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Annales D'endocrinologie Jun 2024Lipomatoses are benign proliferation of adipose tissue. Lipomas (benign fat tumors) are the most common component of lipomatosis. They may be unique or multiple,...
Lipomatoses are benign proliferation of adipose tissue. Lipomas (benign fat tumors) are the most common component of lipomatosis. They may be unique or multiple, encapsulated or not, subcutaneous or sometimes visceral. In some cases, they form large areas of non-encapsulated fat hypertrophy, with a variable degree of fibrosis. They can develop despite the absence of obesity. They may be familial or acquired. At difference with lipodystrophy syndromes, they are not associated with lipoatrophy areas, except in some rare cases such as type 2 familial partial lipodystrophy syndromes (FPLD2). Their metabolic impact is variable in part depending on associated obesity. They may have functional or aesthetic consequences. Lipomatosis may be isolated, be part of a syndrome, or may be visceral. Isolated lipomatoses include multiple symmetrical lipomatosis (Madelung disease or Launois-Bensaude syndrome), familial multiple lipomatosis, the painful Dercum's disease also called Adiposis Dolorosa or Ander syndrome, mesosomatic lipomatosis also called Roch-Leri lipomatosis, familial angiolipomatosis, lipedema and hibernomas. Syndromic lipomatoses include PIK3CA-related disorders, Cowden/PTEN hamartomas-tumor syndrome, some lipodystrophy syndromes, and mitochondrial diseases, especially MERRF, multiple endocrine neoplasia type 1, neurofibromatosis type 1, Wilson disease, Pai or Haberland syndromes. Finally, visceral lipomatoses have been reported in numerous organs and sites: pancreatic, adrenal, abdominal, epidural, mediastinal, epicardial… The aim of this review is to present the main types of lipomatosis and their physiopathological component, when it is known.
PubMed: 38871514
DOI: 10.1016/j.ando.2024.05.003 -
Cureus May 2024An uncommon congenital hamartomatous disorder called Proteus syndrome is characterized by multifocal tissue expansion originating from all three germinal layers....
An uncommon congenital hamartomatous disorder called Proteus syndrome is characterized by multifocal tissue expansion originating from all three germinal layers. Diagnosis mainly relies on clinical and radiological criteria. Here, we present a case of a 13-year-old female child exhibiting bony, soft tissue, and vascular abnormalities, along with developmental delay. We conclude by highlighting the importance of imaging studies in conjunction with physical examination, which are characterized by general and specific criteria to diagnose this rare condition until a specific gene test becomes available.
PubMed: 38860105
DOI: 10.7759/cureus.60072 -
Indian Dermatology Online Journal 2024International Society for the Study of Vascular Anomalies classification defines Congenital Limb Overgrowth Vascular Syndromes (CLOS) as a subset of vascular syndromes...
International Society for the Study of Vascular Anomalies classification defines Congenital Limb Overgrowth Vascular Syndromes (CLOS) as a subset of vascular syndromes with other abnormalities that present with unilateral limb overgrowth. It includes Klippel-Trenaunay Syndrome, Parkes-Weber Syndrome, CLOVES (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Spinal/Skeletal Anomalies/Scoliosis) Syndrome, Proteus Syndrome, PTEN Hamartomatous Syndrome, and Fibroadipose Vascular Anomaly. Due to their rare and complex nature, a multidisciplinary approach to diagnosis and treatment is required. A thorough clinical and radiological workup can go miles in reflecting on the patient's outcome. Here we report five cases of CLOS with their detailed dermato-radiological profiles.
PubMed: 38845672
DOI: 10.4103/idoj.idoj_500_23 -
Frontiers in Medicine 2024Coronavirus disease 2019 (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has had a dramatic...
INTRODUCTION
Coronavirus disease 2019 (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has had a dramatic effect on the world, resulting in millions of deaths worldwide and causing drastic changes in daily life. A study reported that septic complications were associated with high mortality in COVID-19 patients. This study aimed to evaluate how the COVID-19 pandemic changed the pre-pandemic and post-pandemic prevalence of sepsis in ICUs and to evaluate the different risk factors associated with mortality and the different diffusion of microorganisms and their resistance.
MATERIALS AND METHODS
We conducted a single-center retrospective observational clinical study, observing all patients in the ICU of the SS Annunziata Hospital in Chieti (Italy) who were diagnosed with sepsis and had a bacterial isolate from their blood culture. Sepsis was diagnosed by SEPSIIS III criteria. We enrolled all in-patients in the ICU from January 2018 to December 2021. We divided the patients into three groups: (1) non-pandemic period (Np) hospitalized in 2018-2019, (2) pandemic period (Pp)-COVID hospitalized in 2020-2021 with a diagnosis of COVID-19, and (3) Pp-non-COVID patients hospitalized in 2020-2021 without a diagnosis of COVID-19.
RESULTS
From January 2018 to December 2021, 1,559 patients were admitted to the ICU, of which 211 patients [36 (17.1%) in 2018, 52 (24.6%) in 2019, 73 (34.6%) in 2020, and 50 (23.7%) in 2021, respectively] met the selection criteria: 88 patients in period Np, 67 patients in Pp without COVID-19, and 56 patients Pp with COVID-19. The overall mortality of these patients was high (65.9% at 30 days in Np), but decreased during the Pp (60.9%): Pp-non-COVID was 56.7% vs. Pp-COVID 66.1%, with a statistically significant association with APACHE III score (OR 1.08, 95%CI 1.04-1.12, < 0.001), SOFA score (OR 1.12, 95%CI 1.03-1.22, = 0.004), and age (OR 1.04, 95%CI 1.02-1.07, < 0.0001). Between the Np vs. Pp periods, we observed an increase in a few Gram-positive bacteria such as (1 pt. -0.9% vs. 14 pt. -7.65%- = 0.008), , spp., and , as well as a decrease in a case of blood culture positive for , , In Gram-negative bacteria, we observed an increase in cases of spp. (Np 6 pt. -5.1%- vs. Pp 20 pt. -10.9%, = 0.082), and spp., while cases of sepsis decreased from (Np 11 pt. -9.4%- vs. Pp 7 pt. -3.8%, = 0.047), and spp., , spp., and have not changed. Finally, we found that resistance to OXA-48 ( = 0.040), ESBL ( = 0.002), carbapenems ( = 0.050), and colistin ( = 0.003) decreased with time from Np to Pp, particularly in Pp-COVID.
CONCLUSION
This study demonstrated how the COVID-19 pandemic changed the prevalence of sepsis in the ICU. It emerged that the risk factors associated with mortality were APACHE and SOFA scores, age, and, above all, the presence of ESBL-producing bacteria. Despite this, during the pandemic phase, we have observed a significant reduction in the emergence of resistant germs compared to the pre-pandemic phase.
PubMed: 38813381
DOI: 10.3389/fmed.2024.1355144 -
Medicina (Kaunas, Lithuania) May 2024PTEN Hamartoma Tumour Syndrome (PHTS) encompasses diverse clinical phenotypes, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome... (Review)
Review
PTEN Hamartoma Tumour Syndrome (PHTS) encompasses diverse clinical phenotypes, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-like syndrome. This autosomal dominant genetic predisposition with high penetrance arises from heterozygous germline variants in the PTEN tumour suppressor gene, leading to dysregulation of the PI3K/AKT/mTOR signalling pathway, which promotes the overgrowth of multiple and heterogenous tissue types. Clinical presentations of CS range from benign and malignant disorders, affecting nearly every system within the human body. CS is the most diagnosed syndrome among the PHTS group, notwithstanding its weak incidence (1:200,000), for which it is considered rare, and its precise incidence remains unknown among other important factors. The literature is notably inconsistent in reporting the frequencies and occurrences of these disorders, adding an element of bias and uncertainty when looking back at the available research. In this review, we aimed to highlight the significant disparities found in various studies concerning CS and to review the clinical manifestations encountered in CS patients. Furthermore, we intended to emphasize the great significance of early diagnosis as patients will benefit from a longer lifespan while being unceasingly advised and supported by a multidisciplinary team.
Topics: Female; Humans; Hamartoma Syndrome, Multiple; Proteus Syndrome; PTEN Phosphohydrolase; Male
PubMed: 38792950
DOI: 10.3390/medicina60050767 -
Frontiers in Neurology 2024Mutations of the phosphatase and tensin homolog (PTEN) gene have been associated with a spectrum of disorders called PTEN hamartoma tumor syndrome, which predisposes the...
INTRODUCTION
Mutations of the phosphatase and tensin homolog (PTEN) gene have been associated with a spectrum of disorders called PTEN hamartoma tumor syndrome, which predisposes the individual to develop various types of tumors and vascular anomalies. Its phenotypic spectrum includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome, autism spectrum disorders (ASD), some sporadic cancers, Lhermitte-Duclos disease (LDD), and various types of associated vascular anomalies.
CLINICAL PRESENTATION
A previously healthy 27-year-old woman was experiencing visual scintillating scotomas and mild chronic headaches for the past 2 years. The initial computed tomographic (CT) and magnetic resonance imaging (MRI) scans did not reveal any abnormalities, but the possibility of pseudotumor cerebri was considered. Furthermore, a cerebral angiogram showed a posterior fossa dural arteriovenous fistula (dAVF), which was initially treated through embolization. However, in spite of proper treatment, this patient experienced multiple recurrent dAVFs in different locations, requiring multiple embolizations and surgeries. Despite exhibiting altered cerebral perfusion and hemodynamics, the patient did not display any significant symptoms until she experienced a sudden stroke resulting from deep venous thrombosis, which was not associated with any medical procedures or medication use. A comprehensive analysis was performed due to the aggressive nature of the dAVFs. Surprisingly, exome sequencing of a blood sample revealed a PTEN gene variant in chromosome 10, indicative of Cowden syndrome. However, no tumors or other vascular lesions were detected in other systems that would constitute Cowden syndrome.
CONCLUSION
The rapid formation of multiple and complex dAVFs, coupled with not meeting the criteria for any other PTEN-related syndrome, unequivocally leads to the presentation of a novel phenotype of the PTEN germline variant.
PubMed: 38651102
DOI: 10.3389/fneur.2024.1347289 -
BioRxiv : the Preprint Server For... Jan 2024Vascular malformation, a key clinical phenotype of Proteus syndrome, lacks effective models for pathophysiological study and drug development due to limited patient...
Vascular malformation, a key clinical phenotype of Proteus syndrome, lacks effective models for pathophysiological study and drug development due to limited patient sample access. To bridge this gap, we built a human vascular organoid model replicating Proteus syndrome's vasculature. Using CRISPR/Cas9 genome editing and gene overexpression, we created induced pluripotent stem cells (iPSCs) embodying the Proteus syndrome-specific AKT point mutation for organoid generation. Our findings revealed that AKT overactivation in these organoids resulted in smaller sizes yet increased vascular connectivity, although with less stable connections. This could be due to the significant vasculogenesis induced by AKT overactivation. This phenomenon likely stems from boosted vasculogenesis triggered by AKT overactivation, leading to increased vascular sprouting. Additionally, a notable increase in dysfunctional PDGFR+ mural cells, impaired in matrix secretion, was observed in these AKT-overactivated organoids. The application of AKT inhibitors (ARQ092, AZD5363, or GDC0068) reversed the vascular malformations; the inhibitors' effectiveness was directly linked to reduced connectivity in the organoids. In summary, our study introduces an innovative in vitro model combining organoid technology and gene editing to explore vascular pathophysiology in Proteus syndrome. This model not only simulates Proteus syndrome vasculature but also holds potential for mimicking vasculatures of other genetically driven diseases. It represents an advance in drug development for rare diseases, historically plagued by slow progress.
PubMed: 38328122
DOI: 10.1101/2024.01.26.577324 -
Orphanet Journal of Rare Diseases Feb 2024Proteus syndrome is an ultra-rare mosaic overgrowth disorder. Individuals with Proteus syndrome can develop emphysematous and cystic changes of the lung that may lead to...
BACKGROUND
Proteus syndrome is an ultra-rare mosaic overgrowth disorder. Individuals with Proteus syndrome can develop emphysematous and cystic changes of the lung that may lead to progressive respiratory symptoms and require surgical intervention. This retrospective study seeks to quantify the radiographic features of Proteus syndrome-associated lung disease using computed tomography (CT) of the chest. The first method derives a Cystic Lung Score (CLS) by using a computer-aided diagnostic tool to quantify the fraction of cystic involvement of the lung. The second method yields a Clinician Visual Score (CVS), an observer reported scale of severity based on multiple radiographic features. The aim of this study was to determine if these measurements are associated with clinical symptoms, pulmonary function test (PFT) measurements, and if they may be used to assess progression of pulmonary disease.
RESULTS
One hundred and thirteen imaging studies from 44 individuals with Proteus syndrome were included. Dyspnea and oxygen use were each associated with higher CLS (p = 0.001 and < 0.001, respectively) and higher CVS (p < 0.001 and < 0.001). Decreases in percent predicted FVC, FEV, and DLCO each correlated with increased CLS and CVS. The annual increase of CLS in children, 5.6, was significantly greater than in adults, 1.6. (p = 0.03). The annual increase in CVS in children, 0.4, was similar to adults, 0.2 (p = 0.36).
CONCLUSIONS
Proteus syndrome-associated lung disease is progressive. The rate of cystic progression is increased in children. Increased scores in CLS and CVS were associated with clinical symptoms and decreased pulmonary function. Both methods were able to detect change over time and were associated with clinically meaningful outcomes which may enable their use in interventional studies.
Topics: Adult; Child; Humans; Proteus Syndrome; Retrospective Studies; Lung; Tomography, X-Ray Computed; Lung Diseases
PubMed: 38321508
DOI: 10.1186/s13023-023-03013-9 -
Iranian Journal of Otorhinolaryngology Nov 2023Proteus syndrome (PS) is a rare genetic disorder usually caused by mutations in AKT1 or PTEN genes, characterized by multiple, asymmetric tissue overgrowth with high...
INTRODUCTION
Proteus syndrome (PS) is a rare genetic disorder usually caused by mutations in AKT1 or PTEN genes, characterized by multiple, asymmetric tissue overgrowth with high clinical variability. Sinonasal neuroendocrine carcinomas (SNEC) are exceptionally rare tumors encountered in the ethmoid sinus, nasal cavity, or maxillary sinus.
CASE REPORT
We report a 35-year-old patient with PS, who underwent successful surgical removal of a well-differentiated SNEC obstructing his nasal cavity and highlight the role of the otolaryngologist for safe airway management, minimal surgical intervention and coordination of the multidisciplinary care. Histologically, focally hyperplastic mucosal epithelium of respiratory type of the nasal chamber was noticed along with seromucinous glands and capillary congestion of the subepithelial fibrovascular tissue. The limited presence of neoplastic tissue with histomorphological and immunophenotypic features of a neuroendocrine neoplasm was focally observed. Tumor cells grow in the form of islets within a vascular stroma; these neoplastic cells are immunohistochemically positive for synaptophysin, CD56, EMA, Ki67 (low expression, cell proliferation rate: 2%), CD31, chromogranin and pancytokeratin AE1 / AE3 as well as for S-100 protein (weak intensity).
CONCLUSIONS
This first description of a SNEC in a PS patient, might hint towards a common basis between the two conditions, due to the mosaic AKT1 variant and an activated AKT/PIK3CA/PTEN pathway.
PubMed: 38074478
DOI: 10.22038/IJORL.2023.73128.3472 -
European Review For Medical and... Nov 2023Proteus syndrome (PS) is an extremely rare disorder with ocular manifestations. In this study, we aimed to describe the ophthalmic characteristics and the clinical...
BACKGROUND
Proteus syndrome (PS) is an extremely rare disorder with ocular manifestations. In this study, we aimed to describe the ophthalmic characteristics and the clinical course of an unusual PS patient to acquire a comprehensive and intensive understanding of ocular PS and highlight the importance of collaborative treatment by ophthalmologists.
CASE PRESENTATION
A case of PS with atypical ocular features and syndromes was observed in a Chinese female. Her proptosis and vision impairment were relieved after Endoscope-Navigation system (ENS)-aided optic canal decompression. A 1.5-year follow-up showed that the treatment was temporarily effective, but the disease continued to develop. A review of the literature was conducted: forty-eight patients met the inclusion criteria. Although ocular manifestations play important roles in PS diagnosis, only a limited number of cases have been reported to have ocular abnormalities. And to date, almost none of these reports have described the treatment in detail. Therefore, PS patients with ocular manifestations were reviewed.
CONCLUSIONS
PS is a complex disorder with variable characteristics and progressive imbalances. In this paper, the clinical symptoms, molecular characteristics, and differential diagnosis of PS are introduced. More importantly, the ocular manifestations, treatment, and prognosis of PS cases to date are summarized and discussed. This study aimed to acquire a comprehensive and intensive understanding of ocular PS and to reveal the importance of collaborative treatment by ophthalmologists.
Topics: Humans; Female; Proteus Syndrome; Eye
PubMed: 37975355
DOI: 10.26355/eurrev_202311_34306