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Cancers Jun 2024The incidences of anogenital HPV-related cancers in women are on the rise; this is especially true for anal cancer. Medical societies are now beginning to recommend anal...
The incidences of anogenital HPV-related cancers in women are on the rise; this is especially true for anal cancer. Medical societies are now beginning to recommend anal cancer screening in certain high-risk populations, including high-risk women with a history of genital dysplasia. The aim of this study is to investigate national anogenital HPV cancer trends as well as the role of demographics, deprivation, and ethnicity on anogenital cancer incidence in England, in an attempt to better understand this cohort of women which is increasingly affected by anogenital HPV-related disease. Demographic data from the Clinical Outcomes and Services Dataset (COSD) were extracted for all patients diagnosed with anal, cervical, vulval and vaginal cancer in England between 2014 and 2020. Outcomes included age, ethnicity, deprivation status and staging. An age over 55 years, non-white ethnicity and high deprivation are significant risk factors for late cancer staging, as per logistic regression. In 2019, the incidences of anal and vulval cancer in white women aged 55-74 years surpassed that of cervical cancer. More needs to be done to educate women on HPV-related disease and their lifetime risk of these conditions.
PubMed: 38927883
DOI: 10.3390/cancers16122177 -
Bioengineering (Basel, Switzerland) May 2024Esophageal carcinoma is the sixth-leading cause of cancer death worldwide. A precursor to esophageal adenocarcinoma (EAC) is Barrett's Esophagus (BE). Early-stage...
Design and Evaluation of ScanCap: A Low-Cost, Reusable Tethered Capsule Endoscope with Blue-Green Illumination Imaging for Unsedated Screening and Early Detection of Barrett's Esophagus.
Esophageal carcinoma is the sixth-leading cause of cancer death worldwide. A precursor to esophageal adenocarcinoma (EAC) is Barrett's Esophagus (BE). Early-stage diagnosis and treatment of esophageal neoplasia (Barrett's with high-grade dysplasia/intramucosal cancer) increase the five-year survival rate from 10% to 98%. BE is a global challenge; however, current endoscopes for early BE detection are costly and require extensive infrastructure for patient examination and sedation. We describe the design and evaluation of the first prototype of ScanCap, a high-resolution optical endoscopy system with a reusable, low-cost tethered capsule, designed to provide high-definition, blue-green illumination imaging for the early detection of BE in unsedated patients. The tethered capsule (12.8 mm diameter, 35.5 mm length) contains a color camera and rotating mirror and is designed to be swallowed; images are collected as the capsule is retracted manually via the tether. The tether provides electrical power and illumination at wavelengths of 415 nm and 565 nm and transmits data from the camera to a tablet. The ScanCap prototype capsule was used to image the oral mucosa in normal volunteers and ex vivo esophageal resections; images were compared to those obtained using an Olympus CV-180 endoscope. Images of superficial capillaries in intact oral mucosa were clearly visible in ScanCap images. Diagnostically relevant features of BE, including irregular Z-lines, distorted mucosa, and dilated vasculature, were clearly visible in ScanCap images of ex vivo esophageal specimens.
PubMed: 38927792
DOI: 10.3390/bioengineering11060557 -
Genes Jun 2024Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting premature infants, with limited therapeutic options and increased long-term consequences....
Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting premature infants, with limited therapeutic options and increased long-term consequences. Adrenomedullin (), a proangiogenic peptide hormone, has been found to protect rodents against experimental BPD. This study aims to elucidate the molecular and cellular mechanisms through which influences BPD pathogenesis using a lipopolysaccharide (LPS)-induced model of experimental BPD in mice. Bulk RNA sequencing of -sufficient (wild-type or ) and -haplodeficient () mice lungs, integrated with single-cell RNA sequencing data, revealed distinct gene expression patterns and cell type alterations associated with deficiency and LPS exposure. Notably, computational integration with cell atlas data revealed that -haplodeficient mouse lungs exhibited gene expression signatures characteristic of increased inflammation, natural killer (NK) cell frequency, and decreased endothelial cell and type II pneumocyte frequency. Furthermore, in silico human BPD patient data analysis supported our cell type frequency finding, highlighting elevated NK cells in BPD infants. These results underscore the protective role of in experimental BPD and emphasize that it is a potential therapeutic target for BPD infants with an inflammatory phenotype.
Topics: Adrenomedullin; Bronchopulmonary Dysplasia; Animals; Mice; Humans; Sequence Analysis, RNA; Disease Models, Animal; Lipopolysaccharides; Lung; Killer Cells, Natural; Transcriptome
PubMed: 38927741
DOI: 10.3390/genes15060806 -
Genes Jun 2024Cardiomyopathies (CMs), one of the main causes of sudden death among the young population, are a heterogeneous group of myocardial diseases, usually with a genetic...
Cardiomyopathies (CMs), one of the main causes of sudden death among the young population, are a heterogeneous group of myocardial diseases, usually with a genetic cause. Next-Generation Sequencing (NGS) has expanded the genes studied for CMs; however, the yield is still around 50%. The systematic study of Copy Number Variants (CNVs) could contribute to improving our diagnostic capacity. These alterations have already been described as responsible for cardiomyopathies in some cases; however, their impact has been rarely assessed. We analyzed the clinical significance of CNVs in cardiomyopathies by studying 11,647 affected patients, many more than those considered in previously published studies. We evaluated the yield of the systematic study of CNVs in a production context using NGS and a novel CNV detection software tool v2.0 that has demonstrated great efficacy, maximizing sensitivity and avoiding false positives. We obtained a CNV analysis yield of 0.8% that fluctuated depending on the type of cardiomyopathy studied (0.29% HCM, 1.41% DCM, 1.88% ARVC, 1.8% LVNC, 1.45% RCM), and we present the frequency of occurrence for 18 genes that agglutinate the 95 pathogenic/likely pathogenic CNVs detected. We conclude the importance of including in diagnostic tests a systematic study of these genetic alterations for the different cardiomyopathies.
Topics: Humans; DNA Copy Number Variations; Cardiomyopathies; High-Throughput Nucleotide Sequencing; Male; Female; Adult; Clinical Relevance
PubMed: 38927710
DOI: 10.3390/genes15060774 -
Genes May 2024HELIX syndrome (Hypohidrosis-Electrolyte disturbances-hypoLacrimia-Ichthyosis-Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin...
HELIX syndrome (Hypohidrosis-Electrolyte disturbances-hypoLacrimia-Ichthyosis-Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, highlight the skin anomalies as an important clue, and expand the genotypic spectrum. Two adult brothers from consanguineous parents with suspected ectodermal dysplasia (ED) since early childhood were re-evaluated. A comprehensive phenotypic exam and an aCGH + SNP4 × 180 K microarray followed by Sanger sequencing of the gene were performed. They presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. In adulthood, they also developed a salt-losing nephropathy with hypokalemia and hypermagnesemia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the gene [ (NM_0006984.4): c.322_329delGGCTCCGA, p.Gly108fs*] leading to a premature truncation of the protein. Both parents were heterozygous carriers. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults. Given the potential for ED misdiagnosis in infancy, it is important to include the gene in a specific genodermatosis next-generation sequencing (NGS) panel to provide early diagnosis, accurate management, and genetic counseling.
Topics: Humans; Male; Claudins; Adult; Ichthyosis; Hypohidrosis; Ectodermal Dysplasia; Pedigree; Phenotype
PubMed: 38927623
DOI: 10.3390/genes15060687 -
Biomedicines May 2024Exposure to hyperoxia is an important factor in the development of bronchopulmonary dysplasia (BPD) in preterm newborns. MicroRNAs (miRs) have been implicated in the...
Exposure to hyperoxia is an important factor in the development of bronchopulmonary dysplasia (BPD) in preterm newborns. MicroRNAs (miRs) have been implicated in the pathogenesis of BPD and provide a potential therapeutic target. This study was conducted utilizing a postnatal animal model of experimental hyperoxia-induced murine BPD to investigate the expression and function of miR-195 as well as its molecular signaling targets within developing mouse lung tissue. miR-195 expression levels increased in response to hyperoxia in male and female lungs, with the most significant elevation occurring in 40% O (mild) and 60% O (moderate) BPD. The inhibition of miR-195 improved pulmonary morphology in the hyperoxia-induced BPD model in male and female mice with females showing more resistance to injury and better recovery of alveolar chord length, septal thickness, and radial alveolar count. Additionally, we reveal miR-195-dependent signaling pathways involved in BPD and identify PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) as a novel specific target protein of miR-195. Our data demonstrate that high levels of miR-195 in neonatal lungs cause the exacerbation of hyperoxia-induced experimental BPD while its inhibition results in amelioration. This finding suggests a therapeutic potential of miR-195 inhibition in preventing BPD.
PubMed: 38927415
DOI: 10.3390/biomedicines12061208 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2024In infants with severe bronchopulmonary dysplasia (sBPD), severe pulmonary lobar emphysema may occur as a complication, contributing to significant impairment in...
In infants with severe bronchopulmonary dysplasia (sBPD), severe pulmonary lobar emphysema may occur as a complication, contributing to significant impairment in ventilation. Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation. However, prior to the lobectomy, it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively. In addition, preoperative planning and perioperative management are also quite challenging in these patients. This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema. Since infants with sBPD already have poor lung development and significant lung injury, lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution. Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema. However, given the technical difficulty, successful application of this technique requires close collaboration of an experienced interdisciplinary team.
Topics: Humans; Pulmonary Emphysema; Bronchopulmonary Dysplasia; Infant, Newborn; Infant, Premature; Bronchi; Male; Pneumonectomy; Female
PubMed: 38926385
DOI: 10.7499/j.issn.1008-8830.2403014 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2024To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early...
OBJECTIVES
To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.
METHODS
A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.
RESULTS
A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (=3.370, 95%: 1.500-7.568, <0.05), and high gestational age at birth was a protective factor against BPD (<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (=5.017, 95%: 1.040-24.190, <0.05).
CONCLUSIONS
The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.
Topics: Humans; Bronchopulmonary Dysplasia; Risk Factors; Infant, Newborn; Female; Retrospective Studies; Male; Infant, Premature; Twins; Gestational Age; Birth Weight; Logistic Models
PubMed: 38926378
DOI: 10.7499/j.issn.1008-8830.2312005 -
International Journal of Orthopaedic... Jun 2024Guidelines have been proposed for post-operative rehabilitation following periacetabular osteotomy (PAO). However, the perspectives of individuals undergoing PAO have...
Rehabilitation following periacetabular osteotomy for acetabular dysplasia: A qualitative interview study exploring challenges, hopes and expectations among patients in Denmark and Australia.
INTRODUCTION
Guidelines have been proposed for post-operative rehabilitation following periacetabular osteotomy (PAO). However, the perspectives of individuals undergoing PAO have not been considered.
AIM
The present study aimed to explore the perceived challenges of everyday life and hopes for and expectations of post-PAO rehabilitation from the perspective of individuals with acetabular dysplasia living in Denmark and Australia.
METHODS
In this qualitative study, we used a hermeneutic phenomenological approach with semi-structured interviews to explore the perspectives of 25 participants (four males), aged 16-43 years, who underwent a PAO. Purposeful sampling was used to provide variations in age and sex. Inclusion criteria were age above 15 years, radiographic evidence of acetabular dysplasia, PAO within the last seven weeks and undergoing post-operative rehabilitation. Inductive content analysis was adopted to code and analyse interviews.
RESULTS
The analysis of the interview transcripts revealed four major themes: different expectations, self-confidence, tailored rehabilitation and aligning expectations. Several subthemes emerged within each theme, and similar patterns with minor variations were identified across countries. However, the financial burden of self-funded surgery and rehabilitation challenged some Australian participants, whereas none of the Danish participants mentioned this challenge.
CONCLUSION
Our findings elucidate the diverse range of hopes and expectations in individuals undergoing PAO, and how these relate to their perceived challenges. In particular, the findings highlight the importance of aligning expectations between individuals and clinicians when designing the rehabilitation.
PubMed: 38925029
DOI: 10.1016/j.ijotn.2024.101116 -
Journal of Plastic, Reconstructive &... Jun 2024Congenital pseudarthrosis of the forearm bones (CPFBs) is rare, with only 106 reported cases, and is frequently associated with neurofibromatosis (NF). Approximately 5%...
Congenital pseudarthrosis of the forearm bones (CPFBs) is rare, with only 106 reported cases, and is frequently associated with neurofibromatosis (NF). Approximately 5% of patients with NF develop pseudarthrosis, and 50% of patients with pseudarthrosis have NF. Achieving bone union is difficult in congenital pseudarthrosis. Many methods have been attempted, including casting, internal fixation with or without grafting, and electrical stimulation, but failure is frequent. Free vascularized fibular flaps (FVFs) have been used to bridge long bone defects since 1975 and in tibial pseudarthrosis since 1979. In CPFB, FVF is more successful than other methods in achieving union and is the current treatment of choice. Here, we presented three cases of forearm pseudarthrosis treated with FVF, reviewed the literature on CPFB, and discussed some technical aspects of FVF treatment. Three cases of congenital pseudoarthrosis were treated with free fibula flaps, diagnosed at ages of 7 years (ulna), 15 months (radius), and 9 years (radius and ulna). Two flaps were stabilized with intramedullary wires and latterly, one with compression plates. One persistent nonunion received revision nonvascularized bone grafting and plating. All patients achieved union by 11 months after index surgery. Reconstruction with vascularized fibula is the treatment of choice because it offers the highest published union rates and good functional results. Complete resection of the affected bone and stable fixation, latterly with compression plates are critical to success. Surgery is technically demanding, and complications are common. Secondary surgery may be required, but outcomes are favorable. LEVEL OF EVIDENCE: IV.
PubMed: 38924895
DOI: 10.1016/j.bjps.2024.06.015