M cell maturation and cDC activation determine the onset of adaptive immune priming in the neonatal Peyer's patch.

Early-life immune development is critical to long-term host health. However, the mechanisms that determine the pace of postnatal immune maturation are not fully resolved. Here, we analyzed mononuclear phagocytes (MNPs) in small intestinal Peyer's patches (PPs), the primary inductive site of intestinal immunity. Conventional type 1 and 2 dendritic cells (cDC1 and cDC2) and RORgt+ antigen-presenting cells (RORgt+ APC) exhibited significant age-dependent changes in subset composition, tissue distribution, and reduced cell maturation, subsequently resulting in a lack in CD4+ T cell priming during the postnatal period. Microbial cues contributed but could not fully explain the discrepancies in MNP maturation. Type I interferon (IFN) accelerated MNP maturation but IFN signaling did not represent the physiological stimulus. Instead, follicle-associated epithelium (FAE) M cell differentiation was required and sufficient to drive postweaning PP MNP maturation. Together, our results highlight the role of FAE M cell differentiation and MNP maturation in postnatal immune development.

Coronavirus disease 2019 convalescent children: outcomes after congenital heart surgery.

BACKGROUND: Children with exposure to coronavirus disease 2019 in recent times (asymptomatic or symptomatic infection) approaching congenital heart surgery programme are in increasing numbers. Understanding outcomes of such children will help risk-stratify and guide optimisation prior to congenital heart surgery. OBJECTIVE: The objective of the present study was to determine whether convalescent coronavirus disease 2019 children undergoing congenital heart surgery have any worse mortality or post-operative outcomes. DESIGN: Consecutive children undergoing congenital heart surgery from Oct 2020 to May 2021 were enrolled after testing for reverse transcription-polymerase chain reaction or rapid antigen test and immunoglobulin G antibody prior to surgery. Convalescent coronavirus disease 2019 was defined in any asymptomatic patient positive for immunoglobulin G antibodies and negative for reverse transcription-polymerase chain reaction or rapid antigen test anytime 6 weeks prior to surgery. Control patients were negative for any of the three tests. Mortality and post-operative outcomes were compared among the groups. RESULTS: One thousand one hundred and twenty-nine consecutive congenital heart surgeries were stratified as convalescence and control. Coronavirus disease 2019 Convalescent (n = 349) and coronavirus disease 2019 control (n = 780) groups were comparable for all demographic and clinical factors except younger and smaller kids in control. Convalescent children had no higher mortality, ventilation duration, ICU and hospital stay, no higher support with extracorporeal membrane oxygenation, high flow nasal cannula, no higher need for re-intubations, re-admissions, and no higher infections as central line-associated bloodstream infection, sternal site infection, and ventilator-associated pneumonia on comparison with coronavirus disease 2019 control children. CONCLUSIONS: Convalescent coronavirus disease 2019 does not have any unfavourable outcomes as compared to coronavirus disease 2019 control children. Positive immunoglobulin G antibody screening prior to surgery is suggestive of convalescence and supports comparable outcomes on par with control peers.

Extubation in the operating room after cardiac surgery in children: a prospective observational study with multidisciplinary coordinated approach.

OBJECTIVE: This prospective observational study was undertaken to determine the feasibility of extubation of children in the operating room after cardiac surgery. DESIGN: A prospective observational study compared with historic controls. SETTING: A single tertiary care referral hospital. PARTICIPANTS: One thousand consecutive pediatric patients requiring cardiac surgery aged 1 day to 18 years. Patients with spinal deformity, neurologic problems, coagulopathy as diagnosed by high international normalized ratio (INR) more than 1.5, and patients preoperatively on mechanical ventilation were excluded from the study. Data were also reviewed for another 1,000 patients operated before the beginning of this study, which constituted historic controls. INTERVENTIONS: All 1,000 patients were considered as potential candidates for extubation in the operating room after cardiac surgery and managed by a combination of general anesthesia and neuraxial analgesia with a mixture of caudal morphine and dexmedetomidine, and extubation in the operating room was attempted after completion of the surgical procedure. These comprised the study group (SG). Data also were reviewed for another 1,000 patients before the beginning of this study when extubation in the operating room was not attempted and compared with this group to study the impact of extubation in the operating room on intensive care unit (ICU) stay and resource utilization. This data comprised the before-study group (BSG). MEASUREMENTS AND MAIN RESULTS: Eight hundred seventy-one (87.1%) patients were extubated in the operating room. This included 40% of neonates and 70%, 85%, and 91% of patients aged between 1 and 3 months, 3 months to 1 year, and more than 1 year, respectively. Forty-five patients (4.5%) required re-intubation within 24 hours, and 9 patients died among those extubated in the OR, but for reasons thought not to be related to extubation. The ICU stay was significantly less in the study group (2.56±1.84 v 5.4±2.32 days, p<0.0001) as compared to before-study group (BSG). The number of patients in the ICU (34.76±3.19 v 59.98±4.92, p<0.0001) and the number of patients on a ventilator (5.1±1.24 v 24.5±2.88, p<0.0001) on a daily basis were significantly less in the study group, reflecting positive impact on resource utilization. CONCLUSION: Extubation in the operating room was successful in 87.1% of the patients without any increase in mortality and morbidity, but with a decrease in ICU length of stay and less use of hospital resources.

Suture-Based Vascular Closure Versus Surgical Closure of Large Bore Arteriotomies: A Real-World Experience.

INTRODUCTION: With the introduction of transcatheter aortic valve implantation (TAVI), endovascular abdominal aortic aneurysm repair (EVAR), thoracic endovascular aortic aneurysm repair (TEVAR), and frequent use of left ventricular assist devices in complicated percutaneous coronary interventions, the use of large bore arterial access has become a necessity. In the index study, we compared the percutaneous closure of large arteriotomies with open surgical (OS) closure. METHODS: It was a prospective study in which we compared the technical success and vascular complication rate associated with the use of a suture-based vascular closure device (VCD): Perclose ProGlide (PP) with that of OS closure. The study was carried out at Command Hospital Air Force, Bengaluru, India, from January 1, 2016, to December 31, 2020. The inclusion criteria were any percutaneous intervention involving large bore arterial access (≥12 French (F) sheath). The exclusion criteria were any condition where a persistent need for vascular access at the end of the procedure was required. We noted the baseline characteristics and type of anesthesia for all patients. The primary outcome was technical success and major vascular complications, which included major local site bleeding: Bleeding Academic Research Consortium (BARC) 3 or more, failed hemostasis requiring a second intervention, and acute vessel occlusion. Total time taken for the procedure (TTP), time to ambulation (TTA), and time to discharge post-procedure (TTD) were noted for each patient. The secondary outcomes were any bleeding other than major, local hematoma sized >5 cm at 24 hours, pseudo aneurysm formation at 30 days, and acute limb ischemia at 30 days. RESULTS: A total of 120 patients (PP: 60 (males: 54, females: 6), OS: 60 (males: 50, females: 10)) were included in this study. The mean age of patients was comparable in both groups (PP: 71.8 ± 9.62 years and OS: 71.0 ± 7.76 years, p-value: 0.63). Total large arteriotomies (mean size: 18.03F ± 3.34) closed were 184 (PP: 90, OS: 94). The procedures performed were EVAR: 64 (PP: 30, OS: 34), TAVI: 38 (PP: 21, OS: 17), and TEVAR: 18 (PP: 9, OS: 9). All patients in PP group received dual ProGlide with preclose technique. All TEVAR procedures (total arteriotomies: 18) required a vascular sheath of ≥ 24F. There was no statistical difference between the mean size of sheaths used in the two groups. The technical success (PP: 95.55%, OS: 97.87%, 95% CI: -5.78%-10.98%, p-value: 0.48) and rate of major complications were similar in both groups. Three patients in the PP group who had failed hemostasis with two ProGlides were successfully managed with one additional Angioseal (6F) each. The occurrence of hematoma sized larger than 5 cm was significantly more in the PP group compared to the OS group (PP: 7 (7.78%), OS: 0 (0%), p-value: 0.006). While GA was used for all patients who underwent vascular closure with OS, only eight patients (13.33%) in the PP group required GA. The TTP, TTA, and TTD were significantly lower in the PP group as compared to the OS group. CONCLUSION: The percutaneous closure of large bore arteriotomies with suture-based VCDs is equally effective and is not associated with increased major vascular complications. In fact, the TTP, TTA, and TTD are significantly lower in the PP group which can translate to better patient comfort and lower costs.

Non-professional efferocytosis of Salmonella-infected intestinal epithelial cells in the neonatal host.

The intestinal epithelium is the first line of defense against enteric pathogens. Removal of infected cells by exfoliation prevents mucosal translocation and systemic infection in the adult host, but is less commonly observed in the neonatal intestine. Instead, here, we describe non-professional efferocytosis of Salmonella-infected enterocytes by neighboring epithelial cells in the neonatal intestine. Intestinal epithelial stem cell organoid cocultures of neonatal and adult cell monolayers with damaged enterocytes replicated this observation, confirmed the age-dependent ability of intestinal epithelial cells for efferocytosis, and identified the involvement of the "eat-me" signals and adaptors phosphatidylserine and C1q as well as the "eat-me" receptors integrin-αv (CD51) and CD36 in cellular uptake. Consistent with this, massive epithelial cell membrane protrusions and CD36 accumulation at the contact site with apoptotic cells were observed in the infected neonatal host in vivo. Efferocytosis of infected small intestinal enterocytes by neighboring epithelial cells may represent a previously unrecognized mechanism of neonatal antimicrobial host defense to maintain barrier integrity.

Staged Hybrid Approach for Ductal Origin of the Pulmonary Artery in a Low Birth Weight Neonate.

Early recruitment of a discontinuous branch pulmonary artery will give the best long-term outcome for congenitally disconnected pulmonary arteries. This may be achieved using a staged approach. Even in low birth weight neonates, a hybrid approach with the first stage consisting of transcervical (via the common carotid artery) patent ductus arteriosus stenting can be performed to recruit the pulmonary artery where conventional treatment strategies may not be feasible or may be associated with higher risk.

Branch Pulmonary Artery Jailing During Patent Ductus Arteriosus Stenting: Recruitment and Immediate Outcomes.

BACKGROUND: Branch pulmonary artery (PA) occlusion during patent ductus arteriosus (PDA) stenting procedure is the main reason why branch PA origin stenosis was considered as a contraindication for PDA stenting. This study was designed to assess the incidence of branch PA jailing during PDA stenting for cyanotics with duct-dependent pulmonary circulation and its immediate outcome. METHODS: All the completed PDA stenting patients in our hospital between April 2017 and June 2019 were retrospectively analyzed for branch PA jailing and its outcome. RESULTS: Of 63 completed PDA stenting, there was branch PA jailing in 13 (20.6%) patients, all successfully recruited either by strut dilatation or by surgery. The median duration of ventilation was 16 (interquartile range [IQR]: 8-22) hours for jailed patients and 17.5 (IQR: 5.25-34.25) hours for nonjailed patients (P = .978). Median intensive care unit [ICU] stay was 69 (IQR: 47.75-96) hours for jailed patients and 79.5 (IQR: 66.75-135.25) hours for nonjailed patients (P = .394). Procedural mortality was 1 (7.6%) for jailed patients and 3 (6%) for nonjailed patients. Since all the jailed pulmonary arteries were recruited, there was proportionate growth of branch PA till the most recent follow-up. CONCLUSION: Jailing of branch PA does not increase the ventilation duration, ICU stay, or mortality risk if recruited immediately. Proportionate growth of branch PAs can be achieved in spite of jailing, if addressed aggressively. Branch PA stenosis should not be considered as a contraindication for PDA stenting.

Improved Technique for Interventional Extracardiac Fontan.

We have previously reported a simple technique for preparatory staging and subsequent interventional completion of an extracardiac Fontan procedure that anatomically and hemodynamically closely mimics a standard extracardiac Fontan. We describe herein modifications that simplify the original procedural sequence and that may allow wider application. Percutaneous completion can be achieved even without a radiofrequency probe, using electrocautery. Fenestration is also easy to perform if there is a clinical indication.

Hybrid approach for aortic embolization of Amplatzer duct occluder.

Embolization of the patent ductus arteriosus (PDA) device is a known adverse event of percutaneous PDA closure, which can lead to complications. Embolization can occur into the pulmonary artery or into the aorta. Device embolization can be moderate adverse event (when retrieved percutaneously) or major adverse event (when retrieved surgically). We are describing a hybrid approach for aortic embolization of PDA device when the percutaneous retrieval fails, where device retrieval and PDA ligation can be done through thoracotomy incision, thus decreasing the complications.

Late Complication of Amplatzer Duct Occluder: Erosion and Pseudoaneurysm.

We are presenting a delayed complication of an Amplatzer duct occluder (ADO) in which a patient presented with increasing hemoptysis owing to ADO eroding the vessel wall and forming a pseudoaneurysm that communicated with the left main bronchus. Although ADO is considered as the safest for catheter-based patent ductus arteriosus closures, isolated complication as reported can occur. Just like atrial septal defect device closures, which were considered safe initially and found to be having an erosion incidence of 0.1% to 0.3%, this case could represent an isolated event (the index case) or a long-term complication occurring at a very low incidence.

Pathways of migration from gaming to gambling.

Gaming and gambling have been studied in terms of similarity of its manifestations. There is a dearth of empirical-based evidence for the exploration of pathways to understand the shift from gaming to gambling. A 23-year-old male from a nuclear family was assessed using clinical interview for the pathways for shifting from gaming to gambling. The pathways were personality predispositions, maladaptive coping, interpersonal distress, peer pressure, variable reward anticipation, addiction characteristics in the form of craving, loss of control and use despite having consequences. These findings suggest that there is a need to create awareness among young adults about these potential causes related to transition from gaming to gambling.

Digital failure: An emerging reason of anger expression among adolescents.

Network connectivity can often lead to positive as well as negative mood states among regular Internet users. Recently, studies have mainly focused on the impact of Internet abuse/addiction on the various aspects of the individual, in terms of cognitive, emotional, behavioral, and interpersonal domains. However, one of the issues that is not much reported are the issues about what happens to the children who are not able to access the internet due to connectivity issues. Given this, the current article discusses two cases with negative emotional and behavioral manifestations of increased anger and frustration due to reduced Internet connectivity. This can help draw more research and attention to the need for increased cyber-literacy and incorporation of anger management programs into psychological interventions that address Internet Addiction.

Case Report - Pyknodysostosis.

Pyknodysostosis is an extremely rare lysosomal storage disease of the bone. Osteosclerosis of the skeleton is due to a decrease of the bone turnover. A plethora of clinical and radiological findings are observed. Patients are short statured with acroosteolysis and dense bones and develop multiple spontaneous bone fractures. A female patient presented with frontal bossing, small and thick fingers and toes. The classical clinical and radiological findings confirmed it as pyknodysostosis.