Rank and Match Outcomes of In-person and Virtual Anesthesiology Residency Interviews.

BACKGROUND: For the 2019-2020 interview season, the anesthesia residency program at Augusta University offered candidates a choice between in-person (IP) and video conference (VC) interviews to accommodate a greater number of qualified candidates. METHODS: The same applicant selection criteria were used for both interview types. However, we modified the informal interactions with residents, campus tours, and interview formats for VC interviews. We sought to compare the 2 methods by analyzing the respective costs, benefits, and match results. RESULTS: Of 159 candidates interviewed, we ranked 127 and matched with 12. The IP (n = 135) and VC (n = 24) groups were similar in gender distribution but not by the type of medical school, with more international medical graduates interviewing by VC than IP. There was no statistically significant difference between the 2 interview types for being ranked (81% of IP, 71% of VC) or matched (6% of IP, 17% of VC). US Medical Licensing Examination Step 1 and Step 2 scores and type of medical school did not affect the likelihood of being ranked or matched. Program costs per candidate were higher for the IP group ($431 for IP, $294 for VC). CONCLUSION: Our single-center study indicates that the interview type did not affect the likelihood of a candidate being ranked by or matched to our program. Further, VC interviews were more cost-effective and time-effective than IP interviews. Our findings suggest that VC interviews are a viable alternative and should be an option for residency interviews.

Effect of large volume paracentesis performed just prior to transjugular intrahepatic portosystemic shunt on the anesthetic management during the procedure.

BACKGROUND AND AIMS: Patients often undergo paracentesis prior to a transjugular intrahepatic portosystemic shunt (TIPS) procedure to improve respiratory mechanics. However, the effect of large volume paracentesis (LVP) on intraoperative hemodynamics and anesthetic management when it is performed immediately before the TIPS procedure is not well documented. MATERIAL AND METHODS: This is a retrospective study in patients undergoing the TIPS procedure between 2004 and 2017. Patients were divided into two groups based on the volume of preoperative paracentesis, namely, small volume paracentesis (SVP), defined as paracentesis volume less than 5 L and LVP, defined as paracentesis volume of at least 5 L. Patients' demographics and perioperative information were collected through chart review. The Wilcoxon signed-rank test, student's t-test, and Fisher's exact test were used when appropriate. Uni- and multivariate linear regression analyses were used to determine the predictive value of paracentesis volume in relation to intraoperative hemodynamics and management of hypotension. RESULTS: Of 49 patients, 19 (39%) received LVP and the remainder received SVP. Baseline demographics were comparable between groups as were intraoperative hypotension and volume of infused crystalloid and colloid. However, vasopressor use (P = 0.02) and packed red blood cell transfusion (P = 0.01) were significantly higher in the large volume group. Paracentesis volume was an independent predictor of the phenylephrine dose (P = 0.0004), and of crystalloid (P = 0.05) and colloid (P = 0.009) volume administered after adjusting for age, sex, body mass index, alcohol use, hemoglobin, and model for end-stage liver disease score. CONCLUSION: The anesthetic management of patients who undergo LVP just prior to a TIPS procedure may require larger doses of vasopressors and colloids to prevent intraoperative hemodynamic instability during the TIPS placement but may be as well tolerated as SVP.

Supra-massive transfusion and interdisciplinary approach to cesarean hysterectomy due to complex placenta percreta: Case report.

Placenta accreta spectrum encompasses a group of conditions of abnormal placental infiltration of the uterine wall and surrounding tissues. It is associated with significant blood loss, perioperative morbidity, and risk of death. A coordinated interdisciplinary approach to these complex cases and early resuscitation with blood products are critical factors in the successful management of patients affected by this disease. We describe the successful management of a patient with placenta percreta who required supra-massive transfusion of blood products and interventions by different specialized teams in a tertiary care center.

Perioperative takotsubo cardiomyopathy: Implications for anesthesiologist.

Takotsubo cardiomyopathy (TCM) is characterized by transient ventricular dysfunction in the absence of obstructive coronary artery disease that may be triggered by an acute medical illness or intense physical or emotional stress. TCM is often confused with acute myocardial infarction given the similar electrocardiographic changes, cardiac enzymes, hemodynamic perturbations, and myocardial wall motion abnormalities. In the perioperative setting, the clinical picture may be more confusing because of the effect of anesthesia as well as hemodynamic changes related to the surgery itself. However, awareness of various other diagnostic modalities may enable clinicians to distinguish between the two, more systematically and with greater certainty. Despite the large body of literature, there still seems to be an overall paucity in our understanding of the etiopathogenesis, clinical characteristics, natural history, and management of this syndrome, especially in the perioperative setting. This narrative review seeks to present and synthesize the most recent literature on TCM and to identify gaps in current knowledge which can become the basis for future research.

Serum of sickle cell disease patients contains fetal hemoglobin silencing factors secreted from leukocytes.

BACKGROUND: The mechanisms that regulate fetal hemoglobin (HbF) expression in sickle cell disease (SCD) remain elusive. We previously showed that steady-state SCD patients with high HbF levels due to a γ-globin gene mutation demonstrate strong inverse correlations between HbF levels and leukocyte counts, suggesting that leukocytes play a role in regulating HbF in SCD. MATERIALS AND METHODS: To further investigate the role of leukocytes in HbF expression in SCD, we examined the presence of HbF silencing factors in the serum of 82 SCD patients who received hydroxyurea (HU) therapy. RESULTS: HU-mediated HbF induction was associated with elevated total hemoglobin levels and improved red blood cell parameters, but there was no correlation with reticulocyte or platelet counts. Importantly, we again found that HU-induced HbF levels correlated with reductions in both neutrophils and lymphocytes/monocytes, indicating that these cell lineages may have a role in regulating HU-mediated HbF expression. Our in vitro studies using CD34+-derived primary erythroblasts found that patient serum preparations include HbF silencing factors that are distinct from granulocyte-macrophage colony-stimulating factor, and the activity of such factors decreases upon HU therapy. CONCLUSION: Together, these results demonstrate the importance of leukocyte numbers in the regulation of HbF levels for SCD patients both in steady state and under HU therapy, and that leukocytes secrete HbF silencing factors that negatively affect HbF expression in erythroid-lineage cells in SCD.

Iatrogenic atrio-esophageal fistula following a video-assisted thoracoscopic maze procedure: Is esophageal instrumentation justified even when the diagnosis is equivocal?

A 74-year-old female underwent an uneventful bilateral thoracoscopic maze procedure for persistent atrial fibrillation with continuous transesophageal echocardiographic (TEE) guidance. She presented six weeks later with persistent fever and focal neurological signs. Computed tomography of the thorax revealed air in the posterior LA, raising suspicion for an abscess versus an atrioesophageal fistula (AEF). Before undergoing an exploratory median sternotomy, an esophagogastroduodenoscopy (EGD) was performed by the surgeon to check for any esophageal pathology. This however, resulted in sudden hemodynamic compromise that required intensive treatment with vasopressors and inotropes. In this case-report, we review the various intraoperative risk factors associated with the development of AEF during cardiac ablation procedures as well as the potential hazards of esophageal instrumentation with TEE, naso- or oro- gastric devices, and/or an EGD when an AEF is suspected.

Developing Modules to Train Anesthesiology Residents & Medical Students in a Lung Isolation Technique.

BACKGROUND: One-lung ventilation (OLV) can be accomplished by using ether a double-lumen endotracheal tube (DLT) or a bronchial blocker. Patient factors, surgical requirements and the anesthesiologist's expertise influence technique choice. Bronchial blockers are in general less traumatic, safer to place, and suitable in a wider variety of scenarios than DLTs, but require greater technical skill. We designed a study to determine whether trainees can achieve OLV using a bronchial blocker on completion of a 4-week multimodal training module. METHODS: Anesthesia residents and medical students took part in didactic (lecture and video) and clinical simulation training. During simulation training, participants practiced placing a bronchial blocker under supervision until they performed the technique satisfactorily. Trainees could then practice independently as often as they wished. A skills check was performed during the supervised and after the independent practice; feedback was provided. For more advanced learners, practical clinical training was continued in the operating room. Assessments data (test scores and skills checks) were analyzed using the t-test. RESULTS: Difference between pre-test and post-test scores (didactics) was statistically significant (p=0.02) as was the number of skills checks items satisfactorily demonstrated by the 14 participants on the first supervised attempt and the last independent practice (simulation; p<0.01). All eight who performed one-lung isolation in the operating room were technically proficient in achieving adequate OLV to the satisfaction of the supervising attending anesthesiologist. CONCLUSIONS: This multimodal standardized teaching module which incorporates didactics, simulation training, and, for more advanced trainees, practical clinical experience, improves trainees' knowledge and skills in bronchial blocker placement and OLV.

Nitric Oxide-cGMP Signaling Stimulates Erythropoiesis through Multiple Lineage-Specific Transcription Factors: Clinical Implications and a Novel Target for Erythropoiesis.

Much attention has been directed to the physiological effects of nitric oxide (NO)-cGMP signaling, but virtually nothing is known about its hematologic effects. We reported for the first time that cGMP signaling induces human γ-globin gene expression. Aiming at developing novel therapeutics for anemia, we examined here the hematologic effects of NO-cGMP signaling in vivo and in vitro. We treated wild-type mice with NO to activate soluble guanylate cyclase (sGC), a key enzyme of cGMP signaling. Compared to untreated mice, NO-treated mice had higher red blood cell counts and total hemoglobin but reduced leukocyte counts, demonstrating that when activated, NO-cGMP signaling exerts hematopoietic effects on multiple types of blood cells in vivo. We next generated mice which overexpressed rat sGC in erythroid and myeloid cells. The forced expression of sGCs activated cGMP signaling in both lineage cells. Compared with non-transgenic littermates, sGC mice exhibited hematologic changes similar to those of NO-treated mice. Consistently, a membrane-permeable cGMP enhanced the differentiation of hematopoietic progenitors toward erythroid-lineage cells but inhibited them toward myeloid-lineage cells by controlling multiple lineage-specific transcription factors. Human γ-globin gene expression was induced at low but appreciable levels in sGC mice carrying the human ß-globin locus. Together, these results demonstrate that NO-cGMP signaling is capable of stimulating erythropoiesis in both in vitro and vivo settings by controlling the expression of multiple lineage-specific transcription factors, suggesting that cGMP signaling upregulates erythropoiesis at the level of gene transcription. The NO-cGMP signaling axis may constitute a novel target to stimulate erythropoiesis in vivo.

Anticoagulation dilemma in a high-risk patient with On-X valves.

Thromboembolism continues to be a major concern in patients with mechanical heart valves, especially in those with unsatisfactory anticoagulation levels. The new On-X valve (On-X Life Technologies, Austin, TX, USA) has been reported as having unique structural characteristics that offer lower thrombogenicity to the valve. We report a case where the patient received no or minimal systemic anticoagulation after placement of On-X mitral and aortic valves due to development of severe mucosal arterio-venous malformations yet did not show any evidence of thromboembolism. This case report reinforces the findings of recent studies that lower anticoagulation levels may be acceptable in patients with On-X valves and suggests this valve may be particularly useful in those in whom therapeutic levels of anticoagulation cannot be achieved due to increased risk of bleeding.

Glycosylation inhibitors efficiently inhibit P-selectin-mediated cell adhesion to endothelial cells.

Adhesion molecules play a critical role in the adhesive interactions of multiple cell types in sickle cell disease (SCD). We previously showed that anti-P-selectin aptamer efficiently inhibits cell adhesion to endothelial cells (ECs) and permits SCD mice to survive hypoxic stress. In an effort to discover new mechanisms with which to inhibit P-selectin, we examined the role of glycosylation. P-selectin is a 90 kDa protein but was found to migrate as 90 and 140 kDa bands on gel electrophoresis. When P-selectin isolated from ECs was digested with peptide N-glycosidase F, but not O-glycosidase, the 140 kDa band was lost and the 90 kDa band was enhanced. Treatment of ECs with tunicamycin, an N-glycosylation inhibitor, suppressed CD62P (P-selectin) expression on the cell surface as well as the 140 kDa form in the cytoplasm. These results indicate that the 140 kDa band is N-glycosylated and glycosylation is critical for cell surface expression of P-selectin in ECs. Thrombin, which stimulates P-selectin expression on ECs, induced AKT phosphorylation, whereas tunicamycin inhibited AKT phosphorylation, suggesting that AKT signaling is involved in the tunicamycin-mediated inhibition of P-selectin expression. Importantly, the adhesion of sickle red blood cells (sRBCs) and leukocytes to ECs induced by thrombin or hypoxia was markedly inhibited by two structurally distinct glycosylation inhibitors; the levels of which were comparable to that of a P-selectin monoclonal antibody which most strongly inhibited cell adhesion in vivo. Knockdown studies of P-selectin using short-hairpin RNAs in ECs suppressed sRBC adhesion, indicating a legitimate role for P-selectin in sRBC adhesion. Together, these results demonstrate that P-selectin expression on ECs is regulated in part by glycosylation mechanisms and that glycosylation inhibitors efficiently reduce the adhesion of sRBCs and leukocytes to ECs. Glycosylation inhibitors may lead to a novel therapy which inhibits cell adhesion in SCD.

A common signaling pathway is activated in erythroid cells expressing high levels of fetal hemoglobin: a potential role for cAMP-elevating agents in ß-globin disorders.

BACKGROUND: Although erythroid cells prepared from fetal liver, cord blood, or blood from ß-thalassemia patients are known to express fetal hemoglobin at high levels, the underlying mechanisms remain elusive. We previously showed that cyclic nucleotides such as cAMP and cGMP induce fetal hemoglobin expression in primary erythroid cells. Here we report that cAMP signaling contributes to high-level fetal hemoglobin expression in erythroid cells prepared from cord blood and ß-thalassemia. METHODS: The status of the cAMP signaling pathway was investigated using primary erythroid cells prepared from cord blood and the mononuclear cells of patients with ß-thalassemia; erythroid cells from adult bone marrow mononuclear cells served as the control. RESULTS: We found that intracellular cAMP levels were higher in erythroid cells from cord blood and ß-thalassemia than from adult bone marrow. Protein kinase A activity levels and cAMP-response element binding protein phosphorylation were higher in erythroid cells from cord blood or ß-thalassemia than in adult bone marrow progenitors. Mitogen-activated protein kinase pathways, which play a role in fetal hemoglobin expression, were not consistently activated in cord blood or ß-thalassemia erythroid cells. When cAMP signaling was activated in adult erythroid cells, fetal hemoglobin was induced at high levels and associated with reduced expression of BCL11A, a silencer of the ß-globin gene. CONCLUSION: These results suggest that activated cAMP signaling may be a common mechanism among erythroid cells with high fetal hemoglobin levels, in part because of downregulation of BCL11A. Activation of the cAMP signaling pathway with cAMP-elevating agents may prove to be an important signaling mechanism to reactivate fetal hemoglobin expression in erythroid cells.

The proinflammatory cytokine GM-CSF downregulates fetal hemoglobin expression by attenuating the cAMP-dependent pathway in sickle cell disease.

Although reduction in leukocyte counts following hydroxyurea therapy in sickle cell disease (SCD) predicts fetal hemoglobin (HbF) response, the underlying mechanism remains unknown. We previously reported that leukocyte counts are regulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) in SCD patients. Here we examined the roles of GM-CSF in the regulation of HbF expression in SCD. Upon the analysis of retrospective data in 372 patients, HbF levels were inversely correlated with leukocyte counts and GM-CSF levels in SCD patients without hydroxyurea therapy, while HbF increments after hydroxyurea therapy correlated with a reduction in leukocyte counts, suggesting a negative effect of GM-CSF on HbF expression. Consistently, in vitro studies using primary erythroblasts showed that the addition of GM-CSF to erythroid cells decreased HbF expression. We next examined the intracellular signaling pathway through which GM-CSF reduced HbF expression. Treatment of erythroid cells with GM-CSF resulted in the reduction of intracellular cAMP levels and abrogated phosphorylation of cAMP response-element-binding-protein, suggesting attenuation of the cAMP-dependent pathway, while the phosphorylation levels of mitogen-activated protein kinases were not affected. This is compatible with our studies showing a role for the cAMP-dependent pathway in HbF expression. Together, these results demonstrate that GM-CSF plays a role in regulating both leukocyte count and HbF expression in SCD. Reduction in GM-CSF levels upon hydroxyurea therapy may be critical for efficient HbF induction. The results showing the involvement of GM-CSF in HbF expression may suggest possible mechanisms for hydroxyurea resistance in SCD.

Serum ferritin level changes in children with sickle cell disease on chronic blood transfusion are nonlinear and are associated with iron load and liver injury.

Chronic blood transfusion is increasingly indicated in patients with sickle cell disease. Measuring resulting iron overload remains a challenge. Children without viral hepatitis enrolled in 2 trials for stroke prevention were examined for iron overload (STOP and STOP2; n = 271). Most received desferrioxamine chelation. Serum ferritin (SF) changes appeared nonlinear compared with prechelation estimated transfusion iron load (TIL) or with liver iron concentrations (LICs). Averaged correlation coefficient between SF and TIL (patients/observations, 26 of 164) was r = 0.70; between SF and LIC (patients/observations, 33 of 47) was r = 0.55. In mixed models, SF was associated with LIC (P = .006), alanine transaminase (P = .025), and weight (P = .026). Most patients with SF between 750 and 1500 ng/mL had a TIL between 25 and 100 mg/kg (72.8% +/- 5.9%; patients/observations, 24 of 50) or an LIC between 2.5 and 10 mg/g dry liver weight (75% +/- 0%; patients/observations, 8 of 9). Most patients with SF of 3000 ng/mL or greater had a TIL of 100 mg/kg or greater (95.3% +/- 6.7%; patients/observations, 7 of 16) or an LIC of 10 mg/g dry liver weight or greater (87.7% +/- 4.3%; patients/observations, 11 of 18). Although SF changes are nonlinear, levels less than 1500 ng/mL indicated mostly acceptable iron overload; levels of 3000 ng/mL or greater were specific for significant iron overload and were associated with liver injury. However, to determine accurately iron overload in patients with intermediately elevated SF levels, other methods are required. These trials are registered at www.clinicaltrials.gov as #NCT00000592 and #NCT00006182.