A Comprehensive Look at the Development of Asthma in Children.

Asthma, a prevalent chronic respiratory condition affecting millions of children globally, presents a significant health challenge. This review critically examines the developmental pathways of asthma in children, focusing on genetic, environmental, and early-life determinants. Specifically, we explore the impact of prenatal and postnatal factors such as maternal smoking, nutrition, respiratory infections, and allergen exposure on asthma development. Our analysis highlights the intricate interplay of these influences and their contribution to childhood asthma. Moreover, we emphasize targeted strategies and interventions to mitigate its burden, including genetic counseling for at-risk families, environmental modifications to reduce triggers, and early-life immunomodulation. By delving into these preventive measures and interventions, our review aims to provide actionable insights for healthcare professionals in developing tailored strategies to address the complexities of childhood asthma. In summary, this article offers a detailed examination of asthma development in children, aiming to enhance understanding and inform efforts to reduce its burden through targeted interventions.

Approach of Acromegaly during Pregnancy.

Acromegaly-related sub/infertility, tidily related to suboptimal disease control (1/2 of cases), correlates with hyperprolactinemia (1/3 of patients), hypogonadotropic hypogonadism­mostly affecting the pituitary axis in hypopituitarism (10−80%), and negative effects of glucose profile (GP) anomalies (10−70%); thus, pregnancy is an exceptional event. Placental GH (Growth Hormone) increases from weeks 5−15 with a peak at week 37, stimulating liver IGF1 and inhibiting pituitary GH secreted by normal hypophysis, not by somatotropinoma. However, estrogens induce a GH resistance status, protecting the fetus form GH excess; thus a full-term, healthy pregnancy may be possible. This is a narrative review of acromegaly that approaches cardio-metabolic features (CMFs), somatotropinoma expansion (STE), management adjustment (MNA) and maternal-fetal outcomes (MFOs) during pregnancy. Based on our method (original, in extenso, English­published articles on PubMed, between January 2012 and September 2022), we identified 24 original papers­13 studies (3 to 141 acromegalic pregnancies per study), and 11 single cases reports (a total of 344 pregnancies and an additional prior unpublished report). With respect to maternal acromegaly, pregnancies are spontaneous or due to therapy for infertility (clomiphene, gonadotropins or GnRH) and, lately, assisted reproduction techniques (ARTs); there are no consistent data on pregnancies with paternal acromegaly. CMFs are the most important complications (7.7−50%), especially concerning worsening of HBP (including pre/eclampsia) and GP anomalies, including gestational diabetes mellitus (DM); the best predictor is the level of disease control at conception (IGF1), and, probably, family history of 2DM, and body mass index. STE occurs rarely (a rate of 0 to 9%); some of it symptoms are headache and visual field anomalies; it is treated with somatostatin analogues (SSAs) or alternatively dopamine agonists (DAs); lately, second trimester selective hypophysectomy has been used less, since pharmaco-therapy (PT) has proven safe. MNA: PT that, theoretically, needs to be stopped before conception­continued if there was STE or an inoperable tumor (no clear period of exposure, preferably, only first trimester). Most data are on octreotide > lanreotide, followed by DAs and pegvisomant, and there are none on pasireotide. Further follow-up is required: a prompt postpartum re-assessment of the mother's disease; we only have a few data confirming the safety of SSAs during lactation and long-term normal growth and developmental of the newborn (a maximum of 15 years). MFO seem similar between PT + ve and PT − ve, regardless of PT duration; the additional risk is actually due to CMF. One study showed a 2-year median between hypophysectomy and pregnancy. Conclusion: Close surveillance of disease burden is required, particularly, concerning CMF; a personalized approach is useful; the level of statistical evidence is expected to expand due to recent progress in MNA and ART.

Approach of Heterogeneous Spectrum Involving 3beta-Hydroxysteroid Dehydrogenase 2 Deficiency.

We aim to review data on 3beta-hydroxysteroid dehydrogenase type II (3ßHSD2) deficiency. We identified 30 studies within the last decade on PubMed: 1 longitudinal study (N = 14), 2 cross-sectional studies, 1 retrospective study (N = 16), and 26 case reports (total: 98 individuals). Regarding geographic area: Algeria (N = 14), Turkey (N = 31), China (2 case reports), Morocco (2 sisters), Anatolia (6 cases), and Italy (N = 1). Patients' age varied from first days of life to puberty; the oldest was of 34 y. Majority forms displayed were salt-wasting (SW); some associated disorders of sexual development (DSD) were attendant also-mostly 46,XY males and mild virilisation in some 46,XX females. SW pushed forward an early diagnosis due to severity of SW crisis. The clinical spectrum goes to: premature puberty (80%); 9 with testicular adrenal rest tumours (TARTs); one female with ovarian adrenal rest tumours (OARTs), and some cases with adrenal hyperplasia; cardio-metabolic complications, including iatrogenic Cushing' syndrome. More incidental (unusual) associations include: 1 subject with Barter syndrome, 1 Addison's disease, 2 subjects of Klinefelter syndrome (47,XXY/46,XX, respective 47,XXY). Neonatal screening for 21OHD was the scenario of detection in some cases; 17OHP might be elevated due to peripheral production (pitfall for misdiagnosis of 21OHD). An ACTH stimulation test was used in 2 studies. Liquid chromatography tandem-mass spectrometry unequivocally sustains the diagnostic by expressing high baseline 17OH-pregnenolone to cortisol ratio as well as 11-oxyandrogen levels. HSD3B2 gene sequencing was provided in 26 articles; around 20 mutations were described as "novel pathogenic mutation" (frameshift, missense or nonsense); many subjects had a consanguineous background. The current COVID-19 pandemic showed that CAH-associated chronic adrenal insufficiency is at higher risk. Non-adherence to hormonal replacement contributed to TARTs growth, thus making them surgery candidates. To our knowledge, this is the largest study on published cases strictly concerning 3ßHSD2 deficiency according to our methodology. Adequate case management underlines the recent shift from evidence-based medicine to individualized (patient-oriented) medicine, this approach being particularly applicable in this exceptional and challenging disorder.

Triple-valve replacement for Rhizobium radiobacter endocarditis with septic shock in an adult with ventricular septal defect. A case report.

INTRODUCTION AND IMPORTANCE: Triple-valve replacement in active infective endocarditis has rarely been reported. This paper is the first report of a triple-valve replacement performed in endocarditis with septic shock and the first presentation of multivalvular endocarditis due to Rhizobium radiobacter. CASE PRESENTATION: A 26-year-old patient with a neglected ventricular septal defect referred to us in septic shock, with multiple organ failure, severe biventricular dysfunction, and pulmonary hypertension, due to Rhizobium radiobacter infective endocarditis affecting the aortic, tricuspid and pulmonary valves. Initially, he was deemed unfit for surgery. However, after clinical stabilization, triple-valve replacement, aortic annular abscess repair, membranous septum aneurysm resection, and ventricular septal defect patch closure were performed. The postoperative evolution was good; both ventricles showed functional recovery after six months. CLINICAL DISCUSSION: Although surgery provides the best chances of survival in endocarditis with septic shock, reportedly, most cases are considered inoperable. Clinical stabilization under intensive care using specific therapies to manage septic shock, myocardial dysfunction, and pulmonary hypertension was crucial for surgery success. Custodiol® cardioplegia, and replacement of the right-sided valves using a beating-heart technique were used to reduce the myocardial ischemic time. CONCLUSION: Rhizobium radiobacter, an opportunistic gram-negative bacterium, potentially may cause multiple valve endocarditis. Patients with endocarditis and septic shock initially considered inoperable can still benefit from surgery after tenacious intensive care (cytokine hemoadsorption and levosimendan are helpful in this process). In complex multivalvular procedures, a beating heart technique to replace the right-sided valves should be considered to minimize the duration of myocardial ischemia.

Surgery for Functional Tricuspid Regurgitation in Adult Atrial Septal Defect — An Increasing Subject in a Decreasing Matter

ABSTRACT Introduction: Functional tricuspid regurgitation (TR) is known to complicate adult atrial septal defect (ASD), but its management is still under debate. We reviewed our experience in ASD surgery, focusing on associated functional TR and its treatment. Methods: This retrospective study (2005-2019) included 206 consecutive adult ASD surgical cases without associated valve pathology, except functional TR. Variables were statistically compared on TR classes and surgery-defined groups. Results: Mean age of the patients was 40.3±13 years; 19.9% had sinus venosus syndrome. TR severity was directly related to age, pulmonary systolic pressure, right ventricular and tricuspid annulus diameters, and heart failure class. TR ≥ 2 was found in 134 (65%) patients, while TR ≥ 3 in 56 (27.2%) patients. Tricuspid surgery was associated to shunt closure in 66 (32%) patients, almost all through valve repair; indication was directly related to age, right ventricular and tricuspid annulus diameters, and heart failure class ≥ 3. Tricuspid surgery was more efficient than isolated shunt closure in decreasing TR (79±23% vs. 36±26%; P=1.8 E-18). Device closure availability (last four years of the study) was associated with 1/3 reduction of surgical cases but increased the share of cases with TR>2 (> 51% vs. < 31%; P<0.05). Conclusion: In the era of device closure, surgery for adult ASD is less frequent, but the share of significant TR cases is in net increase. To avoid long-term postoperative TR, we plead for valve repair in all patients with severe TR and for considering repair in moderate TR at risk of persistence.

Surgery for Functional Tricuspid Regurgitation in Adult Atrial Septal Defect - An Increasing Subject in a Decreasing Matter.

INTRODUCTION: Functional tricuspid regurgitation (TR) is known to complicate adult atrial septal defect (ASD), but its management is still under debate. We reviewed our experience in ASD surgery, focusing on associated functional TR and its treatment. METHODS: This retrospective study (2005-2019) included 206 consecutive adult ASD surgical cases without associated valve pathology, except functional TR. Variables were statistically compared on TR classes and surgery-defined groups. RESULTS: Mean age of the patients was 40.3±13 years; 19.9% had sinus venosus syndrome. TR severity was directly related to age, pulmonary systolic pressure, right ventricular and tricuspid annulus diameters, and heart failure class. TR ≥ 2 was found in 134 (65%) patients, while TR ≥ 3 in 56 (27.2%) patients. Tricuspid surgery was associated to shunt closure in 66 (32%) patients, almost all through valve repair; indication was directly related to age, right ventricular and tricuspid annulus diameters, and heart failure class ≥ 3. Tricuspid surgery was more efficient than isolated shunt closure in decreasing TR (79±23% vs. 36±26%; P=1.8 E-18). Device closure availability (last four years of the study) was associated with 1/3 reduction of surgical cases but increased the share of cases with TR>2 (> 51% vs. < 31%; P<0.05). CONCLUSION: In the era of device closure, surgery for adult ASD is less frequent, but the share of significant TR cases is in net increase. To avoid long-term postoperative TR, we plead for valve repair in all patients with severe TR and for considering repair in moderate TR at risk of persistence.

Acute Type A Aortic Dissection and Coarctation: Single-Stage Repair Using a Clamshell Incision and a Systematic Literature Review.

BACKGROUND: Aortic coarctation (CoAo) may be discovered only when complicated by acute type A aortic dissection (ATAAD). We present a case with a one-stage repair of this pathologic association and review the relevant literature focusing on the surgical choices. CASE REPORT: A 43-year-old man presented with acute thoracic pain. Computed tomography and echocardiography demonstrated CoAo, ATAAD type II, an ascending aorta aneurysm, and moderate regurgitation of a bicuspid aortic valve. Emergency surgery was performed. A clamshell incision, cardiopulmonary bypass with dual arterial cannulation (axillo-femoral), CoAo repair (by resection-interposition), and supracoronary aorta replacement were performed. Four years later, the patient was healthy and asymptomatic. REVIEW: Thirty surgical cases of ATAAD with CoAo repair after the dissection onset were included. Iatrogenic dissections and formerly repaired CoAo without surgical indication were excluded. RESULTS: The mean patient age was 27.8 ± 12 years; there was a male predominance (76.7%). The patients frequently presented with ascending aorta aneurysm (86.2%), bicuspid aortic valve (69%), and type II dissection (79.3%); dissection never extended below the CoAo. The one-stage treatment (15 patients; 55.5%) included 12 surgical repairs of CoAo (mostly by ascending-to-descending aorta extra-anatomic bypass; 58.3%) and three balloon angioplasties. In patients with uncorrected CoAo at the onset of cardiopulmonary bypass, double arterial perfusion was used in 55.5%. CONCLUSIONS: One-stage repair (hybrid or surgical), double arterial perfusion, and extra-anatomic ascending-to-descending aorta bypass are the most common options for treating ATAAD-CoAo. The clamshell incision provides excellent access for an extended arch procedure and facilitates anatomic isthmus repair.

Skeletal muscle regeneration involves macrophage-myoblast bonding.

Regeneration in adult skeletal muscle relies on the activation, proliferation, and fusion of myogenic precursor cells (MPC), mostly resident satellite cells (SC). However, the regulatory mechanism during this process is still under evaluation, with the final aim to manipulate regeneration when the intrinsic mechanism is corrupted. Furthermore, intercellular connections during skeletal muscle regeneration have not been previously thoroughly documented. Our hypothesis was that a direct and close cellular interaction between SC/MPC and invading myeloid cells is a key step to control regeneration. We tested this hypothesis during different steps of skeletal muscle regeneration: (a) the recruitment of activated SC; (b) the differentiation of MPC; (c) myotubes growth, in a mouse model of crush injury. Samples harvested (3 and 5 days) post-injury were screened by light and confocal microscopy. Ultrastructural analysis was performed by conventional transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM) followed by 3D modeling of electron tomography (ET) data. This revealed a new type of interaction between macrophages and myogenic cells by direct heterocellular surface apposition over large areas and long linear distances. In the analyzed volume, regions spaced below 20 nm, within molecular range, represented 31% of the macrophage membrane surface and more than 27% of the myotube membrane. The constant interaction throughout all stages of myogenesis suggests a potential new type of regulatory mechanism for the myogenic process. Thus, deciphering structural and molecular mechanisms of SC-macrophage interaction following injury might open promising perspectives for improving muscle healing.

Can elastography replace fine needle aspiration?

Endoscopic ultrasound (EUS) is one of the best diagnostic methods for diseases of the digestive tract and surrounding organs. Whereas EUS-guided fine needle aspiration (FNA) has been very useful for providing histological confirmation for previously hard to reach lesions, elastography is aiming to obtain a "virtual biopsy" by assessing differences in elasticity between the normal and pathological - usually malignant - tissue. A question that arises is whether EUS-elastography has reached a stage where it might successfully supplant the use of EUS-FNA in some of its clinical indications. The main indications of EUS-guided FNA are listed in this article and published data on the usage of elastography in these settings is reviewed for each one. In some of the indications, a plethora of studies have been published, notably for the evaluation of solid pancreatic masses and lymph nodes, while in others there is little relevant data (submucosal masses, left liver lesions, left adrenal masses), or elastography simply is not suitable as a diagnostic means (cystic lesions). Our conclusion is that elastography is not yet ready to replace EUS-FNA in its indications, but should complement it in various settings, especially for the assessment of lymph nodes. It can only be considered an alternative on a case-by-case basis, in situations where FNA is regarded as a contraindication. Furthermore, it could be used in conjunction with other imaging techniques, such as contrast-enhanced EUS, in order to further improve the accuracy of non-invasive EUS assessment, possibly making the case for a more limited or targeted use of EUS-FNA in selected cases.