Localized Administration of Mesenchymal Stem Cell-Derived Exosomes for the Treatment of Refractory Perianal Fistula in Crohn's Disease Patients: A Phase II Clinical Trial.

BACKGROUND: Crohn's disease perianal fistulae are often resistant to standard anti-TNF-α therapies. Mesenchymal stem cell (MSC)-derived exosomes are extracellular vesicles that have highly potent anti-inflammatory effects, and the previous phase of this study demonstrated their safety in the treatment of refractory perianal fistulas. OBJECTIVE: To evaluate the efficacy of mesenchymal stem cell-derived exosomes for the treatment of refractory perianal fistulas. DESIGN: Nonrandomized, nonblinded single-center phase II clinical trial. SETTINGS: Tertiary university hospital. PATIENTS: Twenty-three patients were enrolled, 20 of whom completed the study. Refractory perianal fistula was defined as resistance to at least one course of treatment with anti-tumor necrosis facto-α therapy. INTERVENTIONS: After clinical assessment and magnetic resonance imaging, the patients were subjected to general anesthesia, and 5 mL of exosome solution was injected directly into the fistula tracts. The injections were repeated three times at 2-month intervals, and patients were followed monthly for 6 months after the last injection. Tissue samples from the tracts were obtained before each injection and subjected to immunohistopathological assessment. MRI data were obtained before and six months after the last injection. MAIN OUTCOME MEASURES: The primary outcome of this study was fistula tract closure on clinical examination and magnetic resonance imaging. The secondary outcome was an improvement in the discharge from the tracts. RESULTS: Fistula tracts were fully closed in 12 (60%) of the patients. Four patients showed clinical improvement, with some tracts remaining open, and four patients were completely resistant to treatment. A total of 43 fistula tracts were treated during the trial, 30 (69.7%) of which showed complete closure. Histopathological analysis revealed substantial reductions in local inflammation and signs of enhanced tissue regeneration. Immunohistochemical analysis of cluster of differentiation-68, 20 and 31 reaffirmed these results. CONCLUSIONS: MSC-derived exosomes are safe and effective for treating refractory perianal fistulas in patients with Crohn's disease. See Video Abstract.

Association of mammographic and sonographic findings with prognostic molecular factors and hormone receptor expression in malignant breast lesions.

Background: The aim of this study was to determine whether mammographic and sonographic features of malignant breast lesions are correlated with tumor histologic grade, hormonal receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67 status. Materials and Methods: In this retrospective study, imaging and histopathological findings of 187 biopsy-proven breast cancer cases from November 2019 to February 2021 were reviewed. The Chi-square test was used to examine the potential correlation between mammographic and sonographic characteristics with histopathological features such as hormonal receptor, HER2 status, Ki-67 labeling index, and histological grade. Results: We observed that microlobulated margin as well as oval/round morphology in mammograms correlate with triple-negative intrinsic subtype (P = 0.006 and P = 0.004). The presence of calcification in sonography was significantly higher in the luminal-B subtype (P = 0.002). Furthermore, ill-defined margins in mammography were significantly higher in amplified HER2 expression (P = 0.004) in the same manner as an oval/round shape in higher levels of Ki-67 (P = 0.030). Conclusion: Mammography and sonography features may reflect the biological behavior of various subtypes of breast cancer and can detect more aggressive breast cancers that can mimic benign or less malignant appearing lesions. These findings may be an excellent predictor for some subtypes like triple-negative breast cancer. Studying the range of these imaging characteristics may help in better understanding the prognosis, choosing a treatment strategy, and predicting response to treatment.

Safety and efficacy of injection of human placenta mesenchymal stem cells derived exosomes for treatment of complex perianal fistula in non-Crohn's cases: Clinical trial phase I.

BACKGROUND AND AIM: A perianal fistula is an abnormal tract that connects anal canal to skin. Current medical and surgical interventions have a high failure rate particularly in complex and refractory cases. MSC-derived exosomes have demonstrated immunomodulatory effects without the conventional complications; hence, in this study, we evaluated the safety of their application for complex perianal fistula. METHODS: Placenta-derived MSCs were cultured, and exosomes were isolated using ultracentrifugation. Exosome injections were administered in the operating room to 11 patients with complex perianal fistula (presence of fistulas for at least 1 year alongside medical and surgical treatment). The patients were followed for 6 months, and the patients were evaluated using physical examination, face-to-face interviews, and magnetic resonance imaging (MRI). RESULTS: Among 11 patients only one did not show any improvement upon physical examination. Five patients showed complete tract resolve. While the discharge was stopped in eight patients, two patients showed only reduction. None of the patients showed any acute or latent allergic reaction or injection related complications. CONCLUSION: Administration of exosomes isolated from MSCs demonstrates safety and a satisfactory therapeutic effect in treatment complex perianal fistulae; therefore, it can be a candidate for future studies and might play a significant role in treatment.

A rare presentation of primary cardiac myxofibrosarcoma: Case report and literature review.

BACKGROUND: Primary cardiac myxofibrosarcoma is a rare and aggressive malignancy, with the majority of approaching strategies relying on case reports. This article provides insights into its diagnosis and treatment. CASE PRESENTATION: This paper presents the case of a 40-year-old man with sudden onset hemoptysis, leading to the diagnosis of primary cardiac myxofibrosarcoma. Treatment involved open-heart surgery to excise the left atrium tumor, followed by 6 cycles of adjuvant chemotherapy. Unfortunately, brain metastasis developed, leading to the patient's death 1 year after initial diagnosis. CONCLUSION: Primary cardiac myxofibrosarcoma remains a clinical challenge with an unfavorable prognosis. Early diagnosis through advanced imaging is crucial, and research is needed to explore innovative treatments. This case underscores the complexities of managing this rare cardiac malignancy and highlights the necessity for ongoing investigations to enhance patient outcomes.

Biased Deep Learning Methods in Detection of COVID-19 Using CT Images: A Challenge Mounted by Subject-Wise-Split ISFCT Dataset.

Accurate detection of respiratory system damage including COVID-19 is considered one of the crucial applications of deep learning (DL) models using CT images. However, the main shortcoming of the published works has been unreliable reported accuracy and the lack of repeatability with new datasets, mainly due to slice-wise splits of the data, creating dependency between training and test sets due to shared data across the sets. We introduce a new dataset of CT images (ISFCT Dataset) with labels indicating the subject-wise split to train and test our DL algorithms in an unbiased manner. We also use this dataset to validate the real performance of the published works in a subject-wise data split. Another key feature provides more specific labels (eight characteristic lung features) rather than being limited to COVID-19 and healthy labels. We show that the reported high accuracy of the existing models on current slice-wise splits is not repeatable for subject-wise splits, and distribution differences between data splits are demonstrated using t-distribution stochastic neighbor embedding. We indicate that, by examining subject-wise data splitting, less complicated models show competitive results compared to the exiting complicated models, demonstrating that complex models do not necessarily generate accurate and repeatable results.