The CD8+ T cell content of transbronchial biopsies from patients with a first episode of clinically stable grade A1 cellular rejection is associated with future chronic lung allograft dysfunction.

BACKGROUND: T cells drive acute cellular rejection (ACR) and its progression to chronic lung allograft dysfunction (CLAD) following lung transplantation. International Society for Heart and Lung Transplantation grade A1 ACR without associated allograft dysfunction is often untreated, yet some patients develop progressive graft dysfunction. T-cell composition of A1 ACR lesions may have prognostic value; therefore, protein-level and epigenetic techniques were applied to transbronchial biopsy tissue to determine whether differential T-cell infiltration in recipients experiencing a first episode of stable grade A1 ACR (StA1R) is associated with early CLAD. METHODS: Sixty-two patients experiencing a first episode of StA1R were divided into those experiencing CLAD within 2 years (n = 13) and those remaining CLAD-free for 5 or more years (n = 49). Imaging mass cytometry (IMC) was used to profile the spectrum and distribution of intragraft T cell phenotypes on a subcohort (n = 16; 8 early-CLAD and 8 no early-CLAD). Immunofluorescence was used to quantify CD4+, CD8+, and FOXP3+ cells. Separately, CD3+ cells were fluorescently labeled, micro-dissected, and the degree of Treg-specific demethylated region methylation was determined. RESULTS: PhenoGraph unsupervised clustering on IMC revealed 50 unique immune cell subpopulations. Methylation and immunofluorescence analyses demonstrated no significant differences in Tregs between early-CLAD and no early-CLAD groups. Immunofluorescence revealed that patients who developed CLAD within 2 years of lung transplantation showed greater CD8+ T cell infiltration compared to those who remained CLAD-free for 5 or more years. CONCLUSIONS: In asymptomatic patients with a first episode of A1 rejection, greater CD8+ T cell content may be indicative of worse long-term outlook.

The Risk of Ventricular Septal Defects Associated With Prenatal Marijuana Exposure: A Systematic Review and Meta-Analysis.

With the recent legalization of marijuana across the United States, its usage in pregnant women has increased. The aim of this meta-analysis was to determine if prenatal marijuana use increases the likelihood of ventricular septal defects. The analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search strategy identified 4 case-control studies that were ultimately included in the analysis with a combined 381,621 infant records. Quantitative analysis demonstrated prenatal marijuana usage significantly increases the likelihood of ventricular septal defects (odds ratio = 2.39, 95% confidence interval = 1.11-5.18).

Strong Association Between Growth Hormone Therapy and Proximal Tibial Physeal Avulsion Fractures in Children and Adolescents: A Case-Control Study.

BACKGROUND: Published literature describes slipped capital femoral epiphysis as a complication of recombinant human growth hormone (rhGH) therapy that may be related to decreased physeal strength. The purpose of the current investigation was to utilize a case-control study design to determine whether a greater proportion of pediatric patients sustaining physeal avulsion fractures of the proximal tibia were undergoing rhGH therapy at the time of injury compared with a cohort of matched controls. METHODS: A case-control design study design was utilized. Patients 4 to 18 years of age with proximal tibial physeal avulsion fractures (cases) or midshaft tibial fractures (controls) at our institution from February 1, 2016, to May 4, 2023, were identified. Cases and controls were matched 1:1 on the basis of age (within 1 year), sex, and body mass index (within 3 kg/m 2 ). A total of 132 patients were included in the analysis (mean age, 13 ± 2 years). rhGH exposure was compared using conditional logistic regression with Firth correction. RESULTS: We found that 11% of the patients with a proximal tibial physeal avulsion fracture were on rhGH therapy at the time of injury compared with 0% of patients with midshaft tibial fractures (odds ratio [OR], 15.0; 95% confidence interval [CI], 1.8 to 1,946.7; p = 0.007). There was no significant difference in the proportion of sports-related injuries between cases (70%) and controls (67%) (OR, 1.15; 95% CI, 0.55 to 2.39; p = 0.85). Among subjects with proximal tibial avulsion fractures, the proportion requiring surgery did not differ significantly between patients receiving and those not receiving rhGH therapy (43% versus 41%, respectively; p = 0.99). CONCLUSIONS: This study demonstrates that the proportion of subjects who sustained proximal tibial physeal avulsion fractures and were receiving recombinant human growth hormone therapy at the time of injury was significantly greater than that of an age, sex, and body mass index-matched control group with midshaft tibial fractures (11% versus 0%, respectively, representing 15-times greater odds of exposure). This quantifies a previously unreported serious orthopaedic complication associated with rhGH therapy. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Donor Batf3 inhibits murine lung allograft rejection and airway fibrosis.

Chronic lung allograft dysfunction (CLAD) limits survival after lung transplantation. Noxious stimuli entering the airways foster CLAD development. Classical dendritic cells (cDCs) link innate and adaptive immunity and exhibit regional and functional specialization in the lung. The transcription factor basic leucine zipper ATF-like 3 (BATF3) is absolutely required for the development of type 1 cDCs (cDC1s), which reside in the airway epithelium and have variable responses depending on the context. We studied the role of BATF3 in a mouse minor alloantigen-mismatched orthotopic lung transplant model of CLAD with and without airway inflammation triggered by repeated administration of intratracheal lipopolysaccharide (LPS). We found that cDC1s accumulated in allografts compared with isografts and that donor cDC1s were gradually replaced by recipient cDC1s. LPS administration increased the number of cDC1s and enhanced their state of activation. We found that Batf3-/- recipient mice experienced reduced acute rejection in response to LPS; in contrast, Batf3-/- donor grafts underwent enhanced lung and skin allograft rejection and drove augmented recipient cluster of differentiation 8+ T-cell expansion in the absence of LPS. Our findings suggest that donor and recipient cDC1s have differing and context-dependent roles and may represent a therapeutic target in lung transplantation.

Jumping on the Bandwagon: Comparing the Efficacy of Chlorhexidine Versus Povidone-Iodine Preoperative Skin Antiseptic in Preventing Surgical Site Infections Following Pediatric Orthopaedic Surgery.

BACKGROUND: Adult literature has demonstrated chlorhexidine (CH) superiority at preventing surgical-site infections when compared with povidone-iodine (P-I). The purpose of this study is to compare the rate of postoperative infections after preoperative skin cleansing with either CH or P-I in pediatric orthopaedic surgery in an effort to identify superiority. METHODS: We retrospectively identified all patients (18 y and below) that underwent orthopaedic surgery at our institution in 2015, when P-I was the preoperative skin antisepsis of choice, and in 2018, when a change in protocol resulted in more frequent use of CH. Open fractures, infections, neuromuscular, and tumor surgeries were excluded. Orthopaedic surgeries were classified according to their subspecialty (sports-related/upper extremity, hip and lower extremity, trauma-related, or spine procedure). A 1:1 propensity score matching was conducted within each procedure group on the basis of age, sex, and year using nearest-neighbor matching. Spine procedures could not be matched and were subsequently excluded from analyses. RESULTS: Propensity score matching matched 1416 CH cases with 1416 P-I controls. The infection rate for CH was 19 infections per 1000 cases (27/1416; 1.9%) compared with an infection rate of 11 infections per 1000 cases (16/1416; 1.1%) for P-I subjects. No difference was detected in infection rate across preoperative skin antisepsis groups (P=0.12). Moreover, it was found that CH and P-I resulted in significantly equivalent infection rates to within ±1.5% (P=0.004). When stratified by procedure type, CH used in sports/upper extremity procedures resulted in 29 more infections per 1000 cases compared with P-I use (16/450; 3/450; P=0.005). No difference was detected in infection rate across CH and P-I skin antisepsis groups in lower extremity procedures (9/792; 8/792; P=1.00) or in trauma-related procedures (3/174; 4/174; P=1.00). CONCLUSIONS: CH and P-I are both protective against postoperative infections after sports/upper extremity, lower extremity, and trauma-related pediatric orthopaedic procedures. P-I may provide improved protection over CH as a preoperative skin antisepsis in upper extremity and sports-related procedures. LEVEL OF EVIDENCE: Level III-comparative cohort.