Gut resistome linked to sexual preference and HIV infection.

BACKGROUND: People living with HIV (PLWH) are at increased risk of acquisition of multidrug resistant organisms due to higher rates of predisposing factors. The gut microbiome is the main reservoir of the collection of antimicrobial resistance determinants known as the gut resistome. In PLWH, changes in gut microbiome have been linked to immune activation and HIV-1 associated complications. Specifically, gut dysbiosis defined by low microbial gene richness has been linked to low Nadir CD4 + T-cell counts. Additionally, sexual preference has been shown to strongly influence gut microbiome composition in PLWH resulting in different Prevotella or Bacteroides enriched enterotypes, in MSM (men-who-have-sex-with-men) or no-MSM, respectively. To date, little is known about gut resistome composition in PLWH due to the scarcity of studies using shotgun metagenomics. The present study aimed to detect associations between different microbiome features linked to HIV-1 infection and gut resistome composition. RESULTS: Using shotgun metagenomics we characterized the gut resistome composition of 129 HIV-1 infected subjects showing different HIV clinical profiles and 27 HIV-1 negative controls from a cross-sectional observational study conducted in Barcelona, Spain. Most no-MSM showed a Bacteroides-enriched enterotype and low microbial gene richness microbiomes. We did not identify differences in resistome diversity and composition according to HIV-1 infection or immune status. However, gut resistome was more diverse in MSM group, Prevotella-enriched enterotype and gut micorbiomes with high microbial gene richness compared to no-MSM group, Bacteroides-enriched enterotype and gut microbiomes with low microbial gene richness. Additionally, gut resistome beta-diversity was different according to the defined groups and we identified a set of differentially abundant antimicrobial resistance determinants based on the established categories. CONCLUSIONS: Our findings reveal a significant correlation between gut resistome composition and various host variables commonly associated with gut microbiome, including microbiome enterotype, microbial gene richness, and sexual preference. These host variables have been previously linked to immune activation and lower Nadir CD4 + T-Cell counts, which are prognostic factors of HIV-related comorbidities. This study provides new insights into the relationship between antibiotic resistance and clinical characteristics of PLWH.

Donor Dependent Variations in Systemic Oxidative Stress and Their Association with One-Year Graft Outcomes In Kidney Transplantation.

INTRODUCTION: Oxidative stress has been implicated in complications after kidney transplantation (KT), including delayed graft function and rejection. However, its role in long-term post-transplant outcomes remains unclear. METHODS: We investigated oxidative damage and antioxidant defense dynamics, and their impact on the graft outcomes, in 41 KT recipients categorized by type of donation over 12 months. Oxidative status was determined using OxyScore and AntioxyScore indexes, which comprise several circulating biomarkers of oxidative damage and antioxidant defense. Donor types included donation after brain death (DBD [61.0%]), donation after circulatory death (DCD [26.8%]) and living donation (LD [12.1%]). RESULTS: There was an overall increase in oxidative damage early after transplantation, which was significantly higher in DCD as compared to DBD and LD recipients. The multivariate adjustment confirmed the independent association of OxyScore and type of deceased donation with delayed graft function, donor kidney function and induction therapy with anti-thymocyte globulin. There were no differences in terms of antioxidant defense. Lower oxidative damage at day 7 predicted better graft function at one year post-transplant only in DBD recipients. CONCLUSION: DCD induced greater short-term oxidative damage after KT, whereas the early levels of oxidative damage were predictive of the graft function one year after KT among DBD recipients.

Fungal microbiota in newborn infants with and without respiratory distress syndrome.

BACKGROUND: Pneumocytis jirovecii infection in preterm newborns has recently been associated with neonatal respiratory distress syndrome and bronchopulmonary dysplasia. Changes in the bacterial microbiota of the airways have also been described in infants with bronchopulmonary dysplasia. However, until now there has been no information on the airway mycobiota in newborns. The purpose of this study was to describe the airway mycobiota in term and preterm newborns and its possible association with respiratory distress syndrome. METHODS: Twenty-six matched preterm newborns with and without respiratory distress syndrome were studied, as well as 13 term babies. The identification of the fungal microbiota was carried out using molecular procedures in aspirated nasal samples at birth. RESULTS: The ascomycota phylum was identified in 89.7% of newborns, while the basidiomycota phylum was found in 33.3%. Cladosporium was the predominant genus in both term and preterm infants 38.4% vs. 73% without statistical differences. Candida sake and Pneumocystis jirovecii were only found in preterm infants, suggesting a potential relationship with the risk of prematurity. CONCLUSIONS: This is the first report to describe the fungal microbiota of the airways in term and preterm infants with and without respiratory distress syndrome. Although no differences have been observed, the number of cases analyzed could be small to obtain conclusive results, and more studies are needed to understand the role of the fungal microbiota of the airways in neonatal respiratory pathology.

Reducing Postoperative CT Imaging for Children With Complicated Appendicitis: A Pediatric Surgical Quality Collaborative Quality Improvement Project.

BACKGROUND: Despite widespread initiatives to reduce ionizing radiation for appendicitis diagnosis, computed tomography (CT) scanning postoperatively remains common. The Pediatric Surgery Quality Collaborative (PSQC) aimed to identify differences between children's hospitals with high and low postoperative CT usage for complicated appendicitis. METHODS: Using National Surgery Quality Improvement Program Pediatric data from PSQC children's hospitals, we compared postoperative CT imaging for complicated appendicitis (April 2020-March 2021). Key stakeholders from 11 hospitals (5 low CT utilization, 6 high CT utilization) participated in semi-structured interviews regarding postoperative imaging. Qualitative analysis of transcripts was performed deductively and inductively based on the Theoretical Domains Framework (TDF). RESULTS: Five of twelve TDF domains were most prominent in influencing CT use: skills, beliefs about capabilities, intentions/goals, memory and decision processes, and environment. Children's hospitals with lower rates of postoperative CT use tended to: trust and educate the ultrasound technicians; believe US strengths outweigh weaknesses; image no sooner than 7 days postoperatively; have access to sufficient quality improvement resources; maintain trusting relationships between specialties; and prioritize radiation stewardship. CONCLUSION: Hospitals at extremes of postoperative CT use for complicated appendicitis reveal strategies for improvement, which include imaging protocol development and adherence, quality improvement resource availability, interdisciplinary collaboration, and promoting radiation stewardship. LEVEL OF EVIDENCE: Level V.

Survey of Emotional Themes Used in Marketing of Commercial Baby Foods in the UK-Implications for Nutrition Promotion in Early Childhood.

Claims used in the marketing of commercial baby foods are often misleading, and there are concerns that they exploit parental anxieties. We adapted a hierarchical consumer emotions model to explore the emotional themes used in the marketing of commercial baby foods sold in the UK market. A survey administered in three large UK supermarkets collected in-store data on commercial baby food characteristics and the marketing claims used on commercial baby food packaging. The keywords found in these claims were entered in N-Vivo and allocated to four preexisting emotional themes: contentment, happiness, love, and pride. The prevalence of each theme was compared by age suitability (4+, 6+, 9+, and 12+ months) and taste (sweet/savoury) profile. A total of 1666 marketing claims (median 5, IQR 3) and 1003 emotional keywords (median 3, IQR 3) were identified on the packaging of 341 commercial baby foods. Foods suitable for infants aged 6+ months displayed more claims (50%, p < 0.05) and emotional keywords (56%, p = 0.07). Savoury foods displayed more emotional keywords (63%, p < 0.001). The keywords "little", "encourage", "love(ly)", and "tiny" were the most frequently used words under the theme of love (36% total contribution). The emotional connotations of the keywords under the theme "love" are extensively used in the marketing claims on commercial baby food packaging. These might exploit parental vulnerabilities and influence their purchasing of commercial baby foods.

Albumin Redox Modifications Promote Cell Calcification Reflecting the Impact of Oxidative Status on Aortic Valve Disease and Atherosclerosis.

Calcific aortic valve disease (CAVD) and coronary artery disease (CAD) are related cardiovascular diseases in which common mechanisms lead to tissue calcification. Oxidative stress plays a key role in these diseases and there is also evidence that the redox state of serum albumin exerts a significant influence on these conditions. To further explore this issue, we used multimarker scores (OxyScore and AntioxyScore) to assess the global oxidative status in patients with CAVD, with and without CAD, also evaluating their plasma thiol levels. In addition, valvular interstitial cells were treated with reduced, oxidized, and native albumin to study how this protein and its modifications affect cell calcification. The differences we found suggest that oxidative status is distinct in CAVD and CAD, with differences in redox markers and thiol levels. Importantly, the in vitro interstitial cell model revealed that modified albumin affects cell calcification, accelerating this process. Hence, we show here the importance of the redox system in the development of CAVD, emphasizing the relevance of multimarker scores, while also offering evidence of how the redox state of albumin influences vascular calcification. These data highlight the relevance of understanding the overall redox processes involved in these diseases, opening the door to new studies on antioxidants as potential therapies for these patients.

Wine corks decontamination using plasma activated water.

Cork taint provides off-odors and changes negatively wine composition. In fact, it is one of the most important causes of discarding bottled wine. 2,4,6-Trichloroanisole (TCA) is the most known molecule responsible of that problem. In this study, cork stoppers were artificially contaminated with a multi-pattern solution which contained different chloroanisoles and chlorophenols. Contaminated corks were immersed for 3 h in four Plasma Activated Water (PAW) generated during 1.5 min, 5 min, 15 min and 30 min. The products of OH•, NO• and NO2• with phenol were determined by HPLC for each PAW. After treating contaminated corks with PAW generated during 5 min, more than 72 % of TCA was removed and it was suggested OH• as the main reactive species decomposing TCA. Finally, other chloroanisole and chlorophenol molecules were examined after PAW treatments showing successful reductions in almost every molecule. Thus, it was presented PAW treatment as an easy solution for solving cork taint problems in wine industry.

Targeting the TWEAK-Fn14 pathway prevents dysfunction in cardiac calcium handling after acute kidney injury.

Heart and kidney have a closely interrelated pathophysiology. Acute kidney injury (AKI) is associated with significantly increased rates of cardiovascular events, a relationship defined as cardiorenal syndrome type 3 (CRS3). The underlying mechanisms that trigger heart disease remain, however, unknown, particularly concerning the clinical impact of AKI on cardiac outcomes and overall mortality. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are independently involved in the pathogenesis of both heart and kidney failure, and recent studies have proposed TWEAK as a possible therapeutic target; however, its specific role in cardiac damage associated with CRS3 remains to be clarified. Firstly, we demonstrated in a retrospective longitudinal clinical study that soluble TWEAK plasma levels were a predictive biomarker of mortality in patients with AKI. Furthermore, the exogenous application of TWEAK to native ventricular cardiomyocytes induced relevant calcium (Ca2+ ) handling alterations. Next, we investigated the role of the TWEAK-Fn14 axis in cardiomyocyte function following renal ischaemia-reperfusion (I/R) injury in mice. We observed that TWEAK-Fn14 signalling was activated in the hearts of AKI mice. Mice also showed significantly altered intra-cardiomyocyte Ca2+ handling and arrhythmogenic Ca2+ events through an impairment in sarcoplasmic reticulum Ca2+ -adenosine triphosphatase 2a pump (SERCA2a ) and ryanodine receptor (RyR2 ) function. Administration of anti-TWEAK antibody after reperfusion significantly improved alterations in Ca2+ cycling and arrhythmogenic events and prevented SERCA2a and RyR2 modifications. In conclusion, this study establishes the relevance of the TWEAK-Fn14 pathway in cardiac dysfunction linked to CRS3, both as a predictor of mortality in patients with AKI and as a Ca2+ mishandling inducer in cardiomyocytes, and highlights the cardioprotective benefits of TWEAK targeting in CRS3. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Use of Cells, Supplements, and Peptides as Therapeutic Strategies for Modulating Inflammation after Spinal Cord Injury: An Update.

Spinal cord injury is a traumatic lesion that causes a catastrophic condition in patients, resulting in neuronal deficit and loss of motor and sensory function. That loss is caused by secondary injury events following mechanical damage, which results in cell death. One of the most important events is inflammation, which activates molecules like proinflammatory cytokines (IL-1ß, IFN-γ, and TNF-α) that provoke a toxic environment, inhibiting axonal growth and exacerbating CNS damage. As there is no effective treatment, one of the developed therapies is neuroprotection of the tissue to preserve healthy tissue. Among the strategies that have been developed are the use of cell therapy, the use of peptides, and molecules or supplements that have been shown to favor an anti-inflammatory environment that helps to preserve tissue and cells at the site of injury, thus favoring axonal growth and improved locomotor function. In this review, we will explain some of these strategies used in different animal models of spinal cord injury, their activity as modulators of the immune system, and the benefits they have shown.

Recent advances in the combination of cellular therapy with stem cells and nanoparticles after a spinal cord injury.

Background: Currently, combined therapies could help to reduce long-term sequelae of spinal cord injury (SCI); stem cell therapy at the site of injury in combination with other therapies has shown very promising results that can be transferred to the clinical field. Nanoparticles (NPs) are versatile technologies with applications to medical research for treatments of SCI since they could deliver therapeutic molecules to the target tissue and may help to reduce the side effects of non-targeted therapies. This article's purpose is to analyze and concisely describe the diverse cellular therapies in combination with NPs and their regenerative effect after SCI. Methods: We reviewed the literature related to combinatory therapy for motor impairment following SCI that has been published by Web of Science, Scopus, EBSCO host, and PubMed databases. The research covers the databases from 2001 to December 2022. Result: Animal models of SCI have shown that the combination of NPs plus stem cells has a positive impact on neuroprotection and neuroregeneration. Further research is required to better understand the effects and benefits of SCI on a clinical level; therefore, it is necessary to find and select the most effective molecules that are capable of exacerbating the neurorestorative effects of the different stem cells and then try them out on patients after SCI. On the other hand, we consider that synthetic polymers such as poly [lactic-co-glycolic acid] (PLGA) could be a candidate for the design of the first therapeutic strategy that combines NPs with stem cells in patients with SCI. The reasons for the selection are that PLGA has shown important advantages over other NPs, such as being biodegradable, having low toxicity levels, and high biocompatibility; In addition, researchers could control the release time and the biodegradation kinetics, and most importantly, it could be used as NMs on other clinical pathologies (12 studies on www.clinicaltrials.gov) and has been approved by the Federal Food, Drug, and Cosmetic Act (FDA). Conclusion: The use of cellular therapy and NPs may be a worthwhile alternative for SCI therapy; however, it is expected that the data obtained from interventions after SCI reflect an important variability of molecules combined with NPs. Therefore, it is necessary to properly define the limits of this research to be able to continue to work on the same line. Consequently, the selection of a specific therapeutic molecule and type of NPs plus stem cells are crucial to evaluate its application in clinical trials.

Global Oxidative Status Is Linked to Calcific Aortic Stenosis: The Differences Due to Diabetes Mellitus and the Effects of Metformin.

Calcific aortic stenosis (CAS) and type 2 diabetes mellitus (T2DM) are related and often concomitant pathologies, accompanied by common comorbidities such as hypertension or dyslipidemia. Oxidative stress is one of the mechanisms that trigger CAS, and it can drive the vascular complications in T2DM. Metformin can inhibit oxidative stress, yet its effects have not been studied in the context of CAS. Here, we assessed the global oxidative status in plasma from patients with CAS, both alone and with T2DM (and under treatment with metformin), using multimarker scores of systemic oxidative damage (OxyScore) and antioxidant defense (AntioxyScore). The OxyScore was determined by measuring carbonyls, oxidized LDL (oxLDL), 8-hydroxy-20-deoxyguanosine (8-OHdG), and xanthine oxidase (XOD) activity. In contrast, the AntioxyScore was determined through the catalase (CAT) and superoxide dismutase (SOD) activity, as well as the total antioxidant capacity (TAC). Patients with CAS displayed enhanced oxidative stress compared to control subjects, probably exceeding their antioxidant capacity. Interestingly, patients with CAS and T2DM displayed less oxidative stress, possibly due to the benefits of their pharmacological therapy (metformin). Thus, reducing oxidative stress or enhancing antioxidant capacity through specific therapies could be a good strategy to manage CAS, focusing on personalized medicine.

Food insecurity was negatively associated with adherence to the "fruits, vegetables, and foods rich in animal protein" dietary pattern among university students' households: the 2018 Mexican National Household Survey.

BACKGROUND: University students are often affected by food insecurity (FI) and this situation has been associated with low consumption of fruit/vegetables and high intake of added sugars and sweet drinks. However, there needs to be more evidence on the association between FI and dietary patterns (DPs), assessing the overall diet and allowing analysis of commonly consumed food combinations. We aimed to analyze the association between FI and DPs in university students' households. METHODS: We used data from 7659 university student households from the 2018 Mexican National Household Income and Expenditure Survey (ENIGH, for its acronym in Spanish). We obtained FI levels (mild, moderate, and severe) using the validated Mexican Food Security Scale (EMSA, Spanish acronym). Two DPs were identified by principal component analysis based on the weekly frequency of consumption of 12 food groups. Multivariate logistic regression adjusted by university student and household's characteristics was applied. RESULTS: Compared to food security, households with mild-FI (OR:0.34; 95%CI:0.30, 0.40), moderate-FI (OR:0.20; 95%CI:0.16, 0.24) or severe-FI (OR:0.14; 95%CI:0.11, 0.19) were less likely to adhere to the dietary pattern "Fruits, vegetables and foods rich in animal protein" (fruits, vegetables, meat, fish or seafood, dairy products, and starchy vegetables). In addition, people with severe-FI (OR:0.51; 95% CI:0.34, 0.76) were also less likely to adhere to the dietary pattern "Traditional-Westernized" (pulses, oils or fats, sugar, sweets, industrialized drinks, foods made from corn/maize, wheat, rice, oats or bran, coffee, tea and eggs). CONCLUSIONS: In these households FI impairs the ability to consume a healthy dietary pattern (fruits/vegetables and foods rich in animal protein). In addition, the intake of foods typical of the Mexican food culture reflecting the local Western dietary pattern is compromised in households with severe-FI.

Healthcare Utilization Among Infants Discharged From the Neonatal Intensive Care Unit: A Descriptive Cost Analysis.

The cost of readmissions of neonatal intensive care unit (NICU) graduates within 6 months and a year of their life is well-studied. However, the cost of readmissions within 90 days of NICU discharge is unknown. This study's objective was to estimate the overall and mean cost of healthcare use for unplanned hospital visits of NICU graduates within 90 days of discharge A retrospective review of all infants discharged between 1/1/2017 and 03/31/2017 from a large hospital system NICUs was conducted. All unplanned hospital visits (readmissions or stand-alone emergency department (ED) visits) occurring within 90 days post NICU discharge were included. The total and mean cost of unplanned hospital visits were computed and adjusted to 2021 US dollars. The total cost was estimated to be $785 804 with a mean of $1898 per patient. Hospital readmissions accounted for 98% ($768 718) of the total costs and ED visits for 2% ($17 086). The mean cost per readmission and stand-alone ED visit were $25 624 and $475 respectively. The highest mean total cost of unplanned hospital readmission was noted in extremely low birth weight infants ($25 295). Interventions targeted to reduce hospital readmissions after NICU discharge have the potential to significantly reduce healthcare costs for this patient population.

Advances in the Application of Cold Plasma Technology in Foods.

In the last two decades, non-thermal processing technologies have gained widespread attention from the food industry, which is interested in mild and effective processes [...].

Impacts of exhaust gas cleaning systems (EGCS) discharge waters on planktonic biological indicators.

Exhaust Gas Cleaning Systems (EGCS), operating in open-loop mode, continuously release acidic effluents (scrubber waters) to marine waters. Furthermore, scrubber waters contain high concentrations of metals, polycyclic aromatic hydrocarbons (PAHs), and alkylated PAHs, potentially affecting the plankton in the receiving waters. Toxicity tests evidenced significant impairments in planktonic indicators after acute, early-life stage, and long-term exposures to scrubber water produced by a vessel operating with high sulphur fuel. Acute effects on bacterial bioluminescence (Aliivibrio fischeri), algal growth (Phaeodactylum tricornutum, Dunaliella tertiolecta), and copepod survival (Acartia tonsa) were evident at 10 % and 20 % scrubber water, while larval development in mussels (Mytilus galloprovincialis) showed a 50 % reduction at ∼5 % scrubber water. Conversely, larval development and reproductive success of A. tonsa were severely affected at scrubber water concentrations ≤1.1 %, indicating the risk of severe impacts on copepod populations which in turn may result in impairment of the whole food web.

Impact of Cryoanalgesia Use During Minimally Invasive Pectus Excavatum Repair on Hospital Days and Total Hospital Costs Among Pediatric Patients.

INTRODUCTION: Surgical repair of pectus excavatum is a painful procedure requiring multimodal pain control with historically prolonged hospital stay. This study aimed to evaluate the impact of cryoanalgesia during minimally invasive repair of pectus excavatum (MIRPE) on hospital days (HDs), total hospital costs (HCs), and complications. We hypothesized that cryoanalgesia would be associated with reduced HDs and total HCs with no increase in post-operative complications. METHODS: We conducted a retrospective review of pediatric patients who underwent MIRPE from 2011 to 2021. MIRPE details and post-operative outcomes within 90 days were abstracted. Total HDs included the index MIRPE admission and readmissions within 90 days. HCs were obtained from the hospital accounting system, retroactively adjusting for medical inflation. Bayesian generalized linear models with neutral prior assuming no effect were used. Differences between treatment groups were assessed using gamma distribution (HDs and HCs) and poisson (post-operative complications). All models used log link and controlled for age, gender, race, and Haller index. RESULTS: Forty-four patients underwent MIRPE during the study period. Cryoanalgesia was utilized in 29 (66%) patients. The probability of a reduction with cryoanalgesia vs. no cryoanalgesia was 99% for HDs (3.0 vs. 5.4 days; Bayesian RR: 0.6, 95% CrI: 0.5-0.8), 89% for HCs ($18,787 vs. $19,667; RR: 0.9, 95% CrI: 0.8-1.1), and 70% for postoperative complications (17% vs 33%; RR: 0.8, 95% CrI: 0.3-1.9). CONCLUSION: Cryoanalgesia use in MIRPE likely reduced HDs, HCs, and post-operative complications. Further research is warranted to confirm these findings in large prospective studies. LEVEL OF EVIDENCE: Level III.

Household Transmission of SARS-CoV-2 and Long-term Immunity in Children: A Prospective Study in Northern Spain.

BACKGROUND: The role of children in SARS-CoV-2 transmission and their immune response after infection have been profoundly discussed. Hereby, we analyze both aspects in a Spanish pediatric population. METHODS: Prospective, multicentre, longitudinal study performed from July 2020 to September 2021 in children up to 14 years old. Venous blood samples were collected every 6 months and serum was analyzed for antibodies against SARS-CoV-2 using a spike (S) and a nucleocapsid (N) protein assays. Household contacts of seropositive children were tested. Household transmission, antibody dynamics, and durability were analyzed. RESULTS: Two hundred children were recruited and 28 had SARS-CoV-2 antibodies at the end of the study, resulting in an overall seroprevalence of 16.6% (95% CI: 9.5%-19.6%). Most of children (18/28) were secondary cases. The secondary attack rate (SAR) was lower in households with pediatric index cases than in those with adult index cases ( P = 0.023). The median antibody titers in the first positive serology, for the seropositive patients, were 137 BAU/mL (IQR 83.3-427.4) for the S-assay and 132.5 COI (IQR 14.5-170.5) for the N-assay without significant differences between symptomatic and asymptomatic children. The median time between the RT-PCR and the last serology was 7.5 months (IQR 5.2-8.8), and the duration of SARS-CoV-2 antibodies after infection was proven to be at least 18 months. There were no cases of seroreversion. CONCLUSIONS: (1) Children are not the main drivers of SARS-CoV-2 household transmission. (2) They maintain SARS-CoV-2 antibodies for up to 18 months after infection and the titers are similar between symptomatic and asymptomatic children.

Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney Injury.

Acute kidney injury (AKI) is associated with an elevated risk of cardiovascular major events and mortality. The pathophysiological mechanisms underlying the complex cardiorenal network interaction remain unresolved. It is known that the presence of AKI and its evolution are significantly associated with an alteration in the anti-aging factor klotho expression. However, it is unknown whether a klotho deficiency might aggravate cardiac damage after AKI. We examined intracellular calcium (Ca2+) handling in native ventricular isolated cardiomyocytes from wild-type (+/+) and heterozygous hypomorphic mice for the klotho gene (+/kl) in which an overdose of folic acid was administered to induce AKI. Twenty-four hours after AKI induction, cardiomyocyte contraction was decreased in mice with the partial deletion of klotho expression (heterozygous hypomorphic klotho named +/kl). This was accompanied by alterations in Ca2+ transients during systole and an impairment of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) function in +/kl mice after AKI induction. Moreover, Ca2+ spark frequency and the incidence of Ca2+ pro-arrhythmic events were greater in cardiomyocytes from heterozygous hypomorphic klotho compared to wild-type mice after AKI. A decrease in klotho expression plays a role in cardiorenal damage aggravating cardiac Ca2+ mishandling after an AKI, providing the basis for future targeted approaches directed to control klotho expression as novel therapeutic strategies to reduce the cardiac burden that affects AKI patients.

Multicenter Assessment of Cryoanalgesia Use in Minimally Invasive Repair of Pectus Excavatum: A 20-center Retrospective Cohort Study.

OBJECTIVE: To assess the clinical implications of cryoanalgesia for pain management in children undergoing minimally invasive repair of pectus excavatum (MIRPE). BACKGROUND: MIRPE entails significant pain management challenges, often requiring high postoperative opioid use. Cryoanalgesia, which blocks pain signals by temporarily ablating intercostal nerves, has been recently utilized as an analgesic adjunct. We hypothesized that the use of cryoanalgesia during MIRPE would decrease postoperative opioid use and length of stay (LOS). MATERIALS AND METHODS: A multicenter retrospective cohort study of 20 US children's hospitals was conducted of children (age below 18 years) undergoing MIRPE from January 1, 2014, to August 1, 2019. Differences in total postoperative, inpatient, oral morphine equivalents per kilogram, and 30-day LOS between patients who received cryoanalgesia versus those who did not were assessed using bivariate and multivariable analysis. P value <0.05 is considered significant. RESULTS: Of 898 patients, 136 (15%) received cryoanalgesia. Groups were similar by age, sex, body mass index, comorbidities, and Haller index. Receipt of cryoanalgesia was associated with lower oral morphine equivalents per kilogram (risk ratio=0.43, 95% confidence interval: 0.33-0.57) and a shorter LOS (risk ratio=0.66, 95% confidence interval: 0.50-0.87). Complications were similar between groups (29.8% vs 22.1, P =0.07), including a similar rate of emergency department visit, readmission, and/or reoperation. CONCLUSIONS: Use of cryoanalgesia during MIRPE appears to be effective in lowering postoperative opioid requirements and LOS without increasing complication rates. With the exception of preoperative gabapentin, other adjuncts appear to increase and/or be ineffective at reducing opioid utilization. Cryoanalgesia should be considered for patients undergoing this surgery.