Pathophysiological Mechanisms in Long COVID: A Mixed Method Systematic Review.

INTRODUCTION: Long COVID (LC) is a global public health crisis affecting more than 70 million people. There is emerging evidence of different pathophysiological mechanisms driving the wide array of symptoms in LC. Understanding the relationships between mechanisms and symptoms helps in guiding clinical management and identifying potential treatment targets. METHODS: This was a mixed-methods systematic review with two stages: Stage one (Review 1) included only existing systematic reviews (meta-review) and Stage two (Review 2) was a review of all primary studies. The search strategy involved Medline, Embase, Emcare, and CINAHL databases to identify studies that described symptoms and pathophysiological mechanisms with statistical analysis and/or discussion of plausible causal relationships between mechanisms and symptoms. Only studies that included a control arm for comparison were included. Studies were assessed for quality using the National Heart, Lung, and Blood Institute quality assessment tools. RESULTS: 19 systematic reviews were included in Review 1 and 46 primary studies in Review 2. Overall, the quality of reporting across the studies included in this second review was moderate to poor. The pathophysiological mechanisms with strong evidence were immune system dysregulation, cerebral hypoperfusion, and impaired gas transfer in the lungs. Other mechanisms with moderate to weak evidence were endothelial damage and hypercoagulation, mast cell activation, and auto-immunity to vascular receptors. CONCLUSIONS: LC is a complex condition affecting multiple organs with diverse clinical presentations (or traits) underpinned by multiple pathophysiological mechanisms. A 'treatable trait' approach may help identify certain groups and target specific interventions. Future research must include understanding the response to intervention based on these mechanism-based traits.

Robotics in Total Hip Arthroplasty: Current Concepts.

This current concepts article reviews the literature pertaining to the use of robot-assisted systems in total hip arthroplasty (THA). The bulk of the literature is regarding the MAKO (currently the most used system worldwide) and the historic ROBODOC robotic systems. There is a paucity of literature available on other systems, with several still in pilot-phase development. Whilst the evidence shows improved radiological outcomes with robotic THA, functional outcomes are equivocal between conventional and robotic techniques. Acceptance of robotic THA worldwide is limited by its accessibility including cost, and by already exceptional results with the conventional technique. It is, however, a rapidly developing area of orthopaedic surgery. This article discusses the history of robotics in THA, current surgical techniques, functional and radiological outcomes, and ongoing avenues for development.

Psychopathic personality traits in relational aggression among young adults.

Psychopathy is a robust predictor of overt physical aggression that may also be relevant to relational aggression (RA). This study was conducted to investigate the utility of psychopathic personality traits in the prediction of RA in a sample of 291 college students. Hierarchical multiple regression analyses indicated that both primary and secondary psychopathic traits explained additional variance in general/peer and romantic RA beyond physical aggressiveness. Consistent with previous research, no gender differences were found on either form of RA, challenging the popular stereotype of RA as a female behavior. Moreover, psychopathic traits were not differentially predictive of RA by gender or level of physical aggressiveness. Implications of these findings for research and clinical practice are discussed.

Pulmonary vascular remodelling after heart transplantation in patients with cavopulmonary connection.

OBJECTIVES: Pulmonary vascular resistance (PVR) after heart transplantation (HT) is an important predictor of postoperative outcomes. We hypothesize that PVR and pulmonary capillary wedge pressure (PCWP) will exhibit favourable pulmonary vascular remodelling in patients with failing cavopulmonary connection (CPC) after HT. METHODS: Retrospective analysis of patients with superior CPC (SCPC) and total CPC (TCPC) who have undergone HT was performed. Patient data, including age, underlying congenital heart defect, timing of CPC surgery and timing of HT, were reviewed. Right heart catheterization data, including PCWP (mmHg) and PVR indexed (PVRi, Woods Units) from preoperative, at 1 month, 6 months and 12 months after HT, were collected. Paired data were analysed using Student's t-test. RESULTS: Among 21 patients with failing CPC who underwent HT, 10 had SCPC and 11 had TCPC. Average age at HT was 13.3 ± 8 years. Average time after CPC to HT was 8.5 ± 6.2 years. PVRi was noted to trend down over time after HT (PVRi pre-HT versus 6 months after HT, 2.75 vs 2.06, P = 0.06 and pre-HT versus 12 months after HT, 2.79 vs 2.27, P = 0.09). There was a statistically significant decrease in PCWP at 6 months (pre-HT versus 6 months after HT, 12.6 vs 10.8, P = 0.01) and 12 months (pre-HT versus 12 months after HT, 12.9 vs 10.1, P = 0.01) after HT. CONCLUSIONS: Pulmonary vascular changes occur gradually after HT in patients with CPC similar to those shown after HT in patients with cardiomyopathy. However, larger studies are needed to investigate correlation between outcomes and the presence or absence of pulmonary vascular changes after HT in CPC patients.

Early survival after heart transplant in young infants is lowest after failed single-ventricle palliation: a multi-institutional study.

BACKGROUND: Infant heart transplant (HT) recipients have the best long-term survival of any age group, but the small donor pool and high early mortality limit the therapeutic effectiveness. We sought to determine the relationship between pre-HT diagnosis and early HT outcome to better define the mortality risk associated with a diagnosis of congenital heart disease (CHD) and to examine differences between early and current HT eras. METHODS: The Pediatric Heart Transplant Study (PHTS) database was used to identify 739 infant HT recipients at age ≤ 6 months between 1993 and 2008 divided into the following etiologic groups: cardiomyopathy (CM), 18%; hypoplastic left heart syndrome (HLHS) without surgery, 41%; HLHS with surgery, 9%; other CHD without surgery, 16%; and other CHD with surgery, 15%. Severity of illness at HT, post-HT survival, and era effects were compared. RESULTS: At 1 year after HT, survival was 89% for the CM group, which was the best, 79% for CHD without surgery, 82% for CHD with surgery, 79% for HLHS without surgery, and 70% for HLHS with surgery, which was the worst outcome. Hazard function analysis demonstrated the difference occurred within the first 3 months after HT. After adjusting for illness severity, differences in mortality risk persisted across etiologic groups. HT survival was similar in the current surgical era for HLHS with surgery, 71% (1993-1998) vs 70% (1999-2008). CONCLUSIONS: Infant HT recipients with different pre-HT diagnoses have significantly different post-HT outcomes. HLHS infants with surgery have the lowest survival and their outcome is unchanged in the current era.

Would access to device therapies improve transplant outcomes for adults with congenital heart disease? Analysis of the United Network for Organ Sharing (UNOS).

BACKGROUND: Patients with congenital heart disease (CHD) now survive into adulthood and often present with end-stage heart failure (HF). HF management and approach to orthotopic heart transplant (OHT) may differ from adults without CHD. We sought to compare OHT waitlist characteristics and outcomes for these 2 groups. METHODS: The Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) database was used to identify adults (≥18 years) listed for OHT from 2005 to 2009. The cohort was divided into those with or without CHD. RESULTS: Of 9,722 adults included, 314 (3%) had CHD. Adults with CHD were younger (35 ± 13 vs 52 ± 12 years, p < 0.01) and more often had undergone prior cardiac surgery (85% vs. 34%, p < 0.01). Patients with CHD were less likely to have a defibrillator (44% vs 75%, p < 0.01) or ventricular assist device (5% vs 14%, p < 0.01) and were more likely to be listed at the lowest urgency status than patients without CHD (64% vs 44%, p < 0.01). Fewer CHD patients achieved OHT (53% vs 65%, p < 0.001). Although overall waitlist mortality did not differ between groups (10% vs 8%, p = 0.15), patients with CHD were more likely to experience cardiovascular death (60% vs 40%, p = 0.03), including sudden in 44% and due to HF in 16%. CONCLUSIONS: Despite lower urgency status, patients with CHD have greater cardiovascular mortality awaiting OHT than those without. Increased defibrillator use could improve survival to OHT, because sudden death is common. VAD support may benefit select patients, but experience in CHD is limited. Referral to specialized adult congenital heart centers can enhance utilization of device therapies and potentially improve waitlist outcomes.

Rejection with hemodynamic compromise in the current era of pediatric heart transplantation: a multi-institutional study.

BACKGROUND: Survival after pediatric heart transplant has improved over time, as has the incidence of overall rejection. We studied the effect of era on the occurrence and outcome of rejection with hemodynamic compromise (HC). METHODS: Data from 2227 patients who received allografts between 1993 and 2006 at 36 centers in the Pediatric Heart Transplant Study were analyzed to determine incidence, outcome, and risk factors for rejection with HC in early (1993-1999) and recent (2000-2006) eras. Rejection with HC was classified as severe (RSHC) when inotropes were used for circulatory support and mild (RMHC) when inotropes were not used. RESULTS: Of 1217 patients with any episode of rejection, 541 had rejection with HC. Freedom from RMHC improved at 1 year (81% vs 90%, p < 0.001) and at 5 years (74% vs 85%, p < 0.001) in the early vs recent eras, but freedom from RSHC was similar between eras (93% vs 95% at 1 year and 85% vs 87% at 5 years, p = 0.24). Survival after RSHC (63% at 1 year and 49% at 5 years) was worse than after RMHC (87% at 1 year and 72% at 5 years, p < 0.001) and did not change over time. Risk factors for RSHC were non-white race (hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.29-2.32, p < 0.01), older age (HR, 2.85; 95% CI, 1.24-6.53; p = 0.01), and non-A blood type (HR, 1.51;, 95% CI, 1.11-2.04,; p = 0.01), but the only risk factor for RMHC was earlier era of transplant (HR, 1.94; 95% CI, 1.56-2.41; p < 0.001). CONCLUSIONS: The incidence of RMHC has declined over time but the same era effect has not occurred with RSHC. Close follow-up after RSHC is crucial because mortality is so high.

Effect of ABO-incompatible listing on infant heart transplant waitlist outcomes: analysis of the United Network for Organ Sharing (UNOS) database.

BACKGROUND: Midterm heart transplant outcomes of ABO-incompatible (ABO-I) organ use in infants are favorable. ABO-I transplantation has resulted in reduced waitlist mortality in some countries. This study assessed the effect of an ABO-I listing strategy on pre-transplant outcomes in the United States. METHODS: The Organ Procurement and Transplantation Network (OPTN)/United Network of Organ Sharing (UNOS) database was used to identify infants aged younger than 1 year listed as status 1 for heart transplantation between January 1, 2001, and May 20, 2008. The cohort was divided into 2 groups: eligible for ABO-compatible (ABO-C) transplant and eligible for ABO-I transplant. Baseline characteristics, waitlist times, and outcomes were compared in univariate analysis. Competing risks analysis evaluated differences in time to transplant in the presence of other outcomes. RESULTS: Of 1,029 infants listed for transplant, 277 (27%) were listed for an ABO-I transplant. Overall, 92% of transplant recipients received an ABO-C organ regardless of listing type. Among recipients eligible for ABO-I, only 27% received an ABO-I organ. The percentage that underwent transplant in each group did not differ. Although infants listed for an ABO-I organ had a shorter wait time for transplant, waitlist mortality was similar. CONCLUSIONS: Despite the intended merits of ABO-I heart transplantation, ABO-I listing and organ acceptance have not yielded lower waitlist mortality in the United States under the current UNOS allocation algorithm. Consideration should be given to altering the allocation system to one that gives less preference toward blood group compatibility in hopes of improving organ use and reducing waitlist mortality.