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American Journal of Veterinary Research Jun 2024To determine if photobiomodulation causes a premature release of liposomal bupivacaine (LB) suspensions.
OBJECTIVE
To determine if photobiomodulation causes a premature release of liposomal bupivacaine (LB) suspensions.
ANIMALS
A 25-kg mixed breed dog cadaver euthanized for reasons unrelated to this study.
METHODS
In September 2022, a proximomedial tibial incision was made in a dog cadaver, and a tibial plateau leveling osteotomy plate was implanted. A stab incision was made one-half inch distal to the incision, and a tunnel to the plate was created prior to closure of the primary wound. A 3-cc anal sac catheter was advanced through the distal incision until the bulb rested against the face of the plate. Seven treatment groups of treatment power (watts) and total energy (joules/cm2) were defined as: A, 0.5 W, 2.0 J/cm2; B, 0.5 W, 4.0 J/cm2; C, 0.5 W, 6.0 J/cm2; D, 1.0 W, 2.0 J/cm2; E, 1.0 W, 4.0 J/cm2; F, 1.0 W, 6.0 J/cm2; and sham, 0.0 W, 0.0 J/cm2. Ten samples per group of 2 mL of LB were infused into a new catheter and treated percutaneously with a class 3b laser. All samples remained in the catheter for 12 seconds to reflect the longest treatment time. Post-treatment free bupivacaine concentrations were identified with high-performance liquid chromatography.
RESULTS
The median free bupivacaine concentration was reported as: sham, 1.89 mg/mL; A, 1.93 mg/mL; B, 2.01 mg/mL; C, 2.05 mg/mL; D, 1.92 mg/mL; E, 2.03 mg/mL; and F, 2.00 mg/mL. There were no differences in median free bupivacaine concentrations between groups (P = .988).
CLINICAL RELEVANCE
Concurrent LB and photobiomodulation are recommended during the postoperative period. The results of this proof-of-concept study suggest that concurrent use of LB and photobiomodulation may be safe, but in vivo studies at similar and stronger photobiomodulation settings are warranted.
PubMed: 38866042
DOI: 10.2460/ajvr.24.02.0041 -
The Journal of Pediatric Pharmacology... Jun 2024Acetaminophen (APAP) is an alternative to indomethacin and ibuprofen for treatment of patent ductus arteriosus (PDA). The side effect profile of non-steroidal...
OBJECTIVE
Acetaminophen (APAP) is an alternative to indomethacin and ibuprofen for treatment of patent ductus arteriosus (PDA). The side effect profile of non-steroidal anti-inflammatory drugs (NSAIDs) presents enteral feeding safety concerns; however, the safety of enteral feeding on APAP is largely unknown. Optimal feeding strategies during pharmacological PDA treatment are unknown, leading to practice variation. This study aims to assess the incidence of adverse gastrointestinal (GI) outcomes in neonates treated with APAP for PDA closure while receiving enteral feedings.
METHODS
Single-center retrospective cohort study of 59 extremely low birth weight (ELBW), premature neonates who received APAP for PDA treatment divided into Low Volume (LV; ≤ 20 mL/kg/day) and High Volume (HV; > 20 mL/kg/day) enteral feeding groups. The primary outcome was the incidence of any suspected or confirmed necrotizing enterocolitis (NEC). Timing of nutrition milestones, parenteral nutrition (PN) days, and adverse outcomes (feeding intolerance, liver dysfunction, death prior to discharge) were evaluated.
RESULTS
The incidence of suspected or confirmed NEC was 19.5% in the LV group and 13.3% in the HV group (p = 0.593). The HV group reached full feeds 6 days sooner (18 vs 24 days, p = 0.024) and had fewer PN days (17 vs 23.5 days, p = 0.044) with no difference in adverse outcomes.
CONCLUSIONS
Provision of > 20 mL/kg/day of enteral feeds during APAP treatment of PDA decreased time to full feeds and PN days compared to trophic feedings (≤ 20 mL/kg/day) with no difference in adverse GI outcomes. Continuing enteral feeding during APAP PDA treatment appears safe while improving achievement of nutritional milestones.
PubMed: 38863856
DOI: 10.5863/1551-6776-29.3.278 -
MedRxiv : the Preprint Server For... May 2024The binary classification of spina bifida lesions as myelomeningocele (with sac) or myeloschisis (without sac) belies a spectrum of morphologies, which have not been...
IMPORTANCE
The binary classification of spina bifida lesions as myelomeningocele (with sac) or myeloschisis (without sac) belies a spectrum of morphologies, which have not been correlated to clinical characteristics and outcomes.
OBJECTIVE
To characterize spina bifida lesion types and correlate them with preoperative presentation and postoperative outcomes.
DESIGN
Secondary analysis of images and videos obtained during fetoscopic spina bifida repair surgery from 2020-2023.
SETTING
Fetal surgery was performed at a quaternary care center.
PARTICIPANTS
A prospective cohort of patients referred for fetal spina bifida underwent fetoscopic repair under an FDA-approved protocol. Of 60 lesions repaired, 57 had available images and were included in the analysis.
INTERVENTIONS OR EXPOSURES
We evaluated lesion morphology on high-resolution intraoperative images and videos to categorize lesions based on placode exposure and nerve root stretching.
MAIN OUTCOMES AND MEASURES
The reproducibility of the lesion classification was assessed via Kappa interrater agreement. Preoperative characteristics analyzed include ventricle size, tonsillar herniation level, lower extremities movement, and lesion dimensions. Outcomes included surgical time, need for patch for skin closure, gestational age at delivery, preterm premature rupture of membranes (PPROM), and neonatal cerebrospinal fluid (CSF) diversion.
RESULTS
We distinguished five lesion types that differ across a range of sac sizes, nerve root stretching, and placode exposure, with 93% agreement between examiners (p<0.001). Fetal characteristics at preoperative evaluation differed significantly by lesion type, including lesion volume (p<0.001), largest ventricle size (p=0.008), tonsillar herniation (p=0.005), and head circumference (p=0.03). Lesion level, talipes, and lower extremities movement did not differ by type. Surgical and perinatal outcomes differed by lesion type, including need for patch skin closure (p<0.001), gestational age at delivery (p=0.01), and NICU length of stay (p<0.001). PPROM, CSF leakage at birth, and CSF diversion in the NICU did not differ between lesion groups. Linear regression associated severity of ventriculomegaly with lesion type, but not with tonsillar herniation level.
CONCLUSIONS AND RELEVANCE
There is a distinct phenotypic spectrum in open spina bifida with differential baseline presentation and outcomes. Severity of ventriculomegaly is associated with lesion type, rather than tonsillar herniation level. Our findings expand the classification of spina bifida to reveal a spectrum that warrants further study.
PubMed: 38853851
DOI: 10.1101/2024.05.29.24308088 -
Respiratory Research Jun 2024The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes.
METHODS
Multicenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365.
RESULTS
The trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27-0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6-1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3-4.5) in the control group, p = 0.037.
CONCLUSIONS
Use of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03262142, registration date 2017-08-25.
Topics: Humans; Male; Female; Pseudomonas Infections; Anti-Bacterial Agents; Aged; Middle Aged; Pseudomonas aeruginosa; Denmark; Outpatients; Disease Progression; Treatment Outcome; Hospitalization; Pulmonary Disease, Chronic Obstructive
PubMed: 38844921
DOI: 10.1186/s12931-024-02860-9 -
ELife Jun 2024Ninein is a centrosome protein that has been implicated in microtubule anchorage and centrosome cohesion. Mutations in the human gene have been linked to Seckel...
Ninein is a centrosome protein that has been implicated in microtubule anchorage and centrosome cohesion. Mutations in the human gene have been linked to Seckel syndrome and to a rare form of skeletal dysplasia. However, the role of ninein in skeletal development remains unknown. Here, we describe a ninein knockout mouse with advanced endochondral ossification during embryonic development. Although the long bones maintain a regular size, the absence of ninein delays the formation of the bone marrow cavity in the prenatal tibia. Likewise, intramembranous ossification in the skull is more developed, leading to a premature closure of the interfrontal suture. We demonstrate that ninein is strongly expressed in osteoclasts of control mice, and that its absence reduces the fusion of precursor cells into syncytial osteoclasts, whereas the number of osteoblasts remains unaffected. As a consequence, ninein-deficient osteoclasts have a reduced capacity to resorb bone. At the cellular level, the absence of ninein interferes with centrosomal microtubule organization, reduces centrosome cohesion, and provokes the loss of centrosome clustering in multinucleated mature osteoclasts. We propose that centrosomal ninein is important for osteoclast fusion, to enable a functional balance between bone-forming osteoblasts and bone-resorbing osteoclasts during skeletal development.
Topics: Animals; Osteoclasts; Osteogenesis; Mice, Knockout; Mice; Nuclear Proteins; Centrosome; Osteoblasts
PubMed: 38836552
DOI: 10.7554/eLife.93457 -
BMJ Paediatrics Open May 2024To compare the neurodevelopmental outcomes of preterm infants before and during the COVID-19 pandemic.
OBJECTIVE
To compare the neurodevelopmental outcomes of preterm infants before and during the COVID-19 pandemic.
DESIGN
Premature infants born in 2018 were assigned to the pre-pandemic group, while those born in 2019 were assigned to the during-pandemic group.
SETTING
Nationwide cohort study.
PATIENTS
Very low birthweight premature infants registered in the Taiwan Premature Infant Follow-up Network database.
INTERVENTIONS
Anti-epidemic measures, including quarantine and isolation protocols, social distancing, the closure of public spaces and restrictions on travel and gatherings during COVID-19 pandemic.
MAIN OUTCOME MEASURES
Outcomes were measured by Bayley Scales of Infant and Toddler Development Third Edition at corrected ages of 6, 12 and 24 months old. Generalised estimating equation (GEE) was applied to incorporate all measurements into a single model.
RESULTS
Among the 1939 premature infants who were enrolled, 985 developed before the pandemic, while 954 developed during the pandemic. Premature infants whose development occurred during the pandemic exhibited better cognitive composite at the corrected age of 6 months (beta=2.358; 95% CI, 1.07 to 3.65; p<0.001), and motor composite at corrected ages of 12 months (beta=1.680; 95% CI, 0.34 to 3.02; p=0.014). GEE analysis showed that infants who had grown during the pandemic achieved higher scores in cognitive composite (beta=1.416; 95% CI, 0.36 to 2.48; p=0.009).
CONCLUSION
Premature infants in Taiwan who developed during the pandemic showed better neurodevelopment compared with those born before the pandemic.
Topics: Humans; COVID-19; Taiwan; Infant, Premature; Male; Female; Infant, Newborn; Infant; Retrospective Studies; Child Development; SARS-CoV-2; Neurodevelopmental Disorders; Infant, Very Low Birth Weight; Pandemics; Cohort Studies
PubMed: 38823798
DOI: 10.1136/bmjpo-2024-002493 -
Journal of Cardiovascular Development... Apr 2024(1) Background: To identify reasons for the persistence of surgical ligation of the patent ductus arteriosus (PDA) in premature infants after the 2019 Food and Drug...
Who Still Gets Ligated? Reasons for Persistence of Surgical Ligation of the Patent Ductus Arteriosus Following Availability of Transcatheter Device Occlusion for Premature Neonates.
(1) Background: To identify reasons for the persistence of surgical ligation of the patent ductus arteriosus (PDA) in premature infants after the 2019 Food and Drug Administration (FDA) approval of transcatheter device closure; (2) Methods: We performed a 10-year (2014-2023) single-institution retrospective study of premature infants (<37 weeks) and compared clinical characteristics and neonatal morbidities between neonates that underwent surgical ligation before (epoch 1) and after (epoch 2) FDA approval of transcatheter closure; (3) Results: We identified 120 premature infants that underwent surgical ligation ( = 94 before, = 26 after FDA approval). Unfavorable PDA morphology, active infection, and recent abdominal pathology were the most common reasons for surgical ligation over device occlusion in epoch 2. There were no differences in demographics, age at closure, or outcomes between infants who received surgical ligation in the two epochs; (4) Conclusions: Despite increasing trends for transcatheter PDA closure in premature infants, surgical ligation persists due to unfavorable ductal morphology, active infection, or abdominal pathology.
PubMed: 38786954
DOI: 10.3390/jcdd11050132 -
Orphanet Journal of Rare Diseases May 2024Trigonocephaly occurs due to the premature fusion of the metopic suture, leading to a triangular forehead and hypotelorism. This condition often requires surgical...
BACKGROUND
Trigonocephaly occurs due to the premature fusion of the metopic suture, leading to a triangular forehead and hypotelorism. This condition often requires surgical correction for morphological and functional indications. Metopic ridges also originate from premature metopic closure but are only associated with mid-frontal bulging; their surgical correction is rarely required. Differential diagnosis between these two conditions can be challenging, especially in minor trigonocephaly.
METHODS
Two hundred seven scans of patients with trigonocephaly (90), metopic rigdes (27), and controls (90) were collected. Geometric morphometrics were used to quantify skull and orbital morphology as well as the interfrontal angle and the cephalic index. An innovative method was developed to automatically compute the frontal curvature along the metopic suture. Different machine-learning algorithms were tested to assess the predictive power of morphological data in terms of classification.
RESULTS
We showed that control patients, trigonocephaly and metopic rigdes have distinctive skull and orbital shapes. The 3D frontal curvature enabled a clear discrimination between groups (sensitivity and specificity > 92%). Furthermore, we reached an accuracy of 100% in group discrimination when combining 6 univariate measures.
CONCLUSION
Two diagnostic tools were proposed and demonstrated to be successful in assisting differential diagnosis for patients with trigonocephaly or metopic ridges. Further clinical assessments are required to validate the practical clinical relevance of these tools.
Topics: Humans; Craniosynostoses; Female; Male; Infant; Imaging, Three-Dimensional; Skull
PubMed: 38762603
DOI: 10.1186/s13023-024-03197-8 -
Annals of Translational Medicine Apr 2024The remit of this review is confined to the experimental scientific works and surgeries based on the Integral Theory paradigm. The video abstract summarizes the... (Review)
Review
The remit of this review is confined to the experimental scientific works and surgeries based on the Integral Theory paradigm. The video abstract summarizes the anorectal function, how ligaments cause dysfunction and cure of fecal incontinence and obstructed defecation by ligament repair. Anorectal function is reflex and binary, with cortical and peripheral components. The same three oppositely acting reflex muscle forces which open and close the bladder, contract against the pubourethral (PUL) and uterosacral (USL) ligaments: (I) to close the anorectum for continence when the puborectalis muscle (PRM) contracts forwards; (II) to open the anorectum prior to evacuation when the PRM relaxes; (III) to stretch the rectum in opposite directions to support the anorectal stretch receptors "N" to prevent premature activation of the defecation reflex, (fecal urgency). Weak or loose PULs or USLs may cause dysfunction of closure, of evacuation, and inability to control the defecation reflex (fecal urgency). Repair of the PUL and USL can improve or cure these dysfunctions. The perineal body (PB) acts as an anatomical support for the distal vagina, anorectum and external anal sphincter (EAS). It serves as an anchoring point for the forward action of the pubococcygeus muscle (PCM), which tensions the anterior rectal wall during closure and defecation. Bladder and bowel dysfunction have a similar pathogenesis, ligament laxity, mainly pubourethral and uterosacral, with added PB damage for anorectal dysfunction. PB damage can cause obstructive defecation and descending perineal syndrome (DPS). Repair of damaged PUL and USL can restore the closure and evacuation functions of both bladder an anorectum. DPS can be cured by repair of the PB's suspensory ligaments, deep transversus perinei.
PubMed: 38721466
DOI: 10.21037/atm-23-1883 -
Clinical Medicine (London, England) May 2024Spinal epidural abscess is a rare but serious condition with poor outcomes. It's classic triad of new back pain, neurological deficit and fever is only present in 15% of...
Spinal epidural abscess is a rare but serious condition with poor outcomes. It's classic triad of new back pain, neurological deficit and fever is only present in 15% of cases at presentation and is initially misdiagnosed in 75-89%. Delaying treatment is associated with worse outcomes. Delirium is itself a risk factor for mortality but the disturbance in cognition and memory can also complicate clinical assessment. We present a case of delirium caused by, and obscuring, a spinal epidural abscess. This case highlights the difficulties in diagnosing spinal epidural abscesses, the need for a high index of suspicion for the condition and timely action to minimise morbidity. In addition, it demonstrates the value of treating unexplained delirium as an emergency and the danger of diagnostic premature closure. Finally, the importance of persistent clinical examination of the confused and non-cooperative patient.
PubMed: 38705398
DOI: 10.1016/j.clinme.2024.100214