IntroductionStudying cancer tumors’ microenvironment may reveal a novel role in driving cancer progression and metastasis. The biological interaction between stromal (mesenchymal) stem cells (MSCs) and cancer cells remains incompletely understood. Herein, we investigated the effects of tumor cells’ secreted factors as represented by a panel of human cancer cell lines (breast (MCF7 and MDA-MB-231); prostate (PC-3); lung (NCI-H522); colon (HT-29) and head & neck (FaDu)) on the biological characteristics of MSCs.MethodsMorphological changes were assessed using fluorescence microscopy. Changes in gene expression were assessed using Agilent microarray and qRT-PCR. GeneSpring 12.1 and DAVID tools were used for bioinformatic and signaling pathway analyses. Cell migration was assessed using a transwell migration system. SB-431542, PF-573228 and PD98059 were used to inhibit transforming growth factor β (TGFβ), focal adhesion kinase (FAK), and mitogen activated protein kinase kinase (MAPKK) pathways, respectively. Interleukin-1β (IL1β) was measured using ELISA.ResultsMSCs exposed to secreted factors present in conditioned media (CM) from FaDu, MDA-MB-231, PC-3 and NCI-H522, but not from MCF7 and HT-29, developed an elongated, spindle-shaped morphology with bipolar processes. In association with phenotypic changes, genome-wide gene expression and bioinformatics analysis revealed an enhanced pro-inflammatory response of those MSCs. Pharmacological inhibitions of FAK and MAPKK severely impaired the pro-inflammatory response of MSCs to tumor CM (approximately 80% to 99%, and 55% to 88% inhibition, respectively), while inhibition of the TGFβ pathway was found to promote the pro-inflammatory response (approximately 3-fold increase). In addition, bioinformatics and pathway analysis of gene expression data from tumor cell lines combined with experimental validation revealed tumor-derived IL1β as one mediator of the pro-inflammatory phenotype observed in MSCs exposed to tumor CM.MSCs exhibited significant tropism toward secreted factors from the aforementioned tumor cell lines, while both normal and MSCs exposed to tumor CM were capable of attracting human peripheral blood mononuclear cells (PBMCs).ConclusionsOur data revealed tumor-derived IL1β as one mediator of the pro-inflammatory response in MSCs exposed to tumor CM, which was found to be positively regulated by FAK and MAPK signaling and negatively regulated by TGFβ signaling. Thus, our data support a model where MSCs could promote cancer progression through becoming pro-inflammatory cells within the cancer stroma.
SummaryThis prospective, observational volunteer study aimed to describe the appearance of the great auricular nerve using ultrasound and its blockade under ultrasound guidance. An in‐plane needle guidance technique was used for blockade of the great auricular nerve with 0.1 ml mepivacaine 1%. Sensory block was evaluated by pinprick testing in comparison with the contralateral area propriae. The great auricular nerve was successfully seen in all volunteers and the tail of the helix, antitragus, lobula and mandibular angle were blocked in all cases whereas the antihelix and concha were never blocked. Ultrasound imaging of the great auricular nerve can be reliably achieved and successful blockade with minimal volumes of local anaesthetic is another example of the benefits of ultrasound‐guided peripheral nerve blocks.
The results of this investigation enable selective blockade of the MACN via ultrasound. Moreover, our data provide insight regarding the specific anatomic course and the integrity of this sensory nerve, which could be used for plastic and reconstructive surgical indications and for diagnosis of nerve injury.
BACKGROUND Pneumonia, the commonest lower respiratory tract infection, can result in respiratory and non-respiratory complications. Few studies have reported on the prevalence of many complications. OBJECTIVES Identify the prevalence of 18 complications of pneumonia and compare complication rates by age group and type of pneumonia. Identify most prevalent comorbidities, the effect of the number of comorbidities on the presence of complications, and the association between specific comorbidities and specific complications. DESIGN Retrospective, cross-sectional prevalence study. SETTING Tertiary care center in Riyadh. PATIENTS AND METHODS The target population were patients aged 17 years and older, of different nationalities and both genders, diagnosed with pneumonia during the period of 2010 to 2017. Selection was by stratified sampling by year of admission. MAIN OUTCOME MEASURES Complications of pneumonia. SAMPLE SIZE 800. RESULTS Complications were observed in 427 patients (53.4%). The complications were respiratory in 258 patients (32%), sepsis and septic shock in 186 (23%), cardiac in 125 (16%), neurological in 5 (0.6%), and cholestatic jaundice in 2 (0.3%). Pleural effusion was the commonest complication, observed in 230 patients. There was a significant difference ( P <.001) between the complication rates in older patients compared to younger (60% as compared to 41%). For the type of pneumonia, there was a significant difference ( P <.001) between community-acquired pneumonia and hospital-acquired pneumonia in the presence of complications (OR=2.41, 95% CI for OR=1.66, 3.49). The number of comorbidities was significantly associated with the presence of complications ( P =.001) for those with multiple comorbidities (46% for patients with no comorbid illnesses versus 68% in patients with three or more comorbidities). CONCLUSION These results suggest that Saudi Arabia needs to establish better prevention and intervention programs, especially for the high-risk groups identified in this study: older patients, patients with hospital-acquired pneumonia and patients with two or more comorbidities. LIMITATIONS Retrospective design and single-centered.
Coronavirus disease 2019 (COVID-19) is a multi-organ disease with a wide range of manifestations. Coagulopathy is one of the well-recognized complications of COVID-19. We report the case of a 42-year-old man who presented with progressively worsening low back pain of two days in duration. The pain was burning in character, non-radiating, and was not related to movement. The patient had a recent history of severe COVID-19 pneumonia requiring mechanical ventilation and has stayed in the intensive care unit for eight days. He was discharged three days before the acute onset of his back pain. Examination of the lumbar spine was unremarkable. However, lower limb examination revealed coldness and absent pulses bilaterally. The patient underwent computed tomography angiography which revealed complete occlusion of the lower abdominal aorta at its bifurcation. Emergency endovascular treatment was performed to aspirate the clot. The symptoms resolved following the procedure and the patient was discharged on the third post-intervention day. Saddle aortic embolism is a rare life-threatening condition that may present solely with low back pain. The case demonstrated a possible complication of COVID-19 that occurred after the recovery from the acute phase of the disease.
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