Preoperative Feeding Fortification Among Infants with Congenital Heart Disease is Associated with Higher Growth Velocity in the First 30 Days Post-repair and Lower BMI Percentile for Age at 10 Years: A Retrospective Cohort Study.

It remains unclear how preoperative nutrition fortification impacts postoperative growth trajectories and nutritional status among infants with congenital heart disease. A single center retrospective cohort study was performed to evaluate measures of growth among patients who underwent cardiac repair at 0-18 months of age for atrial septal defect, ventricular septal defect, atrioventricular septal defect, or tetralogy of Fallot. Cohorts were analyzed at 0-30 and 31-60 days post-repair as well as at 2, 5, and 10 years of age. Records of 24 patients who received fortified nutrition and 60 patients who received unfortified nutrition preoperatively were reviewed. Those with fortified nutrition had higher growth velocities in the first 30 days post-repair compared to those with unfortified nutrition: 28.4 (23.8-83.3) grams per day versus 16.7 (7.1-21.4) grams per day, p = 0.004. Weight percentile for age was higher in the unfortified group at 2, 5, and 10 years of age (p = 0.02, p = 0.045, and p = 0.01). Body mass index (BMI) percentile for age was higher in the unfortified group at 5 and 10 years of age (p = 0.045 and p = 0.02) with a trend toward higher prevalence of either overweight or obesity compared to the fortified group (p = 0.13). reoperative nutrition fortification among infants with congenital heart disease is associated with higher growth velocity in the first 30 days post-repair and lower BMI percentile for age at 10 years. Further studies are needed to evaluate the association between preoperative nutrition fortification and postoperative outcomes, nutritional status, and prevalence of obesity in adolescence and adulthood.

Assessing the early influence of COVID-19 in an analysis of the immediate implementation of Minimum Pricing for Alcohol on drinkers in Wales.

Background: The Welsh Government has commissioned a number of projects to consider the influence their implementation of Minimum Pricing for Alcohol (MPA) legislation in March 2020 had on the alcohol consumption and related behaviours of drinkers. Given the MPA's overlap with the COVID-19 pandemic and its related lockdown measures and restrictions, this rapidly became a story about the early impact of COVID-19 as it did MPA. This paper captures the core thematic messages from this specific strand of work, and in doing so reflects on (1) how early experiences of COVID-19 and the first lockdown influenced consumption and purchasing of alcohol behaviours and, in turn, (2) how relevant the introduction of MPA was for any of these. Methods: Semi-structured interviews were conducted by telephone with 32 drinkers 9 months after the implementation of the legislation in March 2020. The sample was recruited from three sources: the National Survey for Wales; a third sector organisation offering housing support to the homeless; and through an online survey on MPA. Results: COVID-19 had more relevance than MPA to drinkers. Furthermore, when MPA did have an influence on their behaviour, it was felt most keenly by the harmful drinkers in the study. These drinkers described spending more on alcohol, switching to other potentially more harmful substances, such as crack cocaine and synthetic cannabinoids, and more involvement in acquisitive crime and begging after the price increase. While our results might be an early indication of the influence of MPA on harmful drinkers, the small sample of this group in our study limits the generalisability of the findings. Conclusion: To date, the implementation of MPA has had little influence on the drinking patterns or lives of the drinkers in our sample. It is important that future research examines the longer-term influences of MPA before any conclusions on its effectiveness can be drawn.

Does Sustained Reduction of Functional Mitral Regurgitation Impact Survival?

Functional mitral regurgitation (FMR) is associated with increased mortality and has been considered a marker for advanced heart disease, yet the value of mitral valve repair (MVr) in this population remains unclear. This study aims to evaluate the impact of reducing FMR burden through surgical MVr on survival. Patients with severe FMR who underwent MVr with an undersized, complete, rigid, annuloplasty between 2004 and 2017 were assessed (n = 201). Patients were categorized based on grade of recurrent FMR (0-4). Time-to-event Kaplan-Meier estimations of freedom from death or reoperation were performed using the log-rank test. Cox proportional hazards models evaluated all-cause mortality and reported in hazards ratios (HR) and 95% confidence intervals (CI). Patients were categorized by postoperative recurrent FMR: 45% (91/201) of patients had grade 0, 29% (58/201) grade 1, 20% (40/201) grade 2, 2% (4/201) grade 3%, and 4% (8/201) grade 4. The cumulative incidence of reoperation with death as a competing risk was higher in patients with grades ≥3 recurrent FMR compared to grades ≤2 (44.6% vs 14.6%, subhazard ratio 3.69 [95% CI, 1.17-11.6]; P = 0.026). Overall freedom from death or reoperation was superior for recurrent FMR grades ≤2 compared to grades ≥3 (log-rank P < 0.001). Increasing recurrent FMR grade was independently associated with mortality (HR 1.30 [95% CI, 1.07-1.59] P = 0.009). Reduced postoperative FMR grade resulted in an incrementally lower risk of death or reoperation after MVr. These results suggest that achieving a durable reduction in FMR burden improves long-term survival.

Lessons from the COVID-19 pandemic for substance misuse services: findings from a peer-led study.

BACKGROUND: The measures implemented to contain the spread of the COVID-19 virus disrupted the provision of substance misuse treatment and support. However, little is known about the impact of this disruption on individuals seeking treatment for drug- and/or alcohol-related problems (henceforth service users). This study aimed to help substance misuse services learn lessons and identify ways of optimising delivery and minimising harm in the event of any future lockdowns or global crises. METHODS: The study was co-produced by a team of peer researchers, practitioners, policymakers and academics. Telephone interviews were conducted with 202 substance misuse service users over a 6-month period commencing June 2020. The interviews were conducted by a small group of seven peer researchers each with lived experience of substance use problems. The interview data were recorded by the peers in an anonymous online questionnaire survey and analysed using standard quantitative and qualitative methods. RESULTS: Service users responded to the COVID-19 pandemic in a variety of ways. Diverse responses were noted in relation to their substance use patterns, their personal lives and their substance misuse treatment experiences. For some, the pandemic acted as a new risk environment factor that increased their vulnerability to substance-related harm. For others, it facilitated aspects of the enabling environment, thereby reducing the risk of harm. CONCLUSIONS: Service users are not a homogenous group, and an individualised approach to treatment that recognises the potential for varied responses to the same stimuli is needed. The findings suggest that service users would benefit from having a choice in how they access treatment and from greater access to outreach programmes that take treatments and harm reduction tools such as naloxone into the community. The research also supports the involvement of people with lived experience in substance use research, policy and practice.

Ultrasonic Emulsification of Severe Mitral Annular Calcification During Mitral Valve Replacement.

PURPOSE: Severe mitral annular calcification (MAC) increases surgical complexity and is independently associated with increased operative mortality for mitral valve replacement (MVR). Recently we adopted ultrasonic emulsification/aspiration for annular decalcification to address these risks and describe our early experience with this new technology. DESCRIPTION: Excluding previous mitral valve surgery or endocarditis, 179 patients with MAC underwent MVR at a single institution between January 2015 and March 2020. Of these, 15 consecutive patients with severe MAC (≥50% of the annulus) underwent annular decalcification with ultrasonic emulsification/aspiration as an adjunct treatment during MVR from April 2019 to March 2020. EVALUATION: Mean patient age was 68 ± 12 years, and 72% (n = 128) were female. Mean preoperative left ventricular ejection fraction was 60% ± 11%, and mean mitral valve gradient was 9.1 ± 4.4 mm Hg. Concomitant procedures included antiarrhythmia (n = 52), aortic valve replacement (n = 32), and coronary artery bypass grafting (n = 20). There were no operative deaths or strokes in the group undergoing ultrasonic emulsification and aspiration. CONCLUSIONS: The use of ultrasonic emulsification and aspiration in severe MAC patients may help mitigate the risks of MVR and facilitate operative success in this challenging, high-risk population.

Rheumatic mitral valve repair or replacement in the valve-in-valve era.

OBJECTIVE: For degenerative mitral disease, repair is superior to replacement; however, the best operative strategy for rheumatic mitral disease remains unclear. We evaluated the association between decision-making in choosing repair versus replacement and outcomes across 2 decades of rheumatic mitral surgery. METHODS: Patients undergoing isolated, first-time rheumatic mitral surgery were identified. Era 1 (1997-2008) and Era 2 (2009-2018) were distinguished by intraoperative assessment of anterior leaflet mobility/calcification (Era 2) in deciding between mitral repair versus replacement. Primary outcome was a composite of death, reoperation, and severe valve dysfunction. RESULTS: Among 180 patients, age was 59 ± 14 years, and ejection fraction was 58% ± 10%. A higher proportion in Era 1 (n = 56) compared with Era 2 (n = 124) had preoperative atrial fibrillation (68% vs 46%; P = .006); the groups were otherwise similar. Primary indication was mitral stenosis in 69% (124 out of 180; pure = 35, mixed = 89) and did not differ by era (P = .67). During Era 1, 70% (39 out of 56) underwent repair, compared with 33% (41 out of 124) during Era 2 (P < .001). Freedom from death, reoperation, or severe valve dysfunction at 5 years was higher in Era 2 (72% ± 9%) than Era 1 (54% ± 13%; P = .04). Five-year survival was higher in Era 2 than Era 1, but did not differ between repair versus replacement. Five-year cumulative incidence of reoperation with death as a competing risk did not differ by era, but was higher after repair than replacement. CONCLUSIONS: Careful assessment of anterior leaflet mobility/calcification to determine mitral repair or replacement was associated with improved outcomes. This decision-making strategy may alter the threshold for rheumatic mitral replacement in the current valve-in-valve era.

COVID-19 Modulates Inflammatory and Renal Markers That May Predict Hospital Outcomes among African American Males.

BACKGROUND AND OBJECTIVES: African Americans and males have elevated risks of infection, hospitalization, and death from SARS-CoV-2 in comparison with other populations. We report immune responses and renal injury markers in African American male patients hospitalized for COVID-19. METHODS: This was a single-center, retrospective study of 56 COVID-19 infected hospitalized African American males 50+ years of age selected from among non-intensive care unit (ICU) and ICU status patients. Demographics, hospitalization-related variables, and medical history were collected from electronic medical records. Plasma samples collected close to admission (≤2 days) were evaluated for cytokines and renal markers; results were compared to a control group (n = 31) and related to COVID-19 in-hospital mortality. RESULTS: Among COVID-19 patients, eight (14.2%) suffered in-hospital mortality; seven (23.3%) in the ICU and one (3.8%) among non-ICU patients. Interleukin (IL)-18 and IL-33 were elevated at admission in COVID-19 patients in comparison with controls. IL-6, IL-18, MCP-1/CCL2, MIP-1α/CCL3, IL-33, GST, and osteopontin were upregulated at admission in ICU patients in comparison with controls. In addition to clinical factors, MCP-1 and GST may provide incremental value for risk prediction of COVID-19 in-hospital mortality. CONCLUSIONS: Qualitatively similar inflammatory responses were observed in comparison to other populations reported in the literature, suggesting non-immunologic factors may account for outcome differences. Further, we provide initial evidence for cytokine and renal toxicity markers as prognostic factors for COVID-19 in-hospital mortality among African American males.

High SARS-CoV-2 Viral Load in Urine Sediment Correlates with Acute Kidney Injury and Poor COVID-19 Outcome.

BACKGROUND: AKI is a complication of coronavirus disease 2019 (COVID-19) that is associated with high mortality. Despite documented kidney tropism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are no consistent reports of viral detection in urine or correlation with AKI or COVID-19 severity. Here, we hypothesize that quantification of the viral load of SARS-CoV-2 in urine sediment from patients with COVID-19 correlates with occurrence of AKI and mortality. METHODS: The viral load of SARS-CoV-2 in urine sediments (U-viral load) was quantified by qRT-PCR in 52 patients with PCR-confirmed COVID-19 diagnosis, who were hospitalized between March 15 and June 8, 2020. Immunolabeling of SARS-CoV-2 proteins Spike and Nucleocapsid was performed in two COVID-19 kidney biopsy specimens and urine sediments. Viral infectivity assays were performed from 32 urine sediments. RESULTS: A total of 20 patients with COVID-19 (39%) had detectable SARS-CoV-2 U-viral load, of which 17 (85%) developed AKI with an average U-viral load four-times higher than patients with COVID-19 who did not have AKI. U-viral load was highest (7.7-fold) within 2 weeks after AKI diagnosis. A higher U-viral load correlated with mortality but not with albuminuria or AKI stage. SARS-CoV-2 proteins partially colocalized with the viral receptor ACE2 in kidney biopsy specimens in tubules and parietal cells, and in urine sediment cells. Infective SARS-CoV-2 was not detected in urine sediments. CONCLUSION: Our results further support SARS-CoV-2 kidney tropism. A higher SARS-CoV-2 viral load in urine sediments from patients with COVID-19 correlated with increased incidence of AKI and mortality. Urinary viral detection could inform the medical care of patients with COVID-19 and kidney injury to improve prognosis.

Anterior versus posterior leaflet mitral valve repair: A propensity-matched analysis.

OBJECTIVE: Mitral valve repair is superior to replacement for degenerative disease, but long-term outcomes of anterior versus posterior leaflet repair remain poorly defined. We propensity matched anterior and posterior repairs to compare long-term outcomes. METHODS: Patients undergoing first-time degenerative mitral repair between 1992 and 2018 were identified. Primary outcome was overall survival. Secondary outcomes were postprocedural residual mitral regurgitation and reoperation. From 1025 patients, 1:1 propensity score matching was performed, yielding 309 anterior (isolated anterior = 85, bileaflet = 224) and 309 isolated posterior repairs. RESULTS: Age was 58 ± 15 years, ejection fraction was 57% ± 10%, and matched groups were well balanced. Anterior repairs had longer bypass (122 ± 53 vs 109 ± 43 minutes, P = .001) and crossclamp (94 ± 44 vs 85 ± 62 minutes, P = .033) times. Mean residual mitral regurgitation grade was 0.44 (95% confidence interval, 0.24-0.65) for anterior repair and 0.30 (95% confidence interval, 0.13-0.47) for posterior repair (P = .31). Overall, 92% (569/618) of matched patients had no residual mitral regurgitation, with no differences in mitral regurgitation grade between groups (P = .77). Survival did not differ between anterior (10 years: 72% ± 7%; 15 years: 63% ± 7%) and posterior (10 years: 74% ± 7%; 15 years: 60% ± 8%) groups (log-rank P = .93). Linearized incidence of reoperation was 0.62% per patient-year, including 0.74% for anterior and 0.48% for posterior repairs. Cumulative incidence of reoperation at 15 years was 7.5% after anterior repair and 4.9% after posterior repair (Gray's test P = .26). CONCLUSIONS: No long-term survival or reoperation difference was found between posterior and anterior repair. On the basis of these findings, surgeons at centers of excellence should aim for repair of both anterior and posterior leaflet pathology with the same decision-making threshold over valve replacement for degenerative mitral disease.

HIV Impairs Alveolar Macrophage Function via MicroRNA-144-Induced Suppression of Nrf2.

BACKGROUND: Despite anti-retroviral therapy, HIV-1 infection increases the risk of pneumonia and causes oxidative stress and defective alveolar macrophage (AM) immune function. We have previously determined that HIV-1 proteins inhibit antioxidant defenses and impair AM phagocytosis by suppressing nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Given its known effects on Nrf2, we hypothesize miR-144 mediates the HIV-1 induced suppression of Nrf2. METHODS: Primary AMs isolated from HIV-1 transgenic (HIV-1 Tg) rats and wild type littermates (WT) as well as human monocyte-derived macrophages (MDMs) infected ex vivo with HIV-1 were used. We modulated miR-144 expression using a miR-144 mimic or an inhibitor to assay its effects on Nrf2/ARE activity and AM functions in vitro and in vivo. RESULTS: MiR-144 expression was increased in AMs from HIV-1 Tg rats and in HIV-1-infected human MDMs compared to cells from WT rats and non-infected human MDMs, respectively. Increasing miR-144 with a miR-144 mimic inhibited the expression of Nrf2 and its downstream effectors in WT rat macrophages and consequently impaired their bacterial phagocytic capacity and H2O2 scavenging ability. These effects on Nrf2 expression and AM function were reversed by antagonizing miR-144 ex vivo or in the airways of HIV-1 Tg rats in vivo, but this protection was abrogated by silencing Nrf2 expression. CONCLUSIONS: Our results suggest that inhibiting miR-144 or interfering with its deleterious effects on Nrf2 attenuates HIV-1-mediated AM immune dysfunction and improves lung health in individuals with HIV.