Low-dose ipilimumab combined with anti-PD-1 immunotherapy in patients with metastatic melanoma following anti-PD-1 treatment failure

xlomafota13 shared this article with you from Inoreader Low-dose ipilimumab combined with anti-PD-1 immunotherapy in patients with metastatic melanoma following anti-PD-1 treatment failure Via Melanoma Research - Current Issue Combined immunotherapy is associated with a significant risk of severe and potentially fatal immune-related adverse events (irAEs). Therefore, we retrospectively analyzed the side profile and efficacy of low-dose ipilimumab (1 mg/kg, IPI1) combined with anti-PD-1 immunotherapy in patients who progressed after anti-PD-1 monotherapy. Nine patients with unresectable stage III or IV melanoma treated with combined low-dose ipilimumab (1 mg/kg, IPI1) and anti-PD-1 immunotherapy, following progression after anti-PD-1 treatment, were identified. Treatment response and irAEs were recorded. Grade 3 irAEs occurred in one-third of pat ients. Interestingly, there were no grade 4 or 5 irAEs. In fact, four out of the nine patients experienced no irAEs at all. One patient discontinued combined immunotherapy due to immune-related colitis. The mean time to the onset of grade 3 irAEs was 14.3 weeks. The objective response rate was 33.3% and a disease control rate of 66.7% was achieved. Median progression-free survival (PFS) was 5.7 months and median overall survival (OS) was 21.6 months. The median PFS when IPI1 and anti-PD-1 treatment was administered in the second-line setting was not reached, but only 2.8 months when used in subsequent treatment settings. Combined IPI1 and anti-PD-1 immunotherapy was well tolerated. Its use in the third-line or above setting was associated with a significantly poorer prognosis than in the second-line setting. Larger, prospective studies are required to evaluate the safety and efficacy of this dosing regimen following anti-PD-1 treatment failure. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Association of Quality of Life Measures and Otolaryngologic Care in Cystic Fibrosis Patients

xlomafota13 shared this article with you from Inoreader Association of Quality of Life Measures and Otolaryngologic Care in Cystic Fibrosis Patients Via otol rhinol Ann Otol Rhinol Laryngol. 2021 Sep 11:34894211045636. doi: 10.1177/00034894211045636. Online ahead of print. ABSTRACT OBJECTIVES: Appropriate management of chronic rhinosinusitis (CRS) among patients with cystic fibrosis (CF) is important in improving quality of life. Otolaryngologists play a critical role in reducing CRS symptom burden. This study seeks to evaluate the role of patient-reported quality-of-life measures in guiding interventions for CF-related sinus disease. METHODS: We performed a prospective, cross-sectional study of 105 patients presenting to a CF-accredited clinic between July and September 2018. Demographic data and sinus surgery history were collected, in addition to Sino-Nasal Outcome Test (SNOT-22) and Questionnaire of Olfactory Disorders (QOD-NS) scores. Statistical analysis was conducted using correlation and non-parametric Mann-Whitney U tests. RESULTS: Baseline well-care visits accounted for 71.4% of all clinical evaluations. Prior otolaryngology intervention was noted in 69 (66%) patients, where the majority of these patients (63/69; 91%) underwent endoscopic sinus surgery (ESS). Patients with a history of otolaryngology intervention had an average SNOT-22 score of 33.2 (SD = 20.6) compared to 24.9 (SD = 18.5) for patients without prior intervention (P = .048). The average QOD-NS score was 5.5 (SD = 6.4) among patients referred to otolaryngologists and 3.1 (SD = 5.7) for non-referred patients (P< /i> = .012). SNOT-22 and QOD-NS scores were modestly correlated (R of .43). CONCLUSION: CF patients with symptoms resulting in worse quality-of-life assessments were more likely to have established coordinated care with an otolaryngologist. Further validation of the utility of SNOT-22 and QOD-NS questionnaires as care coordination metrics is necessary in the CF population. PMID:34514873 | DOI:10.1177/00034894211045636 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Objective Analysis Of Voice Quality In Patients With Thyroid Pathology

xlomafota13 shared this article with you from Inoreader Objective Analysis Of Voice Quality In Patients With Thyroid Pathology Via Clinical Otolaryngology Abstract Background One of the symptoms reported by patients with thyroid pathology are the changes in voice. The percentages of vocal alterations found in the literature vary between 16.7% and 68%. Such variability can be explained by different assessment methods used and their reliability. Objective The goal of this study is to analyze the voice in patients with thyroid pathology through two objective indexes with great diagnostic accuracy. Overall vocal quality was evaluated with the Acoustic Voice Quality Index (AVQI v.03.01) and the breathy voice with the Acoustic Breathiness Index (ABI). Method Observational case-control study of fifty-eight subjects, 29 controls and 29 thyroidectomy candidates. All participants with thyroid pathology completed the Spanish version of Voice Handicap Index-10. Also, patient complaints relating to possible laryngeal dysfunction were assessed through closed questions. A sustained vowel and three phonetically balanced sentences were recorded for each subject (118 samples). AVQI v.03.01 and ABI were assessed using the Praat program. Two raters perceptually evaluated each voice sample by using the Grade parameter of GRABS scale. Results Acoustic analysis shows that 55.17% of subjects present values above the pathological threshold of the AVQI, and 58.62% above that of the ABI. Results of the Student's test comparisons of the AVQI and ABI values between the control group and the thyroid group show significantly higher values of AVQI (t[56]=-3.85, p<0.001) and ABI (t[54.39]=-4.82, p<0.001) in thyroidectomy candidates. Conclusion A mild decrease in vocal quality is part of the symptomatology presented by thyroidectomy candidates. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Bone Cement Cranioplasty Reduces Cerebrospinal Fluid Leak Rate after Microvascular Decompression: A Single-Institutional Experience

xlomafota13 shared this article with you from Inoreader Bone Cement Cranioplasty Reduces Cerebrospinal Fluid Leak Rate after Microvascular Decompression: A Single-Institutional Experience Via leak of cerebrospinal fluid J Neurol Surg B Skull Base. 2021 Oct;82(5):556-561. doi: 10.1055/s-0040-1715607. Epub 2020 Aug 20. ABSTRACT Background Microvascular decompression (MVD) is a common surgical treatment for cranial nerve compression, though cerebrospinal fluid (CSF) leak is a known complication of this procedure. Bone cement cranioplasty may reduce rates of CSF leak. Objective To compare rates of CSF leak before and after implementation of bone cement cranioplasty for the reconstruction of cranial defects after MVD. Methods Retrospective chart review was performed of patients who underwent MVD through retrosigmoid craniectomy for cranial nerve compression at a single institution from 1998 to 2017. Study variables included patient demographics, medical history, type of closure, and postoperative complications such as CSF leak, meningitis, lumbar drain placement, and ventriculoperitoneal shunt insertion. Cement and noncement closure groups we re compared, and predictors of CSF leak were assessed using a multivariate logistic regression model. Results A total of 547 patients treated by 10 neurosurgeons were followed up for more than 20 years, of whom 288 (52.7%) received cement cranioplasty and 259 (47.3%) did not. Baseline comorbidities were not significantly different between groups. CSF leak rate was significantly lower in the cement group than in the noncement group (4.5 vs. 14.3%; p < 0.001). This was associated with significantly fewer patients developing postoperative meningitis (0.7 vs. 5.2%; p = 0.003). Multiple logistic regression model demonstrated noncement closure as the only independent predictor of CSF leak (odds ratio: 3.55; 95% CI: 1.78-7.06; p < 0.001). Conclusion CSF leak is a well-known complication after MVD. Bone cement cranioplasty significantly reduces the incidence of postoperative CSF leak and other complications. Modifiable risk factors such as body mass index were not associated with the development of CSF leak. PMID:34513562 | PMC:PMC8421130 | DOI:10.1055/s-0040-1715607 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Heterogeneity in Outcome Reporting in Endoscopic Endonasal Skull Base Reconstruction: A Systematic Review

xlomafota13 shared this article with you from Inoreader Heterogeneity in Outcome Reporting in Endoscopic Endonasal Skull Base Reconstruction: A Systematic Review Via leak of cerebrospinal fluid J Neurol Surg B Skull Base. 2021 Oct;82(5):506-521. doi: 10.1055/s-0040-1714108. Epub 2020 Aug 7. ABSTRACT Objective Presently, there are no standards for reporting outcomes of endoscopic endonasal skull base reconstruction (ESBR). This is problematic as a lack of consistent reporting makes synthesizing findings in systematic reviews and meta-analysis challenging. Thus, the aim of this study was to systematically review and describe the patterns of reporting outcomes in ESBR as a foundation for developing reporting guidelines. Study Design Present study is a systematic review. Methods Embase, PubMed, CINAHL, Cochrane Library, and Web of Science were searched for all publications with ≥25 patients and a focus on ESBR. The reporting patterns of each study's variables and outcomes were assessed. Results A total of 112 studies were included in the review. The most commonly reported demographic variables were the numb er of included patients ( n = 112, 100%) and types of pathologies treated ( n = 104, 92.9%). Meanwhile, the most routinely described preoperative variable was history of prior treatment ( n = 48, 42.9%). Type of reconstruction was a commonly reported intraoperative variable ( n = 110, 98.2%), though the rate of intraoperative cerebrospinal fluid (CSF) leak was noted in only 76 studies (67.9%). With regard to postoperative outcomes, postoperative CSF leak rate was routinely provided ( n = 101, 90.2%), but reporting of other surgical complications was more inconsistent. Ultimately, of the 43 variables and outcomes reviewed, a median of 12 (range: 4-22) was reported in each study. Conclusion There is significant heterogeneity in the outcomes reported in studies relating to ESBR. This highlights the need for the development of standard reporting guidelines to minimize bias and improve interstudy comparability. PMID:34513556 | PMC:PMC8421125 | DOI:10.1055/s-0040-1714108 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Gadolinium chloride pre-treatment reduces the inflammatory response and preserves intestinal barrier function in a rat model of sepsis

xlomafota13 shared this article with you from Inoreader Gadolinium chloride pre-treatment reduces the inflammatory response and preserves intestinal barrier function in a rat model of sepsis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1143. doi: 10.3892/etm.2021.10577. Epub 2021 Aug 9. ABSTRACT The inflammatory response is closely associated with sepsis occurrence and progression. Damage to the function of the intestinal mucosal barrier is considered to be the ῾initiation factor᾿ for the development of multiple organ dysfunction syndrome, which is the most severe progression of sepsis. The aim of the present study was to investigate whether gadolinium chloride (GdCl3) could alleviate the systemic inflammatory response and protect the function of the intestinal mucosal barrier in a rat model of sepsis. The mechanism underlying this protective effect was also explored. Sprague-Dawley rats were divided into four groups: Sham, sham + GdCl3, cecal ligation and puncture (CLP; a model of sepsis) and CLP + GdCl3. In each group, blood was collected from the abdominal aorta, and intestinal tissue was collected after 6, 12 and 24 h of successful modeling. Levels of tumor necrosis factor-α, interleukin (IL)-6 and IL-1β were determined using ELISA. Western blot analysis was used to determine levels of occludin, tight junction protein ZO-1 (ZO-1), myosin light chain kinase 3 (MLCK), NF-κB and caspase-3 in intestinal tissues. Hematoxylin-eosin staining was used to observe the degree of damage to intestinal tissue. The results indicated that in CLP sepsis model rats treated with GdCl3, the release of systemic and intestinal pro-inflammatory factors was reduced and tissue damage was alleviated when compared with untreated CLP rats. Additionally, the expression of occludin and ZO-1 was increased, while that of NF-κB, MLCK, and caspase-3 was reduced in the CLP + GdCl3 rats compared with the CLP rats. GdCl3 may alleviate systemic and intestinal inflammatory responses and reduce the expression of MLCK through inhibition of the activation of NF-kB. The results of the present study also indicated that GdCl3 promoted the expression of occludin and ZO-1. GdCl3 was also demonstrated to reduce cell apoptosis through the inhibition of caspase-3 expression. PMID:34504589 | PMC:PMC8393272 | DOI:10.3892/etm.2021.10577 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Deacetylated Sp1 improves β-glycerophosphate-induced calcification in vascular smooth muscle cells

xlomafota13 shared this article with you from Inoreader Deacetylated Sp1 improves β-glycerophosphate-induced calcification in vascular smooth muscle cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1152. doi: 10.3892/etm.2021.10586. Epub 2021 Aug 10. ABSTRACT The aging of the population has led to an annual increase in the incidence of vascular calcification (VC). Specific protein 1 (Sp1) is a transcriptional activator that serves an important role in VC. The deacetylation of transcription factors represses their binding to the promoters of downstream genes, thereby causing their downregulation. The present study aimed to investigate the role of deacetylated Sp1 in the development of VC. In the present study, western blotting and immunoprecipitation (IP) were performed to detect the protein levels of acetylated Sp1. Western blotting and immunofluorescence staining were used to analyze phenotypic switching in vascular smooth muscle cells (VSMCs). Alizarin red S, alkaline phosphatase (ALP) activity and calcium content assays were used to assess calcium deposition in VSMCs. Western blotting, flow cytomet ry, TUNEL staining and caspase3 activity assay were used to evaluate apoptosis of VSMCs. Chromatin immunoprecipitation (ChIP) assay was used to detect Sp1 binding to the BMP2 promoter. The results indicated that, in a β-glycerophosphate (β-GP)-induced VSMC calcification model, the level of acetylated Sp1 was increased. Western blotting and immunofluorescence staining results showed that, compared with the Sp1 overexpression group (Sp1-WT), deacetylated Sp1 (Sp1-K704A) downregulated the expression of osteogenic markers runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 2 (BMP2), and upregulated the expression of contraction marker α-smooth muscle actin (α-SMA) and calponin 1. In addition, deacetylated Sp1 also reduced the ALP activity and calcium content of calcified VSMCs, and the Alizarin red S assay revealed that the calcium crystallization of Sp1-K704A group was markedly decreased. Western blotting, flow cytometry, TUNEL staining and caspase-3 activity assay were detected to indicate that the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein ratio was increased, and caspase-3 activity and the apoptotic rate of VSMCs were decreased, in the Sp1-K704A group, as compared with the Sp1-WT group. ChIP assay revealed that Sp1 binding to the BMP2 promoter was downregulated in the Sp1-K704A group, compared with that in theSp1-WT group. In conclusion, a deacetylated mutant of Sp1 decreased Sp1 binding to the BMP2 promoter, thus decreasing apoptosis, phenotypic switching and calcium deposition in calcified VSMCs. This finding may indicate potential therapeutic targets for VC. PMID:34504597 | PMC:PMC8394101 | DOI:10.3892/etm.2021.10586 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effect of the combination of astragaloside IV and Panax notoginseng saponins on pyroptosis and necroptosis in rat models of cerebral ischemia-reperfusion

xlomafota13 shared this article with you from Inoreader Effect of the combination of astragaloside IV and <em>Panax notoginseng</em> saponins on pyroptosis and necroptosis in rat models of cerebral ischemia-reperfusion Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1123. doi: 10.3892/etm.2021.10557. Epub 2021 Aug 4. ABSTRACT Pyroptosis and necroptosis are closely associated with the mechanism underlying cerebral ischemia-reperfusion (I/R) injury. The combination of astragaloside IV (AST IV) and Panax notoginseng saponins (PNS) has remarkable effects on the alleviation of cerebral I/R damage. However, whether inhibition of pyroptosis and necroptosis is the mechanism underlying the beneficial effects of this drug combination on cerebral I/R injury remains unclear. To explore the effects and mechanisms of drug treatment, middle cerebral artery occlusion was performed to induce I/R injury in rats, which was verified based on neurological deficit score (NDS), infarct volume and H&E staining. Activation of pyroptosis and necroptosis was detected by western blot analysis of associated proteins. The results of the present study demonstrated that treatment with AST IV and PNS, either alone or in combination, significantly reduced the NDS, cerebral infarct volume and cell injury rate in the cerebral cortex of rats. The treatments also improved pathological injury to the cerebral cortex and reduced the levels of proteins associated with pyroptosis and necroptosis. These effects were stronger in the combination drug group compared with groups treated with a single drug alone. The findings of the present study suggested that the combination of AST IV and PNS exhibited stronger neuroprotective effects in I/R injury than either drug alone, and that the underlying mechanism was associated with inhibition of pyroptosis and necroptosis. PMID:34504577 | PMC:PMC8383753 | DOI:10.3892/etm.2021.10557 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The development of posttraumatic maxillary sinusitis due to transconjunctival penetration of a foreign body with a fracture of the lower wall of the orbit

xlomafota13 shared this article with you from Inoreader The development of posttraumatic maxillary sinusitis due to transconjunctival penetration of a foreign body with a fracture of the lower wall of the orbit Via Vestnik otorinolaringologii Vestn Otorinolaringol. 2021;86(4):111-115. doi: 10.17116/otorino202186041111. ABSTRACT The article presents a clinical example of the course of posttraumatic acute purulent sinusitis with reactive soft tissue phenomena due to the previous injury of the orbit by a foreign body, the introduction of the latter into orbit and the maxillary sinus result in a fracture of the lower wall of the orbit. A feature of the injury is the penetration of a foreign body through the conjunctiva of the lower eyelid and lower conjunctival fornix, without damaging the skin. This case is professionally interesting for both young doctors and experienced specialists in otolaryngology, ophthalmology, maxillofacial surgery and neurosurgery. Experts, analyzing this clinical example, will be able to correctly diagnose, effectively eliminate the inflammatory process in the maxillary sinus. PMID:34499458 | DOI:10.17116/otorino202186041111 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The main steps in treatment of the children with otitis media with effusion

xlomafota13 shared this article with you from Inoreader The main steps in treatment of the children with otitis media with effusion Via Vestnik otorinolaringologii Vestn Otorinolaringol. 2021;86(4):13-16. doi: 10.17116/otorino20218604113. ABSTRACT THE AIM: Of the investigation was to establish the standard and improve the treatment of otitis media with effusion (OME) in children. 361 children at age from 11 months to 18 years were inspected after tympanostomy during 2013-2018 years. The main diagnostic methods were: otoscopy, tympanometry, endoscopy, CT. MATERIAL AND METHODS: Treatment takes into consideration the reveal of OME: surgical initially. The tympanostomy preferable place is anterior-inferior quadrant. RESULTS: In cases with cleft palate or reccurence OME long-term tubes and balloonisation of ET are preferable. CONCLUSION: Authors received normalization of the hearing thresholds in 97.6% cases, but after surgery the patients have to be followed-up during 12-24 months. PMID:34499441 | DOI:10.17116/otorino20218604113 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Functional endoscopic sinus surgery in a patient with cystic fibrosis after lung transplantation

xlomafota13 shared this article with you from Inoreader Functional endoscopic sinus surgery in a patient with cystic fibrosis after lung transplantation Via Vestnik otorinolaringologii Vestn Otorinolaringol. 2021;86(4):73-78. doi: 10.17116/otorino20218604173. ABSTRACT Cystic fibrosis is genetic multisystem disorder with a predominant lesion of the respiratory tract. The duration and quality of life of these patients depends on the state of respiratory function. Progressive lung dysfunction is still the leading cause of mortality patients with cystic fibrosis. End-stage lung diseases in patients with cystic fibrosis, lung transplantation is a viable method of treatment. It has the ability to prolong life of these patients. Survival in cystic fibrosis has steadily increased medical treatment and post-transplant. Chronic rhinosinusitis (with nasal polys and without) impacts almost all cystic fibrosis patients, leading to significant reductions in quality of life. Chronic rhinosinusitis with nasal polyps is prevalent in the cystic fibrosis patients, and it is often a recalcitrant infection with multidrug resistant organi sms. Medical therapies such as nasal irrigations, nasal steroids, and antibiotics are critical for managing symptoms, but functional endoscopic sinus surgery is necessary for refractory cases. The unified airway hypothesis suggests that sanitation bacterial infection in the upper airway can also decrease bacterial burden in the lungs. The article presents a clinical case of successful endoscopic sinus surgery in a 15-year-old patient with chronic rhinosinusitis with nasal polyps and cystic fibrosis after lung transplantation. The intervention was performed under General anesthesia and controlled hypotension. Bilateral antrostomy, ethmoidectomy and Draf IIb frontal sinusotomy were performed by endoscopic endonasal approach. There were no intra - and post-operative rhinosurgical or lung complications. The follow-up period was 18 months. At present, there is no relapse of chronic polypous rhinosinusitis, and there are no indications for revision intervention. PMID:34499452 | DOI:10.17116/otorino20218604173 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.