High germline mutation rates, but not extreme population outbreaks, influence genetic diversity in a keystone coral predator.

Lewontin's paradox, the observation that levels of genetic diversity (π) do not scale linearly with census population size (Nc) variation, is an evolutionary conundrum. The most extreme mismatches between π and Nc are found for highly abundant marine invertebrates. Yet, the influences of new mutations on π relative to extrinsic processes such as Nc fluctuations are unknown. Here, we provide the first germline mutation rate (µ) estimate for a marine invertebrate in corallivorous crown-of-thorns sea stars (Acanthaster cf. solaris). We use high-coverage whole-genome sequencing of 14 parent-offspring trios alongside empirical estimates of Nc in Australia's Great Barrier Reef to jointly examine the determinants of π in populations undergoing extreme Nc fluctuations. The A. cf. solaris mean µ was 9.13 x 10-09 mutations per-site per-generation (95% CI: 6.51 x 10-09 to 1.18 x 10-08), exceeding estimates for other invertebrates and showing greater concordance with vertebrate mutation rates. Lower-than-expected Ne (~70,000-180,000) and low Ne/Nc values (0.0047-0.048) indicated weak influences of population outbreaks on long-term π. Our findings are consistent with elevated µ evolving in response to reduced Ne and generation time length, with important implications for explaining high mutational loads and the determinants of genetic diversity in marine invertebrate taxa.

Medications for alcohol use disorder promote abstinence in alcohol-associated cirrhosis: Results from a systematic review and meta-analysis.

BACKGROUND AND AIMS: The role of medications for alcohol use disorder (MAUD) in patients with cirrhosis is not well established. Evidence on the efficacy and safety of these drugs in these patients is scarce. APPROACH AND RESULTS: We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol guidelines on the efficacy of MAUD in patients with cirrhosis. A search was conducted in PubMed, Embase, and Scopus, including all studies until May 2022. The population was defined as patients with AUD and cirrhosis. The primary outcome was alcohol abstinence. Safety was a secondary outcome. We performed a random-effect analysis and expressed the results as relative risk of alcohol consumption. Heterogeneity was measured by I2 . Out of 4095 unique references, 8 studies on 4 different AUD treatments [baclofen (n = 6), metadoxine (n = 1), acamprosate (n = 1), and fecal microbiota transplant (n = 1)] in a total of 794 patients were included. Four were cohort studies, and 4 were RCTs. Only RCTs were included in the meta-analysis. MAUD was associated with a reduced rate of alcohol consumption [relative risk = 0.68 (CI: 0.48-0.97), P = 0.03], increasing alcohol abstinence by 32% compared to placebo or standard treatment, despite high heterogeneity ( I2 = 67%). Regarding safety, out of 165 serious adverse events in patients treated with MAUD, only 5 (3%) were possibly or probably related to study medications. CONCLUSION: MAUD in patients with cirrhosis is effective in promoting alcohol abstinence and has a good safety profile. Larger studies on the effects of MAUD are needed, especially in patients with advanced liver disease.

The effect of antipsychotic medications on QTc and delirium in paediatric cardiac patients with ICU delirium.

OBJECTIVE: Children with prolonged hospital admissions for CHD often develop delirium. Antipsychotic medications (APMs) have been used to treat delirium but are known to prolong the QTc duration. There is concern for prolongation of the QTc interval in cardiac patients who may be more vulnerable to electrocardiogram (ECG) changes and may have postoperative QTc prolongation already. The goal of this study was to determine the effect of APM on QTc duration in postoperative paediatric cardiac patients and determine the effect of quetiapine and risperidone in treating delirium and QTc prolongation. DESIGN: Retrospective study, July 1, 2017-May 31, 2022. SETTING: Tertiary children's hospital. PATIENTS: Included were patients admitted to the paediatric cardiac ICU at Children's Healthcare of Atlanta. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ECGs, delirium scores, and drug information were collected. Delirium was defined as Cornell Assessment of Pediatric Delirium (CAPD) score >9. Mixed effect models were performed to evaluate the effect of surgery on QTc change and the effect of antipsychotics on QTc and CAPD changes. There were 139 children, 55% male and 67% surgical admissions. Median age was 5.9 months. Mean QTc increased after cardiac surgery by 18 ms (p = 0.014, 95% CI 3.65-32.4). There was no significant change in QTc after antipsychotic administration (p = 0.064). The mean CAPD score decreased (12.5-7.2; p < 0.001). Quetiapine had the most improvement in delirium, and risperidone had the least improvement (77.8%, n = 14; 37.8%, n = 34, respectively; p = 0.002). CONCLUSIONS: The QTc interval did not have a statistically significant change after the administration of antipsychotics, while there was improvement in the CAPD score. APMs may be administered safely without significant prolongation of the QTc and are an effective treatment for delirium.

Effect of beef long-storage under different temperatures and vacuum-packaging conditions on meat quality, oxidation processes and microbial growth.

BACKGROUND: The global beef market demands the meat industry to ensure product quality and safety in markets that are often very distant. The present study aimed to evaluate the effects of chilled (CH, 120 d) and chilled-then-frozen (CHF, 28 d + 92 d) storage conditions of beef vacuum packaged (VP) and vacuum packaged with antimicrobial (VPAM) on meat quality, oxidative status and microbial loads. Treatments resulted from the combination of storage condition and packaging type: VP + CH, VP + CHF, VPAM + CH and VPAM + CHF. RESULTS: Warner-Bratzler shear force values decreased in all treatments after 28 d of chilling. Except for VP + CH, L* values (lightness) of meat color did not differ in each treatment as the storage time increased. Meat from VP + CH had greater a* values than CHF treatments on day 120 of storage. A consumer panel did not detect differences in tenderness, flavor and overall liking between VP and VPAM beef, but they preferred CHF steaks rather than CH beef. TBARS values did not differ between VP and VPAM and between CH and CHF at any time during the storage period. At the end of storage time, all treatments except VP + CHF presented a greater concentration of thiols than at 48 h post-mortem. On day 120 of storage, VP + CH had greater catalase enzyme activity than CHF treatments while VP + CH and VP + CHF showed a greater superoxide dismutase activity than VPAM + CHF. Storage condition (CH or CHF) had a greater impact on microbial counts than the type of packaging. CONCLUSION: Freezing meat after an ageing period represents a suitable strategy to extend beef storage life without a detrimental impact on its quality. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Outcomes and prognostic factors in angioimmunoblastic T-cell lymphoma: final report from the international T-cell Project.

Angioimmunoblastic T-cell lymphoma (AITL) is a unique subtype of peripheral T-cell lymphoma (PTCL) with distinct clinicopathologic features and poor prognosis. We performed a subset analysis of 282 patients with AITL enrolled between 2006 and 2018 in the international prospective T-cell Project (NCT01142674). The primary and secondary end points were 5-year overall survival (OS) and progression-free survival (PFS), respectively. We analyzed the prognostic impact of clinical covariates and progression of disease within 24 months (POD24) and developed a novel prognostic score. The median age was 64 years, and 90% of patients had advanced-stage disease. Eighty-one percent received anthracycline-based regimens, and 13% underwent consolidative autologous stem cell transplant (ASCT) in first complete remission (CR1). Five-year OS and PFS estimates were 44% and 32%, respectively, with improved outcomes for patients who underwent ASCT in CR1. In multivariate analysis, age ≥60 years, Eastern Cooperative Oncology Group performance status >2, elevated C-reactive protein, and elevated ß2 microglobulin were associated with inferior outcomes. A novel prognostic score (AITL score) combining these factors defined low-, intermediate-, and high-risk subgroups with 5-year OS estimates of 63%, 54%, and 21%, respectively, with greater discriminant power than established prognostic indices. Finally, POD24 was a powerful prognostic factor with 5-year OS of 63% for patients without POD24 compared with only 6% for patients with POD24 (P < .0001). These data will require validation in a prospective cohort of homogeneously treated patients. Optimal treatment of AITL continues to be an unmet need, and novel therapeutic approaches are required.

Views on the impact of the COVID-19 pandemic on health in people with Down syndrome from diverse backgrounds.

Down syndrome (DS) has a unique medical and psychological profile. To date, few studies have asked individuals with DS about their views of health, and fewer have explored the impact of COVID-19 on the health of individuals with DS and their families. We used a mixed methods approach including two studies on the health of individuals with DS and their parents conducted during the COVID-19 pandemic: (1) eight virtual focus groups, comprised of 20 parents and 8 individuals with DS to obtain participants' views of health, and (2) a 20-item questionnaire on health care experience of patients with DS who are African American or come from primarily Spanish-speaking homes. Focus group transcripts were coded using a hybrid inductive/deductive framework and thematically analyzed using the Framework Method. This questionnaire included questions regarding the impact of COVID-19 on caregivers and their loved ones with DS; responses to these questions were summarized using descriptive statistics. Individuals with DS discussed the impact of the COVID-19 pandemic on their physical and social health including masking, online learning, and online communication with friends and family. Parents of individuals with DS discussed how the COVID-19 pandemic negatively impacted their child's physical, social, and mental health, as a result of virtual schooling and decreased socialization. There were unexpected positives of the pandemic such as improved hygiene and eased scheduling with telehealth visits. Caregivers noted COVID-19 impacted their own anxiety, employment, and other domains that have potential ripple effects on the health of their children. The COVID-19 pandemic had a pervasive impact on the mental health and wellness of caregivers as well as the physical, social, and mental health of individuals with DS.

Comparison of Aerosol Deposition Between a Cynomolgus Macaque and a 3D Printed Cast Model of the Animal.

PURPOSE: Preclinical aerosol studies using animals are essential for evaluating toxic or therapeutic effects on human respiratory tract. Macaques are relevant animal models for respiratory studies, but they are sensitive, expensive and difficult-to-access. METHODS: In the context of preliminary studies before animal experiments, we set up an alternative in vitro anatomical model of macaque airways to reduce, refine and replace (3Rs) the animals. We printed an in vitro anatomical cast until the third bronchial division from X-ray computed tomography data of a healthy cynomolgus macaque. This in vitro model was then connected to a respiratory pump to mimic macaque's breathing. We assessed the relevance of this in vitro model, by comparing aerosol deposition patterns obtained with the anatomical model and in three macaques using planar gamma camera imaging. DTPA-99mTechnetium aerosols were produced using three jet nebulizers, generating three different particle sizes: 13.1, 3.2 and 0.93 µm in terms of the mass median aerodynamic diameter (MMAD). RESULTS: The data showed no statistical differences between the animal and anatomical in vitro models in terms of total aerosol deposited in the airways. However, the distribution of the deposition in the airways showed a higher deposited fraction in the upper respiratory tract in the animals than the in vitro model for all particle sizes. CONCLUSIONS: The anatomical printed model appears to be a relevant in vitro tool to predict total aerosol deposition in macaque airways.

Correlates of Dapivirine Vaginal Ring Acceptance among Women Participating in an Open Label Extension Trial.

MTN-025/HOPE was an open-label trial of the dapivirine vaginal ring conducted in four African countries between 2016 and 2018. Women were first offered one ring monthly (at baseline, months 1 and 2), thereafter, transitioned to a more applicable real-world dispensation schedule, - 3 rings quarterly (at months 3, 6 and 9). Logistic regression analysis was used to assess correlates of ring acceptance at baseline and through follow-up. A total of 1456 women (median age 31 years) enrolled, 1342 (92.2%) accepted the ring at baseline and 1163 (79.9%) accepted the ring(s) at all visits. Changing ring dispensation from a monthly to a quarterly schedule had no negative effect on acceptance. Having a primary partner and him knowing about the ring being offered in HOPE, use of long-acting contraception (implants, injections, IUDs) or sterilization were associated with ring acceptance, along with prior strong intention to use the ring in the future. Efforts should consider these factors when rolling out the ring for HIV prevention.

Muscle Quality Index is inversely associated with psychosocial variables among Chilean adolescents.

A good muscle quality index (MQI) may have an inverse relationship with psychosocial variables of depression, anxiety, and stress in adolescents. Unfortunately, little scientific evidence has related MQI to psychosocial variables in this population. Therefore, this research aimed to determine the relationship between the MQI and psychosocial variables of depression, anxiety, and stress in Chilean adolescents. In this quantitative correlational design study, sixty adolescents participated voluntarily (mean ± standard deviation [SD]: age 15.11 ± 1.78 years). Anthropometric parameters, prehensile strength, MQI, and psychosocial variables were evaluated. The results showed that adolescents with high levels of MQI presented lower levels of depression (7.50 ± 6.06 vs. 10.97 ± 5.94), anxiety (5.64 ± 4.81 vs. 9.66 ± 5.12), and stress (6.79 ± 5.09 vs. 10 ± 5.58), in addition to reported lower abdominal obesity (WtHR, 0.47 ± 0.07 vs. 0.52 ± 0.07) than those with low levels of MQI. The group with high levels of MQI reported a higher prevalence of nonanxiety (81.3%, p = 0.031) and a lower prevalence of abdominal obesity (55.8%, p = 0.023). Likewise, a significant inverse association was evidenced between MQI and depression (ß; -6.18, 95% CI; -10.11: -2.25, p = 0.003), anxiety (ß; -6.61, 95% CI; -9.83: -3.39, p < 0.001) and stress (ß; -4.90, 95% CI; -8.49: -1.32 p = 0.008). In conclusion, the results suggest that high levels of MQI are associated with a higher prevalence of nonanxiety in adolescents and a significant inverse association between MQI and levels of depression, anxiety, and stress.

Long-term follow-up of an IgA nephropathy cohort: outcomes and risk factors.

AIM: IgA nephropathy (IgAN), the most common glomerulopathy worldwide and in Uruguay, raised treatment controversies. The study aimed to analyze long-term IgAN outcomes and treatment. METHODS: A retrospective analysis of a Uruguayan IgAN cohort, enrolled between 1985 and 2009 and followed up until 2020, was performed. The Ethics Committee approved the study. The inclusion criteria were (a) biopsy-proven IgAN; (b) age ≥12 years; and (c) available clinical, histologic, and treatment data. The patients were divided into two groups, with immunosuppressive (IS) or without (NoIS) treatment. Outcomes (end-stage kidney disease/kidney replacement therapy [ESKD/KRT] or all-cause death) were obtained from mandatory national registries. RESULTS: The study population included 241 patients (64.7% men), median age 32 (19.5) years, baseline blood pressure <130/80 mmHg in 37%, and microhematuria in 67.5% of patients. Baseline proteinuria, glomerulosclerosis, and a higher crescent percentage were significantly more frequent in the IS group. Proteinuria improved in both groups. Renal survival at 20 years was 74.6% without difference between groups. In the overall population and in the NoIS group, bivariate Cox regression analysis showed that baseline proteinuria, endocapillary hypercellularity, tubule interstitial damage, and crescents were associated with a higher risk of ESKD/KRT or death, but in the IS group, proteinuria and endocapillary hypercellularity were not. In the multivariate Cox analysis, proteinuria in the NoIS group, crescents in the IS group and tubule interstitial damage in both groups were independent risk factors. CONCLUSION: The IS group had more severe risk factors than the NoIS group but attained a similar outcome.

Indicators of health in Down syndrome: A virtual focus group study with patients and their parents.

BACKGROUND: Down syndrome has a unique medical and psychological profile. To date, few studies have asked individuals with Down syndrome about their views of health. METHODS: Eight focus groups of 20 parents and 8 individuals with Down syndrome, were conducted virtually via videoconferencing to obtain participants' views of health indicators. Focus group moderators employed some modifications for individuals with Down syndrome, including simplified language and use of graphics. Transcripts were coded using a hybrid inductive/deductive framework and thematically analysed using the Framework Method. RESULTS: We describe lessons learned in conducting virtual focus groups of individuals with Down syndrome and their parents. Individuals with Down syndrome could describe their views of health indicators and identified many of the same topics as their parents. Both groups discussed physical, mental, and social health components. However, people with Down syndrome gave a more restricted range of examples, but with different nuances than parents. CONCLUSION: Partcipants discussed physical, social, and mental well-being components of health in Down syndrome. Interviewing individuals with Down syndrome in virtual focus groups with appropriate modifications added important self-report health information.

Characteristics and clinical outcomes of patients with ALK-positive anaplastic large cell lymphoma: Report from the prospective international T-cell lymphoma project.

The T-cell Lymphoma Project is an international registry prospective study that enrolled patients with newly diagnosed peripheral T-cell and NK-cell lymphomas (PTCL). The main objective was to define the clinical features and outcomes, establishing a robust benchmark for future clinical trials. Seventy-four institutions from 14 countries in North America, South America, Europe, and Asia collected data on patients diagnosed and treated at their respective centers between September 2006 and February 2018. Among 1553 PTCL patients, 131 (8.4% of the total cohort) were confirmed to have anaplastic large cell lymphoma - kinase positive (ALCL, ALK+). The median age of the patients was 39 years (18-84). Sixty-five patients (66%) had advanced-stage disease, although majority (45 patients, 54%) had a low-risk International Prognostic Index (IPI) score (0-1). Of 97 patients treated with chemotherapy, 97% received anthracycline-containing regimens. The overall response rate was 81%, with 69 patients (70%) achieving complete remission. Estimated OS and PFS at 3 years were 77% (95% CI: 54%-99%) and 68% (95% CI: 46%-90%), respectively, and at 5 years were very similar, 77% of OS (95% CI: 62%-92%) and 64% of PFS (95% CI: 34%-94%). Multivariate analysis for PFS showed advanced stage (hazard ratios [HR]: 4.72, 95% CI: 1.43-23.9, p = 0.015), elevated lactate dehidrogenade (LDH) (HR 4.85; 95% CI: 1.73-13.60, p = 0.001), and Eastern Cooperative Oncology Group Performance Status scale (ECOG-PS) ≥2 (HR: 5.25; 95% CI: 1.68-16.4, p = 0.024). For OS, elevated LDH (HR: 3.77; 95% CI: 1.98-14.17, p = 0.014) and ECOG-PS ≥2 (HR: 4.59; 95% CI: 1.46-14.39, p = 0.004) were identified. In summary, although the outcome of ALK+ ALCL is superior to that of other PTCLs, it remains sufficiently favorable, given the young median age of the patients. Our results confirm the usefulness of both IPI and Prognostic Index for T-cell Lymphoma (PIT) in identifying groups of patients with different outcomes. Clinical Trials ID: NCT01142674.

Cariprazine-induced mania: A case series report.

Bipolar depression is the most prevalent phase of bipolar disorder (BD). There is a risk of inducing treatment-emergent affective switches (TEAS) with antidepressants (ADs). Hence, clinical guidelines do not recommend their use in monotherapy. Cariprazine is a dopamine-serotonin partial agonist, with a recent FDA approval as a monotherapy for BD type 1 (BD-I) depression. To our knowledge, there is no significant evidence of cariprazine-induced TEAS in bipolar depression. We describe three clinical cases of patients admitted to our acute psychiatric ward who developed manic episodes after the introduction of low doses of cariprazine. Two of the patients met the DSM-5 criteria for BD-I, and one for schizoaffective disorder, bipolar type. All patients were initially treated with low doses of cariprazine (1.5 mg) during a depressive phase. All three cases were simultaneously treated with mood stabilizers, regardless of which they switched to a manic episode when cariprazine was initiated. In our review of previous studies assessing the efficacy and side effects profile of cariprazine in BD-I, TEAS have not been found to be significant. However, according to our experience, cariprazine may induce affective switches in BD-I patients. Patients and psychiatrists should receive information regarding early warning symptoms and monitor possible cariprazine-induced mood switching.

PHF2 regulates homology-directed DNA repair by controlling the resection of DNA double strand breaks.

Post-translational histone modifications and chromatin remodelling play a critical role controlling the integrity of the genome. Here, we identify histone lysine demethylase PHF2 as a novel regulator of the DNA damage response by regulating DNA damage-induced focus formation of 53BP1 and BRCA1, critical factors in the pathway choice for DNA double strand break repair. PHF2 knockdown leads to impaired BRCA1 focus formation and delays the resolution of 53BP1 foci. Moreover, irradiation-induced RPA phosphorylation and focus formation, as well as localization of CtIP, required for DNA end resection, to sites of DNA lesions are affected by depletion of PHF2. These results are indicative of a defective resection of double strand breaks and thereby an impaired homologous recombination upon PHF2 depletion. In accordance with these data, Rad51 focus formation and homology-directed double strand break repair is inhibited in cells depleted for PHF2. Importantly, we demonstrate that PHF2 knockdown decreases CtIP and BRCA1 protein and mRNA levels, an effect that is dependent on the demethylase activity of PHF2. Furthermore, PHF2-depleted cells display genome instability and are mildly sensitive to the inhibition of PARP. Together these results demonstrate that PHF2 promotes DNA repair by homologous recombination by controlling CtIP-dependent resection of double strand breaks.

Factors associated with self-medication of antibiotics by caregivers in pediatric patients attending the emergency department: a case-control study.

INTRODUCTION: Antibiotic self-medication is a common practice in pediatric caregivers in low-income countries with limited resources and represents a public health problem. Our study sought to determine what factors are associated with this practice, including differences in knowledge or attitudes of caregivers who attend a pediatric emergency service. METHODS: Case-control study based on surveys of caregivers of pediatric patients brought to the emergency room with clinical symptoms suggestive of acute infection. Cases were defined as those caregivers who reported self-medication of antibiotics for the current illness and controls where those who did not report self-medication. Information was collected through a self-administered questionnaire that inquired about demographic and family characteristics, attitudes and knowledge toward self-medication of antibiotics. Data were compared using logistic regression and are presented with odd ratios and confidence intervals. RESULTS: A total of 728 caregivers, 182 cases and 546 controls were included. We found that higher parental education, both in mothers (OR 0.56, 95% CI 0.40-0.79) and fathers (OR 0.62, 95% CI 0.43-0.89) was associated with less self-medication. Attitudes such as always requesting antibiotics from their doctors (OR 3.92, 95% CI 1.59-9.66), frequently buying antibiotics without a prescription (OR 23.66, 95% CI 11.76-47.59) and giving advice on antibiotics among family members (OR 2.90, 95% CI 1.75-4.82) resulted in an increased likelihood of self-medication. There was also a higher probability of antibiotic self-medication in older children (OR 1.13, 95% CI 1.09-1.17), those with a greater number of siblings (OR 1.25, 95% CI 1.09-1.43) and in those cases that received antibiotics within the last 3 months (OR 6.27, 95% CI 4.35-9.04). Overall knowledge of risk of antibiotic self-medication was low. CONCLUSIONS: Some patient and family characteristics such as age, number of siblings, recent antibiotic usage and inappropriate attitudes are strongly related to antibiotic self-medication. These findings will inform future interventions to reduce self-medication in children.

In Vitro Determination of the Skin Anti-Aging Potential of Four-Component Plant-Based Ingredient.

The beauty industry is actively searching for solutions to prevent skin aging. Some of the crucial elements protecting cells from the aging process are telomere shortening, telomerase expression, cell senescence, and homeostasis of the redox system. Modification of these factors using natural antioxidants is an appealing way to support healthy skin aging. Therefore, in this study, we sought to investigate the antiaging efficacy of a specific combination of four botanical extracts (pomegranate, sweet orange, Cistanche and Centella asiatica) with proven antioxidant properties. To this end, normal human dermal fibroblasts were used as a cell model and the following studies were performed: cell proliferation was established by means of the MTT assay and the intracellular ROS levels in stress-induced premature senescence fibroblasts; telomere length measurement was performed under standard cell culture conditions using qPCR and under oxidative stress conditions using a variation of the Q-FISH technique; telomerase activity was examined by means of Q-TRAP; and AGE quantification was completed by means of ELISA assay in UV-irradiated fibroblasts. As a result, the botanical blend significantly reversed the H2O2-induced decrease in cell viability and reduced H2O2-induced ROS. Additionally, the presence of the botanical ingredient reduced the telomere shortening rate in both stressed and non-stressed replicating fibroblasts, and under oxidative stress conditions, the fibroblasts presented a higher median and 20th percentile telomere length, as well as a lower percentage of short telomeres (<3 Kbp) compared with untreated fibroblasts. Furthermore, the ingredient transiently increased relative telomerase activity after 24 h and prevented the accumulation of UVR-induced glycated species. The results support the potential use of this four-component plant-based ingredient as an antiaging agent.

The Nucleocapsid protein triggers the main humoral immune response in COVID-19 patients.

In order to control the COVID-19 pandemic caused by SARS-CoV-2 infection, serious progress has been made to identify infected patients and to detect patients with a positive immune response against the virus. Currently, attempts to generate a vaccine against the coronavirus are ongoing. To understand SARS-CoV-2 immunoreactivity, we compared the IgG antibody response against SARS-CoV-2 in infected versus control patients by dot blot using recombinant viral particle proteins: N (Nucleocapsid), M (Membrane) and S (Spike). In addition, we used different protein fragments of the N and S protein to map immune epitopes. Most of the COVID-19 patients presented a specific immune response against the full length and fragments of the N protein and, to lesser extent, against a fragment containing amino acids 300-685 of the S protein. In contrast, immunoreactivity against other S protein fragments or the M protein was low. This response is specific for COVID-19 patients as very few of the control patients displayed immunoreactivity, likely reflecting an immune response against other coronaviruses. Altogether, our results may help develop method(s) for measuring COVID-19 antibody response, selectivity of methods detecting such SARS-CoV-2 antibodies and vaccine development.

Comparison of different prognostic scores for patients with cirrhosis hospitalized with SARS-CoV-2 infection.

INTRODUCTION AND OBJECTIVES: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the effect of SARS-CoV-2 infection on outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. PATIENTS: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. RESULTS: Overall, 4.6% (CI 3.7-5.6) subjects had cirrhosis (n = 96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14-25). Mortality was 47% in patients with cirrhosis and 16% in patients without cirrhosis (P < .0001). Cirrhosis was independently associated with death [OR 3.1 (CI 1.9-4.8); P < .0001], adjusted by age, gender, and body mass index >30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P < .0001). CONCLUSIONS: SARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIF-C had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection. Clinicaltrials.gov:NCT04358380.

Marcadores de funcionamiento renal en pacientes infectados por SARS-CoV-2. Revisión rápida de la literatura.

 Objetivo. Resumir la evidencia científica sobre las altera-ciones renales asociadas con la infección por SARS-CoV-2. Material y métodos. Se realizó una revisión rápida con la metodología Cochrane. Resultados. La enfermedad renal crónica (ERC) preexistente en pacientes con SARS-CoV-2 varió de 1 a 38% y la lesión renal aguda (LRA), de 2.9 a 86.4%. El pronóstico de la infección fue peor en pacientes con ERC y en aquellos con reserva renal remanente (RRR) intacta que desarrollaron LRA. El riesgo de muerte fue mayor (riesgo relativo combinado = 1.49; IC95%: 1.09-2.04) en pacientes infectados por SARS-CoV-2 con ERC preexistente. Los mar-cadores de RRR mostraron alteraciones en pacientes con SARS-CoV-2 graves y fatales; el marcador más utilizado fue la creatinina sérica. Conclusiones. La evidencia científica muestra la relevancia de la evaluación y monitoreo perma-nente de la RRR en pacientes hospitalizados por SARS-CoV-2 para mejorar el pronóstico de aquellos con ERC preexistente, así como de aquellos sin ERC que desarrollan LRA.

Aortomesenteric clamp: association with Wilkie syndrome and nutcracker syndrome.

A 67-year-old female was referred due to epigastric pain, vomiting and weight loss of 6 kg in the past months. Blood tests were performed showing hematuria. An abdominal Doppler ultrasound did not show anything abnormal. Thus, an abdominal computed tomography (CT) angiography and a magnetic resonance imaging (MRI) enterography were performed, objectifying an aortomesenteric angle of 10.8° (reference range 38-56°), which caused a complete collapse of the left renal vein ("nutcracker phenomenon") and duodenal compression with retrograde dilatation ("Wilkie syndrome"). Conservative measures and nutritional support were adopted during hospitalization. She was discharged due to a good tolerance to an oral diet, the absence of symptoms and a good contrast pass in the esophagogastroduodenal transit.