A National Survey of Pediatric Post-Acute Care Facilities.

OBJECTIVES: To identify and geolocate pediatric post-acute care (PAC) facilities in the United States. DESIGN: Cross-sectional survey using both online resources and telephone inquiry. SETTING: All 50 U.S. states surveyed from June 2022 to May 2023. Care sites identified via state regulatory agencies and the Centers for Medicare & Medicaid Services. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Number, size, and type of facility, scope of practice, and type of care provided. One thousand three hundred fifty-five facilities were surveyed; of these, 18.6% (252/1355) were pediatric-specific units or adult facilities accepting some pediatric patients. There were 109 pediatric-specific facilities identified within 39 U.S. states. Of these, 38 were freestanding with all accepting children with tracheostomies, 97.4% (37/38) accepting those requiring mechanical ventilation via tracheostomy, and 81.6% (31/38) accepting those requiring parenteral nutrition. The remaining 71 facilities were adult facilities with embedded pediatric units or children's hospitals with 88.7% (63/71), 54.9% (39/71), and 54.9% (39/71), accepting tracheostomies, mechanical ventilation via tracheostomy, and parenteral nutrition, respectively. Eleven states lacked any pediatric-specific PAC units or facilities. CONCLUSIONS: The distribution of pediatric PAC is sparse and uneven across the United States. We present an interactive map and database describing these facilities. These data offer a starting point for exploring the consequences of pediatric PAC supply.

Analysis of Perioperative and Long-Term Outcomes Among Presentations of Anomalous Left Coronary Artery from the Pulmonary Artery Diagnosed Beyond Infancy Versus During Infancy.

Anomalous Left Coronary Artery from the Pulmonary Artery (ALCAPA) typically presents in infancy; however, there are cases of patients who survive the infant period and present later in life. We aimed to characterize patients with late ALCAPA diagnoses and to assess perioperative and functional outcomes. A retrospective chart review of patients who underwent ALCAPA repair between 1996 and 2020 at Boston Children's Hospital was performed. This cohort was divided into early ALCAPA (< 1 year) and late ALCAPA (≥ 1 year) groups. Perioperative data were collected. Longitudinal functional assessments were made by echocardiography, exercise stress test, and cardiac magnetic resonance imaging. The median age of the late ALCAPA group was 7.6 years with 25% (6/24) of patients over 18 years. The late ALCAPA group was more likely to present as an incidental finding (63%) and required less preoperative intervention compared to the early group. On preoperative echocardiogram, the late ALCAPA group had less moderate or severe mitral regurgitation (16.7% vs 62%, p < 0.001) or left ventricular dysfunction (16.7% vs 89%, p < 0.001) compared to the early group. Reoperation was uncommon, and both groups demonstrated almost complete resolution of mitral regurgitation and left ventricular dysfunction over time. There are important differences between late and early ALCAPA subtypes. Revascularization results in excellent outcomes in both early and late groups, but long-term surveillance of ALCAPA patients is warranted as they may have functional deficits after repair.

The Relation of Birth Weight and Adiposity Across the Life Course to Semen Quality in Middle Age.

BACKGROUND: Studies of body mass index and semen quality have reported mixed results, but almost all were cross-sectional and many were conducted in selected populations. Longitudinal studies in population-based cohorts are necessary to identify how timing and duration of excess adiposity may affect semen quality. METHODS: In 193 members of the Child Health and Development Studies birth cohort, we examined associations of birth weight and adiposity at six time points spanning early childhood and adulthood with sperm concentration, motility, and morphology at mean age 44 years, as well as with corresponding 2010 World Health Organization (WHO) subfertility reference levels. RESULTS: Birth weight for gestational age percentile was positively associated with square-root sperm concentration (regression coefficient B [95% confidence interval] = 0.02 × 103 sperm/ml [0.004, 0.04]). Overweight/obesity in men's 20s was associated with lower percent progressive motility (B =-5.2 [-9.9, -0.63]), higher odds of low motility (odds ratio (OR) = 2.4 [1.3, 4.4]), and higher odds of poor morphology (OR = 1.9 [0.94, 3.8]). Those who were overweight/obese in their 20s were also more likely to meet two or three WHO subfertility criteria (OR = 3.9 [1.6, 9.4]) compared with normal-weight men. Each additional adult decade in which a participant was overweight/obese was associated with higher odds of low motility (OR = 1.3 [0.96, 1.6]) and higher odds of meeting two or three WHO subfertility criteria (OR = 1.5 [1.0, 2.2]). CONCLUSIONS: In our data, associations among adiposity and sperm concentration, motility, and morphology varied according to timing and duration of exposure, potentially reflecting different biological mechanisms that influence these semen parameters.

Factors Associated With Adverse Outcomes After Repair of Anomalous Coronary From Pulmonary Artery.

BACKGROUND: Successful repair of anomalous origin of coronary artery from the pulmonary artery (ACAPA) is generally associated with a good prognosis. However, risk factors for poor postoperative outcomes have not been well characterized. This study used a multicenter data set to determine predictors of mortality after ACAPA repair. METHODS: A retrospective analysis was performed using The Society of Thoracic Surgeons Congenital Heart Surgery Database's Participant User File. After identification of all patients with ACAPA who underwent repair from 2007 to 2016, demographics, preoperative and intraoperative variables, and postoperative complications were compared between survivors and nonsurvivors. The primary outcomes included (1) in-hospital mortality and (2) the need for postoperative extracorporeal membrane oxygenation (ECMO) support. Multivariable logistic regression was used to determine preoperative and intraoperative risk factors for these outcomes. RESULTS: Of the 703 patients who underwent ACAPA repair, 20 (2.8%) died during the same hospitalization. The odds of mortality were increased if preoperative shock was present (odds ratio [OR], 4.6; 95% confidence interval [CI], 1.4 to 15.1; P = .01) and if postoperative ECMO was required (OR, 11.8; 95% CI, 3.6 to 38.4; P < .001). The odds of postoperative ECMO use were increased if preoperative shock was present (OR, 3.6; 95% CI, 1.6 to 7.6; P = .001). Lower weight was also a risk factor for both mortality and postoperative ECMO. CONCLUSIONS: Lower weight, preoperative shock, and postoperative ECMO use were identified as risk factors for in-hospital mortality in patients undergoing ACAPA repair. These important perioperative factors likely reflect the clinical severity of presentation and suggest a role for early consideration of postoperative mechanical circulatory support to improve outcomes.

Novel nonmajor histocompatibility complex-linked loci from mouse chromosome 17 confer susceptibility to viral-mediated chronic autoimmune myocarditis.

BACKGROUND: Development of viral-induced chronic myocarditis is thought to involve both environmental and genetic factors. However, to date, no susceptibility genes have been identified. METHODS AND RESULTS: We sought to identify loci that confer susceptibility to viral-induced chronic myocarditis with the use of chromosome substitution strain mice that are composed of 1 chromosome from the disease susceptible A/J strain on an otherwise resistant C57BL/6 background. By this method, we identified chromosome 17 to confer susceptibility. To further isolate the region of susceptibility, 8 strains of mice congenic for different portions of chromosome 17 were generated. Characterization of these strains identified at least 4 susceptibility loci on the chromosome. Three of these loci are located in the proximal 22.8 cM, whereas the fourth locus is located in the portion of the chromosome distal to 34.3 cM. CONCLUSIONS: We have identified 4 loci that confer susceptibility of viral-induced chronic myocarditis. Of these loci, 3 were distinct from the major histocompatibility complex locus and thus represent novel susceptibility loci. The close proximately of the 2 novel loci with susceptibility loci for other autoimmune diseases such as type 1 diabetes and chronic experimental autoimmune thyroiditis suggests the presence of global autoimmune susceptibility genes.

Lack of IL-6 during coxsackievirus infection heightens the early immune response resulting in increased severity of chronic autoimmune myocarditis.

BACKGROUND: Chronic myocarditis is often initiated by viral infection, the most common of which is coxsackievirus infection. The precise mechanism by which viral infection leads to chronic autoimmune pathology is poorly understood, however it is clear that the early immune response plays a critical role. Previous results have shown that the inflammatory cytokine interleukin (IL)-6 is integral to the development of experimental-induced autoimmune myocarditis. However, the function of IL-6 during viral-mediated autoimmunity has yet to be elucidated. METHODS AND RESULTS: To address the requirement of IL-6 during disease induction, IL-6 deficient mice were infected with coxsackievirus B3 (CB3). Following infection, mice lacking IL-6 developed increased chronic autoimmune disease pathology compared to wild type controls without a corresponding change in the level of viral replication in the heart. This increase in disease severity was accompanied by elevated levels of TNF-alpha, MCP-1, IL-10, activated T cells and cardiac infiltrating macrophage/monocytes. Injection of recombinant IL-6 early following infection in the IL-6 deficient mice was sufficient to lower the serum cytokines TNF-alpha and IL-10 as well as the serum chemokines MCP-1, MIP-1beta, RANTES and MIG with a corresponding decrease in the chronic disease pathology strongly suggests an important regulatory role for IL-6 during the early response. CONCLUSIONS: While IL-6 plays a pathogenic role in experimental-induced autoimmune disease, its function following viral-induced autoimmunity is not reprised. By regulating the early immune response and thereby controlling the severity of chronic disease, IL-6 directs the outcome of chronic autoimmune myocarditis.

Regulatory T-cells protect from type 1 diabetes after induction by coxsackievirus infection in the context of transforming growth factor-beta.

OBJECTIVE: Coxsackievirus infections have long been associated with the induction of type 1 diabetes. Infection with coxsackievirus B4 (CB4) enhances type 1 diabetes onset in NOD mice by accelerating the presentation of beta-cell antigen to autoreactive T-cells. It has been reported that a progressive defect in regulatory T-cell (Treg) function is, in part, responsible for type 1 diabetes onset in NOD mice. This defect may contribute to susceptibility to viral-induced type 1 diabetes. We asked whether the immune response after CB4 infection could be manipulated to reestablish peripheral tolerance while maintaining the immune response to virus. RESEARCH DESIGN AND METHODS: NOD mice expressing transforming growth factor-beta (TGF-beta) specifically in the beta-cells were infected with CB4, and the functional role of Tregs in disease protection was measured. Systemic treatments with TGF-beta were used to assess its therapeutic potential. RESULTS: Here, we report that Tregs induced after CB4 infection in the presence of TGF-beta prevented type 1 diabetes. The capacity to directly infect pancreatic beta-cells correlated with increased numbers of pancreatic Tregs, suggesting that presentation of beta-cell antigen is integral to induction of diabetogenic protective Tregs. Furthermore, the presence of these viral induced Tregs correlated with protection from type 1 diabetes without altering the antiviral response. Finally, when TGF-beta was administered systemically to NOD mice after infection, the incidence of type 1 diabetes was reduced, thereby signifying a potential therapeutic role for TGF-beta. CONCLUSIONS: We demonstrate manipulations of the immune response that result in Treg-mediated protection from type 1 diabetes without concomitant loss of the capacity to control viral infection.

Genetic profiling of dendritic cells exposed to live- or ultraviolet-irradiated Chlamydia muridarum reveals marked differences in CXC chemokine profiles.

Chlamydia trachomatis is a major cause of sexually transmitted disease worldwide for which an effective vaccine is being actively pursued. Current vaccine efforts will be aided by elucidating the interaction between Chlamydia and dendritic cells (DCs). Protective immunity appears to develop slowly following natural infection in humans, and early vaccine trials using inactivated C. trachomatis resulted in partial, short-lived protection with possible enhanced inflammatory pathology during re-infection. Thus, immunity following natural infection with live chlamydia may differ fundamentally from immune responses induced by immunization with inactivated chlamydia. We explored this conjecture by studying the response of DCs exposed to either viable or inactivated [ultraviolet (UV) -irradiated] chlamydia elementary bodies (EBs; designated as Live-EB and UV-EB, respectively) using Affymetrix GeneChip microarrays. Thirty-one immunologically characterized genes were differentially expressed by DCs following exposure to Live-EB or UV-EB, including two glutamic acid-leucine-arginine cysteine-X-cysteine (ELR CXC) neutrophil chemoattractant chemokines, Cxcl1 (KC), and Cxcl2 (MIP-2). Up-regulation of these genes by Live-EB as compared to UV-EB was verified by quantitative reverse transcription-polymerase chain reaction and increased chemokine secretion was confirmed by enzyme-linked immunosorbent assay both in vitro and in vivo. Immunofluorescence and fluorescence-activated cell sorter analysis of chlamydia-infected lung tissue confirmed that Live-EB but not UV-EB induced significant DC and neutrophil infiltration during infection. These observations demonstrate that the development of an antichlamydial immune response is dramatically influenced by chlamydial viability. This has implications as to why early inactivated chlamydial vaccines were ineffective and suggests that new vaccine design efforts may benefit from in vitro DC screening for ELR chemokine expression profiles.