COVID-19 Vaccination in Patients with Inborn Errors of Immunity Reduces Hospitalization and Critical Care Needs Related to COVID-19: a USIDNET Report.

BACKGROUND: The CDC and ACIP recommend COVID-19 vaccination for patients with inborn errors of immunity (IEI). Not much is known about vaccine safety in IEI, and whether vaccination attenuates infection severity in IEI. OBJECTIVE: To estimate COVID-19 vaccination safety and examine effect on outcomes in patients with IEI. METHODS: We built a secure registry database in conjunction with the US Immunodeficiency Network to examine vaccination frequency and indicators of safety and effectiveness in IEI patients. The registry opened on January 1, 2022, and closed on August 19, 2022. RESULTS: Physicians entered data on 1245 patients from 24 countries. The most common diagnoses were antibody deficiencies (63.7%). At least one COVID-19 vaccine was administered to 806 patients (64.7%), and 216 patients received vaccination prior to the development of COVID-19. The most common vaccines administered were mRNA-based (84.0%). Seventeen patients were reported to seek outpatient clinic or emergency room care for a vaccine-related complication, and one patient was hospitalized for symptomatic anemia. Eight hundred twenty-three patients (66.1%) experienced COVID-19 infection. Of these, 156 patients required hospitalization (19.0%), 47 required ICU care (5.7%), and 28 died (3.4%). Rates of hospitalization (9.3% versus 24.4%, p < 0.001), ICU admission (2.8% versus 7.6%, p = 0.013), and death (2.3% versus 4.3%, p = 0.202) in patients who had COVID-19 were lower in patients who received vaccination prior to infection. In adjusted logistic regression analysis, not having at least one COVID-19 vaccine significantly increased the odds of hospitalization and ICU admission. CONCLUSION: Vaccination for COVID-19 in the IEI population appears safe and attenuates COVID-19 severity.

Respiratory Comorbidities Associated with Bronchiectasis in Patients with Common Variable Immunodeficiency in the USIDNET Registry.

BACKGROUND: Bronchiectasis is a major respiratory complication in patients with common variable immunodeficiency (CVID) and is associated with recurrent pulmonary infections. However, it is unclear whether other infections or non-infectious respiratory conditions are related to its development. OBJECTIVE: To identify respiratory comorbidities associated with bronchiectasis in patients with CVID. METHODS: A total of 1470 CVID patients enrolled in the USIDNET registry were included in a cross-sectional analysis. The primary outcome of our study was to determine the clinical characteristics and other respiratory conditions associated with respiratory comorbidities and physician-reported bronchiectasis. RESULTS: One hundred ninety-seven CVID patients were noted to have bronchiectasis (13.4%). Affected patients were significantly older than patients without bronchiectasis (median age 54 years vs. 49 years, p = 0.0004). These patients also had lower serum IgA (13 mg/dL IQR 60 mg/dL vs. 28.4 mg/dL IQR 66 mg/dL, p = 0.000). Notably, chronic rhinosinusitis (OR = 1.69 95%CI 1.05-2.75), sinusitis (OR = 2.06 95%CI 1.38-3.09), pneumonia (OR = 2.70 95%CI 1.88-3.88), COPD (OR = 2.66 95%CI 1.51-4.67), and interstitial lung disease (OR = 2.34 95%CI 1.41-3.91) were independently associated with the development of bronchiectasis in this population. CONCLUSION: These data suggest that lower and upper respiratory infections, chronic lower airway disease, and interstitial lung diseases are independently associated with bronchiectasis in CVID patients. Further study into predisposing conditions related to the development of bronchiectasis in CVID patients may allow prediction and early intervention strategies to prevent the development of this complication.

Changes in diversity and species composition in the assemblage of live and dead bats at wind farms in a highly diverse region.

Besides direct mortality, wind farms also affect aerial fauna by modifying their communities, reducing species diversity and richness through disturbance. During three consecutive years, we used mist nets and acoustic recorders, and conducted carcass searches, to characterize the assemblage of bat species and to estimate bat mortality at two nearby wind farms sited <5 km apart in a highly biodiverse region. We asked whether the diversity, richness and evenness of the assemblages varied yearly, predicting it would decrease through time. Richness and evenness did not change, but the diversity of species recorded acoustically, 96% being aerial insectivores, was significantly lower the third year. We estimate 4 - 15.7 fatalities/MW/year by wind farm, with 63% of species found as carcasses being aerial insectivores. We found >40% of dissimilarity in the species composition of bat assemblages between wind farms despite the short distance between them, with species turnover accounting for more than half of the dissimilarity every year. Similarly, species turnover accounted for >15% of the dissimilarity in the composition of the assemblage of live bats (captured and recorded acoustically) and the assemblage obtained through carcass searches. Our findings suggest that nearby wind farms impact bat communities differentially and aerial insectivores disproportionally. Long term, multi-method surveys are needed to characterize bat communities in highly diverse regions and to evaluate the post-construction effects that wind farms have on them.

Effect of Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Application in Achilles-Tendon Injury in an Animal Model.

Background: Achilles-tendon rupture prevails as a common tendon pathology. Adipose-derived mesenchymal stem cells (ADMSCs) are multipotent stem cells derived from adipose tissue with attractive regeneration properties; thus, their application in tendinopathies could be beneficial. Methods: Male rabbit ADMSCs were obtained from the falciform ligament according to previously established methods. After tenotomy and suture of the Achilles tendon, 1 × 106 flow-cytometry-characterized male ADMSCs were injected in four female New Zealand white rabbits in the experimental group (ADMSC group), whereas four rabbits were left untreated (lesion group). Confirmation of ADMSC presence in the injured site after 12 weeks was performed with quantitative sex-determining region Y (SRY)-gene RT-PCR. At Week 12, histochemical analysis was performed to evaluate tissue regeneration along with quantitative RT-PCR of collagen I and collagen III mRNA. Results: Presence of male ADMSCs was confirmed at Week 12. No statistically significant differences were found in the histochemical analysis; however, statistically significant differences between ADMSC and lesion group expression of collagen I and collagen III were evidenced, with 36.6% and 24.1% GAPDH-normalized mean expression, respectively, for collagen I (p < 0.05) and 26.3% and 11.9% GAPDH-normalized mean expression, respectively, for collagen III (p < 0.05). The expression ratio between the ADMSC and lesion group was 1.5 and 2.2 for collagen I and collagen III, respectively. Conclusion: Our results make an important contribution to the understanding and effect of ADMSCs in Achilles-tendon rupture.

ß-Catenin Restricts Zika Virus Internalization by Downregulating Axl.

The latest outbreak of Zika virus (ZIKV) in the Americas was associated with significant neurologic complications, including microcephaly of newborns. We evaluated mechanisms that regulate ZIKV entry into human fetal astrocytes (HFAs). Astrocytes are key players in maintaining brain homeostasis. We show that the central mediator of canonical Wnt signaling, ß-catenin, regulates Axl, a receptor for ZIKV infection of HFAs, at the transcriptional level. In turn, ZIKV inhibited ß-catenin, potentially as a mechanism to overcome its restriction of ZIKV internalization through regulation of Axl. This was evident with three ZIKV strains tested but not with a laboratory-adapted strain which has a large deletion in its envelope gene. Finally, we show that ß-catenin-mediated Axl-dependent internalization of ZIKV may be of increased importance for brain cells, as it regulated ZIKV infection of astrocytes and human brain microvascular cells but not kidney epithelial (Vero) cells. Collectively, our studies reveal a role for ß-catenin in ZIKV infection and highlight a dynamic interplay between ZIKV and ß-catenin to modulate ZIKV entry into susceptible target cells. IMPORTANCE ZIKV is an emerging pathogen with sporadic outbreaks throughout the world. The most recent outbreak in North America was associated with small brains (microcephaly) in newborns. We studied the mechanism(s) that may regulate ZIKV entry into astrocytes. Astrocytes are a critical resident brain cell population with diverse functions that maintain brain homeostasis, including neurogenesis and neuronal survival. We show that three ZIKV strains (and not a heavily laboratory-adapted strain with a large deletion in its envelope gene) require Axl for internalization. Most importantly, we show that ß-catenin, the central mediator of canonical Wnt signaling, negatively regulates Axl at the transcriptional level to prevent ZIKV internalization into human fetal astrocytes. To overcome this restriction, ZIKV downregulates ß-catenin to facilitate Axl expression. This highlights a dynamic host-virus interaction whereby ZIKV inhibits ß-catenin to promote its internalization into human fetal astrocytes through the induction of Axl.

Evolution of polypharmacy in a spanish population (2005-2015): A database study.

PURPOSE: To analyze the evolution of the prevalence of polypharmacy and excessive polypharmacy in a Spanish population, and to improve the identification of patients with polypharmacy. METHODS: A descriptive, annual cross-sectional observational study was carried out. PATIENTS: individuals over 14 years of age included in a multiregional primary care database of the Spanish population (BIFAP). ANALYSIS: prescription data. Period 2005-2015. VARIABLES: proportion of patients with polypharmacy (simultaneous prescription of ≥5 drugs) and excessive polypharmacy (≥10 drugs) for at least 6 months, according to sex and age groups. A trend analysis of the studied period was performed (overall, and by sex and age groups). RESULTS: The data are reported on a comparative basis (2005 vs 2015). Number of patients analyzed: 2664743 vs 4 002 877. The prevalence of polypharmacy increased significantly (2.5% vs 8.9%, P-value for trend <0.001), being greater in females throughout the study period and in the group aged ≥80 years (P-value for trends <0.001). The prevalence of excessive polypharmacy also increased significantly (0.1% vs 1%, P-value for trend <0.001), being higher in the group aged ≥80 years (P-value for trend <0.001). The proportion of patients with no chronic treatment decreased (80.2% vs 63.1%). CONCLUSIONS: The prevalence of polypharmacy in this Spanish population has tripled in the period 2005-2015, while excessive polypharmacy has increased 10-fold. These increments are seen in both sexes and in all age groups, particularly in individuals over 80 years of age. The proportion of patients without chronic treatments has decreased.

[Deprescribing to increase people health or when deprescribing could be the best pill]. / Deprescribiendo para mejorar la salud de las personas o cuando deprescribir puede ser la mejor medicina.

The increasing longevity of the population, the increase in morbidity and the consumption of medications have caused that polypharmacy is a priority health problem due to its consequences: increase of adverse effects, pharmacological interactions and favor the functional deterioration of the patient. The clinical situation of the patients changes over time and it is necessary to adjust the medication in each stage, assessing the fragility, the level of dependence and the functional deterioration. Deprescription is complex and requires an adequate clinical and pharmacological formation. In Primary Care lies the greater knowledge of the patient and their environment, and in a shared way with the patient and caregivers, it is necessary to assess which drugs to maintain and which ones to withdraw from a clinical, ethical and social perspective. There are tools to help deprescription that can be useful for Primary Care to facilitate this process and that are detailed in this article.

Development and validation of a noninvasive prediction model for nonalcoholic steatohepatitis resolution after lifestyle intervention.

UNLABELLED: Liver biopsy is the gold standard method to assess nonalcoholic steatohepatitis (NASH) resolution after therapeutic interventions. We developed and validated a simple and noninvasive scoring system to predict NASH resolution without fibrosis worsening after 1 year of lifestyle intervention. This was a prospective cohort study conducted in 261 patients with histologically proven NASH who were treated with lifestyle changes for 52 weeks and underwent a second liver biopsy to confirm NASH resolution. We divided the data into development (140 subjects) and validation (121 individuals) sets. NASH resolution occurred in 28% (derivation group) and 27% (validation group). At the multivariable analysis, weight loss (odds ratio [OR] = 2.75, 95% confidence interval [CI] 1.65-4.58; P < 0.01), type 2 diabetes (OR = 0.04, 95% CI 0.005-0.49; P = 0.01), normal levels of alanine aminotransferase at the end of intervention (OR = 9.84, 95% CI 2.21-44.1; P < 0.01), age (OR = 0.89, 95% CI 0.83-0.97; P = 0.01), and a nonalcoholic fatty liver activity score ≥5 (OR = 0.08, 95% CI 0.01-0.43; P < 0.01) were independent predictors of NASH resolution. The area under the receiver operating characteristic curve of the selected model was 0.956 and 0.945 in the derivation and validation cohorts, respectively. Using a score threshold of ≤46.15, negative predictive values were 92% in the derivation and validation groups, respectively. By applying a cutoff ≥69.72, positive predictive values were 92% and 89% in the derivation and validation groups, respectively. Using both cutoffs, a liver biopsy would have been avoided in 229 (88%) of 261 patients, with a correct prediction in 209 (91%) CONCLUSIONS: A noninvasive prediction model including weight loss, type 2 diabetes, alanine aminotransferase normalization, age, and a nonalcoholic fatty liver activity score ≥5 may be useful to identify NASH resolution in patients under lifestyle intervention. (Hepatology 2016;63:1875-1887).

[Chilaiditi’'s sign and syndrome: rare conditions but diagnostically important in pediatrics. Clinical cases]. / Signo y síndrome de Chilaiditi: condiciones infrecuentes pero con importancia diagnóstica en pediatría. Casos clínicos.

Although infrequent, bowel interposition between diaphragm and liver, Chilaiditi’s sign or syndrome (without or with gastrointestinal symptoms), are a major clinical condition given the possibilities of differential diagnosis, such as pneumoperitoneum, diaphragmatic hernia and subphrenic abscess. OBJECTIVE: To report the cases of two preschool patients with Chilaiditi´s sign and syndrome, as well as to highlight the importance of this clinical condition. CLINICAL CASES: Case 1: A male preschooler evaluated by respiratory disease without abdominal symptoms. Thorax X-ray shows left retrocardiac infiltrates and air in right subdiaphragmatic region. Previous radiographies shows the same image. He was diagnosed with Chilaiditi sign associated with pneumonia, antibiotics were used before discharge. Case 2: A female preschooler, evaluated by abdominal distention and constipation. A previous thorax X-ray shows bowel interposition between diaphragm and liver. Barium enema confirmed the findings. Blood test were normal. A Chilaiditi's syndrome was diagnosed. She received medical treatment with favorable evolution. CONCLUSION: These cases highlight the importance of this clinical condition that, despite being infrequent, constitutes a diagnostic challenge in the emergency services.

The Relationship Between CYP46A1 Polymorphism and Suicide Risk: A Preliminary Investigation.

Suicide is a global public health issue, with a particularly high incidence in individuals suffering from Major Depressive Disorder (MDD). The role of cholesterol in suicide risk remains controversial, prompting investigations into genetic markers that may be implicated. This study examines the association between CYP46A1 polymorphisms, specifically SNPs rs754203 and rs4900442, and suicide risk in a Mexican MDD patient cohort. Our study involved 188 unrelated suicide death victims, 126 MDD patients, and 144 non-suicidal controls. Genotypic and allelic frequencies were assessed using the Real Time-polymerase chain reaction method, and associations with suicide risk were evaluated using chi-square tests. The study revealed significant differences in allelic and genotypic frequencies in rs754203 SNP between suicide death and controls. The CYP46A1 rs754203 genotype G/G was significantly linked with suicide, and the G allele was associated with a higher risk of suicide (OR = 1.370, 95% CI = 1.002-1.873). However, we did not observe any significant differences in genotype distribution or allele frequencies of CYP46A1 rs4900442. Our study suggests that carriers of the CYP46A1 rs754203 G allele (A/G + G/G) may play a role in suicidal behavior, especially in males. Our findings support that the CYP46A1 gene may be involved in susceptibility to suicide, which has not been investigated previously. These results underscore the importance of further research in different populations to elucidate the genetic underpinnings of the role of CYP46A1 in suicide risk and to develop targeted interventions for at-risk populations.