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Δευτέρα 10 Μαΐου 2021

Effects of hypothermia on inflammatory cytokine expression in rat liver following asphyxial cardiac arrest

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Exp Ther Med. 2021 Jun;21(6):626. doi: 10.3892/etm.2021.10058. Epub 2021 Apr 15.

ABSTRACT

Hypothermic treatment is known to protect against cardiac arrest (CA) and improve survival rate. However, few studies have evaluated the CA-induced liver damage and the effects of hypothermia on this damage. Therefore, the aim of the present study was to determine possible protective effects of hypothermia on the liver after asphyxial CA. Rats were subjected to a 5-min asphyxial CA followed by return of spontaneous circulation (ROSC). The body temperature was controlled at 37±0.5˚C (normothermia group) or 33±0.5˚C (hypothermia group) for 4 h after ROSC. Livers were examined at 6, 12 h, 1 and 2 days after ROSC. Histopathological examination was performed by H&E staining. Alterations in the expression levels of pro-inflammatory (TNF-α and interleukin IL-2) and anti-inflammatory cytokines (IL-4 and IL-13) were investigated by immunohistochem istry. Sinusoidal dilatation and vacuolization were observed after asphyxial CA by histopathological examination. However, these CA-induced structural alterations were prevented by hypothermia. In immunohistochemical examination, the expression levels of pro-inflammatory cytokines were reduced in the hypothermia group compared with those in the normothermia group while the expression levels of anti-inflammatory cytokines were increased in the hypothermia group compared with those in the normothermia group. In conclusion, hypothermic treatment for 4 h following asphyxial CA in rats inhibited the increase of pro-inflammatory cytokines and stimulated the expression of anti-inflammatory cytokines compared with the normothermic group. The results of the present study suggested that hypothermic treatment after asphyxial CA reduced liver damage via the regulation of inflammation.

PMID:33968162 | PMC:PMC8097226 | DOI:10.3892/etm.2021.10058

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Effects of Supine and Prone Positions on Nasal Patency in Healthy Individuals

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Ear Nose Throat J. 2021 May 10:1455613211015437. doi: 10.1177/01455613211015437. Online ahead of print.

ABSTRACT

OBJECTIVES: Supine position reduces nasal patency compared with that in the sitting position; however, data on the effects of prone position on nasal patency is lacking.

METHODS: We assessed the nasal patency of 30 healthy individuals without upper respiratory tract disorders by using visual analog scale (VAS) score and acoustic rhinometry in 7 positions: si tting; frontal, right, and left supine; and frontal, right, and left prone.

RESULTS: According to the VAS scores, compared with that in the sitting position, both the supine and prone positions significantly increased subjective nasal obstruction (P < .001). The prone position had a more significant effect than did the supine position (P = .017). The results of minimal cross-sectional area measured through acoustic rhinometry demonstrated that both the supine and prone positions reduced the nasal patency significantly, but without significant differences between the effects of prone and supine positions (P = .794).

CONCLUSION: This is the first study to elucidate that the prone position can significantly reduce the nasal patency in healthy individuals through subjective and objective assessments.

LEVEL OF EVIDENCE: IV.

PMID:33970694 | DOI:10.1177/01455613211015437

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Role of Bilateral Inferior Turbinoplasty as an Adjunct to Septoplasty in Improving Nasal Obstruction and Subjective Performance in Patients With Deviated Nasal Septum Associated With Allergic Rhinitis: An Interventional, Prospective Study

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Ear Nose Throat J. 2021 May 10:1455613211015440. doi: 10.1177/01455613211015440. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with nasal obstruction due to deviated nasal septum (DNS) often have allergic rhinitis (AR) as contributing factor. When optimal medical therapy for AR fails, septoplasty alone may not adequately treat nasal obstruction. Therefore, with bilateral inferior turbinate hypertrophy representing long-standing AR, adding bilateral inferior turbinopla sty (BIT) to septoplasty might be beneficial.

OBJECTIVE: To assess whether septoplasty with/without BIT alleviates nasal obstruction in the above patient cohort and whether adding BIT to septoplasty brings significant benefit.

METHODOLOGY: In this interventional, prospective study, patients with nasal obstruction due to DNS and persistent, moderate-severe AR refractory to optimal medication were randomly allocated into group A (septoplasty alone) and group B (septoplasty with BIT). Nasal Obstruction and Symptom Evaluation (NOSE) score, along with Subjective Performance parameters (days-off/month; number of outdoor visits/month; overall satisfaction score [OSS]) were used to assess the symptom and quality of life, respectively, at follow-up.

RESULTS: Each group had 40 age/sex-matched patients. Friedman test, and subsequent pair-wise comparison within groups without Bonferroni correction, revealed that septoplasty with/without BIT elicited significant reductio n in NOSE scores and in the Subjective Performance parameters (days-off/month; number of outdoor visits/month) at 3 and 6 months. Wilcoxon Signed Rank test revealed that the OSS within groups also improved significantly with time. Further, comparison between groups revealed significant improvement in NOSE scores at all levels of follow-up when BIT was included. However, there were no significant differences between groups in the Subjective Performance parameters at any level of follow-up. Improvement in OSS between groups was significant only at 3 months but not subsequently.

CONCLUSION: Septoplasty with/without BIT is helpful in treating patients with DNS and refractory AR. However, although adding BIT brings significant benefit in decreasing nasal obstruction, it does not significantly improve the Subjective Performance parameters during follow-up, except for OSS at the third month.

PMID:33970700 | DOI:10.1177/01455613211015440

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Κυριακή 9 Μαΐου 2021

Impact of staging on survival outcomes: a nationwide real-world cohort study of metastatic uveal melanoma

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imageNo data exist regarding whether any first-line treatment for metastatic uveal melanoma provides overall survival (OS) benefit, if staged and compared to best supportive care (BSC). We analyzed OS in a nationwide, consecutive cohort diagnosed with metastatic uveal melanoma between January 1999 and December 2016. The Helsinki University Hospital Working Formulation was used to assign patients to stage IVa, IVb and IVc, corresponding to predicted median OS ≥12,
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Extreme elevation of acute phase reactants and shock secondary to dabrafenib–trametinib

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imageThe emerging role of BRAF and MEK tyrosine-kinase inhibitors has shown new opportunities of treatment for patients with advanced melanoma and BRAF mutations. Its use is associated with some toxicities, as pyrexia, that clinicians may not be familiarized with. We present the case of a patient diagnosed with stage IV melanoma BRAF Val600E mutated who was started on dabrafenib and trametinib and developed three severe episodes of fever, hypotension and acute phase reactants elevation during the first 3 months of therapy, in the absence of microbiological demonstration of infection. The episodes were initia lly managed as a septic shock with broad-spectrum antibiotics and vasoactive drugs, while treatment with dabrafenib and trametinib was withheld. After two subsequent dose reduction of dabrafenib, the patient did not experience new episodes of fever.
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BRAF inhibitor treatment is feasible in the oldest-old advanced melanoma patients

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imageAlthough new compounds have improved the treatment landscape of metastatic melanoma, very limited data exist on the efficacy and safety of treating older patients with novel agents. Here, we provide results of BRAF (BRAFi) ± MEK (MEKi) inhibitor treatment in patients over 75 years (oldest-old patients) with metastatic melanoma. Between 2011 and 2020, 34 consecutive patients with metastatic melanoma over 75 years of age (range 75–89) were treated with BRAFi ± MEKi at the Comprehensive Cancer Center of Helsinki University Hospital. Data on clinical and histopathological features, toxicity, respo nse rate (RR), progression-free survival (PFS) and overall survival (OS) were collected. Patients were treated with BRAFi (n = 22) or BRAFi in combination with MEK inhibitor (MEKi) (n = 12). Grade 1–2 adverse events occurred in 68% of the patients, 32% had grade 3 adverse effects, dose reductions were made for 41% of patients and 29% terminated treatment due to toxicity. Overall, the RR was 62%. Complete responses were achieved in 27% of the patients, and 35% had partial responses. The median PFS was 8 months (range 0–57), and the median OS was 15 months (range 0–71). Tailored BRAFi ± MEKi treatment for older patients is feasible. Adverse effects occur frequently but are manageable by dose adjustment. The occurrence of toxicity of monotherapy was similar to that of combination therapy. The RR and median OS from our retrospective study are comparable with those reported in clinical trials and combination therapy produced somewhat more and longer-lasting respons es. Hence, it seems that older patients may benefit from BRAFi treatment.
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A case of hyperprolactinaemia in a patient with metastatic melanoma

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imageEctopic prolactin production from a malignancy is infrequently reported. We report here a 60-year-old gentleman who presented with hyperprolactinaemia (9100 mIU/L) causing expressible galactorrhoea, decreased libido and fatigue thought to be due to ectopic prolactin secretion from a metastatic melanoma. Upon initiation of pembrolizumab, the patient's symptoms resolved and he became normoprolactinaemic. This corresponded with a partial response on radiological imaging. Although the core biopsy of the metastatic melanoma did not exhibit immunostaining for prolactin, we believe that only a subset of the tumour cells possesses prolactin-secreting capacity. This case illustrates the need to consider ectopic prolactin production for a solid malignant tumour as a rare cause of hyperprolactinaemia in patients with a normal pituitary MRI, in the absence of other causes.
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Prognostic impact of thyroid dysfunctions on progression-free survival in patients with metastatic melanoma treated with anti-PD-1 antibodies

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imageThis study aimed to assess the prognostic value of thyroid dysfunctions in metastatic melanoma patients on anti-programmed death-1 (anti-PD-1). A total of 110 stage IV or inoperable stage III melanoma patients treated with anti-PD-1 alone or in association with anti-CTLA-4 (T-lymphocyte antigen-4) antibody from January 2015 to December 2017 at our institution were enrolled in this retrospective study. Median follow-up was 32.8 months. Transitory thyroid dysfunctions and permanent thyroid dysfunctions were distinguished. The main criterion was progression-free survival. Secondary criteria were best response a nd overall survival. Survival curves were compared with log-rank tests and a cox proportional hazard ratio model was used to adjust patients and melanoma characteristics. Thirty-eight (35%) thyroid dysfunctions were observed during the follow-up, including 25 transitory thyroid dysfunctions (23%) and 13 permanent thyroid dysfunctions (12%). Progression-free survival was longer in patients with thyroid dysfunction (18.1 months) than in patients without thyroid dysfunction (3.9 months, P = 0.0085). In multivariate analysis, thyroid dysfunctions were not an independent predictive factor for progression-free survival. Patients with thyroid dysfunction had a longer overall survival (P = 0.0021), and thyroid dysfunctions were associated with a lower mortality risk (hazard ratio = 0.40; P = 0.005). Best response was positively associated with thyroid dysfunctions (P = 0.048). Thyroid dysfunctions induced by anti-PD-1 were not an independent predictive factor for progression-free survival i n metastatic melanoma patients but seemed associated with a better response and increased overall survival.
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Impact of the development of immune related adverse events in metastatic melanoma treated with PD -1 inhibitors

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imageSome clinical trials have described improved outcomes in patients who develop immune-related adverse events (irAEs) while receiving immune checkpoint inhibitors for advanced melanoma. It is unknown if this effect would be seen in a real-world population. This is a single-center retrospective analysis of all patients receiving single-agent PD-1 inhibitor for unresectable stage III or stage IV melanoma between 2012 and 2018. The majority of patients had cutaneous melanoma and were elderly (put in median and range). Totally 33.3% were BRAF mutated and 66.7% had PD-1 inhibitor as first-line treatment for metastat ic disease. Also, 22% of patients had brain metastases at presentation. Of the 87 patients included in this analysis, 48 (55%) developed at least one irAE. Dermatologic toxicities were the most common irAE. The median time to develop any irAE was 12 weeks. Only one patient died of immune-related toxicity. Overall survival in the population of patients that had an irAE was significantly greater than those that did not have any toxicity (21.1 vs. 7.5 months; P 
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Olfactory Neuroblastoma: A Novel Site of Presentation

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Abstract

Olfactory neuroblastoma (ONB) or esthesioneuroblastoma is a rare malignant intranasal tumor, commonly originated from upper part of nasal cavity. Majority of cases presented with nasal obstruction or epistaxis. ONB is rarely reported in ectopic locations. Here we present the first-ever documented case of an olfactory neuroblastoma situated anterior to body of maxilla, presented as left sided facial swelling. This case report is aimed at achieving the consideration of this rare tumour as a differential diagnosis in the lesions of the anatomical region surrounding the commonly known site of origin i.e. the sinonasal cavity.

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Patient Reported Outcomes of Scalp and Forehead Reconstruction for Defects Following Oncological Resections (North-East Indian Tertiary Cancer Centre Study)

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Abstract

Background Approximately 1–2% of all scalp tumours are malignant, but they comprise up to 13% of all malignant cutaneous neoplasms. The current study presents our experience of reconstruction of scalp and forehead for malignant tumours treated at our centre. Methods This is a single institutional observational study conducted at a tertiary cancer centre in North East India. Post-operative outcomes related to quality of life of patients were measured with help of FACE-Q scales. Face-Q –Satisfaction with outcome and FACE-Q- appearance related psychosocial distress scores were analysed. Histograms were used for descriptive statistics. Data were checked for normality using Kolmogorov–Smirnova and Shapiro–Wilk test. For non-normal data Wilcoxon test was used. A p value less than 0.05 was considered as statistically significant at 5% level of significance. Results Mean age of patients was 57.6 ± 14.2 years. The mean defect size was 89.036 ± 81.77 cm2. The mean satisfaction with outcome scores and distress scores at 3-months was 54.9 ± 8.6 and 34.8 ± 8.5 respectively with a statistically significant p value of 0.001.Mean satisfaction scores and psychological distress scores were better at the end of three months when compared to at the time of discharge with a statistical significant p value of < 0.0001. Conclusion Scalp and forehead reconstructions for defects following oncological resections are technically challenging and if chosen carefully with meticulous planning, both local and free tissue transfers give satisfactory outcome in long term follow up. There are lots of reconstruction options for scalp and forehead defects and knowledge of the basic bio-geometry of the each flap is must.

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