Paracrine production of IL-6 promotes a hypercoagulable state in pancreatic cancer

xlomafota13 shared this article with you from Inoreader Paracrine production of IL-6 promotes a hypercoagulable state in pancreatic cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):5992-6003. eCollection 2021. ABSTRACT Venous thromboembolism is the most common complication and the secondary cause of death in pancreatic cancer. Moreover, the hypercoagulable state induces microcirculation dysfunction, acidosis and hypoxia, and further enhances tumor immune evasion, tumor growth and metastasis. Numerous studies have revealed that patients with malignant tumors have high levels of IL-6, which stimulates hepatocytes to synthesize thrombopoietin, causing an increase in platelets. This study found that the concentration of IL-6 in pancreatic cancer patient sera was higher than that in healthy donors, while pancreatic cancer cells had low expression levels of IL-6, which was different from other types of cancer. This contradictory result prompted us to uncover the underlying mechanism. Our data revealed that pancreatic cancer enhanced IL-6 production in fibroblasts via the Jagged/Notch axis, while IL-6 further elevated Jagged-1/2 expression in a paracrine positive feedback loop in pancreatic cancer. Inhibition experiments and RNAi studies demonstrated that IL-6-induced Jagged-1/2 production in pancreatic cancer depended on STAT3 and that Jagged-1/2 enhanced IL-6 mRNA expression in HSFs through the NF-κB pathway. Finally, the animal study showed that knockdown of Jagged-1/2 or blockade of the Jagged/Notch pathway by Nirogacestat could alleviate pancreatic cancer-induced hypercoagulability. Accordingly, our findings clarified the key role of the Jagged/Notch/IL-6/STAT3 feedback loop in the development of a hypercoagulable state in pancreatic cancer, which also provides new therapeutic strategies for pancreatic cancer patients who suffer from hypercoagulability. PMID:35018238 | PMC:PMC8727799 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Diacerein, an inhibitor of IL-1β downstream mediated apoptosis, improves radioimmunotherapy in a mouse model of Burkitt's lymphoma

xlomafota13 shared this article with you from Inoreader Diacerein, an inhibitor of IL-1β downstream mediated apoptosis, improves radioimmunotherapy in a mouse model of Burkitt's lymphoma Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):6147-6159. eCollection 2021. ABSTRACT Lymphoma has the characteristics of a solid tumor. Penetration of monoclonal antibodies is limited in solid tumors during radioimmunotherapy (RIT). Here, we first investigated the use of diacerein (DIA) as a combination drug to improve the penetration and therapeutic efficacy of 131I-rituximab (RTX) using the Burkitt's lymphoma mouse model. We selected DIA through computational drug repurposing and focused on rheumatoid arthritis (RA) drug interaction genes to minimize side effects. Then, the cytotoxicity of DIA was assessed in vitro using three different lymphoma cell lines. DIA-induced apoptosis was confirmed by Western blotting. After confirming apoptosis, we confirmed the enhanced uptake of 131I-RTX in Burkitt's lymphoma mouse model using SPECT/CT. Autoradiography of 131I-RTX confirmed the therapeutic effect of DIA. Finally, t he tumor size and survival rate were assessed to measure the enhanced therapeutic efficacy when DIA was used. In addition, we assessed the dose-dependency of DIA in terms of the accumulation of 131I-RTX in tumor tissue, the tumor size, and the survival rate. The in vitro cytotoxicity was 10.9%. We showed that DIA induced apoptosis which was related to downstream IL-1β signaling by Western blotting. We found increased Annexin V positive apoptosis after DIA administration. Immuno SPECT/CT images demonstrated a higher uptake of 131I-RTX in tumors in the DIA-administered group than that in the PBS-alone group. However, there were no statistical differences of dose-dependency between 20 mg/kg and 40 mg/kg of DIA. Tumor growth was significantly inhibited in the group treated with the combination of DIA plus 131I-RTX at 7 days after injection. Our suggested combination of DIA and 131I-RTX strategies could enhance the efficacy of 131I -RTX treatment. PMID:35018248 | PMC:PMC8727812 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Alpha-fetoprotein response predicts treatment outcomes in patients with unresectable hepatocellular carcinoma receiving immune checkpoint inhibitors with or without tyrosine kinase inhibitors or locoregional therapies

xlomafota13 shared this article with you from Inoreader Alpha-fetoprotein response predicts treatment outcomes in patients with unresectable hepatocellular carcinoma receiving immune checkpoint inhibitors with or without tyrosine kinase inhibitors or locoregional therapies Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):6173-6187. eCollection 2021. ABSTRACT Combined immune checkpoint inhibitors (ICIs) along with tyrosine kinase inhibitors (TKIs) and locoregional therapies have been used increasingly to treat hepatocellular carcinoma (HCC). Biomarkers are required to predict the treatment efficacy of ICIs with or without combination therapies in patients with unresectable HCC. This study enrolled 95 consecutive patients with unresectable HCC from May 2017 to June 2021 from two hospitals retrospectively. Of the 95 patients, 15 and 80 had Barcelona Clinic Liver Cancer stages B and C, respectively. The median ICI treatment duration was 3.43 (1.87-7.87) months, and 77 patients received combination therapies. Radiological imaging was not performed in 13 patients. Objective response and disease control rates were 27.4% and 53.7%, respectively. The duration of progression-free survival (PFS) and overall survival (OS) was 4. 07 (1.59-6.54) months and 14.53 (6.93-22.14) months, respectively. Alpha-fetoprotein (AFP) response was defined as a decline of >15% in the serum AFP level within the initial 3 months of ICI therapy according to Youden's index. AFP response was determined to be a predictor of disease control (odds ratio: 11.657, 95% confidence interval [CI]: 2.834-47.941, P=.001). Macrovascular invasion (MVI), AFP response (hazard ratio [HR]: 0.488, 95% CI: 0.255-0.934, P=.030), combination therapy, and disease control were predictors of PFS, and MVI, AFP response (HR: 0.344, 95% CI: 0.160-0.737, P=.006), and disease control were predictors of OS. AFP response was a predictor of disease control, PFS, and OS. These findings indicate that AFP response can serve as a biomarker to predict treatment outcomes in patients with unresectable HCC receiving ICIs with or without TKIs or locoregional therapies. PMID:35018250 | PMC:PMC8727811 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Factors associated with colorectal cancer screening intent and uptake among adult Non-Hispanic Black men

xlomafota13 shared this article with you from Inoreader Factors associated with colorectal cancer screening intent and uptake among adult Non-Hispanic Black men Via American Journal of Cancer Research Am J Cancer Res. 2021 Dec 15;11(12):6200-6213. eCollection 2021. ABSTRACT Non-Hispanic (NH) Black men in the United States have the lowest five-year colorectal cancer (CRC) survival rate across all racial/ethnic and sex subgroups and are less likely than their NH White counterparts to complete CRC screening. We hypothesized that greater masculinity barriers to medical care (MBMC) would be negatively associated with CRC screening uptake. Employing a survey design, we examined the MBMC scale and other psychosocial factors influencing CRC screening intent and uptake in a sample of 319 NH Black men aged 45 to 75 years residing in Minnesota, Ohio, and Utah. A series of ordinary least squares and logistic regression models were run with intention and uptake as the outcome variable while controlling for various demographic characteristics. Independent variables in all models included average score on the MBMC; CRC screening knowledge, beliefs and values; and barriers to and social support for CRC screening. Social support, marital status, and age were positively associated with CRC screening intention. Increased CRC screening knowledge and older age were associated with a greater likelihood of completing a stool-based screening test for CRC. Fewer masculinity-related and CRC screening barriers were associated with a greater likelihood of undergoing a sigmoidoscopy or colonoscopy. Contrary to our primary hypothesis, lesser MBMC-related perceptions were associated with increased CRC screening uptake among NH Black men. Our findings inform future CRC promotion programs and emphasize the need for multilevel interventions tailored toward this marginalized population to reduce disparities in screening and survival. PMID:35018252 | PMC:PMC8727804 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Subclinical Hypothyroidism with Negative for Thyroid Peroxidase Antibodies in Pregnancy: Intellectual Development of Offspring

xlomafota13 shared this article with you from Inoreader Subclinical Hypothyroidism with Negative for Thyroid Peroxidase Antibodies in Pregnancy: Intellectual Development of Offspring Via liebertpub1 Thyroid, Ahead of Print. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Exercise-based dysphagia rehabilitation for adults with oesophageal cancer: a systematic review

xlomafota13 shared this article with you from Inoreader Exercise-based dysphagia rehabilitation for adults with oesophageal cancer: a systematic review Via swallowing exercises BMC Cancer. 2022 Jan 10;22(1):53. doi: 10.1186/s12885-021-09155-y. ABSTRACT BACKGROUND: Dysphagia is prevalent in oesophageal cancer with significant clinical and psychosocial complications. The purpose of this study was i) to examine the impact of exercise-based dysphagia rehabilitation on clinical and quality of life outcomes in this population and ii) to identify key rehabilitation components that may inform future research in this area. METHODS: Randomised control trials (RCT), non-RCTs, cohort studies and case series were included. 10 databases (CINAHL Complete, MEDLINE, EMBASE, Web of Science, CENTRAL, and ProQuest Dissertations and Theses, OpenGrey, PROSPERO, RIAN and SpeechBITE), 3 clinical trial registries, and relevant conference abstracts were searched in November 2020. Two independent authors assessed articles for eligibility before completing data extraction, quality assessment using ROBINS-I and Downs and Black Checklist, followed by descriptive data analysis. The primary outcomes included oral intake, respiratory status and quality of life. All comparable outcomes were combined and discussed throughout the manuscript as primary and secondary outcomes. RESULTS: Three single centre non-randomised control studies involving 311 participants were included. A meta-analysis could not be completed due to study heterogeneity. SLT-led post-operative dysphagia intervention led to significantly earlier start to oral intake and reduced length of post-operative hospital stay. No studies found a reduction in aspiration pneumonia rates, and no studies included patient reported or quality of life outcomes. Of the reported secondary outcomes, swallow prehabilitation resulted in significantly improved swallow efficiency following oesophageal surgery compared to the control group, and rehabilitation following surgery resulted in significantly reduced vallecular and pyriform sinus residue. The three studies were found to have 'serious' to 'critical' risk of bias. CONCLUSIONS: This systematic review highlights a low-volume of low-quality evidence to support exercise-based dysphagia rehabilitation in adults undergoing surgery for oesophageal cancer. As dysphagia is a common symptom impacting quality of life throughout survivorship, findings will guide future research to determine if swallowing rehabilitation should be included in enhanced recovery after surgery (ERAS) programmes. This review is limited by the inclusion of non- randomised control trials and the reliance on Japanese interpretation which may have resulted in bias. The reviewed studies were all of weak design with limited data reported. PMID:35012495 | DOI:10.1186/s12885-021-09155-y View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Frequency-specific prediction model of hearing outcomes in patients with idiopathic sudden sensorineural hearing loss

xlomafota13 shared this article with you from Inoreader Frequency-specific prediction model of hearing outcomes in patients with idiopathic sudden sensorineural hearing loss Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Eur Arch Otorhinolaryngol. 2022 Jan 11. doi: 10.1007/s00405-021-07246-x. Online ahead of print. ABSTRACT PURPOSE: The hearing outcome of idiopathic sudden sensorineural hearing loss (ISSNHL) is hard to predict. We herein constructed a multiple regression model for hearing outcomes in each frequency separately in an attempt to achieve practical prediction in ISSNHL. METHODS: We enrolled 235 consecutive in-patients with ISSNHL who were treated in our department from 2015 to 2020 (average hearing level at 250-4000 Hz ≥ 40 dB; time from onset to treatment ≤ 14 days; 126 males/109 females; age range 17-87 years (average 61.0 years)). All patients received systemic prednisolone administration combined with intratympanic dexamethasone injection. The pure-tone hearing threshold of 125-8000 Hz was measured at every octave before (HLpre) and after (HLpost) treatment. A multiple regression model was constructed for HLpost (dependent variable) using five explanatory variables (age, days from onset to treatment, presence of vertigo, HLpre, and hearing level of the contralateral ear). RESULTS: The multiple correlation coefficient increased as the frequency increased. Strong correlations were seen in high frequencies, with multiple correlation coefficients of 0.784/0.830 for 4000/8000 Hz. The width of the 70% prediction interval was narrower for 4000/8000 Hz (± 18.2/16.3 dB) than for low to mid-frequencies. Among the five explanatory variables, HLpre showed the largest partial correlation coefficient for any frequency. The partial correlation coefficient for HLpre increased as the frequency increased, which may partially explain the high multiple correlation coefficients for high frequencies. CONCLUSION: The present model would be of practical use for predicting hearing outcomes in high frequencies in patients with ISSNHL. PMID:35015092 | DOI:10.1007/s00405-021-07246-x View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prevention and treatment of CSF leaks in congenital complex spinal lipomas

xlomafota13 shared this article with you from Inoreader Prevention and treatment of CSF leaks in congenital complex spinal lipomas Via leak of cerebrospinal fluid Acta Neurochir (Wien). 2022 Jan 11. doi: 10.1007/s00701-021-05095-5. Online ahead of print. ABSTRACT BACKGROUND: Congenital complex spinal lipomas (CSL) are challenging lesions to treat. Cerebrospinal fluid (CSF) leaks are feared complications due to the risk of infection, and subsequent scarring that may promote retethering. Much has been written in the literature on the surgical technique of CSL resection with less emphasis placed on the prevention and management of CSF leak. METHOD: The authors describe the nuances in the prevention and management of CSF leaks in the context of CSL, including the operative approach, resection, closure and recommended postoperative care. CONCLUSION: CSF leaks are complications that can be minimized with deliberate steps and meticulous surgical technique. PMID:35015155 | DOI:10.1007/s00701-021-05095-5 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Reconstruction of Subtotal Defect of the Lower Lip: Combined Use of Karapandzic and Nasolabial Flap

xlomafota13 shared this article with you from Inoreader Reconstruction of Subtotal Defect of the Lower Lip: Combined Use of Karapandzic and Nasolabial Flap Via Otolaryngology Indian Abstract Subtotal reconstruction of the lower lip after excision of the tumor is always a challenge for surgeons. It is because of the difficulty in  regaining the function of the lip, including the oral competency and restoring the aesthetic subunit. A 46-year-old patient presented with an ulceroproliferative growth involving 70% of the lower lip, including the right commissure. After the confirmation to be a malignancy, patient underwent excision of the tumour and reconstruction of the lower lip using the left Karapandzic flap and right nasolabial flap. The patient was on regular follow-up in the postoperative period to assess the surgical outcomes. The combined use of Karapandzic flap and the nasolabial flap can be reliably used for subtotal reconstruction of the lower lip in advanced oral cavity malignancy, involving one of the commissures. Later can ensure good postoperative results in terms of aesthetic and functional lip reconstruction without any significant intraoperative or postoperative complications. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Epidemiology, Clinical Features and Management of Rhino Orbital Mucormycosis in Post COVID 19 Patients

xlomafota13 shared this article with you from Inoreader Epidemiology, Clinical Features and Management of Rhino Orbital Mucormycosis in Post COVID 19 Patients Via Otolaryngology Indian Abstract COVID 19 infections may be associated with a wide range of bacterial and fungal co-infections. Mucormycosis is a fungal infection primarily affecting immunocompromised individuals. We have observed sudden rise of mucormycosis cases in post COVID 19 patients. Here we have reported 100 cases of mucormycosis associated with COVID 19. To study epidemiology and clinical features of rhino orbital mucormycosis in post COVID 19 patients. To evaluate efficacy of medical as well as surgical treatment in such patients. This was an observational mixed (retrospective + prospective) study with a duration of 2 months. After noting demographic data, necessary radiological investigation was advised and representative tissue was sent for KOH and histopathological examination. Medical and surgical treatment was planned accordingly. Most patients (55%) presented with complaint of headache and facial pain. Hard palate involvement was observed in 45% patients. Unilateral pr esentation (68%) was more common. Only 25% patients who presented early had normal vision. We reported 22 patients with complete loss of vision. Eye movements were restricted in 58% patients. Diabetes mellitus is most common predisposing factor (65%). 9 patients required orbital exentration. Only 18% patients required Amphotericin for more than 14 days. Immune dysregulation caused by COVID 19 infection in addition to widespread use of steroids and broad-spectrum antibiotics may lead to the development mucormycosis. Diabetes Mellitus type II is another important risk factor and the presence of both have additional effect in causing mucormycosis. Headache and facial pain should be considered highly suspicious of mucormycosis. Early diagnosis with efficient treatment can improve prognosis. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Brain Herniation Secondary to Cerebrospinal Fluid Leak Following Elective Lumbar Spine Surgery

xlomafota13 shared this article with you from Inoreader Brain Herniation Secondary to Cerebrospinal Fluid Leak Following Elective Lumbar Spine Surgery Via leak of cerebrospinal fluid Cureus. 2021 Dec 8;13(12):e20266. doi: 10.7759/cureus.20266. eCollection 2021 Dec. ABSTRACT Lumbar spine surgery can be complicated by perioperative cerebrospinal fluid (CSF) leak. However, development of brain herniation secondary to CSF leak following lumbar spine surgery has not been previously reported in the current literature. This case report describes a 48-year-old woman who, after a revision lumbar decompression and fusion, experienced CSF leak followed by development of brain herniation, which resulted in patient demise. The postoperative period was complicated by patient nonadherence to conservative management of CSF leak. PMID:35004068 | PMC:PMC8735843 | DOI:10.7759/cureus.20266 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.