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Cell Reports. Medicine Jun 2024Resistance to targeted therapy remains a major clinical challenge in melanoma. To uncover resistance mechanisms, we perform single-cell RNA sequencing on fine-needle...
Resistance to targeted therapy remains a major clinical challenge in melanoma. To uncover resistance mechanisms, we perform single-cell RNA sequencing on fine-needle aspirates from resistant and responding tumors of patients undergoing BRAFi/MEKi treatment. Among the genes most prominently expressed in resistant tumors is POSTN, predicted to signal to a macrophage population associated with targeted therapy resistance (TTR). Accordingly, tumors from patients with fast disease progression after therapy exhibit high POSTN expression levels and high numbers of TTR macrophages. POSTN polarizes human macrophages toward a TTR phenotype and promotes resistance to targeted therapy in a melanoma mouse model, which is associated with a phenotype change in intratumoral macrophages. Finally, polarized TTR macrophages directly protect human melanoma cells from MEKi-induced killing via CD44 receptor expression on melanoma cells. Thus, interfering with the protective activity of TTR macrophages may offer a strategy to overcome resistance to targeted therapy in melanoma.
PubMed: 38942020
DOI: 10.1016/j.xcrm.2024.101611 -
Respiratory Investigation Jun 2024Gastroesophageal reflux disease (GERD) is one of the most common comorbidities of chronic obstructive pulmonary disease (COPD). Decreased lower and upper esophageal... (Review)
Review
Gastroesophageal reflux disease (GERD) is one of the most common comorbidities of chronic obstructive pulmonary disease (COPD). Decreased lower and upper esophageal sphincter pressures, esophageal dysmotility, high transdiaphragmatic pressure, and decreased saliva secretion have been implicated as mechanisms leading to the development of GERD in COPD. Clinically, comorbid GERD in COPD is reportedly associated with worse symptoms, quality of life, and lung function, as well as a high risk of exacerbations. Aspiration of regurgitation and the cholinergic-mediated esophagobronchial reflex play a significant role in the pathophysiology. Abnormal swallowing reflexes and discoordination of swallowing can worsen aspiration. The diagnosis of GERD is not based on a single criterion; however, various approaches, including questionnaires and endoscopic evaluations, can be widely applied in clinical settings. Due to the increased risk of esophageal and gastric cancers in patients with COPD, the threshold for endoscopic examination should be low. Acid inhibitory agents, such as proton pump inhibitors and histamine H2 receptor antagonists, and prokinetic agents, including mosapride and itopride, are clinically used to treat GERD. Endoscopic fundoplication can be performed in patients with GERD refractory to medical treatment. There is still insufficient evidence, but an increasing number of studies have suggested the clinical efficacy of treatment in patients with COPD and GERD. As GERD is an evaluative and treatable common disease, and access to evaluation and treatment is relatively easy, clinicians should provide adequate care for GERD in the management of COPD.
PubMed: 38941760
DOI: 10.1016/j.resinv.2024.06.004 -
Rheumatology (Oxford, England) Jun 2024Recurrent monoarthritis (RM) is a major challenge of many rheumatic diseases. Ablation is a well-known technique in the treatment of benign or malign lesions of...
OBJECTIVES
Recurrent monoarthritis (RM) is a major challenge of many rheumatic diseases. Ablation is a well-known technique in the treatment of benign or malign lesions of different etiologies. We aimed to to investigate the success and safety of microwave ablation (MWA) as an adjunctive therapy in a cohort of medical treatment-resistant RM.
METHODS
Patients with RM associated with different inflammatory diseases were included. MWA was performed after measuring the size of synovial hypertrophy with 15 or 20-watt power and different durations until microbubbles were shown indicating necrosis. Both clinical and radiologic data were recorded.
RESULTS
We applied MWA in total of 24 knee joints of 10 female and 12 male patients aged between 22-71 years. Median intra-articular aspiration (IAA) need in the last 6 months before MWA was 5 (0-15). The median follow-up was 10 (3-16) months. Overall IAA count in the last 6 months before MWA in total of 144 months was 129 and decreased to 7 in post-MWA in total of 226 months (0.89 vs 0.03 per month, p< 0.001). The second MWA session was needed for 3 patients and a third session for 1. Functional disability and pain scores were improved significantly (median score from 9 to 1, p< 0.00001, in both). In magnetic resonance imaging, follow-up significant regression in synovial hypertrophy size was shown especially after 6th month. No complication was observed during the procedure or follow-up.
CONCLUSION
As a less invasive technique compared with the surgical approach, MWA of synovial hypertrophy showed significant clinical improvement in RM safely. MWA seems promising as a treatment option candidate in the management of RM.
PubMed: 38941501
DOI: 10.1093/rheumatology/keae348 -
Medicine Jun 2024Thyroglossal duct carcinoma, a rare clinical condition characterized by ectopic thyroid adenocarcinoma within thyroglossal duct cysts (TGDCs), typically confirmed... (Review)
Review
RATIONALE
Thyroglossal duct carcinoma, a rare clinical condition characterized by ectopic thyroid adenocarcinoma within thyroglossal duct cysts (TGDCs), typically confirmed through intraoperative rapid pathology, this condition generally has a favorable prognosis. Nevertheless, comprehensive treatment guidelines across all disease stages are lacking, the purpose of this study is to report 1 case of the disease and propose the treatment plan for each stage of the disease.
PATIENT CONCERNS
A patient presented with thyroid swelling, classified as C-TIRADS 4A following a physical examination. Preoperative thyroid puncture identified papillary thyroid carcinoma, and genetic testing revealed a BRAF gene exon 15-point mutation. Ancillary tests showed a slightly decreased thyroid stimulating hormone (TSH) level (0.172) with no other significant abnormalities.
DIAGNOSES
Preoperative fine-needle aspiration cytology (FNAC) confirmed right-side thyroid cancer. Intraoperative exploration uncovered a TGDC and intraoperative rapid pathology confirmed thyroglossal duct carcinoma.
INTERVENTIONS
A Sistrunk operation and ipsilateral thyroidectomy were performed.
OUTCOMES
Postoperative recovery was satisfactory.
LESSONS
Thyroglossal duct carcinoma is a rare disease affecting the neck. Due to limited clinical cases and the favorable prognosis associated with this condition, there is currently no established set of diagnostic and treatment guidelines. According to tumor size, lymph node metastasis, thyroid status and other factors, the corresponding treatment methods were established for each stage of thyroglossal duct cancer, which laid the foundation for the subsequent treatment development of this disease.
Topics: Humans; Thyroglossal Cyst; Thyroid Neoplasms; Thyroid Cancer, Papillary; Female; Thyroidectomy; Male; Proto-Oncogene Proteins B-raf; Adult; Biopsy, Fine-Needle
PubMed: 38941410
DOI: 10.1097/MD.0000000000038540 -
Journal of Assisted Reproduction and... Jun 2024To examine outcomes of oocyte retrievals completed by Reproductive Endocrinology and Infertility (REI) fellows versus faculty physicians.
PURPOSE
To examine outcomes of oocyte retrievals completed by Reproductive Endocrinology and Infertility (REI) fellows versus faculty physicians.
METHODS
This retrospective cohort study examined patients who underwent oocyte retrievals at Mayo Clinic from July 15, 2009, to December 15, 2016. The primary outcome was the oocyte retrieval rate (ORR) calculated per retrieval as the number of oocytes retrieved per follicles aspirated. The Wilcoxon signed-rank test was used to compare follicle and oocyte counts and ORR between fellows and faculty during the same bilateral retrieval.
RESULTS
The study cohort included the first bilateral retrieval from 845 unique patients completed by 11 fellows and seven faculty. The median ORR was not statistically different for fellows and faculty (0.79 versus 0.80, p = 0.46). To assess for a learning curve, the outcomes of seven fellows who completed at least 80 retrievals in their first year were examined as four chronologically ordered sets of 20. When these sets were compared to the faculty physician mean ORR, no significant differences were found (p-values of 0.69, 0.69, 0.81, and 0.81, respectively).
CONCLUSION
There were no significant differences in oocyte retrieval rates between fellows versus faculty over a 7-year period, with no significant learning curve observed. These findings suggest that fellows possess the requisite skills for successful oocyte retrieval upon entering REI fellowship following their OB/GYN residency. However, this does not diminish the critical role of comprehensive fellowship training and close supervision, especially in initial and complex cases.
PubMed: 38941004
DOI: 10.1007/s10815-024-03177-8 -
Sarcoidosis, Vasculitis, and Diffuse... Jun 2024Endobronchial biopsy (EBBX) has been reported to increase diagnostic yield for pulmonary sarcoidosis. The purpose of this study is to investigate the diagnostic yield...
The role for endobronchial biopsy in the era of endobronchial ultrasound guided transbronchial needle aspiration for the diagnosis of sarcoidosis: a single center experience.
BACKGROUND AND AIM
Endobronchial biopsy (EBBX) has been reported to increase diagnostic yield for pulmonary sarcoidosis. The purpose of this study is to investigate the diagnostic yield for EBBX following endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA).
METHODS
We identified a cohort of patients in the University of Minnesota Sarcoidosis Registry who had EBBx and EBUS-TBNA as part of workup for abnormal chest imaging. Data regarding demographics, biopsy approach and technique were recorded.
RESULTS
Our cohort included 37 patients (53.24±9.5, Male, 22±0.57; 3.8% were African American). In these patients who had EBBX, EBUS-TBNA was performed in 100% of patients and TBBX was performed in 2 patients (5%). EBBX was positive in 9 patients (24%) and EBUS-TBNA was positive in 34 patients (92%). TBBX was diagnostic in one of two patients. EBBX was the only diagnostic tissue in 3 of the 37 patients (8%). Conclusion: The diagnostic yield of EBBX is lower than previously reported, with only 8% of EBBXs demonstrating granulomatous inflammation. However, instrumentation used for obtaining EBBX as well as the presence of visible lesions does influence the diagnostic yield. Studies with adequate power are needed before implementing changes in clinical practice. When performed alongside EBUS-TBNA, EBBX did not significantly add to the diagnostic yield in sarcoidosis unless visible lesions were observed.
PubMed: 38940717
DOI: 10.36141/svdld.v41i2.14192 -
Acta Medica Philippina 2024The benefits of rapid on-site evaluation (ROSE) of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid masses have not been convincingly shown in...
Evaluation of Fine Needle Biopsy (FNB) for Endoscopic Ultrasound (EUS)-guided Tissue Acquisition of Pancreatic Masses to Negate the Need for Rapid On-site Evaluation: A Randomized Control Trial.
BACKGROUND AND OBJECTIVES
The benefits of rapid on-site evaluation (ROSE) of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid masses have not been convincingly shown in large, randomized trials. New equipment using EUS-guided fine needle biopsy (FNB) allows for more material to be acquired that may obviate the need for ROSE. This study aimed to evaluate if EUS-FNB without ROSE was non-inferior to EUS-FNA with ROSE in solid pancreatic masses (SPMs).
METHODS
Patients with SPMs requiring tissue sampling were randomly assigned to undergo either EUS-FNA with ROSE or EUS-FNB without ROSE. The touch-imprint cytology technique was used to perform ROSE. The primary endpoint was diagnostic accuracy and secondary endpoints were specimen quality, complication rates, and procedure time.
RESULTS
Seventy-eight patients were randomized and analyzed (39 EUS-FNA with ROSE and 39 EUS-FNB without ROSE). Non-significantly different diagnostic accuracies were noted in both groups (97% with ROSE and 100% without ROSE, P < 0.371). The bloodiness of histologic samples and complication rates were not significantly different between groups. A significantly shorter mean sampling procedural time was noted for EUS-FNB over EUS-FNA with ROSE (30.4 ± 10.4 vs 35.8 ± 9.8 minutes, P < .02).
CONCLUSIONS
EUS-FNB demonstrated equal diagnostic accuracy with shorter procedure times in evaluating SPMs compared to EUS-FNA with ROSE. These new-generation FNB needles may obviate the need for ROSE.
PubMed: 38939857
DOI: 10.47895/amp.vi0.6817 -
Frontiers in Pharmacology 2024Current guidelines recommend that glycoprotein IIb/IIIa inhibitor (GPI) and manual aspiration thrombectomy should not be routinely used in patients with ST-segment...
Current guidelines recommend that glycoprotein IIb/IIIa inhibitor (GPI) and manual aspiration thrombectomy should not be routinely used in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI), although there is a lack of dedicated studies. The aim of this study was to examine the impact of combined usage of a potent P2Y12 inhibitor, GPI, and manual aspiration thrombectomy on long-term survival after STEMI. All STEMI patients treated by pPCI in a tertiary center who have been included prospectively in the local PCI registry between January 2016 and December 2022 were analyzed in this study. Patients were excluded if they required oral anticoagulation or bridging between clopidogrel or ticagrelor during hospitalization. A total of 1,210 patients were included in the present study, with a median follow-up of 2.78 (1.00-4.88) years. Ticagrelor significantly reduced all-cause and cardiovascular-cause mortality [HR = 0.27 (0.21-0.34), < 0.0001 and HR = 0.23 (0.17-0.30), < 0.0001, respectively]. Eptifibatide significantly reduced all-cause and cardiovascular-cause mortality [HR = 0.72 (0.57-0.92), = 0.002, and HR = 0.68 (0.52-0.89), = 0.001, respectively]. Manual thrombus aspiration had no significant effect on both all-cause and cardiovascular-cause mortality. In multivariate Cox regression, all-cause mortality was reduced by ticagrelor, while eptifibatide or manual thrombus aspiration had no significant effect. However, cardiovascular-cause mortality was reduced by both ticagrelor and eptifibatide, while manual thrombus aspiration had no significant effect. Ticagrelor consistently reduced cardiovascular and all-cause mortality, while eptifibatide reduced only cardiovascular mortality. Manual thrombus aspiration provided no long-term benefit. Our findings support the current guideline recommendation that GPI and manual aspiration thrombectomy should not be routinely used in treatment of STEMI with pPCI.
PubMed: 38939835
DOI: 10.3389/fphar.2024.1415025 -
JACC. Advances May 2024
PubMed: 38939641
DOI: 10.1016/j.jacadv.2024.100923 -
Cureus May 2024Introduction In females, carcinoma of the breast is a common malignancy. Disease management can be challenging for the treating clinician if the condition is presented...
Introduction In females, carcinoma of the breast is a common malignancy. Disease management can be challenging for the treating clinician if the condition is presented in a locally advanced stage. Clinical presentation of a disease in a defined area provides a comprehensive map to target the at-risk population efficiently and select the appropriate intervention accordingly. In this retrospective study, we analyzed different factors that can affect breast carcinoma outcomes by assessing patients for a specific period of one year. Methods This is a retrospective study of carcinoma of breast patients and was conducted between 2017 and 2018. Results We reported a 25.83% incidence of breast cancer during the study period. A painful breast lump was present in 54.2% of patients, axillary nodes were present in 50% of patients, ulcers were present in 10% of patients, and nipple discharge was present in 8.5% of patients. According to the side and quadrant of involvement, the right side was the most common site of involvement in 55.7% of patients, and the upper outer quadrant was the most common quadrant involved in 61.4% of patients. The most familiar stage of the presentation was stage II, presented in 45.7% of patients. The most common histology was infiltrating ductal carcinoma, presented in 85.7% of patients. Conclusions This retrospective cohort study shows that carcinoma of the breast is a predominant malignancy among middle-aged females in developing countries such as India. This predominance is due to unawareness regarding disease symptoms and the fear of diagnosed malignancy during the investigation of symptoms. Early detection by screening and intervention at an early stage is the core of treatment success in this malignant disease. However, it is still challenging to apply screening as a tool to pick up early malignant disease in developing countries like India.
PubMed: 38939257
DOI: 10.7759/cureus.61239