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1.
J Rheumatol ; 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38879192

ABSTRACT

OBJECTIVE: Psoricatic disease remains underdiagnosed and undertreated. We developed and validated a suite of novel, smartphone sensor-based assessments that can be self-administered to measure cutaneous and musculoskeletal signs and symptoms of psoriatic disease. METHODS: Participants with psoriasis, psoriatic arthritis, or healthy controls were recruited between June 5, 2019, and November 10, 2021, at two academic medical centers. Concordance and accuracy of digital measures and image-based machine learning models were compared to their analogous clinical measures from trained rheumatologists and dermatologists. RESULTS: Of 104 study participants, 51 (49%) were female and 53 (51%) were male, with a mean age of 42.3 years (SD: 12.6). Seventy-nine (76%) participants had psoriatic arthritis, 16 (15.4%) had psoriasis and 9 (8.7%) were healthy controls. Digital patient assessment of percent body surface area (BSA) affected with psoriasis demonstrated very strong concordance (CCC = 0.94, [95%CI = 0.91-0.96]) with physician-assessed BSA. The in-clinic and remote target-lesion Physician Global Assessments showed fair to moderate concordance (CCCerythema=0.72 [0.59-0.85]; CCCinduration=0.72 [0.62-0.82]; CCCscaling=0.60 [0.48-0.72]). Machine learning models of hand photos taken by patients accurately identified clinically-diagnosed nail psoriasis with an accuracy of 0.76. The Digital Jar Open assessment categorized physician-assessed upper extremity involvement, considering joint tenderness or enthesitis (AUROC = 0.68 (0.47-0.85)). CONCLUSION: The Psorcast digital assessments achieved significant clinical validity, although they require further validation in larger cohorts before use in evidence-based medicine or clinical trial settings. The smartphone software and analysis pipelines from the Psorcast suite are open source and freely available.

2.
Clin Exp Dermatol ; 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38733332

ABSTRACT

BACKGROUND: Early identification, diagnosis and symptom control of psoriatic arthritis (PsA) in patients with psoriasis remain unmet medical needs. OBJECTIVES: To compare the impact of disease and other characteristics between patients with psoriasis who screened positive for PsA using the Psoriasis Epidemiology Screening Tool (PEST) (screen-positive group) and patients who (i) have PsA (PsA group) or (ii) screened negative for PsA (screen-negative group). Also, to determine the proportion of patients at a patient-acceptable symptom state (PASS) in the screen-positive and PsA groups. METHODS: This was a cross-sectional analysis of the CorEvitas Psoriasis Registry. We included a convenience sample of patients with psoriasis from the screen-positive and PsA groups who completed the Psoriatic Arthritis Impact of Disease-12 (PsAID12), and a comparator screen-negative group who did not complete the PsAID12. We report descriptive summaries of demographics, comorbidities, psoriasis characteristics, patient-reported outcome measures and the proportion of patients at PASS (i.e. PsAID12 ≤ 4). RESULTS: The screen-positive, PsA and screen-negative groups included 369, 70 and 4724 patients, respectively. The screen-positive and PsA groups had a similar impact of disease, demographics, comorbidities and psoriasis characteristics (d < 0.337). Mean PsAID12 scores were 3.1 (SD 2.3) and 3.7 (SD 2.6) in the screen-positive and PsA groups, respectively. Compared with patients who screened negative for PsA, patients who screened positive exhibited higher rates of selected known predictors of PsA such as older age, longer psoriasis duration, nail disease and inverse psoriasis. The proportion of patients at PASS was 56% and 67% for the PsA and screen-positive groups, respectively. CONCLUSIONS: The similar profiles between screen-positive and PsA groups, in comparison with the screen-negative group, support observations of possible underdiagnosis of PsA and the increased impact of disease, especially musculoskeletal disease, among patients who screen positive for PsA. The high percentage of patients not at an acceptable symptom state in the PsA and screen-positive groups highlights the need to optimize care in PsA.

3.
J Drugs Dermatol ; 23(4): e118-e119, 2024 04 01.
Article in English | MEDLINE | ID: mdl-38564398

ABSTRACT

Interleukin (IL)-4-targeted therapies have revolutionized management of inflammatory dermatoses.


Subject(s)
Biological Products , Neoplasms , Psoriasis , Humans , Interleukin-4 , Neoplasms/drug therapy , Psoriasis/therapy , Biological Therapy
4.
Oncologist ; 29(5): e665-e671, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38297990

ABSTRACT

BACKGROUND: Multigene panel testing is an important component of cancer treatment plans and risk assessment, but there are many different panel options and choosing the most appropriate panel can be challenging for health care providers and patients. Electronic tools have been proposed to help patients make informed decisions about which gene panel to choose by considering their preferences and priorities. MATERIALS AND METHODS: An electronic decision aid (DA) tool was developed in line with the International Patient Decision Aids Standards collaboration. The multidisciplinary project team collaborated with an external health care communications agency and the MGH Cancer Center Patient and Family Advisory Council (PFAC) to develop the DA. Surveys of genetic counselors and patients were used to scope the content, and alpha testing was used to refine the design and content. RESULTS: Surveys of genetic counselors (n = 12) and patients (n = 228) identified common themes in discussing panel size and strategies for helping patients decide between panels and in identifying confusing terms for patients and distribution of patients' choices. The DA, organized into 2 major sections, provides educational text, graphics, and videos to guide patients through the decision-making process. Alpha testing feedback from the PFAC (n = 4), genetic counselors (n = 3) and a group of lay people (n = 8) identified areas to improve navigation, simplify wording, and improve layout. CONCLUSION: The DA developed in this study has the potential to facilitate informed decision-making by patients regarding cancer genetic testing. The distinctive feature of this DA is that it addresses the specific question of which multigene panel may be most suitable for the patient. Its acceptability and effectiveness will be evaluated in future studies.


Subject(s)
Decision Support Techniques , Genetic Counseling , Genetic Testing , Ovarian Neoplasms , Humans , Female , Genetic Testing/methods , Ovarian Neoplasms/genetics , Ovarian Neoplasms/diagnosis , Genetic Counseling/methods , Decision Making , Middle Aged , Adult
5.
J Drugs Dermatol ; 23(2): e60-e63, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38306123

ABSTRACT

Tumor necrosis factor-alpha inhibitors (TNF-i) are commonly used to treat immune-mediated diseases such as psoriasis, psoriatic arthritis (PsA), inflammatory bowel disease (IBD), spondyloarthritis (SpA) and rheumatoid arthritis (RA). However, paradoxical psoriasis induced by TNF-i has been described and is not uncommon, particularly with infliximab and etanercept. The presentation of TNF-i-induced psoriasis is most commonly plaque or palmoplantar morphology. Optimal treatment strategies for recalcitrant psoriatic disease are not well understood. In this case series, we report three patients with TNF-i-induced psoriasis who were treated with upadacitinib and experienced complete resolution of their psoriatic eruptions. The efficacy of Janus kinase inhibitors (JAK-i) is possibly explained by mechanisms involving uncontrolled production of type 1 IFNs as well as increases in IL-23 and T-helper 17 cells upstream of relevant JAK/STAT pathways. We also offer a proposed treatment algorithm that includes the use of JAK-i as a promising management option in patients with recalcitrant disease. However, larger studies are needed to confirm the efficacy and safety of JAK-i in this patient population. J Drugs Dermatol. 2024;23(2): doi:10.36849/JDD.7645.


Subject(s)
Arthritis, Psoriatic , Heterocyclic Compounds, 3-Ring , Psoriasis , Tumor Necrosis Factor Inhibitors , Humans , Antibodies, Monoclonal/therapeutic use , Arthritis, Psoriatic/drug therapy , Psoriasis/chemically induced , Psoriasis/diagnosis , Psoriasis/drug therapy , Tumor Necrosis Factor Inhibitors/adverse effects
6.
J Rheumatol ; 2023 May 01.
Article in English | MEDLINE | ID: mdl-37127321

ABSTRACT

OBJECTIVE: The aim of this systematic review and metaanalysis is to summarize evidence regarding the relationship between psoriatic arthritis (PsA) and sleep problems. METHODS: We identified 36 eligible studies-26 cross-sectional, 7 cohort, and 3 interventional studies-in PubMed and Embase. RESULTS: The prevalence of self-reported sleep problems in patients with PsA ranged from 30% to 85%. A metaanalysis of 6 studies that used the Pittsburgh Sleep Quality Index revealed a prevalence of poor sleep quality for patients with PsA of 72.9% (95% CI 63-81.8; I2 = 78%), which was statistically higher than in healthy controls (26.9%, 95% CI 11.7-45.4; I2 = 81%) but not significantly different than in patients with psoriasis (59.8%, 95% CI 46.9-72.1; I2 = 51%). Sleep disturbance was ranked in the top 4 health-related quality of life domains affected by PsA. One study suggested a bidirectional relationship between PsA and obstructive sleep apnea. Predictors of sleep problems included anxiety, pain, erythrocyte sedimentation rate, depression, fatigue, physical function, and tender or swollen joint count. Tumor necrosis factor inhibitors, guselkumab, and filgotinib (a Janus kinase inhibitor) were associated with improved sleep outcomes. CONCLUSION: Poor sleep quality is prevalent in patients with PsA. Objective sleep measures (ie, actigraphy and polysomnography) have not been used in PsA studies, and evidence on the validity of patient-reported sleep measures in PsA is lacking. Future studies should validate self-reported sleep measures in PsA, explore how sleep quality relates to PsA disease activity and symptoms using both objective and subjective sleep measures, assess the efficacy of strategies to manage sleep problems, and assess the effects of such management on symptoms and disease signs in patients with PsA.

7.
J Clin Med ; 11(22)2022 Nov 18.
Article in English | MEDLINE | ID: mdl-36431294

ABSTRACT

Acute kidney injury is one of the most frequent and prognostically relevant complications in cardiogenic shock. The purpose of this study was to evaluate the potential effect of the Impella® pump on hemodynamics and renal organ perfusion in patients with myocardial infarction complicating cardiogenic shock. Between January 2020 and February 2022 patients with infarct-related cardiogenic shock supported with the Impella® pump were included in this single-center prospective short-term study. Changes in hemodynamics on different levels of Impella® support were documented with invasive pulmonal arterial catheter. As far as renal function is concerned, renal perfusion was assessed by determining the renal resistive index (RRI) using Doppler sonography. A total of 50 patients were included in the analysis. The increase in the Impella® output by a mean of 1.0 L/min improved the cardiac index (2.7 ± 0.86 to 3.3 ± 1.1 p < 0.001) and increased central venous oxygen saturation (62.6 ± 11.8% to 67.4 ± 10.5% p < 0.001). On the other side, the systemic vascular resistance (1035 ± 514 N·s/m5 to 902 ± 371 N·s/m5p = 0.012) and the RRI were significantly reduced (0.736 ± 0.07 to 0.62 ± 0.07 p < 0.001). Furthermore, in the overall cohort, a baseline RRI ≥ 0.8 was associated with a higher frequency of renal replacement therapy (71% vs. 39% p = 0.04), whereas the consequent reduction of the RRI below 0.7 during Impella® support improved the glomerular filtration rate (GFR) during hospital stay (15 ± 3 days; 53 ± 16 mL/min to 83 ± 16 mL/min p = 0.04). Impella® support in patients with cardiogenic shock seems to improve hemodynamics and renal organ perfusion. The RRI, a well-known parameter for the early detection of acute kidney injury, can be directly influenced by the Impella® flow rate. Thus, a targeted control of the RRI by the Impella® pump could mediate renal organ protection.

8.
J Drugs Dermatol ; 21(8): 867-874, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35946973

ABSTRACT

BACKGROUND: International Dermatology Outcome Measures (IDEOM) is a non-profit organization founded in 2013. It is composed of researchers and stakeholders who work to develop evidenced-based outcome measures to enhance research and treatment recommendations of dermatologic diseases. SUMMARY: The 2021 IDEOM Virtual Annual Meeting occurred from November 19-20, 2021. Contributions were made by leaders and stakeholders from the psoriasis, psoriatic arthritis, pediatric hidradenitis suppurativa, acne, vitiligo, actinic keratosis, alopecia areata, itch, and cutaneous lymphoma workgroups. The psoriasis, psoriatic arthritis, and actinic keratosis workgroups provided an overview of their respective instruments for treatment satisfaction and symptom measurement. The inaugural meetings of the itch, alopecia areata, and cutaneous lymphoma workgroups identified unmet needs of their respective diseases and future goals. The acne, vitiligo, and pediatric hidradenitis suppurativa workgroups discussed concerns of quality of life, instruments for symptom measurement, and screening tools. Additionally, a representative from the US Food and Drug Administration was in attendance and presented an update on topical drugs and generics. This report provides a summary of workgroup updates from the past year and future directions established during the meeting. KEY MESSAGES: This report summarizes progress made by each IDEOM workgroup at the 2021 IDEOM Virtual Annual Meeting. J Drugs Dermatol. 2022;21(8):867-874. doi:10.36849/JDD.6974.


Subject(s)
Acne Vulgaris , Alopecia Areata , Arthritis, Psoriatic , Dermatology , Hidradenitis Suppurativa , Keratosis, Actinic , Psoriasis , Vitiligo , Arthritis, Psoriatic/diagnosis , Child , Humans , Outcome Assessment, Health Care , Psoriasis/drug therapy , Quality of Life
9.
Nature ; 606(7912): 160-164, 2022 06.
Article in English | MEDLINE | ID: mdl-35585231

ABSTRACT

Cellular iron homeostasis is vital and maintained through tight regulation of iron import, efflux, storage and detoxification1-3. The most common modes of iron storage use proteinaceous compartments, such as ferritins and related proteins4,5. Although lipid-bounded iron compartments have also been described, the basis for their formation and function remains unknown6,7. Here we focus on one such compartment, herein named the 'ferrosome', that was previously observed in the anaerobic bacterium Desulfovibrio magneticus6. Using a proteomic approach, we identify three ferrosome-associated (Fez) proteins that are responsible for forming ferrosomes in D. magneticus. Fez proteins are encoded in a putative operon and include FezB, a P1B-6-ATPase found in phylogenetically and metabolically diverse species of bacteria and archaea. We show that two other bacterial species, Rhodopseudomonas palustris and Shewanella putrefaciens, make ferrosomes through the action of their six-gene fez operon. Additionally, we find that fez operons are sufficient for ferrosome formation in foreign hosts. Using S. putrefaciens as a model, we show that ferrosomes probably have a role in the anaerobic adaptation to iron starvation. Overall, this work establishes ferrosomes as a new class of iron storage organelles and sets the stage for studying their formation and structure in diverse microorganisms.


Subject(s)
Ferric Compounds , Gram-Negative Bacteria , Multigene Family , Organelles , Bacterial Proteins/genetics , Desulfovibrio , Gram-Negative Bacteria/cytology , Gram-Negative Bacteria/genetics , Organelles/genetics , Organelles/metabolism , Phylogeny , Proteomics , Rhodopseudomonas , Shewanella putrefaciens
10.
J Genet Couns ; 31(4): 956-964, 2022 08.
Article in English | MEDLINE | ID: mdl-35246915

ABSTRACT

This study explored the experiences of patients with pathogenic or likely pathogenic variants in the moderate penetrance breast cancer genes, ATM and CHEK2. There were 139 eligible female patients who received genetic counseling at the Massachusetts General Hospital Center for Cancer Risk Assessment (MGH CCRA) from 2014 to 2018. They were sent surveys assessing their understanding of the clinical significance of their genetic test results, adherence to medical management recommendations, dissemination of genetic test results to relatives, and informational resource needs. In total, 66 surveys were returned with a response rate of 47.5%. Most participants reported understanding the clinical implications of their genetic test results and adhering to medical management recommendations. Although 20.3% found it upsetting, nearly all participants shared their genetic test results with relatives. When asked about resource needs, 54.5% reported seeking out additional resources. Our ATM/CHEK2 sample appears to have a good understanding of the personal and familial implications of their genetic test results but may benefit from additional resources. It is unclear whether similar results would be found in patients who do not receive genetic counseling from a board-certified genetic counselor, and this should be examined. This study is one of the first to assess the experiences and needs of the moderate risk population.


Subject(s)
Breast Neoplasms , Ataxia Telangiectasia Mutated Proteins/genetics , Breast Neoplasms/epidemiology , Checkpoint Kinase 2/genetics , Female , Genetic Counseling , Genetic Predisposition to Disease , Genetic Testing/methods , Humans , Penetrance
11.
J Pediatr ; 213: 235-240, 2019 10.
Article in English | MEDLINE | ID: mdl-31235381

ABSTRACT

We describe an infant with a phenotype typical of early onset Marfan syndrome whose genetic evaluation, including Sanger sequencing and deletion/duplication testing of FBN1 and exome sequencing, was negative. Ultimately, genome sequencing revealed a deletion missed on prior testing, demonstrating the unique utility of genome sequencing for molecular genetic diagnosis.


Subject(s)
Fibrillin-1/genetics , Marfan Syndrome/diagnosis , Marfan Syndrome/genetics , Sequence Analysis, DNA , Exome , Fatal Outcome , Gene Deletion , Gene Dosage , Genetic Variation , Genome, Human , Humans , Infant , Male , Phenotype , Polymerase Chain Reaction
12.
Appl Environ Microbiol ; 84(22)2018 11 15.
Article in English | MEDLINE | ID: mdl-30194101

ABSTRACT

Magnetosomes are complex bacterial organelles that serve as model systems for studying bacterial cell biology, biomineralization, and global iron cycling. Magnetosome biogenesis is primarily studied in two closely related Alphaproteobacteria of the genus Magnetospirillum that form cubooctahedral-shaped magnetite crystals within a lipid membrane. However, chemically and structurally distinct magnetic particles have been found in physiologically and phylogenetically diverse bacteria. Due to a lack of molecular genetic tools, the mechanistic diversity of magnetosome formation remains poorly understood. Desulfovibrio magneticus RS-1 is an anaerobic sulfate-reducing deltaproteobacterium that forms bullet-shaped magnetite crystals. A recent forward genetic screen identified 10 genes in the conserved magnetosome gene island of D. magneticus that are essential for its magnetic phenotype. However, this screen likely missed mutants with defects in crystal size, shape, and arrangement. Reverse genetics to target the remaining putative magnetosome genes using standard genetic methods of suicide vector integration have not been feasible due to the low transconjugation efficiency. Here, we present a reverse genetic method for targeted mutagenesis in D. magneticus using a replicative plasmid. To test this method, we generated a mutant resistant to 5-fluorouracil by making a markerless deletion of the upp gene that encodes uracil phosphoribosyltransferase. We also used this method for targeted marker exchange mutagenesis by replacing kupM, a gene identified in our previous screen as a magnetosome formation factor, with a streptomycin resistance cassette. Overall, our results show that targeted mutagenesis using a replicative plasmid is effective in D. magneticus and may also be applied to other genetically recalcitrant bacteria.IMPORTANCE Magnetotactic bacteria (MTB) are a group of organisms that form intracellular nanometer-scale magnetic crystals though a complex process involving lipid and protein scaffolds. These magnetic crystals and their lipid membranes, termed magnetosomes, are model systems for studying bacterial cell biology and biomineralization and are potential platforms for biotechnological applications. Due to a lack of genetic tools and unculturable representatives, the mechanisms of magnetosome formation in phylogenetically deeply branching MTB remain unknown. These MTB contain elongated bullet-/tooth-shaped magnetite and greigite crystals that likely form in a manner distinct from that of the cubooctahedral-shaped magnetite crystals of the genetically tractable MTB within the Alphaproteobacteria Here, we present a method for genome editing in Desulfovibrio magneticus RS-1, a cultured representative of the deeply branching MTB of the class Deltaproteobacteria This marks a crucial step in developing D. magneticus as a model for studying diverse mechanisms of magnetic particle formation by MTB.


Subject(s)
Desulfovibrio/genetics , Gene Editing/methods , Genome, Bacterial , Reverse Genetics/methods , Anaerobiosis , Desulfovibrio/metabolism , Magnetosomes/genetics , Magnetosomes/metabolism , Mutagenesis , Plasmids/genetics , Plasmids/metabolism
13.
Annu Rev Cell Dev Biol ; 34: 217-238, 2018 10 06.
Article in English | MEDLINE | ID: mdl-30113887

ABSTRACT

Uncovering the mechanisms that underlie the biogenesis and maintenance of eukaryotic organelles is a vibrant and essential area of biological research. In comparison, little attention has been paid to the process of compartmentalization in bacteria and archaea. This lack of attention is in part due to the common misconception that organelles are a unique evolutionary invention of the "complex" eukaryotic cell and are absent from the "primitive" bacterial and archaeal cells. Comparisons across the tree of life are further complicated by the nebulous criteria used to designate subcellular structures as organelles. Here, with the aid of a unified definition of a membrane-bounded organelle, we present some of the recent findings in the study of lipid-bounded organelles in bacteria and archaea.


Subject(s)
Archaea/genetics , Bacteria/genetics , Cell Compartmentation/genetics , Organelles/genetics , Cell Membrane/chemistry , Cell Membrane/genetics , Lipids/chemistry , Lipids/genetics , Organelles/chemistry
14.
Cancer ; 120(10): 1557-64, 2014 May 15.
Article in English | MEDLINE | ID: mdl-24522996

ABSTRACT

BACKGROUND: Large rearrangements in BRCA1 and BRCA2 occur in a small percentage (< 1%) of patients tested for hereditary breast (BC) and ovarian cancer. It is unclear what factors predict BRACAnalysis Large Rearrangement Test (BART) positivity. METHODS: Data from 6 centers were included in this analysis. Individuals with negative Comprehensive BRACAnalysis tested for BART were included. RESULTS: From 1300 individuals, 42 (3.2%) were BART positivity. Factors positively associated with BART positivity were Myriad score, first-degree relatives with BC, infiltrating BC with ductal carcinoma in situ, younger age at BC diagnosis, estrogen receptor-negative BC for both the first and second BC, and Latin American/Caribbean ethnicity. Presence of unilateral BC was inversely associated with BART positivity. Several analyses were performed on the variables available to find the model that best predicts for BART positivity. The BART predictive model, including first BC, ovarian cancer, primary maternal ancestry being Latin America/Caribbean, number of first-degree relatives with BC of 1 or more versus 0, and family history of prostate and pancreatic cancer, had good predictive ability with an area under the curve of 0.77. CONCLUSIONS: Several factors are significantly associated with BART positivity. Among them we have found that Latin American/Caribbean ancestry, Myriad score, first degree relatives with BC, younger age at BC diagnosis, estrogen receptor-negative status of BC, and infiltrating ductal carcinoma with ductal carcinoma in situ features are significantly associated with BART positivity. A BART predictive model may help in a clinical setting.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/genetics , Carrier Proteins/genetics , Exons/genetics , Gene Deletion , Gene Duplication , Genes, BRCA1 , Genes, BRCA2 , Ovarian Neoplasms/genetics , Adenocarcinoma, Mucinous/genetics , Adult , Black or African American/genetics , Black or African American/statistics & numerical data , Aged , Aged, 80 and over , Area Under Curve , Biomarkers, Tumor/analysis , Breast Neoplasms/ethnology , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/genetics , Carcinoma, Intraductal, Noninfiltrating/genetics , Carcinoma, Lobular/genetics , Caribbean Region/ethnology , Europe/ethnology , Female , Genetic Predisposition to Disease , Hispanic or Latino/genetics , Hispanic or Latino/statistics & numerical data , Humans , Jews/genetics , Jews/statistics & numerical data , Middle Aged , Mutation , Ovarian Neoplasms/ethnology , Predictive Value of Tests , Risk , Transcription Factors , United States , White People/genetics , White People/statistics & numerical data
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