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American Journal of Respiratory and... Apr 2024Bronchiectasis is a pathological dilatation of the bronchi in the respiratory airways associated with environmental or genetic causes (e.g., cystic fibrosis, primary...
RATIONALE
Bronchiectasis is a pathological dilatation of the bronchi in the respiratory airways associated with environmental or genetic causes (e.g., cystic fibrosis, primary ciliary dyskinesia and primary immunodeficiency disorders), but most cases remain idiopathic.
OBJECTIVES
To identify novel genetic defects in unsolved cases of bronchiectasis presenting with severe rhinosinusitis, nasal polyposis, and pulmonary infection.
METHODS
DNA was analyzed by next-generation or targeted Sanger sequencing. RNA was analyzed by quantitative PCR and single-cell RNA sequencing. Patient-derived, cells, cell cultures and secretions (mucus, saliva, seminal fluid) were analyzed by Western blotting and immunofluorescence microscopy, and mucociliary activity was measured. Blood serum was analyzed by electrochemiluminescence immunoassay. Protein structure and proteomic analyses were used to assess the impact of a disease-causing founder variant.
MEASUREMENTS AND MAIN RESULTS
We identified bi-allelic pathogenic variants in in 11 individuals from 10 unrelated families originating from the United States, Europe, Asia, and Africa. Expression of was detected predominantly in secretory cells of control airway epithelium and also in submucosal glands. We demonstrate that WFDC2 is below the limit of detection in blood serum and hardly detectable in samples of saliva, seminal fluid, and airway surface liquid from -deficient individuals. Computer simulations and deglycosylation assays indicate that the disease-causing founder variant p.Cys49Arg structurally hampers glycosylation and thus secretion of mature WFDC2.
CONCLUSIONS
dysfunction defines a novel molecular etiology of bronchiectasis characterized by the deficiency of a secreted component of the airways. A commercially available blood test combined with genetic testing allows its diagnosis. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
PubMed: 38626355
DOI: 10.1164/rccm.202308-1370OC -
International Archives of... Apr 2024Despite the high level of patient satisfaction with functional endoscopic sinus surgery (FESS) and the clinical improvement, polyp recurrence is observed in 23% to...
Despite the high level of patient satisfaction with functional endoscopic sinus surgery (FESS) and the clinical improvement, polyp recurrence is observed in 23% to 87% of patients and requires reoperation. To assess the prognostic value of polypoid changes of the middle turbinate (PCMT) in relapse of paranasal sinus polyps in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) after FESS and the effect of partial middle turbinectomy (PMT) on the outcome of surgery. We conducted a prospective clinical study on 60 patients with CRSwNP with and without PCMT. The patients were allocated into three groups: group I included twenty patients without PCMT; group II, twenty patients with PCMT; and group III included twenty patients with PCMT submitted to PMT. The patients were evaluated endoscopically according to the Lund-Kennedy endoscopic scoring system, radiologically according to the Lund-Mackay scoring system, and symptomatically through the 22-item Sinonasal Outcome Test (SNOT-22). The total postoperative Lund-Kennedy score differed significantly among the 3 groups ( < 0.001), with a group II presenting a significantly higher total score compared to groups I and III. The Preoperative SNOT-22 score differed significantly among the three groups ( = 0.013), with group II presenting a significantly higher score compared to group I. There was a significant association involving the 3 groups and relapse at 12 months ( = 0.029); relapse was higher in group II (50.0%) than in groups I (20%) and III (15.0%). There was a significant association between PCMT and the relapse of nasal polyps. Also, nasal polyposis recurred at a lower rate in the group submitted to middle turbinate resection compared to the group in whom it was preserved.
PubMed: 38618592
DOI: 10.1055/s-0043-1776730 -
Clinical Endoscopy May 2024Cronkhite-Canada syndrome is a rare gastrointestinal polyposis syndrome with distinctive clinical features and endoscopic findings. Diagnosis can be challenging without...
Cronkhite-Canada syndrome is a rare gastrointestinal polyposis syndrome with distinctive clinical features and endoscopic findings. Diagnosis can be challenging without suspicion, and the disease carries high mortality due to complications such as infection, gastrointestinal bleeding, and malignancies. This paper presents two cases of Cronkhite-Canada syndrome occurring after coronavirus disease 2019 (COVID-19) mRNA vaccination. Both cases exhibited typical clinical findings, including hypogeusia, onychodystrophy, alopecia, and weight loss. Typical polyposis in the gastrointestinal tract was confirmed through endoscopies. As symptomatic treatment did not improve the symptoms, corticosteroids were administered, and symptoms and laboratory test results improved immediately. The patients improved upon corticosteroids tapering. These cases illustrate typical presentations of Cronkhite-Canada syndrome and the course of the disease following corticosteroid treatment. Additionally, they suggest the possibility that Cronkhite-Canada syndrome may be triggered by COVID-19 mRNA vaccination.
PubMed: 38605688
DOI: 10.5946/ce.2023.268 -
ACG Case Reports Journal Apr 2024A 70-year-old man presented to the clinic with a 6-month history of dysgeusia, followed by chronic, non-bloody diarrhea and 45 lb unintentional weight loss....
A 70-year-old man presented to the clinic with a 6-month history of dysgeusia, followed by chronic, non-bloody diarrhea and 45 lb unintentional weight loss. Esophagogastroduodenoscopy discovered confluent nodularity in the gastric antrum and examined duodenum, but a normal esophagus. Colonoscopy uncovered patches of polypoid nodular mucosa throughout the entire colon. Biopsies of the nodular mucosa were consistent with hamartomatous polyps while biopsies of the intervening, normal-appearing mucosa demonstrated edema with crypt architectural distortion. Other hereditary polyposis syndromes were excluded with genetic testing, confirming a diagnosis of Cronkhite-Canada syndrome. Adalimumab therapy was initiated with clinical improvement after nonresponse to prednisone.
PubMed: 38586820
DOI: 10.14309/crj.0000000000001331 -
Cureus Mar 2024The MYUTH gene plays a critical role in preserving the integrity of the human genome, with mutations being identified in several different cancer diagnoses. It serves...
The MYUTH gene plays a critical role in preserving the integrity of the human genome, with mutations being identified in several different cancer diagnoses. It serves its purpose by encoding a DNA glycosylase enzyme responsible for preventing oxidative damage through the excision of adenine that is incorrectly paired with guanine or cytosine. Mutations of the MUTYH gene have been most frequently associated with MUTYH-associated polyposis (MAP) and colorectal cancer. Biallelic mutations of the MUTYH gene are implicated in MAP, and carriers of this mutation have an increased lifetime risk of developing colorectal cancer of 43% to 100%, depending on the appropriate screening and surveillance steps taken. This case describes a patient with recurrent basal cell carcinomas (BCC) and subsequent genetic testing that revealed a pathogenic monoallelic mutation of the MUTYH gene, as well as the interventions that were subsequently performed. It highlights a potentially new patient population that would benefit from early screening to assess the risk of developing colorectal cancers as well as BCC.
PubMed: 38586659
DOI: 10.7759/cureus.55677 -
Cureus Apr 2024Desmoid tumors (DTs) are rare, aggressive malignancies developing from clonal fibroblastic proliferation originating from soft tissues. Despite their low metastatic...
Desmoid tumors (DTs) are rare, aggressive malignancies developing from clonal fibroblastic proliferation originating from soft tissues. Despite their low metastatic potential, their invasiveness towards neighboring organs and a high recurrence rate contribute significantly to morbidity and mortality, thereby impacting the quality of life of patients. Several therapeutic options are available, but standardized protocols are lacking. In this study, we reviewed 14 cases of DT retrospectively over a period of 15 years, from September 2008 to December 2023. The most prevalent tumor locations were in the extremities, and the majority of patients were female. We identified risk factors in two patients, those being surgical trauma and familial adenomatous polyposis (FAP). Half of the patients underwent surgery for DT, and two received salvage radiotherapy. Systemic therapy was used in the first and second lines and comprised of chemotherapy, endocrine therapy, and non-steroidal anti-inflammatory drugs (NSAI). Active surveillance was proposed in three patients. This is the first retrospective study to assess the characteristics of DT in Moroccan patients in a tertiary care setting. It aims to shed light on the challenges faced in treating these rare tumors in the context of a lack of therapeutic standardization.
PubMed: 38586227
DOI: 10.7759/cureus.57768 -
Clinical Case Reports Apr 2024Gardner's syndrome with the complete manifestation of colonic and extracolonic features is uncommon. Therefore, every clinician should view extracolonic features with a...
Gardner's syndrome with the complete manifestation of colonic and extracolonic features is uncommon. Therefore, every clinician should view extracolonic features with a high index of suspicion. This may be key to early diagnosis, definitive management in these patients and importantly, helps prevent malignant transformation of existing colonic polyps.
PubMed: 38576527
DOI: 10.1002/ccr3.8735 -
Journal of Medical Genetics Apr 2024Both hereditary haemorrhagic telangiectasia (HHT) and juvenile polyposis syndrome (JPS) are known to be caused by pathogenic variants, with overlapping symptoms for...
BACKGROUND
Both hereditary haemorrhagic telangiectasia (HHT) and juvenile polyposis syndrome (JPS) are known to be caused by pathogenic variants, with overlapping symptoms for both disorders in some patients. Additional connective tissue disorders have also been reported. Here, we describe carriers of variants followed in an HHT reference centre to further delineate the phenotype.
METHODS
Observational study based on data collected from the Clinical Investigation for the Rendu-Osler Cohort database.
RESULTS
Thirty-three participants from 15 families, out of 1114 patients with HHT, had an variant (3%).Regarding HHT, 26 out of 33 participants (88%) had a definite clinical diagnosis based on Curaçao criteria. Complication frequencies were as follows: epistaxis (n=27/33, 82%), cutaneous telangiectases (n=19/33, 58%), pulmonary arteriovenous malformations (n=17/32, 53%), hepatic arteriovenous malformations (AVMs) (n=7/18, 39%), digestive angiodysplasia (n=13/22, 59%). No cerebral AVMs were diagnosed.Regarding juvenile polyposis, 25 out of 31 participants (81%) met the criteria defined by Jass for juvenile polyposis syndrome. Seven patients (21%) had a prophylactic gastrectomy due to an extensive gastric polyposis incompatible with endoscopic follow-up, and four patients (13%) developed a digestive cancer.Regarding connective tissue disorders, 20 (61%) had at least one symptom, and 4 (15%) participants who underwent echocardiography had an aortic dilation.
CONCLUSION
We describe a large cohort of variant carriers in the context of HHT. Digestive complications are frequent, early and diffuse, justifying endoscopy every 2 years. The HHT phenotype, associating pulmonary and hepatic AVMs, warrants systematic screening. Connective tissue disorders broaden the phenotype associated with gene variants and justify systematic cardiac ultrasound and skeletal complications screening.
PubMed: 38575304
DOI: 10.1136/jmg-2023-109632 -
Polish Archives of Internal Medicine May 2024
Topics: Humans; Adenomatous Polyposis Coli; Proctocolectomy, Restorative; Colonic Pouches; Adenocarcinoma; Male; Female; Adult; Ileal Neoplasms
PubMed: 38573197
DOI: 10.20452/pamw.16722