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Communications Medicine May 2024Small extracellular vesicle (sEV) analysis can potentially improve cancer detection and diagnostics. However, this potential has been constrained by insufficient...
BACKGROUND
Small extracellular vesicle (sEV) analysis can potentially improve cancer detection and diagnostics. However, this potential has been constrained by insufficient sensitivity, dynamic range, and the need for complex labeling.
METHODS
In this study, we demonstrate the combination of PANORAMA and fluorescence imaging for single sEV analysis. The co-acquisition of PANORAMA and fluorescence images enables label-free visualization, enumeration, size determination, and enables detection of cargo microRNAs (miRs).
RESULTS
An increased sEV count is observed in human plasma samples from patients with cancer, regardless of cancer type. The cargo miR-21 provides molecular specificity within the same sEV population at the single unit level, which pinpoints the sEVs subset of cancer origin. Using cancer cells-implanted animals, cancer-specific sEVs from 20 µl of plasma can be detected before tumors were palpable. The level plateaus between 5-15 absolute sEV count (ASC) per µl with tumors ≥8 mm. In healthy human individuals (N = 106), the levels are on average 1.5 ASC/µl (+/- 0.95) without miR-21 expression. However, for stage I-III cancer patients (N = 205), nearly all (204 out of 205) have levels exceeding 3.5 ASC/µl with an average of 12.2 ASC/µl (±9.6), and a variable proportion of miR-21 labeling among different tumor types with 100% cancer specificity. Using a threshold of 3.5 ASC/µl to test a separate sample set in a blinded fashion yields accurate classification of healthy individuals from cancer patients.
CONCLUSIONS
Our techniques and findings can impact the understanding of cancer biology and the development of new cancer detection and diagnostic technologies.
PubMed: 38796532
DOI: 10.1038/s43856-024-00514-x -
Journal of Orthopaedic Case Reports May 2024Neonatal compartment syndrome is a rare phenomenon with a limited number of cases reported in the literature with varying etiologies. Current literature categorizes...
INTRODUCTION
Neonatal compartment syndrome is a rare phenomenon with a limited number of cases reported in the literature with varying etiologies. Current literature categorizes etiologies as either intrinsic or extrinsic. To the best of our knowledge, difficult delivery and delivery through vacuum are the only two iatrogenic etiologies that have been reported in the literature. Thus, this may be the first reported case of neonatal compartment syndrome secondary to a failed peripherally inserted central catheter (PICC) insertion.
CASE REPORT
We present a case of a pre-mature neonate with diffuse discoloration, paralysis, and loss of palpable pulses of the right upper extremity after a failed PICC insertion. The clinical features led to a diagnosis of compartment syndrome. Interventions were not carried out due to the pre-maturity and instability of the patient. The patient passed away at 38 days of age due to refractory hypotension and patent ductus arteriosus.
CONCLUSION
We present a case of neonatal compartment syndrome caused by a previously unreported etiology, highlighting the current dearth of knowledge. Clinicians should be aware of the unique clinical presentation of neonatal compartment syndrome and maintain high suspicion even without an obvious etiology.
PubMed: 38784880
DOI: 10.13107/jocr.2024.v14.i05.4458 -
Veterinary Medicine and Science Jul 2024A 14-year-old male tiger developed anorexia with elevated blood urea nitrogen and creatinine levels. The patient had a palpable abdominal mass and demonstrated...
A 14-year-old male tiger developed anorexia with elevated blood urea nitrogen and creatinine levels. The patient had a palpable abdominal mass and demonstrated neutrophilic leukocytosis and anaemia. Leukocytes, yeast and bacteria were present in the urine. The animal was non-responsive to therapy and was subsequently euthanised. Extensive acute renal papillary necrosis (RPN) with pyelonephritis, chronic nephritis and polycystic renal disease were evident during gross and microscopic pathology examinations. The histologic occurrence of fungal spores and pseudohyphae morphologically consistent with Candida species were observed within the necrotic papillary regions of the kidney and within multiple foci of mild parakeratotic hyperkeratosis present in the gingiva and tongue. Candida albicans along with a slight growth of Escherichia coli were recovered from kidney cultures. Possible contributory factors for the renal candidiasis and associated RPN include predisposing oral candidiasis, polycystic renal disease, ischaemic nephrosclerosis, age-associated or other forms of immunodeficiency and therapy with meloxicam, a non-steroidal anti-inflammatory drug. The absence of apparent lower urinary tract involvement coupled with the presence of intravascular renal 'Candida emboli' suggest that chronic oral candidiasis was the probable source of the kidney infection.
Topics: Animals; Male; Tigers; Candidiasis; Kidney Papillary Necrosis; Candida albicans; Animals, Zoo; Kidney Diseases
PubMed: 38779883
DOI: 10.1002/vms3.1421 -
International Journal of... Jan 2024Tuberculosis (TB) remains a significant global health concern and kills millions of people every year. While TB can affect any organ in the body, breast TB is relatively... (Review)
Review
Tuberculosis (TB) remains a significant global health concern and kills millions of people every year. While TB can affect any organ in the body, breast TB is relatively uncommon. This study presents a comprehensive review of literature spanning 23 years, with a focus on cases of breast TB in Iran. Among the 96 cases found, the majority (89.6%) fell within the age range of 20-60, with a striking prevalence among women (98.9%). Common symptoms included pain and palpable mass, each presenting in approximately 60.4% of cases. Notably, only a quarter of patients had a confirmed history of exposure to a known TB case. Left breast involvement was more prevalent (58.3%), with ipsilateral lymph node enlargement observed in 40.6% of cases. Given the clinical presentation of breast TB, which often leads to misdiagnosis, a significant proportion of cases (68.7%) were diagnosed through excisional biopsy. Following a standard 6-month regimen of anti-TB drugs, relapse occurred in only 4.2% of cases. This study highlights the need for heightened awareness and vigilance in diagnosing breast TB, especially in regions with a high burden. Although breast TB poses diagnostic challenges, with prompt identification and treatment, the prognosis is generally favorable, with a low incidence of relapse.
Topics: Humans; Iran; Female; Tuberculosis; Adult; Antitubercular Agents; Prevalence; Breast Diseases; Middle Aged; Young Adult; Male; Breast
PubMed: 38771272
DOI: 10.4103/ijmy.ijmy_32_24 -
JMIR Medical Informatics May 2024A large language model is a type of artificial intelligence (AI) model that opens up great possibilities for health care practice, research, and education, although...
BACKGROUND
A large language model is a type of artificial intelligence (AI) model that opens up great possibilities for health care practice, research, and education, although scholars have emphasized the need to proactively address the issue of unvalidated and inaccurate information regarding its use. One of the best-known large language models is ChatGPT (OpenAI). It is believed to be of great help to medical research, as it facilitates more efficient data set analysis, code generation, and literature review, allowing researchers to focus on experimental design as well as drug discovery and development.
OBJECTIVE
This study aims to explore the potential of ChatGPT as a real-time literature search tool for systematic reviews and clinical decision support systems, to enhance their efficiency and accuracy in health care settings.
METHODS
The search results of a published systematic review by human experts on the treatment of Peyronie disease were selected as a benchmark, and the literature search formula of the study was applied to ChatGPT and Microsoft Bing AI as a comparison to human researchers. Peyronie disease typically presents with discomfort, curvature, or deformity of the penis in association with palpable plaques and erectile dysfunction. To evaluate the quality of individual studies derived from AI answers, we created a structured rating system based on bibliographic information related to the publications. We classified its answers into 4 grades if the title existed: A, B, C, and F. No grade was given for a fake title or no answer.
RESULTS
From ChatGPT, 7 (0.5%) out of 1287 identified studies were directly relevant, whereas Bing AI resulted in 19 (40%) relevant studies out of 48, compared to the human benchmark of 24 studies. In the qualitative evaluation, ChatGPT had 7 grade A, 18 grade B, 167 grade C, and 211 grade F studies, and Bing AI had 19 grade A and 28 grade C studies.
CONCLUSIONS
This is the first study to compare AI and conventional human systematic review methods as a real-time literature collection tool for evidence-based medicine. The results suggest that the use of ChatGPT as a tool for real-time evidence generation is not yet accurate and feasible. Therefore, researchers should be cautious about using such AI. The limitations of this study using the generative pre-trained transformer model are that the search for research topics was not diverse and that it did not prevent the hallucination of generative AI. However, this study will serve as a standard for future studies by providing an index to verify the reliability and consistency of generative AI from a user's point of view. If the reliability and consistency of AI literature search services are verified, then the use of these technologies will help medical research greatly.
PubMed: 38771247
DOI: 10.2196/51187 -
BMC Women's Health May 2024Successful efforts to encourage uptake of subdermal contraceptive implants, with a lifespan of three to five years, necessitate planning to ensure that quality removal...
BACKGROUND
Successful efforts to encourage uptake of subdermal contraceptive implants, with a lifespan of three to five years, necessitate planning to ensure that quality removal services are available when desired. In Burkina Faso, implant use has tripled over the past 8 years and now comprises almost half of the contraceptive method mix. Population Monitoring for Action (PMA) surveys identified barriers to obtaining quality removal when desired, particularly when the implant is not palpable, or providers lack needed skills or supplies. The Expanding Family Planning Choices (EFPC) project supported ministries of health in four countries with evaluation and strengthening of implant removal services.
METHODS
An implant removal landscape assessment was conducted at 24 health facilities in three regions of Burkina Faso with high implant use that included provider observations of implant removal, interviews with providers and health facility managers, and facility readiness surveys. The project used landscape data to mobilize stakeholders through a series of participatory workshops to develop a collaborative roadmap and commit to actions supporting quality implant removals.
RESULTS
Landscape findings revealed key gaps in provision of quality removal services, including high levels of provider confidence for implant insertion and removal (82% and 71%, respectively), low competence performing simple and difficult removals (19.2% and 11.1%, respectively), inadequate supplies and equipment (no facilities had all necessary materials for removal), lack of difficult removal management systems, and a lack of standard data collection tools for removal. Exposure to the data convinced stakeholders to focus on removals rather than expanding insertion services. While not all roadmap commitments were achieved, the process led to critical investments in quality implant removals.
CONCLUSION
Landscape data revealed that facilities lack needed supplies and equipment, and providers lack skills needed to perform quality implant removals, limiting client reproductive choice. Disseminating this data enabled stakeholders to identify and commit to evidence-based priority actions. Stakeholders have since capitalized on program learnings and the roadmap, including following MOH guidance for implant removal supplies and health provider training. Our experience in Burkina Faso offers a replicable model of how data can direct collective action to improve quality of contraceptive implant removals.
Topics: Burkina Faso; Humans; Female; Device Removal; Drug Implants; Family Planning Services; Stakeholder Participation; Contraceptive Agents, Female; Health Facilities
PubMed: 38769558
DOI: 10.1186/s12905-024-03121-z -
Annals of Pediatric Cardiology 2023Tuberculous (TB) involvement of the vascular system has been reported in the preantibiotic era. We, hereby, report a case involving a teenage boy who presented to us...
Tuberculous (TB) involvement of the vascular system has been reported in the preantibiotic era. We, hereby, report a case involving a teenage boy who presented to us with left upper limb pain followed by gradually progressive motor and sensory deficit over 1 month with preceding history of tuberculosis. Examination revealed a palpable, noncompressible, nonpulsatile swelling superior to the lateral third of the clavicle. Imaging through ultrasonography, computed tomography, and magnetic resonance imaging confirmed the presence of a pseudoaneurysm with compression of the underlying nerves. The child underwent surgical thrombectomy with pseudoaneurysm repair and arteriorrhaphy along with antitubercular medications with complete recovery at 6 months. The tissue staining, nucleic acid amplification tests, and histopathology confirmed TB etiology. Tuberculosis continues to remain a major health concern, especially in the developing world. High index of suspicion is necessary to diagnose such manifestations to avoid catastrophic sequelae.
PubMed: 38766448
DOI: 10.4103/apc.apc_156_23 -
Research Square May 2024Ductal carcinoma (DCIS) constitutes an array of morphologically recognized intraductal neoplasms in the mammary ductal tree defined by an increased risk for subsequent...
Ductal carcinoma (DCIS) constitutes an array of morphologically recognized intraductal neoplasms in the mammary ductal tree defined by an increased risk for subsequent invasive carcinomas at or near the site of biopsy detection. However, only 15-45% of untreated DCIS cases progress to invasive cancer, so understanding mechanisms that prevent progression is key to avoid overtreatment and provides a basis for alternative therapies and prevention. This study was designed to characterize the tumor microenvironment and molecular profile of high-risk DCIS that grew to a large size but remained as DCIS. All patients had DCIS lesions >5cm in size with at least one additional high-risk feature: young age (<45 years), high nuclear grade, hormone receptor negativity, HER2 positivity, the presence of comedonecrosis, or a palpable mass. The tumor immune microenvironment was characterized using multiplex immunofluorescence to identify immune cells and their spatial relationships within the ducts and stroma. Gene copy number analysis and whole exome DNA sequencing identified the mutational burden and driver mutations, and quantitative whole-transcriptome/gene expression analyses were performed. There was no association between the percent of the DCIS genome characterized by copy number variants (CNAs) and recurrence events (DCIS or invasive). Mutations, especially missense mutations, in the breast cancer driver genes and were common in this high-risk DCIS cohort (47% of evaluated lesions). Tumor infiltrating lymphocyte (TIL) density was higher in DCIS lesions with TP53 mutations (p=0.0079) compared to wildtype lesions, but not in lesions with mutations (p=0.44). Immune infiltrates were negatively associated with hormone receptor status and positively associated with HER2 expression. High levels of CD3+CD8- T cells were associated with good outcomes with respect to any subsequent recurrence (DCIS or invasive cancer), whereas high levels of CD3+Foxp3+ Treg cells were associated with poor outcomes. Spatial proximity analyses of immune cells and tumor cells demonstrated that close proximity of T cells with tumor cells was associated with good outcomes with respect to any recurrence as well as invasive recurrences. Interestingly, we found that myoepithelial continuity (distance between myoepithelial cells surrounding the involved ducts) was significantly lower in DCIS lesions compared to normal tissue (p=0.0002) or to atypical ductal hyperplasia (p=0.011). Gene set enrichment analysis identified several immune pathways associated with low myoepithelial continuity and a low myoepithelial continuity score was associated with better outcomes, suggesting that gaps in the myoepithelial layer may allow access/interactions between immune infiltrates and tumor cells. Our study demonstrates the immune microenvironment of DCIS, in particular the spatial proximity of tumor cells and T cells, and myoepithelial continuity are important determinants for progression of disease.
PubMed: 38766192
DOI: 10.21203/rs.3.rs-4126092/v1 -
Clinical, Cosmetic and Investigational... 2024Rare studies have reported pilomatricoma in twins, and extremely rare cases showed lesions in the same part of the body position. We reported a case of monozygotic twins...
INTRODUCTION
Rare studies have reported pilomatricoma in twins, and extremely rare cases showed lesions in the same part of the body position. We reported a case of monozygotic twins with pilomatricoma in the same location on the skin of the right upper extremity.
CASE PRESENTATION
Seven-year-old monozygotic twins presented to our department with a palpable, painless, and solid mass in the subcutaneous tissue of the right upper limb. A 1.5-cm diameter nodule was seen on the anterolateral aspect of the right upper extremity of the twins. The node was irregular in shape, and upon palpation, the patients reported no noticeable tenderness. Following the administration of local anesthesia, the twins underwent surgical procedure to excise the solid mass. Finally, they were diagnosed with pilomatricoma based on the clinical and histopathological features. Complete surgical resection followed by primary closure was performed. During a follow-up period of three years, there has been no recurrence observed in the twins.
CONCLUSION
We reported a case of monozygotic twins with pilomatricoma in the same location on the skin of the right upper arm. Our findings underscore the requirement of considering genetic factors in the diagnosis and treatment of the rare conditions.
PubMed: 38765195
DOI: 10.2147/CCID.S455880 -
Journal of Inflammation Research 2024Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disease resulting from the interaction of various factors such... (Review)
Review
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disease resulting from the interaction of various factors such as social elements, autoimmunity, genetics, and gut microbiota. Alarmingly, recent epidemiological data points to a surging incidence of IBD, underscoring an urgent imperative: to delineate the intricate mechanisms driving its onset. Such insights are paramount, not only for enhancing our comprehension of IBD pathogenesis but also for refining diagnostic and therapeutic paradigms. Monocytes, significant immune cells derived from the bone marrow, serve as precursors to macrophages (Mφs) and dendritic cells (DCs) in the inflammatory response of IBD. Within the IBD milieu, their role is twofold. On the one hand, monocytes are instrumental in precipitating the disease's progression. On the other hand, their differentiated offsprings, namely moMφs and moDCs, are conspicuously mobilized at inflammatory foci, manifesting either pro-inflammatory or anti-inflammatory actions. The phenotypic spectrum of these effector cells, intriguingly, is modulated by variables such as host genetics and the subtleties of the prevailing inflammatory microenvironment. Notwithstanding their significance, a palpable dearth exists in the literature concerning the roles and mechanisms of monocytes in IBD pathogenesis. This review endeavors to bridge this knowledge gap. It offers an exhaustive exploration of monocytes' origin, their developmental trajectory, and their differentiation dynamics during IBD. Furthermore, it delves into the functional ramifications of monocytes and their differentiated progenies throughout IBD's course. Through this lens, we aspire to furnish novel perspectives into IBD's etiology and potential therapeutic strategies.
PubMed: 38764499
DOI: 10.2147/JIR.S450801