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The American Journal of Surgical... Nov 2023The latest World Health Organization classification of breast tumors recommends diagnosing malignant phyllodes tumors (MPTs) when all 5 morphologic features are present:...
The latest World Health Organization classification of breast tumors recommends diagnosing malignant phyllodes tumors (MPTs) when all 5 morphologic features are present: permeative borders, marked stromal cellularity, marked stromal cytologic atypia, ≥10 mitoses per 10 high-power fields (HPF), and stromal overgrowth. We assessed the performance of this recommendation to capture MPTs and features predictive of distant metastasis in a multi-institutional retrospective study. Of 65 MPTs, most cases had at least focally permeative borders (58, 89%), with marked stromal cellularity in 40 (61.5%), marked atypia in 38 (58.5%), ≥10 mitoses per 10 HPF in 50 (77%), and stromal overgrowth in 56 (86%). Distant metastases were observed in 20 (31%) patients (median follow-up 24.5 mo, 1 to 204). Only 13 of 65 (20%) cases had all 5 morphologic features, while only 7 of 20 (35%) cases with distant metastases had all 5 features. In univariate analysis, only marked stromal atypia ( P =0.004) and cellularity ( P =0.017) were associated with decreased distant metastasis-free survival. In multivariate Cox regression, the combination of stromal overgrowth, marked stromal cellularity, and atypia (C-index 0.721, 95% CI: 0.578, 0.863) was associated with decreased distant metastasis-free survival. The current World Health Organization recommendation will miss a significant number of MPTs with distant metastases. We propose refined diagnostic criteria for MPTs: (1) stromal overgrowth combined with ≥1 feature(s) (marked cellularity, marked atypia, or ≥10 mitoses per 10 HPF), or (2) in the absence of stromal overgrowth, marked cellularity combined with ≥1 feature(s) (permeative borders, marked atypia, or ≥10 mitoses per 10 HPF).
PubMed: 37694517
DOI: 10.1097/PAS.0000000000002109 -
Journal of Atherosclerosis and... Aug 2023
Topics: Humans; Cholesterol, HDL; Cholesterol, LDL; East Asian People; Triglycerides
PubMed: 36696973
DOI: 10.5551/jat.ED223 -
ELife Feb 2024Pheochromocytomas (PCCs) are rare neuroendocrine tumors that originate from chromaffin cells in the adrenal gland. However, the cellular molecular characteristics and...
Pheochromocytomas (PCCs) are rare neuroendocrine tumors that originate from chromaffin cells in the adrenal gland. However, the cellular molecular characteristics and immune microenvironment of PCCs are incompletely understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on 16 tissues from 4 sporadic unclassified PCC patients and 1 hereditary PCC patient with Von Hippel-Lindau (VHL) syndrome. We found that intra-tumoral heterogeneity was less extensive than the inter-individual heterogeneity of PCCs. Further, the unclassified PCC patients were divided into two types, metabolism-type (marked by NDUFA4L2 and COX4I2) and kinase-type (marked by RET and PNMT), validated by immunohistochemical staining. Trajectory analysis of tumor evolution revealed that metabolism-type PCC cells display phenotype of consistently active metabolism and increased metastasis potential, while kinase-type PCC cells showed decreased epinephrine synthesis and neuron-like phenotypes. Cell-cell communication analysis showed activation of the annexin pathway and a strong inflammation reaction in metabolism-type PCCs and activation of FGF signaling in the kinase-type PCC. Although multispectral immunofluorescence staining showed a lack of CD8 T cell infiltration in both metabolism-type and kinase-type PCCs, only the kinase-type PCC exhibited downregulation of molecules that possibly regulated by , suggesting the potential of combined therapy with kinase inhibitors and immunotherapy for kinase-type PCCs; in contrast, the application of immunotherapy to metabolism-type PCCs (with antigen presentation ability) is likely unsuitable. Our study presents a single-cell transcriptomics-based molecular classification and microenvironment characterization of PCCs, providing clues for potential therapeutic strategies to treat PCCs.
Topics: Humans; Pheochromocytoma; Tumor Microenvironment; Adrenal Gland Neoplasms; Antigen Presentation; CD8-Positive T-Lymphocytes
PubMed: 38407266
DOI: 10.7554/eLife.87586 -
Acta Neuropsychiatrica Oct 2023The pandemic caused by the coronavirus disease 2019 (COVID-19, SARS-CoV-2 virus) has infected more than 646 million people and caused more than 6.6 million deaths...
OBJECTIVE
The pandemic caused by the coronavirus disease 2019 (COVID-19, SARS-CoV-2 virus) has infected more than 646 million people and caused more than 6.6 million deaths worldwide (December/2022). It is surprising that a virus that affects airways can trigger neurological manifestations. The aim of this study was to create and apply specific questionnaires/evaluations for post-COVID-19 patients to profile any neurofunctional sequelae.
METHODS
Epidemiological and psychomotor aspects as well as the intensity of cognitive, memory, attention, and concentration impairment were assessed. A total of 184 subjects post-COVID-19 and a control group ( = 30) were evaluated.
RESULTS
The most prevalent blood types in the COVID-19 group were the same as those from control group and in Brazilian population (no influence). Loss of smell/taste and headache were the most common reported symptoms. Talking about psychomotor and neurofunctional aspects, COVID-19 induced marked impairments in the tests: fine motor development (diadochokinesis, puppets, fan, and knead paper); balance (immobility, static balance, feet in line, and persistence); episodic memory after distractors; verbal fluency; and clock, compared to the control group data. There was also marked increase of synkinesis. Therefore, COVID-19 induced impairments in psychomotor assessments and in different cognitive aspects of the Mini-Mental State Examination. These results are more surprising considering that most participants did not report pre-existing disease and did not require hospitalisation.
CONCLUSION
COVID-19 induced psychomotor, neurofunctional, and memory impairments, including in young and healthy subjects. The present study revealed neurological impairments, which should be considered in the development of rehabilitation protocols for patients affected by COVID-19.
Topics: Humans; COVID-19; SARS-CoV-2; Surveys and Questionnaires; Pandemics; Brazil
PubMed: 36606540
DOI: 10.1017/neu.2023.2 -
Allergology International : Official... Oct 2023Poorly controlled asthma is especially common in low resource countries. Aside from lack of access to, or poor technique with, inhaled beta-2 agonists and... (Review)
Review
Poorly controlled asthma is especially common in low resource countries. Aside from lack of access to, or poor technique with, inhaled beta-2 agonists and corticosteroids, the most problematic forms of asthma are frequently associated with both fungal allergy and exposure, especially in adults leading to more asthma exacerbations and worse asthma. The umbrella term 'fungal asthma' describes many disorders linked to fungal exposure and/or allergy to fungi. One fungal asthma endotype, ABPA, is usually marked by a very high IgE and its differential diagnosis is reviewed. Both ABPA and fungal bronchitis in bronchiectasis are marked by thick excess airway mucus production. Dermatophyte skin infection can worsen asthma and eradication of the skin infection improves asthma. Exposure to fungi in the workplace, home and schools, often in damp or water-damaged buildings worsens asthma, and remediation improves symptom control and reduces exacerbations. Antifungal therapy is beneficial for fungal asthma as demonstrated in nine of 13 randomised controlled studies, reducing symptoms, corticosteroid need and exacerbations while improving lung function. Other useful therapies include azithromycin and some biologics approved for the treatment of severe asthma. If all individuals with poorly controlled and severe asthma could be 'relieved' of their fungal allergy and infection through antifungal therapy without systemic corticosteroids, the health benefits would be enormous and relatively inexpensive, improving the long term health of over 20 million adults and many children. Antifungal therapy carries some toxicity, drug interactions and triazole resistance risks, and data are incomplete. Here we summarise what is known and what remains uncertain about this complex topic.
Topics: Child; Adult; Humans; Antifungal Agents; Asthma; Azithromycin; Bronchiectasis; Adrenal Cortex Hormones
PubMed: 37544851
DOI: 10.1016/j.alit.2023.07.003 -
Neurology International Apr 2024The perception of pain is strongly influenced by various social, emotional, and cognitive factors. A psychological variable which has consistently been shown to exert... (Review)
Review
The perception of pain is strongly influenced by various social, emotional, and cognitive factors. A psychological variable which has consistently been shown to exert its influence on pain is a cognitive process referred to as pain catastrophizing. Numerous studies have found it to be a strong predictor of pain intensity and disability across different clinical populations. It signifies a maladaptive response to pain marked by an exaggerated negative assessment, magnification of symptoms related to pain, and, in general, a tendency to experience marked pain-related worry, as well as experiencing feelings of helplessness when it comes to dealing with pain. Pain catastrophizing has been correlated to many adverse pain-related outcomes, including poor treatment response, unsatisfactory quality of life, and high disability related to both acute and chronic pain. Furthermore, there has been consistent evidence in support of a correlation between pain catastrophizing and mental health disorders, such as anxiety and depression. In this review, we aim to provide a comprehensive overview of the current state of knowledge regarding pain catastrophizing, with special emphasis on its clinical significance, and emerging treatment modalities which target it.
PubMed: 38804476
DOI: 10.3390/neurolint16030036 -
Medicina (Kaunas, Lithuania) Oct 2023The history of esophagectomy reflects a journey of dedication, collaboration, and technical innovation, with ongoing endeavors aimed at optimizing outcomes and reducing... (Review)
Review
The history of esophagectomy reflects a journey of dedication, collaboration, and technical innovation, with ongoing endeavors aimed at optimizing outcomes and reducing complications. From its early attempts to modern minimally invasive approaches, the journey has been marked by perseverance and innovation. Franz J. A. Torek's 1913 successful esophageal resection marked a milestone, demonstrating the feasibility of transthoracic esophagectomy and the potential for esophageal cancer cure. However, its high mortality rate posed challenges, and it took almost two decades for similar successes to emerge. Surgical techniques evolved with the left thoracotomy, right thoracotomy, and transhiatal approaches, expanding the indications for resection. Mechanical staplers introduced in the early 20th century transformed anastomosis, reducing complications. The advent of minimally invasive techniques in the 1990s aimed to minimize complications while maintaining oncological efficacy. Robot-assisted esophagectomy further pushed the boundaries of minimally invasive surgery. Collaborative efforts, particularly from the Worldwide Esophageal Cancer Collaboration and the Esophageal Complications Consensus Group, standardized reporting and advanced the understanding of outcomes. The introduction of risk prediction models aids in making informed decisions. Despite significant improvements in survival rates and postoperative mortality, anastomotic leaks remain a concern, with recent rates showing an increase. Prevention strategies include microvascular anastomosis and ischemic preconditioning, yet challenges persist.
Topics: Humans; Esophagectomy; Postoperative Complications; Esophageal Neoplasms; Anastomotic Leak; Robotic Surgical Procedures; Treatment Outcome
PubMed: 37893504
DOI: 10.3390/medicina59101786 -
JAMA Otolaryngology-- Head & Neck... May 2024
PubMed: 38722617
DOI: 10.1001/jamaoto.2024.0905 -
Brain Sciences Oct 2023Elevated glucocorticoid levels triggered by stress potentially contribute to sleep disturbances in stress-induced depression. However, sleep changes in response to...
Elevated glucocorticoid levels triggered by stress potentially contribute to sleep disturbances in stress-induced depression. However, sleep changes in response to elevated corticosterone (CORT), the major glucocorticoid in rodents, remain unclear. Here, we investigated the effects of acute or chronic CORT administration on sleep using electroencephalogram (EEG) and electromyography (EMG) recordings in freely moving mice. Acute CORT exposure rapidly promoted wakefulness, marked by increased episodes and enhanced EEG delta power, while simultaneously suppressing rapid eye movement (REM) and non-rapid eye movement (NREM) sleep, with the latter marked by decreased mean duration and reduced delta power. Prolonged 28-day CORT exposure led to excessive wakefulness and REM sleep, characterized by higher episodes, and decreased NREM sleep, characterized by higher episodes and reduced mean duration. EEG theta activity during REM sleep and delta activity during NREM sleep were attenuated following 28-day CORT exposure. These effects persisted, except for REM sleep amounts, even 7 days after the drug withdrawal. Elevated plasma CORT levels and depressive phenotypes were identified and correlated with observed sleep changes during and after administration. Fos expression significantly increased in the lateral habenula, lateral hypothalamus, and ventral tegmental area following acute or chronic CORT treatment. Our findings demonstrate that CORT exposure enhanced wakefulness, suppressed and fragmented NREM sleep, and altered EEG activity across all stages. This study illuminates sleep alterations during short or extended periods of heightened CORT levels in mice, providing a neural link connecting insomnia and depression.
PubMed: 37891839
DOI: 10.3390/brainsci13101472