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.

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.

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.

Metabolic reprogramming of synovial fibroblasts in osteoarthritis by inhibition of pathologically overexpressed pyruvate dehydrogenase kinases.

Osteoarthritis (OA) is the most common degenerative joint disease and a major cause of age-related disability worldwide, mainly due to pain, the disease's main symptom. Although OA was initially classified as a non-inflammatory joint disease, recent attention has been drawn to the importance of synovitis and fibroblast-like synoviocytes (FLS) in the pathogenesis of OA. FLS can be divided into two major populations: thymus cell antigen 1 (THY1)- FLS are currently classified as quiescent cells and assumed to destroy bone and cartilage, whereas THY1+ FLS are invasively proliferative cells that drive synovitis. Both THY1- and THY1+ FLS share many characteristics with fibroblast-like progenitors - mesenchymal stromal cells (MSC). However, it remains unclear whether synovitis-induced metabolic changes exist in FLS from OA patients and whether metabolic differences may provide a mechanistic basis for the identification of approaches to precisely convert the pathologically proliferative synovitis-driven FLS phenotype into a healthy one. To identify novel pathological mechanisms of the perpetuation and manifestation of OA, we analyzed metabolic, proteomic, and functional characteristics of THY1+ FLS from patients with OA. Proteome data and pathway analysis revealed that an elevated expression of pyruvate dehydrogenase kinase (PDK) 3 was characteristic of proliferative THY1+ FLS from patients with OA. These FLS also had the highest podoplanin (PDPN) expression and localized to the sublining but also the lining layer in OA synovium in contrast to the synovium of ligament trauma patients. Inhibition of PDKs reprogrammed metabolism from glycolysis towards oxidative phosphorylation and reduced FLS proliferation and inflammatory cytokine secretion. This study provides new mechanistic insights into the importance of FLS metabolism in the pathogenesis of OA. Given the selective overexpression of PDK3 in OA synovium and its restricted distribution in synovial tissue from ligament trauma patients and MSC, PDKs may represent attractive selective metabolic targets for OA treatment. Moreover, targeting PDKs does not affect cells in a homeostatic, oxidative state. Our data provide an evidence-based rationale for the idea that inhibition of PDKs could restore the healthy THY1+ FLS phenotype. This approach may mitigate the progression of OA and thereby fundamentally change the clinical management of OA from the treatment of symptoms to addressing causes.

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.

Gastrostomy Tube for Nutrition and Malignant Bowel Obstruction in Patients With Cancer.

BACKGROUND: Gastrostomy tubes (G-tubes) are invaluable clinical tools that play a role in palliation and nutrition in patients with cancer. This study aimed to better understand the risks and benefits associated with the placement and maintenance of G-tubes. METHODS: Patients who underwent placement of a G-tube for cancer from January 2013 through December 2017 at a tertiary care center were considered for inclusion. Clinical data were retrospectively collected from medical records. RESULTS: A total of 242 patients with cancer, whose average age at diagnosis was 61 years (range, 21-94 years), underwent G-tube placement for nutrition (76.4%), decompression (22.7%), or both (0.8%). Successful insertion was achieved in 96.8%, but 8 patients required >1 attempted method of insertion. In the decompression group, minor postplacement complications were less common (23.6% vs 53.5%; P<.001) and survival was shorter (P<.001) compared with the nutrition group. For those with decompressive G-tubes, 45.5% had a palliative care consult; 56.4% were seen by social workers; and 46.3% went to hospice. The frequency of hospice discharge was higher in patients who had consults (53.7% vs 23.1%; P=.01). CONCLUSIONS: Half of the patients who received decompressive G-tubes presented with stage IV disease and died within 1 month of placement. Those with >1 consult were more likely to be discharged to hospice. Patients with G-tubes for nutrition saw no change in functionality, complication rate, or survival, regardless of adjunct chemotherapy status. These findings illustrate the need for a tool to allow a better multidisciplinary approach and interventional decision-making for patients with cancer.

Untargeted Phylogenetic Group III of Multi-drug-Resistant Bacillus cereus Isolated Using Fraser Medium from Retail Chickens in Ho Chi Minh City.

The prevalence of food-borne bacteria in developing countries is less well understood than in developed countries. The ISO11290-1 isolation method is commonly used to study Listeria contamination in chicken; however, all isolates are identified as untargeted Bacillus cereus. This study aimed to determine the classification, antibiotic susceptibility, and virulence genes of B. cereus isolated from retail chickens in Vietnam. Bacterial isolation using the ISO11290-1 method yielded 12 strains of B. cereus from seven out of 60 chickens. For determining bacterial diversity, panC and multilocus sequence typing (MLST) analyses were performed. PanC analysis showed that all seven strains belong to the phylogenetic group III, to which the highest risk of foodborne illnesses was associated. MLST analysis showed that most strains contained a ST205 complex; further, all strains were found to be resistant to ampicillin, ciprofloxacin, and tetracycline. Virulence genes were also investigated. ces, a cereulide-related gene, was detected in 50% of the isolated strains, followed by cytK, nheA, and hblA enterotoxins in 41.7%, 16.7%, and 25% of the strains, respectively. In conclusion, B. cereus may be erroneously detected when attempting to detect Listeria in food using the ISO11290-1 method. Further study of the prevalence of B. cereus in Vietnamese food is needed to improve food safety.

Efficient approach to superior vena cava baffle stenosis following the Mustard procedure: Expanding the role of a mechanical rotating dilator sheath for lead extraction.

INTRODUCTION: In adult congenital patients with transposition of the great arteries originally treated with the Mustard (atrial switch) procedure, the most common reason for re-intervention is baffle stenosis. This may be exacerbated by permanent transvenous pacemaker lead placement across the baffle. CASE REPORT: A 47-year-old female status post Mustard procedure performed at 15 months old presented with a high-grade stenosis of the superior vena cava (SVC) baffle from the SVC to the left atrium, with a nonfunctional permanent pacemaker lead passing through the baffle. A mechanical rotating dilator sheath was used for attempted lead extraction, relieving the baffle stenosis almost completely as a secondary effect, before the placement of a 10 × 27 mm Visipro balloon-expandable stent in the SVC baffle. CONCLUSIONS: Use of the mechanical rotating dilator sheath is an evolving treatment strategy in adult congenital heart disease to minimize the risk of bleeding, trauma to surrounding structures, and death. Its ability to fully alleviate baffle stenosis even when full lead extraction is not feasible or is associated with significant procedural risk, further demonstrates its expanded role in this patient population. A multidisciplinary approach and great diligence must be employed to avoid potential complications.

Left innominate vein creation using left internal jugular vein tunneled to right internal jugular vein.

BACKGROUND: Left innominate vein occlusion is a known complication of pacemaker and central venous catheter placement. For dialysis-dependent patients with an arteriovenous fistula (AVF), this can prevent successful hemodialysis and may require surgical intervention. CASE REPORT: An 8-month-old male was diagnosed with hemolytic uremic syndrome and became dialysis-dependent at 11 months of age. After multiple vascular access and peritoneal dialysis complications, the patient had construction of a brachiobasalic AVF in his left arm at 13 years old. While waiting for the AVF to mature, an attempt to remove a previously placed left subclavian vein port-a-cath was unsuccessful and a follow-up imaging revealed that the vessel had become occluded. The fistula remained patent, but due to arm swelling and venous obstruction, his fistula was not accessible. Multiple attempts to percutaneously cross the left innominate vein were unsuccessful and the patient was referred for surgical intervention. At 15 years old, the patient was taken to the operating room for transposition of the left internal jugular vein (LIJ) to the right internal jugular vein (RIJ). The LIJ was transected under the mandible and anastomosed to the RIJ. Subsequently the patient underwent VWING insertion rather than venous transposition for constant site dialysis. Although he has required frequent transcatheter dilation of the LIJ-RIJ anastomosis, the patient was successfully dialyzed using this fistula for 5 years. The patient received a cadaveric renal transplant at 5 years 20 days. CONCLUSIONS: In cases of left innominate vein stenosis, transposing the LIJ can create a new left innominate vein that can alleviate venous hypertension and preserve fistula function. This procedure avoids sternotomy and only requires one anastomosis.

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.

catena-Poly[ammonium [aqua-bis-(µ-2,3,5,6-tetra-oxo-4-nitro-pyridin-4-ido)argentate(I)]].

In the title compound, {(NH4)[Ag(C5HN2O6)2(H2O)]} n , the Ag(I) cation is seven-coordinated and is surrounded by four oxo O atoms of the 2,3,5,6-tetra-oxo-4-nitro-pyridin-4-ide species [Ag-O = 2.3848 (19), 2.4931 (18), 2.5361 (18) and 2.573 (2) Å], two nitro O atoms [Ag-O = 2.644 (2) and 2.661 (2) Å], and one water mol-ecule [Ag-O = 2.3133 (19) Å]. The pyridin-4-ide mono-anions act as polydentate bridging ligands and form a three-dimensional network that is stabilized through O-H⋯O and N-H⋯O hydrogen bonds involving the coordinating water mol-ecule and the imide function as donator groups. The ammonium cations are located in the cavities of the framework and are also involved in hydrogen bonding to O atoms of the ligand.

Hexa-aqua-bis-[3,5-bis-(hy-droxy-imino)-1-methyl-2,4,6-trioxo-cyclo-hexa-nido-κ(2) N (3),O (4)]barium tetrahydrate.

In the title compound, [Ba(C7H5N2O5)2(H2O)6]·4H2O, the Ba(2+) cation lies on a twofold rotation axis and is ten-coordinated by two 3,5-bis-(hy-droxy-imino)-1-methyl-2,4,6-trioxo-cyclo-hexa-n-ide oxo O atoms [Ba-O = 2.8715 (17) Å], two hy-droxy-imino N atoms [Ba-N = 3.036 (2) Å], and six water mol-ecules [Ba-O = 2.847 (2), 2.848 (2), and 2.880 (2) Å]. The 3,5-bis-(hy-droxy-imino)-1-methyl-2,4,6-trioxo-cyclo-hexa-nide monoanions act in a bidentate chelating manner, coordinating through an N atom of the non-deprotonated hy-droxy-imino group and an O atom of the neighboring oxo group. Two lattice water mol-ecules are located in the cavities of the framework and are involved in hydrogen bonding to O atoms of one of the coordinating water mol-ecules and the O atom of a keto group of the ligand. As a result, a three-dimensional network is formed.

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.

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.

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.

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.

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.

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.