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Arthroscopy : the Journal of... Jun 2024Hip arthroscopy (HA) is preferred for surgical management of femoroacetabular impingement syndrome, while periacetabular osteotomy (PAO) is the gold standard for frank...
Hip arthroscopy (HA) is preferred for surgical management of femoroacetabular impingement syndrome, while periacetabular osteotomy (PAO) is the gold standard for frank developmental hip dysplasia in young adults. Borderline hip dysplasia (BHD) is a conundrum, with data supporting the use of either or both, not to mention that BHD is defined by varying lateral center-edge angle thresholds between 18°-25° or 20°-25° and features generalized ligamentous laxity and variations in acetabular and femoral version. That said, HA for BDH has been shown to have 10-year survivorship of 82%. In a revision situation after HA in patients with BHD, PAO seems a logical next step, but HA may be indicated under very narrow indications. From a technical standpoint, capsular preservation, labral function restoration, and avoiding acetabular rim over-resection are key points when performing HA in BHD. Most important, particularly in the revision setting, is to determine the root cause of failure. Primarily, instability-driven symptoms are an indication for PAO.
PubMed: 38936560
DOI: 10.1016/j.arthro.2024.06.026 -
Pathology, Research and Practice Jun 2024Oral leukoplakia (OLK) is the most common oral potentially malignant disorder (OPMD), which can be malignantly transformed into oral squamous cell carcinoma (OSCC)....
BACKGROUND
Oral leukoplakia (OLK) is the most common oral potentially malignant disorder (OPMD), which can be malignantly transformed into oral squamous cell carcinoma (OSCC). Peroxiredoxin1(Prx1) has been predicted to bind to Prohibitin2 (PHB2), which confers to affect OLK progression; however, the mechanism of Prx1/PHB2 mediated mitophagy involved in OLK remains unclear.
METHODS
This study aimed to explore the mechanism of the Prx1/PHB2 axis on senescence in OLK through mediating mitophagy. The positive rate of Ki67 and the expression of p21, p16, PHB2, and LC3 in human normal, OLK, and OSCC tissues were detected by immunohistochemical staining. The mitophagy and mitochondrial function changes were then analyzed in Prx1 knockdown and Prx1C52S mutations in dysplastic oral keratinocyte (DOK) cells treated with HO. In situ Proximity Ligation Assay combined with co-immunoprecipitation was used to detect the interaction between Prx1 and PHB2.
RESULTS
Clinically, the positive rate of Ki67 progressively increased from normal to OLK, OLK with dysplasia, and OSCC. Higher p21, p16, PHB2, and LC3 expression levels were observed in OLK with dysplasia than in normal and OSCC tissues. In vitro, PHB2 and LC3II expression gradually increased with the degree of DOK cell senescence. Prx1/PHB2 regulated mitophagy and affected senescence in HO-induced DOK cells. Furthermore, Prx1C52S mutation specifically reduced interaction between Prx1 and PHB2. Prx1Cys52 is associated with mitochondrial reactive oxygen species (ROS) accumulated and cell cycle arrest.
CONCLUSION
Prx1Cys52 functions as a redox sensor that binds to PHB2 and regulates mitophagy in the senescence of OLK, suggesting its potential as a clinical target.
PubMed: 38936092
DOI: 10.1016/j.prp.2024.155411 -
JAMA Network Open Jun 2024The overutilization of antibiotics in very preterm infants (VPIs) at low risk of early-onset sepsis (EOS) is associated with increased mortality and morbidities....
IMPORTANCE
The overutilization of antibiotics in very preterm infants (VPIs) at low risk of early-onset sepsis (EOS) is associated with increased mortality and morbidities. Nevertheless, the association of early antibiotic exposure with bronchopulmonary dysplasia (BPD) remains equivocal.
OBJECTIVE
To evaluate the association of varying durations and types of early antibiotic exposure with the incidence of BPD in VPIs at low risk of EOS.
DESIGN, SETTING, AND PARTICIPANTS
This national multicenter cohort study utilized data from the Chinese Neonatal Network (CHNN) which prospectively collected data from January 1, 2019, to December 31, 2021. VPIs less than 32 weeks' gestational age or with birth weight less than 1500 g at low risk of EOS, defined as those born via cesarean delivery, without labor or rupture of membranes, and no clinical evidence of chorioamnionitis, were included. Data analysis was conducted from October 2022 to December 2023.
EXPOSURE
Early antibiotic exposure was defined as the total number of calendar days antibiotics were administered within the first week of life, which were further categorized as no exposure, 1 to 4 days of exposure, and 5 to 7 days of exposure.
MAIN OUTCOMES AND MEASURES
The primary outcome was the composite of moderate to severe BPD or mortality at 36 weeks' post menstrual age (PMA). Logistic regression was employed to assess factors associated with BPD or mortality using 2 different models.
RESULTS
Of the 27 176 VPIs included in the CHNN during the study period (14 874 male [54.7%] and 12 302 female [45.3%]), 6510 (23.9%; 3373 male [51.8%] and 3137 female [48.2.%]) were categorized as low risk for EOS. Among them, 1324 (20.3%) had no antibiotic exposure, 1134 (17.4%) received 1 to 4 days of antibiotics treatment, and 4052 (62.2%) received 5 to 7 days of antibiotics treatment. Of the 5186 VPIs who received antibiotics, 4098 (79.0%) received broad-spectrum antibiotics, 888 (17.1%) received narrow-spectrum antibiotics, and 200 (3.9%) received antifungals or other antibiotics. Prolonged exposure (5-7 days) was associated with increased likelihood of moderate to severe BPD or death (adjusted odds ratio [aOR], 1.23; 95% CI, 1.01-1.50). The use of broad-spectrum antibiotics (1-7 days) was also associated with a higher risk of moderate to severe BPD or death (aOR, 1.27; 95% CI, 1.04-1.55).
CONCLUSIONS AND RELEVANCE
In this cohort study of VPIs at low risk for EOS, exposure to prolonged or broad-spectrum antibiotics was associated with increased risk of developing moderate to severe BPD or mortality. These findings suggest that VPIs exposed to prolonged or broad-spectrum antibiotics early in life should be monitored for adverse outcomes.
Topics: Humans; Bronchopulmonary Dysplasia; Anti-Bacterial Agents; Infant, Newborn; Female; Male; Infant, Premature; Sepsis; China; Cohort Studies; Risk Factors; Incidence; Gestational Age; Infant, Very Low Birth Weight
PubMed: 38935376
DOI: 10.1001/jamanetworkopen.2024.18831 -
Neonatology Jun 2024Ureaplasma species are considered commensals of the adult urogenital tract. Yet, in pregnancy, Ureaplasma parvum and Ureaplasma urealyticum have been associated with... (Review)
Review
BACKGROUND
Ureaplasma species are considered commensals of the adult urogenital tract. Yet, in pregnancy, Ureaplasma parvum and Ureaplasma urealyticum have been associated with chorioamnionitis and preterm birth. In preterm infants, Ureaplasma respiratory tract colonization has been correlated with the development of bronchopulmonary dysplasia and has been implicated in the pathogenesis of other complications of prematurity. Controversies on the impact of Ureaplasma exposure on neonatal morbidity, however, remain, and recommendations for screening practices and therapeutic management in preterm infants are missing.
SUMMARY
In this review, we outline clinical and experimental evidence of Ureaplasma-driven fetal and neonatal morbidity, critically examining inconsistencies across some of the existing studies. We explore underlying mechanisms of Ureaplasma-associated neonatal morbidity and discuss gaps in the current understanding including the interplay between Ureaplasma and the maternal urogenital tract and the preterm airway microbiome. Ultimately, we highlight the importance of adequate diagnostics and review the potential efficacy of anti-infective therapies.
KEY MESSAGES
There is strong evidence that perinatal Ureaplasma exposure is causally related to the development of bronchopulmonary dysplasia, and there are conclusive data of the role of Ureaplasma in the pathogenesis of neonatal central nervous system infection. Observational and experimental findings indicate immunomodulatory capacities that might promote an increased risk of secondary infections. The burden of Ureaplasma exposure is inversely related to gestational age - leaving the tiniest babies at highest risk. A better knowledge of contributing pathogen and host factors and modulating conditions remains paramount to define screening and treatment recommendations allowing early intervention in preterm infants at risk.
PubMed: 38934167
DOI: 10.1159/000539613 -
American Journal of Medical Genetics.... Jun 2024We report three siblings homozygous for CSF1R variant c.1969 + 115_1969 + 116del to expand the phenotype of "brain abnormalities, neurodegeneration, and...
Leukoencephalopathy with calcifications, developmental brain abnormalities and skeletal dysplasia due to homozygosity for a hypomorphic CSF1R variant: A report of three siblings.
We report three siblings homozygous for CSF1R variant c.1969 + 115_1969 + 116del to expand the phenotype of "brain abnormalities, neurodegeneration, and dysosteosclerosis" (BANDDOS) and discuss its link with "adult leukoencephalopathy with axonal spheroids and pigmented glia" (ALSP), caused by heterozygous CSF1R variants. We evaluated medical, radiological, and laboratory findings and reviewed the literature. Patients presented with developmental delay, therapy-resistant epilepsy, dysmorphic features, and skeletal abnormalities. Secondary neurological decline occurred from 23 years in sibling one and from 20 years in sibling two. Brain imaging revealed multifocal white matter abnormalities and calcifications during initial disease in siblings two and three. Developmental brain anomalies, seen in all three, were most severe in sibling two. During neurological decline in siblings one and two, the leukoencephalopathy was progressive and had the MRI appearance of ALSP. Skeletal survey revealed osteosclerosis, most severe in sibling three. Blood markers, monocytes, dendritic cell subsets, and T-cell proliferation capacity were normal. Literature review revealed variable initial disease and secondary neurological decline. BANDDOS presents with variable dysmorphic features, skeletal dysplasia, developmental delay, and epilepsy with on neuro-imaging developmental brain anomalies, multifocal white matter abnormalities, and calcifications. Secondary neurological decline occurs with a progressive leukoencephalopathy, in line with early onset ALSP. Despite the role of CSF1R signaling in myeloid development, immune deficiency is absent. Phenotype varies within families; skeletal and neurological manifestations may be disparate.
PubMed: 38934054
DOI: 10.1002/ajmg.a.63800 -
JGH Open : An Open Access Journal of... Jun 2024Atrophic gastritis (AG) and gastric intestinal metaplasia (GIM) are early changes in the stepwise progression to gastric adenocarcinoma. There is heterogeneity in...
BACKGROUND AND AIM
Atrophic gastritis (AG) and gastric intestinal metaplasia (GIM) are early changes in the stepwise progression to gastric adenocarcinoma. There is heterogeneity in international guidelines regarding the endoscopic diagnosis and surveillance of AG and GIM. This study aims to determine the prevalence of GIM in an Australian center and assess the approach of Australian endoscopists for these two conditions.
METHODS
We conducted a single-center retrospective study of adult patients between January 2015 and December 2020 diagnosed with GIM on gastric biopsy following upper gastric endoscopy. A web-based, 25-question, investigator-designed, multiple-choice survey was distributed among all registered endoscopists in Australia.
RESULTS
The overall prevalence of GIM within a single Australian center was 11.7% over 5 years. Of the 1026 patients identified, only 58.7% underwent mapping biopsies using the modified Sydney protocol. Among the cohort, 1.6% had low-grade dysplasia, 0.9% had high-grade dysplasia, and 1.8% had malignancy on initial gastroscopy. Two hundred and sixty-seven (7.2%) endoscopists completed the survey, 44.2% indicated they would perform mapping for all patients, and 36% only for high-risk patients. Only 1.5% ( = 4) of respondents were able to correctly identify all six endoscopic photos of GIM/AG.
CONCLUSION
This study demonstrates that in a large tertiary center, GIM is a prevalent endoscopic finding, but the associated rates of dysplasia and cancer were low. Additionally, among a small proportion of surveyed Australian endoscopists, there is notable variability in the endoscopic approach for AG and GIM and significant knowledge gaps. More training is required to increase the recognition of GIM and compliance with histological mapping.
PubMed: 38933895
DOI: 10.1002/jgh3.13115 -
Journal of Clinical Medicine Jun 2024Advances in perinatal intensive care have significantly enhanced the survival rates of extremely low gestation-al-age neonates but with continued high rates of... (Review)
Review
Advances in perinatal intensive care have significantly enhanced the survival rates of extremely low gestation-al-age neonates but with continued high rates of bronchopulmonary dysplasia (BPD). Nevertheless, as the survival of these infants improves, there is a growing awareness of associated abnormalities in pulmonary vascular development and hemodynamics within the pulmonary circulation. Premature infants, now born as early as 22 weeks, face heightened risks of adverse development in both pulmonary arterial and venous systems. This risk is compounded by parenchymal and airway abnormalities, as well as factors such as inflammation, fibrosis, and adverse growth trajectory. The presence of pulmonary hypertension in bronchopulmonary dysplasia (BPD-PH) has been linked to an increased mortality and substantial morbidities, including a greater susceptibility to later neurodevelopmental challenges. BPD-PH is now recognized to be a spectrum of disease, with a multifactorial pathophysiology. This review discusses the challenges associated with the identification and management of BPD-PH, both of which are important in minimizing further disease progression and improving cardiopulmonary morbidity in the BPD infant.
PubMed: 38929946
DOI: 10.3390/jcm13123417 -
Life (Basel, Switzerland) Jun 2024The RASopathies are a group of syndromes caused by genetic variants that affect the RAS-MAPK signaling pathway, which is essential for cell response to diverse stimuli.... (Review)
Review
Exploring New Drug Repurposing Opportunities for MEK Inhibitors in RASopathies: A Comprehensive Review of Safety, Efficacy, and Future Perspectives of Trametinib and Selumetinib.
The RASopathies are a group of syndromes caused by genetic variants that affect the RAS-MAPK signaling pathway, which is essential for cell response to diverse stimuli. These variants functionally converge towards the overactivation of the pathway, leading to various constitutional and mosaic conditions. These syndromes show overlapping though distinct clinical presentations and share congenital heart defects, hypertrophic cardiomyopathy (HCM), and lymphatic dysplasia as major clinical features, with highly variable prevalence and severity. Available treatments have mainly been directed to target the symptoms. However, repurposing MEK inhibitors (MEKis), which were originally developed for cancer treatment, to target evolutive aspects occurring in these disorders is a promising option. Animal models have shown encouraging results in treating various RASopathy manifestations, including HCM and lymphatic abnormalities. Clinical reports have also provided first evidence supporting the effectiveness of MEKi, especially trametinib, in treating life-threatening conditions associated with these disorders. Nevertheless, despite notable improvements, there are adverse events that occur, necessitating careful monitoring. Moreover, there is evidence indicating that multiple pathways can contribute to these disorders, indicating a current need to more accurate understand of the underlying mechanism of the disease to apply an effective targeted therapy. In conclusion, while MEKi holds promise in managing life-threatening complications of RASopathies, dedicated clinical trials are required to establish standardized treatment protocols tailored to take into account the individual needs of each patient and favor a personalized treatment.
PubMed: 38929714
DOI: 10.3390/life14060731 -
Medicina (Kaunas, Lithuania) May 2024: Our aim was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of...
: Our aim was to perform a retrospective analysis of the volume of cervical screening tests, the number of patients treated with an excision method, and the incidence of invasive and non-invasive cervical during a pandemic and pre-pandemic period of 24 months. : The study compared 404 patients who underwent cervical cone biopsy for cervical cancer. The study examined patients' specimens based on histopathological characteristics and categorized cervical lesions based on pap smear. : There was a statistically significant age difference between the two study periods. The mean difference was 32 years before the pandemic and 35 years during the pandemic (-value > 0.05). The biggest patient loss ratio identified by age group was in the 50-59-year group, with a 14.53% loss in the pre-pandemic period and a 9.1% loss in the pandemic period. In the pandemic period, patients from rural areas presented in the clinical trial with a lower rate of 39.52% (83 patients) vs. 60.47% (127 patients) in urban areas. A higher percentage of patients experiencing cervicorrhagia as a clinical manifestation in the pandemic period vs. the pre-pandemic period, with an increase in more severe lesions in the pandemic period, had a statistical significance of 8% more newly diagnosed compared to the pre-pandemic period. : The addressability of the patients during the COVID period was not affected in a drastic way in our study. We encountered a decrease in appointments in the age group of 50-59 years and a decrease in patients with rural residence. In our study, we found an increase in cervical bleeding as a reason for consultation in the pandemic period with a higher lesion degree, both on a pap smear and on a cervical biopsy.
Topics: Humans; Female; COVID-19; Retrospective Studies; Middle Aged; Uterine Cervical Neoplasms; Adult; SARS-CoV-2; Papanicolaou Test; Early Detection of Cancer; Aged; Pandemics; Vaginal Smears
PubMed: 38929526
DOI: 10.3390/medicina60060909 -
Antioxidants (Basel, Switzerland) Jun 2024Bronchopulmonary dysplasia (BPD) is a chronic condition affecting preterm infants, characterized by lung alveolar simplification/hypoalveolarization and vascular...
Bronchopulmonary dysplasia (BPD) is a chronic condition affecting preterm infants, characterized by lung alveolar simplification/hypoalveolarization and vascular remodeling. The nuclear factor erythroid 2 like 2 (Nfe2l2, or Nrf2) plays a critical role in the cytoprotective response to neonatal hyperoxia, and its global deficiency exacerbates hypoalveolarization in mice. The abnormal recruitment and activation of myeloid cells are associated with the pathogenesis of BPD. Therefore, we employed a genetic approach to investigate the role of myeloid Nrf2 in regulating hyperoxia-induced hypoalveolarization. Pups, both wild-type () and those with a myeloid Nrf2 deletion (abbreviated as ), were exposed to hyperoxia for 72 h at postnatal day 1 (Pnd1), and then sacrificed at either Pnd4 or Pnd18 following a two-week recovery period. We analyzed the hypoalveolarization, inflammation, and gene expression related to cytoprotective and inflammatory responses in the lungs of these pups. The hypoalveolarization induced by hyperoxia was significantly greater in pups compared to their counterparts (35.88% vs. 21.01%, respectively) and was accompanied by increased levels of inflammatory cells and IL-1β activation in the lungs. Antioxidant gene expression in response to neonatal hyperoxia was lower in pups compared to their counterparts. Furthermore, -deficient macrophages exposed to hyperoxia exhibited markedly decreased cytoprotective gene expression and increased IL-1β levels compared to Nrf2-sufficient cells. Our findings demonstrate the crucial role of myeloid Nrf2 in mitigating hyperoxia-induced lung hypoalveolarization and inflammatory responses in neonatal mice.
PubMed: 38929137
DOI: 10.3390/antiox13060698