Incidence of Nerve Palsies During Pavlik Harness Treatment for Developmental Dysplasia of the Hip: A Retrospective Cohort Study.

BACKGROUND: The Pavlik harness has been used for approximately a century to treat developmental dysplasia of the hip (DDH). Femoral nerve palsy is a documented complication of Pavlik harness use, with an incidence ranging from 2.5% to 11.2%. Rare reports of brachial plexus palsy have also been documented. The primary purpose of the current study was to evaluate the incidence of various nerve palsies in patients undergoing Pavlik harness treatment for DDH. Secondary aims were to identify patient demographic or hip characteristics associated with nerve palsy. METHODS: We performed a retrospective review of patients diagnosed with DDH and treated with a Pavlik harness from February 1, 2016, to April 1, 2023, at a single tertiary care orthopaedic hospital. Hip laterality, use of a subsequent rigid abduction orthosis, birth order, breech positioning, weight, and family history were collected. The median (and interquartile range [IQR]) or mean (and standard deviation [SD]) were reported for all continuous variables. Independent 2-sample t tests and Mann-Whitney U tests were conducted to identify associations between the variables collected at the initiation of Pavlik harness treatment and the occurrence of nerve palsy. RESULTS: Three hundred and fifty-one patients (547 hips) were included. Twenty-two cases of femoral nerve palsy (4% of all treated hips), 1 case of inferior gluteal nerve palsy (0.18%), and 2 cases of brachial plexus palsy (0.37%) were diagnosed. Patients with nerve palsy had more severe DDH as measured by the Graf classification (p < 0.001) and more severe DDH as measured on physical examination via the Barlow and Ortolani maneuvers (p = 0.003). CONCLUSIONS: Nerve palsies were associated with more severe DDH at the initiation of Pavlik harness use. Upper and lower-extremity neurological status should be scrutinized at initiation and throughout treatment to assess for nerve palsies. The potential for femoral, gluteal, and brachial plexus palsies should be included in the discussion of risks at the beginning of treatment. Families may be reassured that nerve palsies associated with Pavlik harness can be expected to resolve with a short break from treatment. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Maternal Serum, an Isolation and Expansion Tool for Umbilical Cord Matrix Mesenchymal Stromal Cells.

The umbilical cord offers a source of readily available mesenchymal stromal cells (MSCs) for use in research and ultimately therapeutic application. However, methods of isolating these cells vary between investigators, and no standard method has been adopted. The aims of this work were to (i) develop a methodology for the isolation of umbilical cord matrix cells without the use of enzymatic digestion or complicated dissection; (ii) investigate the use of pooled maternal serum (MS) as a media supplement; and (iii) demonstrate that the cells isolated were MSCs. We have demonstrated that incubating tissue explants of less than 2 mm3 in serum for an hour, followed by the gradual addition of serum containing culture medium can increase cell yield compared to incubation in serum containing culture medium alone. More importantly, our method demonstrated that the use of pooled serum from women >37 weeks pregnant (pooled MS) yields higher cell numbers than the use of fetal bovine serum or pooled umbilical cord serum. Irrespective of the type of serum used, the isolated cells were MSCs according to the minimal criteria set out by the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy. In conclusion, MS has the potential to be used as an alternative to fetal bovine serum for isolation and expansion of umbilical cord MSCs for clinical purposes.

Expression and function of NOD-like receptors by human term gestation-associated tissues.

INTRODUCTION: Nucleotide-binding oligomerization domain (NOD)-like receptors or NOD-like receptors (NLRs) have been implicated in several disease pathologies associated with inflammation. Since local and systemic inflammation is a hallmark of both term and preterm labour, a role for NLRs at the materno-fetal interface has been postulated. METHODS: Gene expression and immunolocalisation of NLR family members in human placenta, choriodecidua, and amnion were examined. Tissue explants were used to examine the response to activators of NOD1 (Tri-DAP), NOD2 (MDP) and NLRP3 (nigericin). Cell/tissue-free supernatants were examined for the production of interleukin (IL)-1ß, IL-6, IL-8 and IL-10 using specific ELISAs. RESULTS: Expression of transcripts for NOD1, NOD2, NLRP3, NLRC4, NLRX1, NLRP1 and NAIP and protein expression of NOD1, NOD2 and NLRP3 were a broad feature of all term gestation-associated tissues. Production of cytokines was increased significantly in response to all ligands in placenta and choriodecidua, except for MDP-induced IL-10. Similarly, there was a significant in the amnion except for MDP induced IL-1ß and IL-10 response to either agonist. IL-1ß production was dependent on caspase-1 regardless of agonist used or tissue examined. DISCUSSION: Term human gestation-associated tissues express functional NLRs which likely play a role in both sterile and pathogen-driven inflammatory responses at the materno-fetal interface.

Production and regulation of interleukin-1 family cytokines at the materno-fetal interface.

IL-1 family members regulate innate immune responses, are produced by gestation-associated tissues, and have a role in healthy and adverse pregnancy outcomes. To better understand their role at the materno-fetal interface we used a human tissue explant model to map lipopolysaccharide (LPS)-stimulated production of IL-1α, IL-1ß, IL-18, IL-33, IL-1Ra, IL-18BPa, ST2 and IL-1RAcP by placenta, choriodecidua and amnion. Caspase-dependent processing of IL-1α, IL-1ß, IL-18, and IL-33 and the ability of IL-1α, IL-1ß, IL-18, and IL-33 to regulate the production of IL-1RA, IL-18BPa, ST2 and IL-1RAcP was also determined. LPS acted as a potent inducer of IL-1 family member expression especially in the placenta and choriodecidua with the response by the amnion restricted to IL-1ß. Caspases-1, 4 and 8 contributed to LPS-stimulated production of IL-1ß and IL-18, whereas calpain was required for IL-1α production. Exogenous administration of IL-1α, IL-1ß, IL-18, and IL-33 lead to differential expression of IL-1Ra, IL-18BPa, ST2 and IL-1RAcP across all tissues examined. Most notable were the counter-regulatory effect of LPS on IL-1ß and IL-1Ra in the amnion and the broad responsiveness of the amnion to IL-1 family cytokines for increased production of immunomodulatory peptides and soluble receptors. The placenta and membranes vary not only in their output of various IL-1 family members but also in their counter-regulatory mechanisms through endogenous inhibitory peptides, processing enzymes and soluble decoy receptors. This interactive network of inflammatory mediators likely contributes to innate defence mechanisms at the materno-fetal interface to limit, in particular, the detrimental effects of microbial invasion.

Interleukin 4 and interleukin 13 downregulate the lipopolysaccharide-mediated inflammatory response by human gestation-associated tissues.

Inflammation is a key feature of preterm and term labor. Proinflammatory mediators are produced by gestation-associated tissues in response to pathogen-associated molecular patterns and damage-associated molecular patterns. Interleukin (IL)4, IL10, and IL13 are anti-inflammatory cytokines with potential as anti-inflammatory therapies to prevent preterm birth. The objective of this study was to determine if IL4 and IL13 exert anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated production of proinflammatory cytokines produced by human term gestation-associated tissues (placenta, choriodecidua, and amnion). Both IL4 and IL13 reduced LPS-stimulated IL1B and macrophage inflammatory protein1A; this effect diminished with delay to exposure to either cytokine. There was no effect on LPS-stimulated prostaglandin production. Interleukin 4 receptor alpha (IL4RA) was expressed throughout the placenta, choriodecidua, and amnion, and the inhibitory effects of IL4 and IL13 were IL4RA dependent. Combined IL4 and IL13 did not enhance the anti-inflammatory potential of either cytokine; however, a combination of IL4 and IL10 had a greater anti-inflammatory effect than either cytokine alone. These findings demonstrate that human term gestation-associated tissues are responsive to the anti-inflammatory cytokines IL4 and IL13, which could downregulate LPS-induced cytokine production in these tissues. Anti-inflammatory cytokines might offer an adjunct to existing therapeutics to prevent adverse obstetric outcome.

Biochemical prey recognition by planktonic protozoa.

Planktonic flagellates and ciliates are the major consumers of phytoplankton and bacterioplankton in aquatic environments, playing a pivotal role in carbon cycling and nutrient regeneration. Despite certain unicellular predators using chemosensory responses to locate and select their prey, the biochemical mechanisms behind prey reception and selection have not been elucidated. Here we identify a Ca(2+)-dependent, mannose-binding lectin on the marine dinoflagellate Oxyrrhis marina, which is used as a feeding receptor for recognizing prey. Blocking the receptor using 20 microM mannose-BSA inhibited ingestion of phytoplankton prey, Isochrysis galbana, by 60%. In prey selection studies, O. marina ingested twice as many 6 mum diameter beads coated with mannose-BSA as those coated with galNac-BSA. When pre-incubated with mannose-BSA, O. marina was no longer able to discriminate between different sugar-coated beads. Thus, these findings reveal molecular mechanisms of protozoan prey recognition. Our results also indicate the functional similarity between cellular recognition used by planktonic protozoa to discriminate between different prey items, and those used by metazoan phagocytic blood cells to recognize invading microorganisms.

Nutritional status and diet composition affect the value of diatoms as copepod prey.

The role of diatoms as key food for copepods at the base of pelagic food chains has been questioned recently on the grounds of toxicity. We show, using unialgal versus mixed algal diets of different nutritional status (i.e., nitrogen:carbon ratio) fed to Acartia tonsa, that diatoms per se are not toxic but that single-diatom diets are inadequate. Additionally, the nutritional state of the phytoplankton has a profound effect on copepod growth and growth efficiency. The ecological significance of laboratory demonstrations of diatom toxicity needs to be reconsidered.