ABSTRACT
Alloreactive memory T cells have been implicated as central drivers of transplant rejection. Perplexingly, innate cytokines, such as IL-6, IL-1ß, and IL-12, are also associated with rejection of organ transplants. However, the pathways of innate immune activation in allogeneic transplantation are unclear. While the role of microbial and cell death products has been previously described, we identified alloreactive memory CD4 T cells as the primary triggers of innate inflammation. Memory CD4 T cells engaged MHC II-mismatched dendritic cells (DCs), leading to the production of innate inflammatory cytokines. This innate inflammation was independent of several pattern recognition receptors and was primarily driven by TNF superfamily ligands expressed by alloreactive memory CD4 T cells. Blocking of CD40L and TNFα resulted in dampened inflammation, and mice genetically deficient in these molecules exhibited prolonged survival of cardiac allografts. Furthermore, myeloid cell and CD8 T cell infiltration into cardiac transplants was compromised in both CD40L- and TNFα-deficient recipients. Strikingly, we found that priming of naive alloreactive CD8 T cells was dependent on licensing of DCs by memory CD4 T cells. This study unravels the key mechanisms by which alloreactive memory CD4 T cells contribute to destructive pathology and transplant rejection.
Subject(s)
CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Dendritic Cells , Graft Rejection , Heart Transplantation , Immunity, Innate , Inflammation , Animals , Graft Rejection/immunology , Mice , Dendritic Cells/immunology , CD8-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , Inflammation/immunology , Immunity, Innate/immunology , Mice, Inbred C57BL , CD40 Ligand/immunology , CD40 Ligand/metabolism , Memory T Cells/immunology , Mice, Knockout , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/immunology , Cytokines/metabolism , Cytokines/immunologyABSTRACT
PURPOSES: Autofusion (AF) during growing rod (GR) instrumentation for early-onset scoliosis (EOS) has been reported, but AF incidence, causation, and clinical implications remain unknown. This article aims to (1) quantify frequency and severity of AF, (2) determine risk factors for AF, and (3) assess the influence of AF on final curve correction and spinal lengthening. METHODS: EOS patients were prospectively enrolled (2016-2021). Patients underwent evaluation, GR implantation, lengthenings, and posterior spinal fusion (PSF). Cobb angle and spinal length measurements were collected. AF was assessed and graded, with grades I-II being low-grade and III-V being high-grade. Exposure analysis quantified risk factors' impact via odds ratios and Pearson regression correlates. Statistical significance was p ≤ 0.05 or ≥ 0.95. RESULTS: 28 patients, with variable EOS diagnoses, were included. On average, GR were implanted at 8.54-year-old and lengthened over 4.66 years. 53.6% of patients received magnetically controlled GR (MCGR) and 46.4% traditional GR (TGR). The average construct bridged 13.4 levels. Over the lengthening period, for all indications, patients averaged 2.9 total open procedures. Curves corrected from 68.5º preoperatively to 35.3º after index GR to 35.6º after PSF. Spinal length increased from 30.0 cm preoperatively to 33.9 cm after index GR to 39.5 cm after PSF. AF grading was: 28.6% Grade I, 25.0% Grade II, 17.9% Grade III, 25.0% Grade IV, and 3.6% Grade V. Idiopathic EOS tended to have lower AF grades (p = 0.37). AF risk factors included GR age < 8 (10.4×, p = 0.01), any interval open procedures (6.3×, p = 0.05), and residual curve > 30º after index GR (13.7×, p = 0.02). Protective factors included preoperative spinal length of > 30.0 cm (0.11×, p = 0.01) and index MCGR (0.16×, p = 0.03). Maintenance of Cobb angles from index GR through PSF was relatively better in low-grade patients (p = 0.08). Spinal length gained was no different between low- and high-grade AF (p = 0.50). CONCLUSIONS: This largest-to-date evaluation found AF is nearly ubiquitous in GR constructs, but with variable severity. Both risk factors and protective factors coincide with AF. Ultimately, even in high-grade AF, curve correction was maintained, and spinal lengthening was achieved. LEVEL OF EVIDENCE: Level II-prospective cohort study.
Subject(s)
Scoliosis , Spinal Fusion , Humans , Scoliosis/surgery , Child , Risk Factors , Female , Male , Spinal Fusion/adverse effects , Spinal Fusion/instrumentation , Spinal Fusion/methods , Prospective Studies , Age of Onset , Spine/surgery , Child, PreschoolABSTRACT
Progressive spinal curvature in juvenile idiopathic scoliosis (JIS) is challenging to treat. When conservative management fails, treatments include growing rods (GRs) or posterior spinal fusion (PSF). The purpose of this study is to compare the patient characteristics and outcomes of GR and PSF treatment of JIS. We performed a retrospective review of demographic, radiographic, and surgical data for all JIS patients requiring surgical treatment between 2012 and 2020. Patients who underwent any GR treatment were compared to PSF patients. A total of 36 patients (13 GR, 23 PSF) were reviewed. PSF patients had a larger pre-operative spinal height (p = 0.002), but similar pre-operative major curve magnitudes (p = 0.558). PSF treatment resulted in similar change in the T1-S1 length (p = 0.002), but a greater correction of the curve magnitude (p < 0.055) compared to GR patients. Eight patients initially treated with GRs later underwent definitive PSF treatment. This subset of patients had a greater spinal height before PSF (p = 0.006), but similar immediate post-PSF T1-S1 lengths (p = 0.437) and smaller changes in spinal height from PSF (p = 0.020) than primary PSF patients. At final follow-up, patients who underwent primary PSF versus PSF after GR had similar spinal heights (p = 0.842). The surgical intervention chosen to manage progressive JIS often differs based on patient characteristics. While this choice may impact immediate outcomes, the outcomes at final follow up are similar.
ABSTRACT
Cognate interaction between CD4+ effector memory T (TEM) cells and dendritic cells (DCs) induces innate inflammatory cytokine production, resulting in detrimental autoimmune pathology and cytokine storms. While TEM cells use tumor necrosis factor (TNF) superfamily ligands to activate DCs, whether TEM cells prompt other DC-intrinsic changes that influence the innate inflammatory response has never been investigated. We report the surprising discovery that TEM cells trigger double-strand DNA breaks via mitochondrial reactive oxygen species (ROS) production in interacting DCs. Initiation of the DNA damage response in DCs induces activation of a cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS)-independent, non-canonical stimulator of interferon genes (STING)-TNF receptor-associated factor 6 (TRAF6)-nuclear factor κB (NF-κB) signaling axis. Consequently, STING-deficient DCs display reduced NF-κB activation and subsequent defects in transcriptional induction and functional production of interleukin-1ß (IL-1ß) and IL-6 following their interaction with TEM cells. The discovery of TEM cell-induced innate inflammation through DNA damage and a non-canonical STING-NF-κB pathway presents this pathway as a potential target to alleviate T cell-driven inflammation in autoimmunity and cytokine storms.
Subject(s)
Dendritic Cells , Inflammation , Memory T Cells , Humans , Cytokine Release Syndrome , Dendritic Cells/metabolism , DNA Damage , Inflammation/pathology , Memory T Cells/metabolism , NF-kappa B/metabolism , Nucleotidyltransferases/metabolismSubject(s)
Hernias, Diaphragmatic, Congenital , Humans , NF-kappa B , Organogenesis , Signal Transduction , LungABSTRACT
RATIONALE: Bronchopulmonary dysplasia (BPD) is the most common morbidity affecting very preterm infants. Gut fungal and bacterial microbial communities contribute to multiple lung diseases and may influence BPD pathogenesis. METHODS: We performed a prospective, observational cohort study comparing the multikingdom fecal microbiota of 144 preterm infants with or without moderate to severe BPD by sequencing the bacterial 16S and fungal ITS2 ribosomal RNA gene. To address the potential causative relationship between gut dysbiosis and BPD, we used fecal microbiota transplant in an antibiotic-pseudohumanized mouse model. Comparisons were made using RNA sequencing, confocal microscopy, lung morphometry, and oscillometry. RESULTS: We analyzed 102 fecal microbiome samples collected during the second week of life. Infants who later developed BPD showed an obvious fungal dysbiosis as compared to infants without BPD (NoBPD, p = 0.0398, permutational multivariate ANOVA). Instead of fungal communities dominated by Candida and Saccharomyces, the microbiota of infants who developed BPD were characterized by a greater diversity of rarer fungi in less interconnected community architectures. On successful colonization, the gut microbiota from infants with BPD augmented lung injury in the offspring of recipient animals. We identified alterations in the murine intestinal microbiome and transcriptome associated with augmented lung injury. CONCLUSIONS: The gut fungal microbiome of infants who will develop BPD is dysbiotic and may contribute to disease pathogenesis.
ABSTRACT
PURPOSE: Neuromuscular scoliosis (NMS) patients tend to have significant comorbidities with complex medical and surgical histories. When undergoing posterior spinal fusion (PSF), NMS risks can be much higher than the idiopathic population. This study aimed to identify the impact of two experienced pediatric cosurgeons (CS) compared to a single spine surgeon (SS) on the intra- and postoperative results of NMS PSF. METHODS: A database of NMS patients who had undergone PSF 2016-2021 identified 53 patients, of which 32 were CS, while 21 were SS. Patients' sex, age, weight, diagnosis, curve severity, fusion performed, estimated blood loss (EBL), transfusion rates, hemoglobin, anesthesia and surgical times, length of stay, and complications were collected. RESULTS: Patient demographics were similar between groups. Curves were more severe in the CS group (p = 0.013). Intraoperatively, CS patients underwent larger corrections (p = 0.089) but in significantly shorter anesthetic (p = 0.0018) and operative (p = 0.0025) times. Blood loss and transfusions were similar. Postoperatively, intensive-care unit (ICU) admission and length of stay (LOS) were similar, but SS had higher rates of both unplanned ICU admissions (p = 0.36) and 30 day readmissions (p = 0.053). Complications overall were similar between the groups both within 30 days (p = 0.40) and in the short-term period (31-90 days, p = 0.76), though the CS cohort had less Grade 2 immediate postoperative pulmonary complications (p = 0.16). CONCLUSION: Utilizing CS for NMS PSF has been found to reduce operative times. Downstream, additional potential impacts trended toward fewer unplanned ICU admissions, less-frequent postoperative pulmonary complications, and reduced 30-day readmission rates.
Subject(s)
Neuromuscular Diseases , Scoliosis , Surgeons , Humans , Child , Scoliosis/surgery , Retrospective Studies , Spine , Neuromuscular Diseases/complications , Postoperative Complications/etiologyABSTRACT
Intestinal epithelial cells (IECs) constitute a critical first line of defense against microbes. While IECs are known to respond to various microbial signals, the precise upstream cues regulating diverse IEC responses are not clear. Here, we discover a dual role for IEC-intrinsic interleukin-1 receptor (IL-1R) signaling in regulating intestinal homeostasis and inflammation. Absence of IL-1R in epithelial cells abrogates a homeostatic antimicrobial program including production of antimicrobial peptides (AMPs). Mice deficient for IEC-intrinsic IL-1R are unable to clear Citrobacter rodentium (C. rodentium) but are protected from DSS-induced colitis. Mechanistically, IL-1R signaling enhances IL-22R-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation in IECs leading to elevated production of AMPs. IL-1R signaling in IECs also directly induces expression of chemokines as well as genes involved in the production of reactive oxygen species. Our findings establish a protective role for IEC-intrinsic IL-1R signaling in combating infections but a detrimental role during colitis induced by epithelial damage.
Subject(s)
Colitis , Receptors, Interleukin-1 , Mice , Animals , Receptors, Interleukin-1/genetics , Receptors, Interleukin-1/metabolism , Intestines , Colitis/metabolism , Inflammation/metabolism , Epithelial Cells/metabolism , Homeostasis , Intestinal Mucosa/metabolismABSTRACT
PURPOSE: Early onset scoliosis (EOS) is defined as spinal curvature affecting children below 10 years of age. Non-operative treatment can consist of casting and bracing. When curvature progresses despite these treatments, operative intervention is indicated. Traditional growing rods (TGR) have been a mainstay of treatment. Unfortunately, TGR's require planned return to the operating room every 6-9 months. Magnetic controlled growing rods (MCGR) ideally provide curve correction and allow the spine to grow without frequent surgeries. However, the ability to correct and maintain correction after MCGR has not been well-characterized. The purpose of this study is to evaluate maintenance of curve correction in patients treated primarily with MCGR and analyze the rate of complications including unplanned return to the operating room (UPROR). METHODS: 24 patients with EOS were retrospectively reviewed. These patients were subdivided into 4 subcategories: congenital, idiopathic, neuromuscular (NMS), and syndromic. The major curve correction (%) and T1-S1 distance were assessed utilizing scoliosis plain film radiographs over time. Complications and return to the operating room for any reason were recorded. Patients were followed until conversion to posterior spinal fusion (PSF) or most recent lengthening of MCGR. RESULTS: There were 11 male and 13 female patients averaging 8 years at the time of index surgery. The average preoperative curve angle was 61.1°. Initial curve correction with MCGR obtained at the index procedure was 46.2%, reducing the mean curve angle to 32.7° (p < 0.05). Curve correction at a mean 6.2 years (2.4-7.4) follow-up was 36.1°, 40.9% curve correction. 75% of patients underwent conversion to PSF during the study period 4.8 years (2.4-7.0) after initial MCGR surgery. 15% of patients were still undergoing MCGR lengthening after 6.1 years. 54.2% of patients had at least one UPROR. CONCLUSIONS: For patients with EOS with curve progression, MCGRs can maintain curve correction well after 2 years. Furthermore, MCGR allowed patients to grow over time to safely delay timing to definitive fusion. On average, patients underwent conversion to PSF after 4.7 years at an average age of 13.5. Although the complication rate in the first 2 years is relatively low, 54.2% of patients underwent an UPROR. As the use of MCGR increases, surgeons should be aware of possible complications associated with this technology and counsel patients accordingly. Further research is needed to continue to evaluate the efficacy and safety of MCGR in this challenging patient population.
Subject(s)
Scoliosis , Child , Humans , Male , Female , Adolescent , Scoliosis/surgery , Follow-Up Studies , Operating Rooms , Retrospective Studies , Spine/surgeryABSTRACT
It is important to focus on common pediatric fractures seen in community emergency rooms, including supracondylar humerus, elbow, forearm, distal radius, and femoral shaft fractures, along with periarticular fractures around the knee and ankle in children. The principles of surgical and nonsurgical management of these fractures are based on the fracture type and age of the patient. The orthopaedic surgeon should be aware of important tips and tricks to help manage these injuries and be familiar with common complications that may occur when these injuries are encountered during trauma call.
Subject(s)
Humeral Fractures , Orthopedics , Child , Humans , Forearm , Humeral Fractures/complications , Humeral Fractures/surgery , HumerusABSTRACT
Preterm birth contributes significantly to neonatal mortality and morbidity. Despite its global significance, there has only been limited progress in preventing preterm birth. Spontaneous preterm birth (sPTB) results from a wide variety of pathological processes. Although many non-genetic risk factors influence the timing of gestation and labor, compelling evidence supports the role of substantial genetic and epigenetic influences and their interactions with the environment contributing to sPTB. To investigate a common and complex disease such as sPTB, various approaches such as genome-wide association studies, whole-exome sequencing, transcriptomics, and integrative approaches combining these with other 'omics studies have been used. However, many of these studies were typically small or focused on a single ethnicity or geographic region with limited data, particularly in populations at high risk for sPTB, or lacked a robust replication. These studies found many genes involved in the inflammation and immunity-related pathways that may affect sPTB. Recent studies also suggest the role of epigenetic modifications of gene expression by the environmental signals as a potential contributor to the risk of sPTB. Future genetic studies of sPTB should continue to consider the contributions of both maternal and fetal genomes as well as their interaction with the environment.
Subject(s)
Premature Birth , Epigenesis, Genetic , Female , Fetus/pathology , Genome-Wide Association Study , Humans , Infant, Newborn , Premature Birth/genetics , Premature Birth/pathology , TranscriptomeABSTRACT
BACKGROUND: The independent risk for neurodevelopmental impairments attributed to chorioamnionitis in premature infants remains controversial. Delayed brain maturation or injury identified on magnetic resonance imaging at term-equivalent age can be used as a surrogate measure of neurodevelopmental impairments that is less confounded by postdelivery neonatal intensive care unit environmental factors to investigate this relationship more clearly. OBJECTIVE: This study aimed to determine whether preterm infants born with moderate to severe acute histologic chorioamnionitis would have a higher magnetic resonance imaging-determined global brain abnormality score, independent of early premature birth, when compared with preterm infants with no or mild chorioamnionitis. STUDY DESIGN: This was a prospective, multicenter cohort study involving infants born very prematurely ≤32 weeks' gestational age with acute moderate to severe histologic chorioamnionitis, graded using standard histologic criteria. Brain abnormalities were diagnosed and scored using a well-characterized, standardized scoring system captured using a high-resolution 3 Tesla magnetic resonance imaging research magnet. In secondary analyses, total brain volume and 4 magnetic resonance imaging metrics of cortical maturation (cortical surface area, sulcal depth, gyral index, and inner cortical curvature) were calculated using an automated algorithm and correlated with chorioamnionitis. The association of funisitis (any grade) with brain abnormalities was also explored. We investigated if premature birth mediated the relationship between histologic chorioamnionitis and brain abnormality score using mediation analysis. RESULTS: Of 353 very preterm infants, 297 infants had mild or no chorioamnionitis (controls), and 56 were diagnosed with moderate to severe acute histologic chorioamnionitis. The primary outcome brain abnormality score was significantly higher in histologic chorioamnionitis-exposed infants than in the controls (median, 4 vs 7; P<.001). Infants with acute histologic chorioamnionitis had significantly lower brain tissue volume (P=.03) and sulcal depth (P=.04), whereas other morphometric indices did not differ statistically. In the multiple regression analysis, we observed persistent significant relationships between moderate to severe acute histologic chorioamnionitis and brain abnormality scores (ß=2.84; 1.51-4.16; P<.001), total brain volume (P=.03), and sulcal depth (P=.02). Funisitis was also significantly associated with brain abnormality score after adjustment for clinical confounders (P=.005). Mediation analyses demonstrated that 50% of brain abnormalities was an indirect consequence of premature birth, and the remaining 50% was a direct effect of moderate to severe acute histologic chorioamnionitis when compared with preterm infants with no or mild chorioamnionitis exposure. Examining gestational age as a mediator, funisitis did not exert a significant direct effect on brain abnormalities after the significant indirect effects of preterm birth were accounted for. CONCLUSION: Acute histologic chorioamnionitis increases the risk for brain injury and delayed maturation, both directly and indirectly, by inducing premature birth.
Subject(s)
Chorioamnionitis , Infant, Premature, Diseases , Nervous System Malformations , Pregnancy Complications , Premature Birth , Brain/diagnostic imaging , Brain/pathology , Chorioamnionitis/diagnosis , Cohort Studies , Female , Fetal Growth Retardation/pathology , Gestational Age , Humans , Infant , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/diagnostic imaging , Infant, Premature, Diseases/epidemiology , Magnetic Resonance Imaging , Pregnancy , Pregnancy Complications/pathology , Premature Birth/epidemiology , Prospective StudiesABSTRACT
Cytokine storm and sterile inflammation are common features of T cell-mediated autoimmune diseases and T cell-targeted cancer immunotherapies. Although blocking individual cytokines can mitigate some pathology, the upstream mechanisms governing overabundant innate inflammatory cytokine production remain unknown. Here, we have identified a critical signaling node that is engaged by effector memory T cells (TEM) to mobilize a broad proinflammatory program in the innate immune system. Cognate interactions between TEM and myeloid cells led to induction of an inflammatory transcriptional profile that was reminiscent, yet entirely independent, of classical pattern recognition receptor (PRR) activation. This PRR-independent "de novo" inflammation was driven by preexisting TEM engagement of both CD40 and tumor necrosis factor receptor (TNFR) on myeloid cells. Cytokine toxicity and autoimmune pathology could be completely rescued by ablating these pathways genetically or pharmacologically in multiple models of T cell-driven inflammation, indicating that TEM instruction of the innate immune system is a primary driver of associated immunopathology. Thus, we have identified a previously unknown trigger of cytokine storm and autoimmune pathology that is amenable to therapeutic interventions.
Subject(s)
Autoimmune Diseases/immunology , CD4-Positive T-Lymphocytes/immunology , CD40 Antigens/immunology , Inflammation/immunology , Myeloid Cells/immunology , Receptors, Tumor Necrosis Factor/immunology , Animals , Immunity, Innate/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Mutant StrainsABSTRACT
PURPOSE: Magnetically controlled growing rod (MCGR) for the treatment of early-onset scoliosis (EOS) is a relatively innovative technique. MCGR benefits over traditional growing rods are known but limitations and complications are being revealed. The purpose of this study was to examine the importance of tissue depth on rod lengthening. METHODS: A single-institution retrospective review of 72 MCGR patients was performed. Ultrasound measured rod distraction. Differences in programmed and actual distraction, and complications were recorded. Tissue depths and achieved length were averaged and used to construct a regression to account for variability. RESULTS: Percentage of std and offset orientation rod lengthening relative to the programmed distraction was inversely proportional to rod depth (std R = 0.50, p = 0.002) (offset R = 0.60, p < 0.001). Expected std rod lengthening achieved decreased by 1.46%/mm depth. Expected offset rod lengthening achieved decreased by 1.68%/mm depth. 28 pts (38.9%) sustained complications. Age, sex, BMI, standard tissue depth, and/or offset tissue depth had no predictive ability with respect to complications sustained (overall model R = 0.31, p = 0.36). CONCLUSION: In a series of EOS surgical patients treated with MCGRs, the relationship between percentage of programmed lengthening achieved as well as total lengthening was inversely proportional to tissue depth of the rod. There was a trend towards increasing frequency of complications recorded with decreasing tissue depth though this was not significant. These data can help with surgical planning during MCGR placement.
Subject(s)
Osteogenesis, Distraction , Scoliosis , Humans , Osteogenesis, Distraction/adverse effects , Reoperation , Retrospective Studies , Scoliosis/diagnostic imaging , Scoliosis/etiology , Scoliosis/surgery , UltrasonographyABSTRACT
STUDY DESIGN: Retrospective cohort study. PURPOSE: To determine whether implant density impact three-dimensional deformity correction in posterior spinal fusion (PSF) without Ponte osteotomies (POs) for patients with Lenke 1 and 2 adolescent idiopathic scoliosis (AIS). OVERVIEW OF LITERATURE: Currently, the optimal pedicle screw (PS) density for flexible moderate-sized thoracic AIS curve correction is still controversial. There are limited data regarding the impact of implant density on three-dimensional correction in PSF without the use of PO for thoracic AIS surgery. METHODS: A database of patients with AIS with Lenke 1 and 2 curves treated with PSF without PO and instrumented with PSs and ≥2-year follow-up was reviewed. The preoperative, immediate, and final follow-up postoperative radiographs were analyzed. The correlation between PS density and the following factors were determined: major curve correction (MCC), correction index (CI; MCC/curve flexibility), kyphosis angle change, and rib index (RI) correction. Then, patients were divided into low-density (LD) and high-density (HD) groups according to mean PS density for the entire cohort (1.5 PS per level). Demographics and radiographic and clinical outcomes were compared between groups. RESULTS: The study included 99 patients with Lenke 1 and 23 patients with Lenke 2 AIS. The average MCC was 67.2%. There was no correlation between screw density and these parameters: MCC (r=0.10, p=0.26), CI (r=0.16, p=0.07), change in T2-T12 kyphosis angle (r=-0.13, p=0.14), and RI correction (r=-0.09, p=0.37). Demographic and preoperative radiographic parameters were similar between the LD and HD groups. At the latest follow-up, there were no differences between the two groups in regard to MCC, CI, change in T2-T12 kyphosis angle, RI correction, and Scoliosis Research Society-30 scores (all p>0.05). CONCLUSIONS: This study revealed no significant correlation between screw density and curve correction in any planes. HD construct may not provide better deformity correction in patients with flexible and moderate thoracic AIS undergoing PSF without PO.
ABSTRACT
Chorioamnionitis or intrauterine inflammation is a frequent cause of preterm birth. Chorioamnionitis can affect almost every organ of the developing fetus. Multiple microbes have been implicated to cause chorioamnionitis, but "sterile" inflammation appears to be more common. Eradication of microorganisms has not been shown to prevent the morbidity and mortality associated with chorioamnionitis as inflammatory mediators account for continued fetal and maternal injury. Mounting evidence now supports the concept that the ensuing neonatal immune dysfunction reflects the effects of inflammation on immune programming during critical developmental windows, leading to chronic inflammatory disorders as well as vulnerability to infection after birth. A better understanding of microbiome alterations and inflammatory dysregulation may help develop better treatment strategies for infants born to mothers with chorioamnionitis.
Subject(s)
Chorioamnionitis/physiopathology , Chorioamnionitis/immunology , Chorioamnionitis/microbiology , Chorioamnionitis/therapy , Cytokines/metabolism , Female , Humans , Infant, Newborn , Male , Pregnancy , Pregnancy Outcome , Premature BirthABSTRACT
PURPOSE: To investigate the risk and predictive factors of junctional issues after conversion from Traditional growing rod (TGR) to definitive spinal fusion in Early-onset scoliosis (EOS). METHODS: Retrospective review of a multicenter EOS database. TGR patients who received final fusion with at least two-year follow-up were included. Proximal (PJA) and Distal junctional angles (DJA) on pre-final fusion, post-final fusion (within one year of surgery), and at latest follow-up were measured on lateral upright spinal radiographs. Differences in values among designated time points and predictive factors of junctional issues were evaluated statistically. RESULTS: Forty-six of 251 patients (28 females, 18 males and mean age at final fusion: 12 ± 2 [9-17] years) met the inclusion criteria. Mean follow-up between first postoperative measurement and latest follow-up was 49 ± 22 (24-112) months. No statistical differences in PJA and DJA values were available at pre-fusion, first post-fusion, or latest follow-up (p = 0.827, p = 0.076). Fifty percent of patients had extension of TGR instrumentation at fusion, either proximal or distal. No factor including sex and etiology, lumbar lordosis, thoracic kyphosis, major curve magnitude, PJA, and DJA at pre-fusion was found to be a predictive issue for extension of index TGR instrumentation, except the history of at least one implant-related complication during the period from index surgery to the definitive fusion. CONCLUSION: PJA and DJA remained stable when transitioning from TGR to final posterior spinal fusion. But 50% of patients had extension of construction at fusion, either proximal or distal.
Subject(s)
Kyphosis , Scoliosis , Spinal Fusion , Female , Follow-Up Studies , Humans , Kyphosis/diagnostic imaging , Kyphosis/epidemiology , Kyphosis/surgery , Male , Prevalence , Retrospective Studies , Scoliosis/diagnostic imaging , Scoliosis/epidemiology , Scoliosis/surgery , Spinal Fusion/adverse effectsABSTRACT
OBJECTIVE: To assess whether a citywide structured book-sharing program (NICU Bookworms) designed to promote reading to infants while admitted in the neonatal intensive care unit (NICU) would increase parental reading behaviors (≥3-4 days/week) in the NICU and after discharge home, including high-risk parents who do not themselves enjoy reading. STUDY DESIGN: The NICU Bookworms program comprised staff training, parent education, and building a literacy-rich environment. In this quasi-experimental intervention study, parents of medically high-risk NICU graduates <6 months of age were administered a questionnaire at their first NICU follow-up clinic visit. The survey incorporated questions from the StimQ-I READ subscale to assess home reading environment and shared reading practices. RESULTS: A total of 317 infants were enrolled, 187 in an unexposed comparison group and 130 in the intervention group. Parents exposed to Bookworms were significantly more likely to read ≥3-4 days per week while in the NICU (34.5% vs 51.5%; P = .002; aOR, 2.2; 95% CI, 1.2-4.0), but reading at home did not differ (67.9% vs 73.1%; P = .28; aOR, 0.99; 95% CI, 0.5-1.8). However, among parents who did not themselves enjoy reading, frequency was significantly higher both in the NICU (18.4% vs 46.1%; P = .009; aOR, 5.0; 95% CI, 1.2-21.5) and at home (36.9% vs 70%; P = .003; aOR, 3.7; 95% CI, 1.1-12.9). A qualitative thematic analysis found that Bookworms decreased parental stress, enhanced bonding, and supported positive parent-infant interactions. CONCLUSIONS: A book-sharing intervention in the NICU increased parent-reported reading aloud during hospitalization and among parents disinclined to read for pleasure, both in the NICU and following discharge. This change may have been mediated by enhancement of parent-infant interactions.