: Systematic review of literature. OBJECTIVE: To perform a comprehensive English language systematic literature review of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF), concentrating on incidence, risk factors, health related quality of life impact, prevention strategy, and classification systems. SUMMARY OF BACKGROUND DATA: PJK and PJF are well described clinical pathologies and are a frequent cause of revision surgery. The development of a PJK classification that correlates with clinical outcomes and guides treatment decisions and possible prevention strategies would be of significant benefit to patients and surgeons. METHODS: The phrases "proximal junctional," "proximal junctional kyphosis," and "proximal junctional failure" were used as search terms in PubMed for all years up to 2014 to identify all articles that included at least one of these terms. RESULTS: Fifty-three articles were identified overall. Eighteen articles assessed for risk factors. Eight studies specifically reviewed prevention strategies. There were no randomized prospective studies. There were 3 published studies that have attempted to classify PJK. The reported incidence of PJK ranged widely, from 5% to 46% in patients undergoing spinal instrumentation and fusion for adult spinal deformity. It is reported that 66% of PJK occurs within 3 months and 80% within 18 months after surgery. The reported revision rates due to PJK range from 13% to 55%. Modifiable and nonmodifiable risk factors for PJK have been characterized. CONCLUSION: PJK and PJF affect many patients after long segment instrumentation after the correction of adult spinal deformity. The epidemiology and risk factors for the disease are well defined. A PJK and PJF scoring system may help describe the severity of disease and guide the need for revision surgery. The development and prospective validation of a PJK classification system is important considering the prevalence of the problem and its clinical and economic impact. LEVEL OF EVIDENCE: N/A.

Timing and perioperative risk factors for in-hospital and post-discharge venous thromboembolism after colorectal cancer resection.

INTRODUCTION: We postulated that the risk of venous thromboembolic disease (VTE) may persist after discharge and tested this hypothesis in patients undergoing colorectal resection for cancer. METHODS: The American College of Surgeons National Surgery Quality Improvement Program database was queried for patients undergoing colorectal resections for cancer from 2005 to 2009. The outcome analyzed was a 30-day deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Multivariable forward stepwise regression was used to identify independent predictors of VTE. RESULTS: The database contained 21 943 colorectal cancer resections. The 30-day DVT rate was 1.4% (306 of 21 943), 29% (89 of 306) were diagnosed post-discharge. The 30-day PE rate was 0.8% (180 of 21 943), 33% (60 of 180) was diagnosed post-discharge, the combined DVT/PE rate was 2.0% (446 of 21 943). The median time to diagnosis of VTE was 9 days (interquartile range 4-16) after surgery. Post-discharge VTE rates in patients with length of stay (LOS) less than 1 week (0.6%) were similar to patients with LOS greater than 1 week (0.7%, Fisher exact P not significant). Independent risk factors for post-discharge VTE were preoperative steroid use for chronic condition (odds ratio [OR] 2.90, 95% confidence interval [CI] 1.51-5.57, P = .001) and preoperative systemic inflammatory response syndrome (OR 2.26, 95% CI 1.24-4.10, P = .008). CONCLUSIONS: Diagnosis of almost one third of postoperative VTE in this patient population occurred after discharge. The duration of the prothrombotic stimulus of surgery is not well defined, and patients with malignancy are at high risk of VTE; thromboprophylaxis after discharge should be considered for these patients.

Mutant LGI1 inhibits seizure-induced trafficking of Kv4.2 potassium channels.

Activity-dependent redistribution of ion channels mediates neuronal circuit plasticity and homeostasis, and could provide pro-epileptic or compensatory anti-epileptic responses to a seizure. Thalamocortical neurons transmit sensory information to the cerebral cortex and through reciprocal corticothalamic connections are intensely activated during a seizure. Therefore, we assessed whether a seizure alters ion channel surface expression and consequent neurophysiologic function of thalamocortical neurons. We report a seizure triggers a rapid (<2h) decrease of excitatory postsynaptic current (EPSC)-like current-induced phasic firing associated with increased transient A-type K(+) current. Seizures also rapidly redistributed the A-type K(+) channel subunit Kv4.2 to the neuronal surface implicating a molecular substrate for the increased K(+) current. Glutamate applied in vitro mimicked the effect, suggesting a direct effect of glutamatergic transmission. Importantly, leucine-rich glioma-inactivated-1 (LGI1), a secreted synaptic protein mutated to cause human partial epilepsy, regulated this seizure-induced circuit response. Human epilepsy-associated dominant-negative-truncated mutant LGI1 inhibited the seizure-induced suppression of phasic firing, increase of A-type K(+) current, and recruitment of Kv4.2 surface expression (in vivo and in vitro). The results identify a response of thalamocortical neurons to seizures involving Kv4.2 surface recruitment associated with dampened phasic firing. The results also identify impaired seizure-induced increases of A-type K(+) current as an additional defect produced by the autosomal dominant lateral temporal lobe epilepsy gene mutant that might contribute to the seizure disorder.

Long-term results of iliac wing fixation below extensive fusions in ambulatory adult patients with spinal disorders.

STUDY DESIGN: Case series, level of evidence therapeutic IV. OBJECTIVE: Examine the results of bilateral iliac wing fixation in long fusions to the pelvis in ambulatory adult patients. SUMMARY OF BACKGROUND DATA: Adult spinal deformity surgery is an endeavor often fraught with complications. One particularly debilitating problem with long fusions of the spine in adults with spinal diseases such as degenerative scoliosis and spondylolysis is failure of the lumbosacral (spinal-pelvic) junction owing to nonunion, implant failure, or sacral fracture. This can result in continued pain, continued curve progression and deformity, progressive sagittal imbalance, and the need for reoperation. Some deformity surgeons have speculated fusion rates at the caudal end of long constructs to the sacrum could be improved by the addition of spinopelvic fixation. Iliac wing screws have been successfully used in nonambulatory patients for the treatment of neuromuscular scoliosis, but concerns exist over use in ambulatory patients. Prominence, local irritation of the screws, screw breakage, infection, and sacroiliac joint pathology are all concerns. The purpose of this study was to examine the results of long fusions to the sacrum using bilateral iliac wing screw fixation in ambulatory adults with spinal deformities. METHODS: This case series consisted of 78 patients followed for at least 2 years (average 3.7 y, range: 2 to 8 y). All patients were ambulatory adults who received bilateral iliac wing fixation below long fusion constructs (average 9 levels fused). All but 3 patients were above 50 years old and the average age in the study was 67.6 years. There were 66 females and 12 males in the study. The operative indications for posterior spinal fusion were fixed sagittal imbalance spondylolysis (23 patients), idiopathic scoliosis (22 patients), degenerative scoliosis (15 patients), pseudarthrosis below long fusions (13 patients), and traumatic kyphosis (5 patients). Patients were analyzed clinically and radiographically and all complications were noted. Correction of coronal deformity and correction of fixed sagittal imbalance were measured by comparing preoperative and postoperative radiographic measurements. All patients completed the Zuckerman written questionnaire to assess patient's subjective clinical result. RESULTS: Twelve of 78 patients (15.3%) developed pseudarthrosis with broken implants; however only 5 of 78 (6.4%) nonunions occurred at the lumbosacral junction. Six of 78 patients (7.7%) required removal of the iliac screws for pain or painful prominence. Forty-two patients had one or more complications with an overall complication rate of 54%. Despite the overall complication and revision rate, 78% of patients reported good or excellent results with the Zuckerman questionnaire. Excellent correction of sagittal balance and coronal deformity was achieved. Average sagittal balance preoperatively was+10 and improved to an average of+2.5 postoperatively. Average major curve coronal plane deformity preoperatively was 61 degree and improved to an average of 29 degree postoperatively. There were no sacral fractures, sacral screw failures, or significant sacroiliac joint degeneration on follow-up radiographs. CONCLUSIONS: In this series, nonunions continue to be a problem, with a rate of 15.3%, however only 6.4% of nonunions were at the lumbosacral junction. Complications specific to iliac screw placement were minimal. These difficult surgeries are known to be plagued with problems and our complication rate is consistent with what is present in the current literature. The use of iliac wing fixation seems to dramatically improve lumbosacral fusion rates with an acceptable complication rate; in addition there seems to be a protective effect in preventing sacral fractures, sacral screw failure, and sacroiliac arthritis.

Red blood cell arginase suppresses Jurkat (T cell) proliferation by depleting arginine.

BACKGROUND: Transfusion of packed red blood cells (PRBC) suppresses immunity, but the mechanisms are incompletely understood. PRBCs contain arginase, an enzyme which converts arginine to ornithine and depletes arginine in vitro. Arginine depletion suppresses proliferation of Jurkat T cells in other models. We hypothesize that PRBC arginase-mediated arginine depletion will suppress proliferation of T cells. METHODS: A transfusion model was designed adding PRBC to culture RPMI media with or without an irreversible arginase blocker (nor-NOHA), incubating for 6-48 hours and then removing the PRBCs. Amino acid concentrations in the media were measured using liquid chromatography mass spectrometry. T cells were then added to the pre-conditioned media, cultured for 24 hours, and proliferation was measured. RESULTS: PRBC depleted arginine significantly and increased ornithine in media compared to baseline PRBC treated wells and significantly decreased T cell proliferation. These effects were enhanced with volume of PRBC exposure. Nor-NOHA inhibition of arginase restored T cell proliferation in PRBC treated cultures. CONCLUSIONS: Jurkat T cell proliferation was impaired by PRBC in clinically relevant volumes. The mechanism influencing T cell impairment appears to result from arginine depletion by arginase. Arginine depletion by PRBC arginase may be a novel mechanism for immunosuppression after transfusion.