-
Archives of Virology May 2024Chinese bayberry is a fruit that is appreciated for its taste. A novel totivirus associated with rolling, disfiguring, chlorotic and vein-clearing symptoms on the leaf...
Chinese bayberry is a fruit that is appreciated for its taste. A novel totivirus associated with rolling, disfiguring, chlorotic and vein-clearing symptoms on the leaf apices of Chinese bayberry was identified by transcriptome sequencing and reverse transcription PCR (RT-PCR). The complete genome of the virus was determined to be 4959 nucleotides long, and it contains two open reading frames (ORFs). Its genomic organization is similar to that of previously reported totiviruses. ORF1 encodes a putative coat protein (CP) of 765 aa, and ORF2 encodes an RNA-dependent RNA polymerase (RdRp) of 815 aa. These two putative proteins share 55.1% and 62.6%, amino acid sequence identity, respectively, with the corresponding proteins of Panax notoginseng virus A, respectively. According to the demarcation criteria for totivirus species established by the International Committee on Taxonomy of Viruses (ICTV), the new virus should be considered a member of a new species in the genus totivirus, family Orthototiviridae, which we have tentatively named ''Myrica rubra-associated totivirus'' (MRaTV).
Topics: Genome, Viral; Open Reading Frames; Phylogeny; Plant Diseases; Plant Leaves; Myrica; Whole Genome Sequencing; Totivirus; Viral Proteins; RNA-Dependent RNA Polymerase; RNA, Viral
PubMed: 38753216
DOI: 10.1007/s00705-024-06048-w -
The Journal of Clinical Endocrinology... May 2024Proptosis in Thyroid Eye Disease (TED) can result in facial disfigurement and visual dysfunction. Treatment with Insulin-like growth factor I receptor (IGF-IR)...
CONTEXT
Proptosis in Thyroid Eye Disease (TED) can result in facial disfigurement and visual dysfunction. Treatment with Insulin-like growth factor I receptor (IGF-IR) inhibitors has been shown to be effective in reducing proptosis but with side effects.
OBJECTIVE
To test the hypothesis that inhibition of IGF-IR indirectly and more selectively with PAPP-A inhibitors attenuates IGF-IR signaling in TED.
DESIGN
Informed consent was obtained from TED patients undergoing surgery, and retro-orbital tissue collected for fibroblast isolation and culture.
SETTING
Surgeries were performed in Mayo Clinic operating suites. Cell culture was performed in a sterile tissue culture facility.
PATIENT SAMPLES
Retro-orbital tissue was collected from 19 TED patients.
INTERVENTIONS
Treatment of TED fibroblasts with pro-inflammatory cytokines. Flow separation of CD34- and CD34+ orbital fibroblasts, the latter representing infiltrating fibrocytes into the orbit in TED.
MAIN OUTCOME MEASURES
PAPP-A expression and proteolytic activity, IGF-I stimulation of phosphatidylinositol 3 kinase/Akt pathway and inhibition by immuno-neutralizing antibodies against PAPP-A, CD34+ status and associated PAPP-A and IGF-IR expression.
RESULTS
Pro-inflammatory cytokines markedly increased PAPP-A expression in TED fibroblasts. IGF-IR expression was not affected by cytokine treatment. Inhibition of PAPP-A's proteolytic activity suppressed IGF-IR activation in orbital fibroblasts from TED patients. TED fibroblasts that were CD34+ represented ∼80% of the cells in culture and accounted for ∼70% of PAPP-A and IGF-IR expressing cells.
CONCLUSIONS
These results support a role for PAPP-A in TED pathogenesis and indicate the potential for novel therapeutic targeting of the IGF axis.
PubMed: 38752390
DOI: 10.1210/clinem/dgae339 -
World Journal of Oncology Jun 2024Desmoid fibromatosis of the breast (also known as desmoid tumor of the breast) is a rare entity infrequently encountered by oncologists and surgeons caring for patients... (Review)
Review
Desmoid fibromatosis of the breast (also known as desmoid tumor of the breast) is a rare entity infrequently encountered by oncologists and surgeons caring for patients with breast disease. The current body of literature is highly reliant on case series and extrapolations from other sites of desmoid tumor-related disease. Much remains unclear regarding the pathological origins, natural history, and response to treatment of this condition. Traditional treatment strategies have centered on surgical resection, which may result in significantly disfiguring cosmetic and functional outcomes, frequent need for re-operation, and associated morbidity. There are limited data to support the superiority of upfront surgical resection when compared to medical therapy or watchful waiting strategies. Current treatment guidelines for desmoid tumors do not focus on the breast as a site of disease and are purposefully ambiguous due to the paucity of evidence available. We aim to review the literature concerning desmoid fibromatosis of the breast and propose an algorithm for current evidence-based management of this rare disease in the context of our experience with this pathology at a high-volume quaternary referral center.
PubMed: 38751692
DOI: 10.14740/wjon1844 -
Supportive Care in Cancer : Official... May 2024Cutaneous adverse reactions to epidermal growth factor receptor inhibitors (EGFRi) are some of the most common side effects that patients experience. However, cutaneous...
INTRODUCTION
Cutaneous adverse reactions to epidermal growth factor receptor inhibitors (EGFRi) are some of the most common side effects that patients experience. However, cutaneous adverse reactions that cause dyspigmentation in patients have been rarely reported. Erythema dyschromicum perstans (EDP) is a rare pigmentary condition that causes ashy-grey hyperpigmented macules and patches, with a few cases reported from EGFRi in the literature. The disfiguration caused by this condition may negatively impact patients' quality of life. Our study aimed to describe the clinical characteristics of EDP induced by EGFRi to better recognize and manage the condition.
METHODS
We conducted a multicenter retrospective review at three academic institutions to identify patients with EDP induced by EGFRi from 2017 to 2023 and included sixteen patients in our study.
RESULTS
The median age of patients was 66 years old, with 63% female and 37% male (Table 1). The majority of our patients were Asian (88%). All patients had non-small cell lung cancer and most patients received osimertinib. Median time to EDP was 6 months. The most common areas of distribution were the head/neck region, lower extremities, and upper extremities. Various topical ointments were trialed; however, approximately less than half had improvement in their disease and most patients had persistent EDP with no resolution. All patients desired treatment except one with EDP on the tongue, and there was no cancer treatment discontinuation or interruption due to EDP. Table 1 Patient demographics and clinical characteristics of 16 patients with EDP induced by EGFRi Case no Demographics: age, race, and sex Fitzpatrick skin type Cancer type EGFR therapy Concomitant photosensitive drug(s) Time to EDP (months) Clinical features Distribution Symptoms Treatments and clinical course EDP status from most recent follow up 1 47 y/o Asian male III Stage IV NSCLC Erlotinib None Unknown Brown-blue-gray hyperpigmented patches Bilateral shins Left thigh Xerosis Pruritus Triamcinolone 0.1% ointment for 4 months, improvement of blue discoloration Tacrolimus 0.1% BID for 9 months, improvement but no resolution Ongoing 2 62 y/o Asian female IV Stage IV NSCLC Osimertinib None 4 Gray-brown hyperpigmented patches Bilateral arms Back Forehead Neck Right shin None Tacrolimus 0.1% ointment for 1 year with minor improvement Ongoing 3 69 y/o Asian female IV Stage IV NSCLC Osimertinib None 4 Gray-brown macules and patches Chest Face Forehead Bilateral legs None Tacrolimus 0.1% ointment for 10 months, no improvement Ongoing 4 79 y/o White male II Stage IV NSCLC Osimertinib None 15 Mottled grey-blue hyperpigmented patches and plaques with mild scaling Bilateral arms Back Forehead Neck None Photoprotection, no improvement Ongoing 5 69 y/o Asian female III Stage IV NSCLC Osimertinib Ibuprofen 4 Blue-grey hyperpigmented macules and patches Abdomen Bilateral arms None Tacrolimus 0.1% ointment for 7 months, no improvement Ongoing 6 65 y/o Asian male III Stage IV NSCLC Osimertinib None 20 Hyperpigmented blue gray macules and patches Helix Bilateral shins None Photoprotection, no improvement Ongoing 7 66 y/o Asian female IV Stage IV NSCLC Erlotinib TMP-SMX 6 Ashy grey-brown thin plaques Back Forehead None 2.5% hydrocortisone ointment for 8 months, resolved Resolved 8 82 y/o Asian male III Stage III NSCLC Erlotinib Simvastatin 20 Ash-grey hyperpigmented patches Dorsal feet Forehead Scalp None Photoprotection Ongoing 9 57 y/o Asian female III Stage II NSCLC Erlotinib None 1 Bue-grey discoloration Tongue None No intervention Ongoing 10 51 y/o Asian female III Stage IV NSCLC Osimertinib None 9 Blue-grey hyperpigmented macules and patches Bilateral arms Axillae Groin Neck Trunk None 2.5% hydrocortisone ointment, triamcinolone 0.1% ointment, photoprotection with mild improvement Ongoing 11 67 y/o Asian male III Stage IV NSCLC Osimertinib None 7 Gray-blue macules and patches with mild background erythema and scaling Bilateral arms Ears Face Bilateral shins None Triamcinolone 0.1% ointment, protection for 6 months with mild improvement Ongoing 12 75 y/o Asian female IV Stage III NSCLC Osimertinib TMP-SMX 3 Gray-blue hyperpigmented patches Bilateral arms Abdomen Back Face Bilateral shins Pruritus Triamcinolone 0.1% and betamethasone 0.01% with relief of pruritus, lesions unchanged Triluma cream 6 months, mild improvement Ongoing 13 42 y/o Asian male IV Stage IV NSCLC Afatinib TMP-SMX 24 Grey-brown hyperpigmented patches Back Face None Hydroquinone 4% cream for 2 years with mild improvement Ongoing 14 74 y/o White female III Stage II NSCLC Osimertinib Atorvastatin 4 Grey-brown hyperpigmented patches Bilateral legs Trunk None Photoprotection Ongoing 15 64 y/o Asian female IV Stage IV NSCLC Osimertinib None 3 Gray-brown hyperpigmentation Abdomen Bilateral arms Back Bilateral legs Pruritus Triamcinolone 0.1% cream; No change, minimal concern to patient Ongoing 16 52 y/o Asian female IV Stage IV NSCLC Osimertinib None 42 Gray hyperpigmented patches with digitate shape Abdomen Bilateral flanks None Triamcinolone 0.1% cream Ongoing NSCLC, non-small cell lung cancer, TMP-SMX, Trimethoprim/Sulfamethoxazole CONCLUSIONS: We highlight the largest case series describing EDP from EGFR inhibitors, which mostly affected Asian patients with lung malignancy and on EGFR tyrosine kinase inhibitors. Clinicians should be able to recognize this condition in their patients and assess how it is affecting their quality of life, and refer to dermatology to help with management.
Topics: Humans; Male; Female; Aged; Retrospective Studies; ErbB Receptors; Lung Neoplasms; Middle Aged; Carcinoma, Non-Small-Cell Lung; Erythema; Acrylamides; Drug Eruptions; Aged, 80 and over; Antineoplastic Agents; Protein Kinase Inhibitors; Quality of Life
PubMed: 38750379
DOI: 10.1007/s00520-024-08551-x -
Cell Reports Methods May 2024Localized cutaneous neurofibromas (cNFs) are benign tumors that arise in the dermis of patients affected by neurofibromatosis type 1 syndrome. cNFs are benign lesions:...
Localized cutaneous neurofibromas (cNFs) are benign tumors that arise in the dermis of patients affected by neurofibromatosis type 1 syndrome. cNFs are benign lesions: they do not undergo malignant transformation or metastasize. Nevertheless, they can cover a significant proportion of the body, with some individuals developing hundreds to thousands of lesions. cNFs can cause pain, itching, and disfigurement resulting in substantial socio-emotional repercussions. Currently, surgery and laser desiccation are the sole treatment options but may result in scarring and potential regrowth from incomplete removal. To identify effective systemic therapies, we introduce an approach to establish and screen cNF organoids. We optimized conditions to support the ex vivo growth of genomically diverse cNFs. Patient-derived cNF organoids closely recapitulate cellular and molecular features of parental tumors as measured by immunohistopathology, methylation, RNA sequencing, and flow cytometry. Our cNF organoid platform enables rapid screening of hundreds of compounds in a patient- and tumor-specific manner.
Topics: Humans; Organoids; Skin Neoplasms; Neurofibroma; Neurofibromatosis 1
PubMed: 38744290
DOI: 10.1016/j.crmeth.2024.100772 -
Current Opinion in Allergy and Clinical... Aug 2024The aim of this review is to provide an account of the focus of therapeutic strategies for hereditary angioedema (HAE), give a brief overview of those used in the past... (Review)
Review
PURPOSE OF REVIEW
The aim of this review is to provide an account of the focus of therapeutic strategies for hereditary angioedema (HAE), give a brief overview of those used in the past and set aside and toughly discuss those currently available as first line. Further research is ongoing and the future therapeutic approaches that are still in different phases of study will be reviewed as well.
RECENT FINDINGS
In the last two decades, major research advancements on HAE pathophysiology and management were made and numerous novel therapeutic options are now available. Compared to the past, drugs available nowadays are more effective, well tolerated, and possibly have a more convenient administration route. Moreover, numerous other drugs with innovative mechanisms of action are under development.
SUMMARY
HAE is a rare genetic disease that if not promptly treated, it can lead to death from asphyxiation. Furthermore, due to its disfiguring and painful manifestations, HAE implies an important burden on the quality of life. Recently, following great research progresses on HAE therapy, evidence-based guidelines on HAE management were released. The therapeutic landscape of HAE is still under florid development, and it is possible novel treatments will remarkably revolutionize HAE management in the future.
Topics: Humans; Angioedemas, Hereditary; Quality of Life; Complement C1 Inhibitor Protein
PubMed: 38743499
DOI: 10.1097/ACI.0000000000000992 -
Diagnostics (Basel, Switzerland) Apr 2024In light of falling global autopsy rates, one of the causes of which is the resulting body disfigurement, it has become crucial to search for new, minimally invasive...
In light of falling global autopsy rates, one of the causes of which is the resulting body disfigurement, it has become crucial to search for new, minimally invasive post-mortem diagnostic tools. One of these methods is videoautopsy, a minimally invasive autopsy technique using endoscopic methods. In the years 2020-2023, 15 videoautopsies were conducted at the Department of Forensic Medicine of the Poznan University of Medical Sciences in order to determine the usefulness of the method in forensic approaches. Each post-mortem examination included laparoscopy and thoracoscopy, followed by a classic autopsy to assess the effectiveness of the method. In total, the endoscopic examination allowed for determining the cause of death in 53.3% of cases, and when the cause of death was located in the abdominal cavity or chest, the percentage increased to 80%. Traumatic lesions had good recognition efficiency. In addition, it was also possible to collect material for histopathological and toxicological tests. Retroperitoneal organs were difficult to assess. The main limitation of the method is the inability to assess the inside of the skull and the structures of the central nervous system. Videoautopsy may become an important tool in post-mortem diagnostics and in forensic cases, especially when the alternative is to not perform an autopsy. Further research is necessary to standardise the examination protocol, optimise the instrumentation, and assess the potential synergistic effect with other methods of minimally and non-invasive post-mortem examination.
PubMed: 38732299
DOI: 10.3390/diagnostics14090884 -
PLoS Neglected Tropical Diseases May 2024Mycetoma is a serious, destructive, disfiguring chronic granulomatous inflammatory disease affecting the subcutaneous tissues that spread to involve the skin, deep...
Mycetoma is a serious, destructive, disfiguring chronic granulomatous inflammatory disease affecting the subcutaneous tissues that spread to involve the skin, deep tissues and bone. The disease predominately affects the limbs, and extrapedal mycetoma is rarely reported. The reported extrapedal ones are characterised by high morbidity and mortality. This communication reports on 420 patients with extrapedal mycetoma seen and managed at the Mycetoma Research Centre (MRC), University of Khartoum, between January 1991 and December 2021. In this descriptive, cross-sectional, hospital-based study, the electronic records of all mycetoma-confirmed patients seen during the study period were carefully and meticulously reviewed. The confirmed patients with extrapedal mycetoma were included in this study. The study included 420 patients with extrapedal mycetoma, 298 (70.7%) had eumycetoma, and 122 (29.3%) had actinomycetoma. There were 343 male patients (81.7%) and 77 (18.3%) females, with a male-to-female ratio of 4:1. Their ages ranged between 1.5 and 95 years, with a median of 28 years. Most of the patients were students and farmers. The majority of patients were from El Gezira, North Kordofan, and the White Nile States. Mycetoma was painful in 21%, and a family history of mycetoma was recorded in 11.5% of patients. The buttocks (37.9%) and head and neck (16.9%) were affected most. Less frequently affected sites were the trunk and back (12%) each, abdominal and chest walls (4.5%) each and loin (1%). The prominent clinical presentation findings were multiple sinuses discharging grains (55%), massive swellings (46%), and lymphadenopathy (11.5%). Less commonly observed clinical findings were local hyperhidrosis (5.3%) and dilated tortuous veins close to mycetoma lesions (0.5%). The study showed that 204 patients (48.6%) had clinical improvement in terms of decreased lesion size and healing of sinuses following medical therapy. Sixty-six patients (15.7%) had no noticeable improvement. The lesion continued progressing despite treatment in 44 patients (10.5%). In the study, 118 patients were on regular follow-up, and in this group, a cure was documented in 25 patients (21.1%) with eumycetoma and 23 (19.4%) with actinomycetoma. Post-operative recurrence among eumycetoma patients was 40%, with a 1% mortality rate. The treatment outcome was unsatisfactory, characterised by a low cure rate, high recurrence (40%) and follow-up dropout (57%) rates. This emphasises the importance of early case detection and management, objective health education programmes and thorough patient counselling to urge people to seek treatment early and reduce dropouts.
Topics: Humans; Mycetoma; Male; Female; Adult; Middle Aged; Adolescent; Child; Young Adult; Cross-Sectional Studies; Child, Preschool; Aged; Infant; Aged, 80 and over; Antifungal Agents
PubMed: 38728359
DOI: 10.1371/journal.pntd.0011841 -
Aging May 2024Thyroid-associated ophthalmopathy (TAO) is the most prevalent orbital disease in adults caused by an autoimmune disorder, which can lead to disfigurement and vision...
Thyroid-associated ophthalmopathy (TAO) is the most prevalent orbital disease in adults caused by an autoimmune disorder, which can lead to disfigurement and vision impairment. Developing effective treatments for this condition presents challenges due to our limited understanding of its underlying immune aberrations. In this study, we profiled the immune components in the peripheral blood of patients with TAO as well as healthy individuals, utilizing single-cell RNA sequencing and B-cell receptor repertoires (BCR) analysis. We observed a significant reduction in the proportions of regulatory B cells (Bregs) and type 2 conventional dendritic cells (DCs) in patients with TAO during the active phase. Conversely, there was a significant increase in the proportion of type 1 DCs. Further analysis of cell differentiation trajectory revealed potential impairment in the transition of B cells towards Breg phenotype during the active phase of TAO. Besides, the activation process of TAO appeared to involve inflammation and immune dysfunction, as indicated by the dynamic changes in the activities of key regulators. The abnormalities in the peripheral immune system, such as the reduced capacity of Bregs to suppress inflammation, were primarily driven by the enhanced interaction among Breg, DCs, and monocytes (i.e., CD22-PTPRC and BTLA-TNFRSF14). Collectively, our findings offer a comprehensive insight into the molecular regulation and cellular reconfiguration during the active phase of TAO at the single-cell level, in order to explore the pathogenesis of TAO and provide new ideas for the future treatment of TAO.
Topics: Humans; Graves Ophthalmopathy; Single-Cell Analysis; Gene Expression Profiling; Female; Middle Aged; Male; Receptors, Antigen, B-Cell; Dendritic Cells; Adult; Transcriptome; B-Lymphocytes, Regulatory
PubMed: 38728262
DOI: 10.18632/aging.205814 -
Special Care in Dentistry : Official... May 2024This study aimed to examine whether surgical treatment for a facial disfigurement influenced an individual's quality of life.
AIMS
This study aimed to examine whether surgical treatment for a facial disfigurement influenced an individual's quality of life.
METHODS AND RESULTS
One-on-one interviews were conducted with the aim of synthesizing participant's medical experiences into common themes. Additionally, participants completed the World Health Organization's Quality of Life Brief Version (WHOQOL-BREF) questionnaire. The WHOQL-BREF is a standardized testing instrument with four domains of 26 questions, meant to analyze participants' overall quality of health, physical health, psychological status, social relationships, and environmental health. Our study revealed that women with visible facial differences experienced a quality of life below the average of the general population. However, in those who reported above-average quality of life, a key theme emerged: active participation in the choice to undergo surgical treatment. Participants who felt this sense of agency in the decision-making process also reported a more positive healthcare experience. They felt more respected by others, indicating a strong connection between personal agency, surgical choices, and overall well-being.
CONCLUSIONS
These findings reveal that personal agency plays an important role in the decision-making process for patients undergoing surgical treatment for facial differences, as it improves quality of life and has a positive impact on overall healthcare experience and well-being.
PubMed: 38715214
DOI: 10.1111/scd.13017