The Association of Oxygen Delivery and Transfusion on Cardiopulmonary Bypass with Acute Kidney Injury.

OBJECTIVES: To estimate whether the association of transfusion and acute kidney injury (AKI) has a threshold of oxygen delivery below which transfusion is beneficial but above which it is harmful. DESIGN: Retrospective study SETTING: Cardiovascular operating room and intensive care unit PARTICIPANTS: Patients undergoing cardiac surgery with continuous oxygen delivery monitoring during cardiopulmonary bypass INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Logistic regression was used to estimate the associations between oxygen delivery (mean, cumulative deficit, and bands of oxygen delivery), transfusion, and their interaction and AKI. A subgroup analysis of transfused and nontransfused patients with exact matching on cumulative oxygen deficit and time on bypass with adjustment for propensity to receive a transfusion using logistic regression. Nine hundred ninety-one of 4,203 patients developed AKI within 7 days. After adjustment for confounders, lower mean oxygen delivery (odds ratio [OR], 0.968; 95% confidence interval [CI], 0.949-0.988; p = 0.002) and transfusions (OR, 1.442; 95% CI, 1.077, 1.932; p = 0.014) were associated with increased odds of AKI by 7 days. As oxygen delivery decreased, the risk of AKI increased, with the slope of the OR steeper at <160 mL/m2/min. In the subgroup analysis, matched transfused patients were more likely than matched nontransfused patients to develop AKI (45% [n = 145] v 31% [n = 101]; p < 0.001). However, after propensity score adjustment, the difference was nonsignificant (OR, 1.181; 95% CI, 0.796-1.752; p = 0.406). CONCLUSIONS: We found a nonlinear relationship between oxygen delivery and AKI. We found no level of oxygen delivery at which transfusion was associated with a decreased risk of AKI.

Improved implicit self-esteem is associated with extended antidepressant effects following a novel synergistic intervention.

INTRODUCTION: In a previously published randomized controlled trial, automated self-association training (ASAT), a novel digital intervention, was found to extend the rapid antidepressant effect of a single infusion of ketamine for at least 30 days. In this secondary analysis, we aimed to understand the potential role of implicit self-esteem in the combined antidepressant effect of ketamine and ASAT training, by investigating the novel synergistic treatment's effects on implicit self-associations and their relation to symptom improvement. METHODS: A total of 154 adults (ages 18-60) with treatment-resistant unipolar depression and lower-than-normative explicit self-esteem were randomized in a double-blind, parallel-arm design to receive one of three treatment allocations: an active/active treatment combination consisting of one infusion of ketamine (0.5 mg/kg) followed by four days of ASAT ( ~ 30-40 min/day), or one of two control arms that lacked either the active drug or the active behavioral component. The Implicit Association Test (IAT) was used to behaviorally assess the strength of association between self-related stimuli and negative concepts. Linear regression models were used to test the relationship between group assignment, IAT scores acquired immediately post-treatment, and both acute and extended clinical outcomes (% change in Montgomery-Asberg Depression Rating Scale scores, relative to pre-treatment baseline) in the trial. RESULTS: The group assigned to ketamine + ASAT intervention, compared to the other groups, had a pattern of IAT scores indicating more positive self-associations immediately after treatment relative to the control arms (F(1, 131) = 3.979; p = 0.048). In regression models, IAT scores tracked with concurrent (acute post-treatment) % change in MADRS scores across all treatment arms (p = 0.001), and mediated more extended (Day 30) depression improvements specifically for the ketamine+ASAT arm (group * IAT interaction term: ß = -0.201; p = 0.049). DISCUSSION: Our findings suggest that changing implicit self-worth during a post-ketamine 'plasticity window' is one key mechanism whereby the novel ketamine+ASAT treatment combination exerts its antidepressant benefit, confirming the intended treatment target at the level of implicit cognition. Future studies should seek to further enhance the reliability of the biobehavioral intervention's impact on implicit cognition, as this mechanism appears linked to the intervention's enduring clinical benefits.

Impact of Frailty in Patients Undergoing Minimally Invasive Mitral Valve Surgery.

OBJECTIVE: Psoas muscle size is a reliable marker of sarcopenia and frailty that correlates with adverse outcomes after cardiac surgery. However, its use in mitral and minimally invasive cardiac surgery is lacking. We sought to determine whether frailty, as measured by psoas muscle index, increases surgical risk for minimally invasive mitral valve surgery. METHODS: Patients undergoing isolated minimally invasive mitral surgery via right minithoracotomy were identified. Patients who underwent maze, tricuspid intervention, and those who were emergent were excluded. Total psoas muscle area was calculated using the average cross-sectional area at the L3 vertebra on computed tomography scan and indexed to body surface area. Sarcopenia was defined as <25th gender-specific percentile. Patients were stratified by sarcopenia status and outcomes compared. RESULTS: Of 287 total patients, 192 patients met inclusion criteria. Sarcopenic patients were 6 years older (66 vs 60 years, P = 0.01), had lower preoperative albumin levels (4.0 vs 4.3 g/dL, P < 0.001), and had higher Society of Thoracic Surgeons risk of morbidity/mortality (13.1% vs 9.0%, P = 0.003). Operative major morbidity or mortality was 6.4% versus 5.5% (P = 0.824), while the 1-year mortality rate was 2.1% versus 0% (P = 0.08). After risk adjustment, psoas index did not predict operative morbidity or mortality. However, sarcopenia was associated with higher odds of readmission (odds ratio = 0.74, P = 0.02). CONCLUSIONS: Contrary to other cardiac operations, for patients undergoing isolated minimally invasive mitral valve surgery, sarcopenia was not associated with increased perioperative risk except for higher readmission rates. Minimally invasive surgical approaches should be strongly considered as the approach of choice in frail patients.

Whole blood transcriptomics identifies subclasses of pediatric septic shock.

BACKGROUND: Sepsis is a highly heterogeneous syndrome, which has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies. The goal of this study was to elucidate pathophysiological pathways and identify pediatric septic shock subclasses based on whole blood RNA expression profiles. METHODS: The subjects were critically ill children with cardiopulmonary failure who were a part of a prospective randomized insulin titration trial to treat hyperglycemia. Genome-wide expression profiling was conducted using RNA sequencing from whole blood samples obtained from 46 children with septic shock and 52 mechanically ventilated noninfected controls without shock. Patients with septic shock were allocated to subclasses based on hierarchical clustering of gene expression profiles, and we then compared clinical characteristics, plasma inflammatory markers, cell compositions using GEDIT, and immune repertoires using Imrep between the two subclasses. RESULTS: Patients with septic shock depicted alterations in innate and adaptive immune pathways. Among patients with septic shock, we identified two subtypes based on gene expression patterns. Compared with Subclass 2, Subclass 1 was characterized by upregulation of innate immunity pathways and downregulation of adaptive immunity pathways. Subclass 1 had significantly worse clinical outcomes despite the two classes having similar illness severity on initial clinical presentation. Subclass 1 had elevated levels of plasma inflammatory cytokines and endothelial injury biomarkers and demonstrated decreased percentages of CD4 T cells and B cells and less diverse T cell receptor repertoires. CONCLUSIONS: Two subclasses of pediatric septic shock patients were discovered through genome-wide expression profiling based on whole blood RNA sequencing with major biological and clinical differences. Trial Registration This is a secondary analysis of data generated as part of the observational CAF-PINT ancillary of the HALF-PINT study (NCT01565941). Registered March 29, 2012.

Anti-SARS-CoV-2 activity of cyanopeptolins produced by Nostoc edaphicum CCNP1411.

Despite the advances in contemporary medicine and availability of numerous innovative therapies, effective treatment and prevention of SARS-CoV-2 infections pose a challenge. In the search for new anti-SARS-CoV-2 drug candidates, natural products are frequently explored. Here, fifteen cyanopeptolins (CPs) were isolated from the Baltic cyanobacterium Nostoc edaphicum and tested against SARS-CoV-2. Of these depsipeptides, the Arg-containing structural variants showed the strongest inhibition of the Delta SARS-CoV-2 infection in A549ACE2/TMPRSS2 cells. The functional assays indicated a direct interaction of the Arg-containing CP978 with the virions. CP978 also induced a significant decline in virus replication in the primary human airway epithelial cells (HAE). Of the four tested SARS-CoV-2 variants, Wuhan, Alpha, Omicron and Delta, only Wuhan was not affected by CP978. Finally, the analyses with application of confocal microscopy and with the SARS-CoV-2 pseudoviruses showed that CP978-mediated inhibition of viral infection results from the direct binding of the cyanopeptolin with the coronaviral S protein. Considering the potency of viral inhibition and the mode of action of CP978, the significance of the peptide as antiviral drug candidate should be further explored.

Whole Blood Transcriptomics Identifies Subclasses of Pediatric Septic Shock.

Background: Sepsis is a highly heterogeneous syndrome, that has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies. The goal of this study was to elucidate pathophysiological pathways and identify pediatric septic shock subclasses based on whole blood RNA expression profiles. Methods: The subjects were critically ill children with cardiopulmonary failure who were a part of a prospective randomized insulin titration trial to treat hyperglycemia. Genome-wide expression profiling was conducted using RNA-sequencing from whole blood samples obtained from 46 children with septic shock and 52 mechanically ventilated noninfected controls without shock. Patients with septic shock were allocated to subclasses based on hierarchical clustering of gene expression profiles, and we then compared clinical characteristics, plasma inflammatory markers, cell compositions using GEDIT, and immune repertoires using Imrep between the two subclasses. Results: Patients with septic shock depicted alterations in innate and adaptive immune pathways. Among patients with septic shock, we identified two subtypes based on gene expression patterns. Compared with Subclass 2, Subclass 1 was characterized by upregulation of innate immunity pathways and downregulation of adaptive immunity pathways. Subclass 1 had significantly worse clinical outcomes despite the two classes having similar illness severity on initial clinical presentation. Subclass 1 had elevated levels of plasma inflammatory cytokines and endothelial injury biomarkers and demonstrated decreased percentages of CD4 T cells and B cells, and less diverse T-Cell receptor repertoires. Conclusions: Two subclasses of pediatric septic shock patients were discovered through genome-wide expression profiling based on whole blood RNA sequencing with major biological and clinical differences. Trial Registration: This is a secondary analysis of data generated as part of the observational CAF PINT ancillary of the HALF PINT study (NCT01565941). Registered 29 March 2012.

Academic Rank and Productivity Among United States Cardiothoracic Surgeons.

BACKGROUND: Despite a significant growth of women trainees in cardiothoracic surgery recently, women remain a minority of cardiothoracic surgeons and hold a minority of leadership positions. This study evaluates differences in cardiothoracic surgeon subspecialty choices, academic rank, and academic productivity between men and women. METHODS: The Accreditation Council for Graduate Medical Education database was used to identify 78 cardiothoracic surgery academic programs in the United States, including integrated, 4+3, and traditional fellowships, as of June 2020. A total of 1179 faculty members were identified within these programs, 585 adult cardiac surgeons (50%), 386 thoracic surgeons (33%), and 168 congenital surgeons (14%), and other, 40 (3%). Data were collected using institutional websites, ctsnet.org, doximity.com, linkedin.com, and Scopus. RESULTS: Of the 1179 surgeons, only 9.6% were women. Overall, women composed 6.7% of adult cardiac, 15% of thoracic, and 7.7% of congenital surgeons. Among subspecialties, women represent 4.5% (17 of 376) of full professors and 5% (11 of 195) of division chiefs in cardiothoracic surgery in the United States, have shorter career durations, and lower h-indices compared with men. However, women had similar m-indices, which factors in career length, compared with men in adult cardiac (0.63 vs 0.73), thoracic (0.77 vs 0.90), and congenital (0.67 vs 0.78) surgeons. CONCLUSIONS: Career duration, including cumulative research productivity, appears to be the most important factors predicting full professor rank, potentially contributing to persistent sex-based disparities in academic cardiothoracic surgery.

Giant coronary artery fistula: A case report.

Coronary artery fistulas (CAFs) are abnormal connections of coronary arteries where venous circuits bypass the normal capillaries in the myocardium. CAFs are rare, and most patients are asymptomatic. However, CAFs are the most common coronary artery anomalies affecting coronary hemodynamics. While most CAFs are asymptomatic in young patients, symptoms and complications become more frequent with increasing age. CAFs are characterized by variable clinical manifestations based on their size, origin, and drainage site. We describe a 35-year-old woman presenting with the shortness of breath after walking. Despite attempting medical treatment, the patient continued to experience dyspnea, fatigue, fainting the and chest pain episodes. After admission, cardiac imaging was immediately performed and recorded symptomatic CAFs. Percutaneous transcatheter closure treatment was indicated. The patient was discharged with clinical recovery. The treatment of symptomatic CAFs often requires the clear cardiac imaging and endovascular approach to achieve the best clinical results.

Oxygen Delivery Thresholds During Cardiopulmonary Bypass and Risk for Acute Kidney Injury.

BACKGROUND: Postoperative acute kidney injury (AKI) in cardiac surgery patients is multifactorial and associated with low oxygen delivery (DO2) during cardiopulmonary bypass. METHODS: Cardiac surgical patients undergoing full cardiopulmonary bypass between May 1, 2016 and December 31, 2021 were included, whereas those on preoperative dialysis, undergoing circulatory arrest procedures, or lacking minute-to-minute physiologic data were excluded. A 5-minute running average of indexed DO2 (DO2i, mL/min/m2) was calculated ([pump flow] × [hemoglobin] × 1.36 [hemoglobin saturation] + 0.003 [arterial oxygen tension]/body surface area). AKI was defined using established Kidney Disease: Improving Global Outcomes criteria. The threshold of nadir DO2i on the effect of AKI was estimated using risk-adjusted Constrained Broken-Stick models. RESULTS: Postoperative AKI occurred among 1155 patients (29.4%), with 276 (7.0%) having stage 2 to 3 AKI. The median nadir DO2i was lower for those with (vs without) AKI (197.9 mL/min/m2 [interquartile range {IQR}, 166.3-233.2] vs 217.2 mL/min/m2 [IQR, 184.5-252.2], P < .001) and stage 2 to 3 AKI relative to stage 1 or none (186.9 mL/min/m2 [IQR, 160.1-220.5] vs 213.8 mL/min/m2 [IQR, 180.4-249.4]). In risk-adjusted analyses the estimated threshold for nadir DO2i was 231.2 mL/min/m2 (95% CI, 173.6-288.8) for any AKI and 103.3 (95% CI, 68.4-138.3) for stage 2 to 3 AKI. CONCLUSIONS: Decreasing nadir DO2i was associated with an increased risk of AKI. The identified nadir DO2i thresholds suggest management and treatment of nadir DO2i during cardiopulmonary bypass may decrease a patient's postoperative AKI risk.

Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression.

Intravenous ketamine is posited to rapidly reverse depression by rapidly enhancing neuroplasticity. In human patients, we quantified gray matter microstructural changes on a rapid (24-h) timescale within key regions where neuroplasticity enhancements post-ketamine have been implicated in animal models. In this study, 98 unipolar depressed adults who failed at least one antidepressant medication were randomized 2:1 to a single infusion of intravenous ketamine (0.5 mg/kg) or vehicle (saline) and completed diffusion tensor imaging (DTI) assessments at pre-infusion baseline and 24-h post-infusion. DTI mean diffusivity (DTI-MD), a putative marker of microstructural neuroplasticity in gray matter, was calculated for 7 regions of interest (left and right BA10, amygdala, and hippocampus; and ventral Anterior Cingulate Cortex) and compared to clinical response measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms-Self-Report (QIDS-SR). Individual differences in DTI-MD change (greater decrease from baseline to 24-h post-infusion, indicative of more neuroplasticity enhancement) were associated with larger improvements in depression scores across several regions. In the left BA10 and left amygdala, these relationships were driven primarily by the ketamine group (group * DTI-MD interaction effects: p = 0.016-0.082). In the right BA10, these associations generalized to both infusion arms (p = 0.007). In the left and right hippocampus, on the MADRS only, interaction effects were observed in the opposite direction, such that DTI-MD change was inversely associated with depression change in the ketamine arm specifically (group * DTI-MD interaction effects: p = 0.032-0.06). The acute effects of ketamine on depression may be mediated, in part, by acute changes in neuroplasticity quantifiable with DTI.

High Dietary Cation and Anion Difference and High-Dose Ascorbic Acid Modify Acid-Base and Antioxidant Balance in Dairy Goats Fed under Tropical Conditions.

High ambient temperature (HTa) causes acid-base imbalance and systemic oxidative stress, and this may indirectly affect the mammary gland. Furthermore, HTa induces intracellular oxidative stress, which has been proposed to affect cell metabolism directly. We previously showed in dairy goats that the negative effect of HTa was compromised by enhancing heat dissipation during a high dietary cation and anion difference (DCAD) regimen. Moreover, high-dose vitamin C or ascorbic acid (AA) supplements have been used to manage oxidative stress in ruminants. The present study hypothesized that high DCAD and AA supplements that could alleviate the HTa effect would influence the milk synthesis pathway and mammary gland function. The results showed that goats fed with high DCAD had higher blood pH than control goats in the 4th week. The high dose of AA supplement decreases urine pH in the 8th week. The percent reduction of urine pH from the AA supplement was significant in the DCAD group. The high-dose AA supplement decreased plasma glutathione peroxidase activity and malonaldehyde. This effect was enhanced by a high DCAD supplement. In addition, supplementation with AA increased milk protein and citrate and decreased milk FFA. These alterations indicate the intracellular biochemical pathway of energy metabolism and milk synthesis. It can be concluded that a high DCAD regimen and AA supplement in dairy goats fed under HTa could influence the milk synthesis pathway. The evidence suggests that HTa decreases mammary gland function by modification of acid-base homeostasis and oxidative stress.

Large isolated major aortopulmonary collateral artery causing dilated left ventricle.

Isolated major aortopulmonary collateral artery (MAPCA), in the absence of evidence of structural heart disease, is a very rare observation. This anomaly usually appears in preterm newborns. In the majority of babies, isolated MAPCAs cause no symptoms and regress spontaneously after birth and their conservative management is usually sufficient. We report a case of an asymptomatic full-term 5-month-old infant presenting with heart murmur as the only sign during clinical evaluation. Echocardiography revealed a dilated left ventricle, with no pulmonary hypertension. Computed tomography angiogram showed a large MAPCA arising from the descending thoracic aorta and supplying blood to the left lower lobe. The condition was managed successfully by percutaneous obliteration with Amplatzer vascular plugs. Isolated MAPCA is usually a benign anomaly, presenting no clinical finding and requiring no specific treatment. However, in a small minority of infants, this congenital disorder may progress, with detrimental impacts on cardiac structure before clinical symptoms appear. Early intervention may be required to prevent irreversible sequelae.

Outcomes of cardiac surgical procedures performed by trainees versus consultants: A systematic review with meta-analysis.

OBJECTIVES: Cardiac surgery is highly demanding and the ideal teaching method to reach competency is widely debated. Some studies have shown that surgical trainees can safely perform full operations with equivocal outcomes compared with their consultant colleagues while under supervision. We aimed to compare outcomes after cardiac surgery with supervised trainee involvement versus consultant-led procedures. METHODS: We systematically reviewed databases (PubMed/MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Google Scholar) and reference lists of relevant articles for studies that compared outcomes of cardiac surgery performed by trainees versus consultants. Primary end points included: operative mortality, coronary events, neurological/renal complications, reoperation, permanent pacemaker implantation, and sternal complications. Secondary outcomes included cardiopulmonary bypass and aortic cross-clamp times and intensive care/in-hospital length of stay. Random effects meta-analysis was performed. RESULTS: Thirty-three observational studies that reported on a total of 81,616 patients (trainee: 20,154; consultant: 61,462) were included. There was a difference favoring trainees in terms of operative mortality in the main analysis and in an analysis restricted to propensity score-matched samples, whereas other outcomes were not consistently different in both analyses. Overall cardiopulmonary bypass and aortic cross-clamp times were longer in the trainee group but did not translate in longer intensive care unit or hospital stay. CONCLUSIONS: In the right conditions, good outcomes are possible in cardiac surgery with trainee involvement. Carefully designed training programs ensuring graduated hands-on operative exposure as primary operator with appropriate supervision is fundamental to maintain high-quality training in the development of excellent cardiac surgeons.

A Complicated Case Report of Coronary Artery Fistula.

Background: Coronary artery fistulas (CAFs), also, known as coronary arteriovenous malformation, are aberrant connections between coronary arteries and other structures, such as other artery branches or heart chambers. CAFs are infrequent and asymptomatic in young patients, but symptoms and complications become more frequent with age. CAFs can affect hemodynamic parameters and lead to complications, such as myocardial ischemia, heart failure, arrhythmia, and infective endocarditis. Objective: The aim of this article was to present a typical CAF case with severe symptoms who underwent successful embolization to resolve their symptoms. Case presentation: A 50-year-old Vietnamese male visited our cardiac outpatient clinic (S.I.S General Hospital, Can Tho, Vietnam) because of exertional dyspnea and chest pain. Signs of congestive heart failure and abnormal murmur were not presented on chest auscultation. Diagnostic digital subtraction angiography was performed to determine the detailed angioarchitecture of the CAF, revealing a fistulous connection between the left anterior descending artery (LAD) and the LV chamber through an aneurysm. In addition, the RCA measured 7 mm in diameter with a fistula (16 × 9 mm) draining into an aneurysm and then terminating into the LV chamber. The patient had an RCA aneurysm with a fistula into the LV. It was treated successfully by closing the fistula with a vascular plug. Access to the fistula was complex and difficult because of complications due to the CAF. After the procedure, the patient had no chest pain or shortness of breath and was discharged after three days. After six months, he was taking dual antiplatelet therapy and antihypertensive medications and felt better. We performed contrast computed tomography (CT) to examine the fistula after a year, which showed the successful closure of the fistula without any relevant alteration in the coronary artery. Conclusion: CAF closure is indicated if patients have symptoms or secondary complications, and percutaneous closure is a safe and effective method to manage CAF. A CAF is rare and does not have specific symptoms, making it difficult to diagnose. Most patients are asymptomatic and have serious recent complications. Currently, the percutaneous transcatheter method is popular because it is noninvasive and successful in most patients.

Effects of Low Dietary Cation and Anion Difference on Blood Gas, Renal Electrolyte, and Acid Excretions in Goats in Tropical Conditions.

Goats can suffer from intermittent heat stress in high ambient temperature (HTa) conditions, which causes sporadic respiratory hypocapnia. Obstructive urolithiasis is a common urological problem in goats. Sandy uroliths can be partially relieved by urine acidification with short-term ammonium chloride (NH4Cl) treatment. However, the outcome of urine acidification and the physiological responses to short-term NH4Cl supplementation under respiratory hypocapnia of HTa have rarely been reported. The present study investigated the effect of NH4Cl supplementation that produced a low dietary cation-anion different (l-DCAD) diet on acid-base balance and renal function under HTa conditions. The first experiment investigated the physiological responses to natural HTa to prove whether the peak HTa during the afternoon could induce HTa responses without a change in the plasma cortisol. The partial pressure of CO2 also tended to decrease during the afternoon. The second experiment examined the short-term effect of l-DCAD under HTa conditions. Although the blood pH was within the normal range, there was a clear acid-base response in the direction of metabolic acidosis. The major responses in renal function were an increase in tubular function and acid excretion. With a comparable level of creatinine clearance, the fractional excretions (FE) of chloride and calcium increased, and the FE of potassium decreased. Acid excretion increased significantly in the l-DCAD group. We conclude that under HTa conditions, the tubular excretion of electrolytes and acids was the major response to acid loading without changing the filtration rate. The l-DCAD formulation can be used to acidify urine effectively.

A Novel, Brief, Fully Automated Intervention to Extend the Antidepressant Effect of a Single Ketamine Infusion: A Randomized Clinical Trial.

OBJECTIVE: Intravenous ketamine, which displays rapid antidepressant properties, is posited to reverse depression by rapidly enhancing neuroplasticity. The authors tested whether an automated, computer-based approach could efficiently leverage enhanced neuroplasticity to extend the durability of rapid clinical response. METHODS: A total of 154 adults (ages 18-60) with treatment-resistant unipolar depression were randomized in a double-blind, parallel-arm design to receive an active/active treatment combination (ketamine plus active "automated self-association training" [ASAT]; N=53) or one of two control arms that lacked either the active drug component (saline plus active ASAT; N=51) or the active behavioral component (ketamine plus sham ASAT; N=50). One day after a single infusion of intravenous ketamine (0.5 mg/kg over 40 minutes) or inert placebo (saline), active ASAT-targeting self-worth through automated "evaluative conditioning" training delivered by computer-or sham ASAT (consisting of identical computer tasks that included no positive or self-referential stimuli) was given, delivered twice daily over 4 consecutive days (eight sessions, ≤20 minutes per session). The prespecified primary outcome measure throughout the main (30-day) study period was score on the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Ketamine rapidly and significantly reduced depression scores at 24 hours postinfusion (group-by-time interaction: standardized beta [ß]=-1.30, 95% CI=-1.89, -0.70; t=-4.29, df=150). In intent-to-treat linear mixed models, depression scores in the ketamine+ASAT group remained significantly and stably low over the 30-day study period relative to those of the saline+ASAT group (ß=-0.61, 95% CI=-0.95, -0.28; t=-3.62, df=148). By contrast, depression scores following ketamine+sham treatment followed a significant, increasing linear trajectory from 24 hours to 30 days, approaching the levels observed in the saline+ASAT group (group-by-time interaction relative to the saline+ASAT group: ß=0.015, 95% CI=0.003, 0.03; t=2.35, df=568). CONCLUSIONS: After priming the brain with ketamine, training positive self-associations could provide an efficient, low-cost, portable, noninvasive, and highly dissemination-ready strategy for leveraging and extending ketamine's rapid antidepressant effects.

Invited commentary: Total anomalous pulmonary venous connection remains a challenging pediatric disease.

Cervantes-Salazar and colleagues report the long-term surgical outcomes of 414 patients with total anomalous pulmonary venous connection (TAPVC) from January 2003 to June 2019. With an overall survival rate of 87.2% from 2003 to 2019, the authors found that an increased mortality risk was associated with infracardiac TAPVC, pulmonary venous obstruction, and postoperative mechanical ventilation. Their comprehensive study with a large sample size of varying age groups, and patients with late referrals for surgery, provide valuable insight into TAPVC surgical outcomes. Improved survival for these patients continues to be a major goal of clinical teams striving to transform treatment paradigms. The promising result of the study reported by Cervantes-Salazar and colleagues gives our field hope for a better future for these patients.

Diagnostic Value of hTERT mRNA and in Combination With AFP, AFP-L3%, Des-γ-carboxyprothrombin for Screening of Hepatocellular Carcinoma in Liver Cirrhosis Patients HBV or HCV-Related.

Diagnosis of hepatocellular carcinoma (HCC) in early-stage, to give an effective treatment option and improve quality of life for cancer patients, is an important medical mission globally. Combination of AFP with some biomarkers may be more supportive in both diagnosis and screening of HCC, but the range value of these markers can be applied as daily markers were unclearly. In some studies, human telomerase reverse transcriptase (hTERT mRNA) was reported as an advantage marker to diagnose cancer. The present study identified serum of 340 patients that were infected chronic hepatitis B virus or hepatitis C virus and divided in 2 groups including Hepatocellular carcinoma (HCC) and liver cirrhosis (LC) to measure their values of hTERT mRNA, AFP, AFP-L3%, and DCP, as well as combination of them. As a result, the concentration of hTERT mRNA, AFP, AFP-L3%, and DCP in HCC groups were significantly higher than that in LC group (P < .01). For detecting HCC, hTERT mRNA had sensitivity of 88% and specificity of 96% (at the cutoff value of 31.5 copies/mL), AFP sensitivity of 73% and specificity of 92% (at the cutoff value of 5.1 ng/mL), AFP-L3% sensitivity of 69% and specificity of 90% (at the cutoff value of 1.05%), DCP sensitivity of 82% and specificity of 92% (at the cutoff value of 29.01 mAU/mL). The largest area under the curve (AUC) of combination hTERT mRNA with DCP was 0.932 (sensitivity of 98.2% and specificity of 88.2%). New combination of DCP with hTERT mRNA gave a useful choice for screening of HCC in chronic HBV or HCV patients associated liver cirrhosis.