Temperature and luminosity outputs of endoscopes used in transcanal endoscopic ear surgery: an experimental study.

OBJECTIVE: To establish the relationship between endoscope temperatures and luminosity with a variety of light source types, endoscope ages, endoscope sizes, angles and operative distance in transcanal endoscopic ear surgery. METHODS: Transcanal endoscopic ear surgery was simulated in an operating theatre using 7 mm plastic suction tubing coated in insulating tape. An ATP ET-959 thermometer was used to record temperatures, and a Trotec BF06 lux meter was used to measure luminosity. Luminosity and temperature recordings were taken at 0 mm and 5 mm from the endoscope tip. RESULTS: Thermal energy transfer from operating endoscopes is greatest when: the light intensity is high, there is a light-emitting diode light source and the endoscope is touching the surface. Additionally, larger-diameter endoscopes, angled endoscopes and new endoscopes generated greater heat. CONCLUSION: It is recommended that operative light intensity is maintained at the lowest level possible, and that the surgeon avoids contact between patient tissues and the endoscope tip.

Transcriptomic changes during stage progression of mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, which in the early patch/plaque stages runs an indolent course. However, ~25% of patients with MF develop skin tumours, a hallmark of progression to the advanced stage, which is associated with high mortality. The mechanisms involved in stage progression are poorly elucidated. OBJECTIVES: We sought to address the hypothesis of MF cell trafficking between skin lesions by comparing transcriptomic profiles of skin samples in different clinical stages of MF. METHODS: We performed whole-transcriptome and whole-exome sequencing of malignant MF cells from skin biopsies obtained by laser-capture microdissection. We compared three types of MF lesions: early-stage plaques (ESP, n = 12) as well as plaques and tumours from patients in late-stage disease [late-stage plaques (LSP, n = 10) and tumours (TMR, n = 15)]. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to determine pathway changes specific for different lesions which were linked to the recurrent somatic mutations overrepresented in MF tumours. RESULTS: The key upregulated pathways during stage progression were those related to cell proliferation and survival (MEK/ERK, Akt-mTOR), T helper cell (Th)2/Th9 signalling [interleukin (IL)4, STAT3, STAT5, STAT6], meiomitosis (CT45A1, CT45A3, STAG3, GTSF1, REC8) and DNA repair (PARP1, MYCN, OGG1). Principal coordinate clustering of the transcriptome revealed extensive gene expression differences between early (ESP) and advanced-stage lesions (LSP and TMR). LSP and TMR showed remarkable similarities at the level of the transcriptome, which we interpreted as evidence of cell percolation between lesions via haematogenous self-seeding. CONCLUSIONS: Stage progression in MF is associated with Th2/Th9 polarization of malignant cells, activation of proliferation, survival, as well as increased genomic instability. Global transcriptomic changes in multiple lesions may be caused by haematogenous cell percolation between discrete skin lesions.

Providing more balanced information on the harms and benefits of cervical cancer screening: A randomized survey among US and Norwegian women.

We aimed to identify how additional information about benefits and harms of cervical cancer (CC) screening impacted intention to participate in screening, what type of information on harms women preferred receiving, from whom, and whether it differed between two national healthcare settings. We conducted a survey that randomized screen-eligible women in the United States (n = 1084) and Norway (n = 1060) into four groups according to the timing of introducing additional information. We found that additional information did not significantly impact stated intentions-to-participate in screening or follow-up testing in either country; however, the proportion of Norwegian women stating uncertainty about seeking precancer treatment increased from 7.9% to 14.3% (p = 0.012). Women reported strong system-specific preferences for sources of information: Norwegians (59%) preferred it come from a national public health agency while Americans (59%) preferred it come from a specialist care provider. Regression models revealed having a prior Pap-test was the most important predictor of intentions-to-participate in both countries, while having lower income reduced the probabilities of intentions-to-follow-up and seek precancer treatment among U.S. women. These results suggest that additional information on harms is unlikely to reduce participation in CC screening but could increase decision uncertainty to seek treatment. Providing unbiased information would improve on the ethical principle of respect for autonomy and self-determination. However, the clinical impact of additional information on women's understanding of the trade-offs involved with CC screening should be investigated. Future studies should also consider country-specific socioeconomic barriers to screening if communication re-design initiatives aim to improve CC screening participation.

Reducing potential aerosol generation in flexible nasolaryngoscopy: a novel method.

BACKGROUND: Fibre-optic nasoendoscopy and fibre-optic laryngoscopy are high-risk procedures in the coronavirus disease 2019 era, as they are potential aerosol-generating procedures. Barrier protection remains key to preventing transmission. METHODS: A device was developed that patients can wear to reduce potential aerosol contamination of the surroundings. CONCLUSION: This device is simple, reproducible, easy to use, economical and well-tolerated. Full personal protection equipment should additionally be worn by the operator.

Feasibility of ovine and synthetic temporal bone models for simulation training in endoscopic ear surgery.

OBJECTIVE: Comparing the feasibility of ovine and synthetic temporal bones for simulating endoscopic ear surgery against the 'gold standard' of human cadaveric tissue. METHODS: A total of 10 candidates (5 trainees and 5 experts) performed endoscopic tympanoplasty on 3 models: Pettigrew temporal bones, ovine temporal bones and cadaveric temporal bones. Candidates completed a questionnaire assessing the face validity, global content validity and task-specific content validity of each model. RESULTS: Regarding ovine temporal bone validity, the median values were 4 (interquartile range = 4-4) for face validity, 4 (interquartile range = 4-4) for global content validity and 4 (interquartile range = 4-4) for task-specific content validity. For the Pettigrew temporal bone, the median values were 3.5 (interquartile range = 2.25-4) for face validity, 3 (interquartile range = 2.75-3) for global content validity and 3 (interquartile range = 2.5-3) for task-specific content validity. The ovine temporal bone was considered significantly superior to the Pettigrew temporal bone for the majority of validity categories assessed. CONCLUSION: Tympanoplasty is feasible in both the ovine temporal bone and the Pettigrew temporal bone. However, the ovine model was a significantly more realistic simulation tool.

Toward personalized dose-prescription in locally advanced non-small cell lung cancer: Validation of published normal tissue complication probability models.

PURPOSE: To identify published normal tissue complication probability (NTCP) models suitable for patient-specific dose-prescription in locally advanced non-small cell lung cancer (LA-NSCLC) through in-house validation. MATERIAL AND METHODS: From eight previously published candidate NTCP models (≥grade 2 acute esophagitis and radiation pneumonitis; AE2, RP2), patient-specific dose-responses were calculated using model variables and fractionation-corrected doses for 241 LA-NSCLC patients treated with chemo-IMRT to 50-80 Gy@1.8-2.0 Gy between 2004 and 2014 (AE2/RP2 rate: 50%/12%). A model was judged final if it significantly predicted AE2 or RP2 (p ≤ 0.05), was discriminative and well calibrated (AUC > 0.60; Hosmer-Lemeshow test pHL > 0.05), which were assessed as the median over 1000 bootstrap samples. RESULTS: Models for AE2 had superior discrimination to RP2 models (AUC = 0.63-0.65 vs. 0.51-0.65). The final AE2 model included mean esophageal dose and concurrent chemotherapy (AUC = 0.65; p < 0.0001). The final RP2 model was a slightly adjusted version of the RP2 model with the best discrimination, and included age, mean lung dose, and pulmonary comorbidity (AUC = 0.73; p < 0.0001). CONCLUSION: Of the eight investigated and published NTCP models, one model successfully described AE2 and one slightly adjusted model successfully described RP2 in the independent cohort. Estimates from these two NTCP models will, therefore, be considered internally when prescribing patient-specific doses in LA-NSCLC patients.

Preliminary outcomes of endoscopic middle-ear surgery in 103 cases: a UK experience.

BACKGROUND: Totally endoscopic ear surgery and endoscope-assisted microsurgery are still new concepts, with relatively few centres in the UK performing them. Advantages include better visualisation of difficult to reach areas, such as the sinus tympani, and limited external incisions. This paper reports our short-term outcomes for endoscopic middle-ear surgery. METHODS: A prospective review was conducted of the first 103 consecutive patients undergoing totally endoscopic ear surgery or endoscope-assisted microsurgery in 1 centre performed by 1 operator. The outcomes assessed were: tympanic membrane healing, audiological data and complications. RESULTS: Twenty-five patients underwent endoscope-assisted microsurgery, while 78 had totally endoscopic ear surgery. There were no reported cases of dead ear or permanent facial nerve palsy. The average air-bone gap following stapedectomy was 7.38 dB. The tympanic membrane healing rate was 89 per cent. CONCLUSION: Our results confirm that endoscopic middle-ear surgery is safe, and the short-term outcomes are comparable with conventional surgery.

The effect of light intensity on image quality in endoscopic ear surgery.

OBJECTIVES: Endoscopic ear surgery is a rapidly developing field with many advantages. But endoscopes can reach temperatures of over 110°C at the tip, raising safety concerns. Reducing the intensity of the light source reduces temperatures produced. However, quality of images at lower light intensities has not yet been studied. We set out to study the effect of light intensity on image quality in EES. DESIGN: Prospective study of patients undergoing EES from April to October 2016. Consecutive images of the same operative field at 10%, 30%, 50% and 100% light intensities were taken. Eight international experts were asked to each evaluate 100 anonymised, randomised images. SETTING: District General Hospital. PARTICIPANTS: Twenty patients. MAIN OUTCOME MEASURES: Images were evaluated on a 5-point Likert scale (1 = significantly worse than average; 5 = significantly better than average) for detail of anatomy; colour contrast; overall quality; and suitability for operating. RESULTS: Mean scores for photographs at 10%, 30%, 50% and 100% light intensity were 3.22 (SD 0.93), 3.15 (SD 0.84), 3.08 (SD 0.88) and 3.10 (SD 0.86), respectively. In ANOVA models for the scores on each of the scales (anatomy, colour contrast, overall quality and suitability for operating), the effects of rater and patient were highly significant (P < .0005) but light intensity was non-significant (P = .34, .32, .21, .15, respectively). CONCLUSION: Images taken during surgery by our endoscope and operative camera have no loss of quality when taken at lower light intensities. We recommend the surgeon considers use of lower light intensities in endoscopic ear surgery.

Promoter-Specific Hypomethylation Correlates with IL-1ß Overexpression in Tuberous Sclerosis Complex (TSC).

In tuberous sclerosis complex (TSC), overexpression of numerous genes associated with inflammation has been observed. Among different proinflammatory cytokines, interleukin-1ß (IL-1ß) has been shown to be significantly involved in epileptogenesis and maintenance of seizures. Recent evidence indicates that IL-1ß gene expression can be regulated by DNA methylation of its promoter. In the present study, we hypothesized that hypomethylation in the promoter region of the IL-1ß gene may underlie its overexpression observed in TSC brain tissue. Bisulfite sequencing was used to study the methylation status of the promoter region of the IL-1ß gene in TSC and control samples. We identified hypomethylation in the promoter region of the IL-1ß gene in TSC samples. IL-1ß is overexpressed in tubers, and gene expression is correlated with promoter hypomethylation at CpG and non-CpG sites. Our results provide the first evidence of epigenetic modulation of the IL-1ß signaling in TSC. Thus, strategies that target epigenetic alterations could offer new therapeutic avenues to control the persistent activation of interleukin-1ß-mediated inflammatory signaling in TSC brain.

Expression of microRNAs miR21, miR146a, and miR155 in tuberous sclerosis complex cortical tubers and their regulation in human astrocytes and SEGA-derived cell cultures.

Tuberous sclerosis complex (TSC) is a genetic disease presenting with multiple neurological symptoms including epilepsy, mental retardation, and autism. Abnormal activation of various inflammatory pathways has been observed in astrocytes in brain lesions associated with TSC. Increasing evidence supports the involvement of microRNAs in the regulation of astrocyte-mediated inflammatory response. To study the role of inflammation-related microRNAs in TSC, we employed real-time PCR and in situ hybridization to characterize the expression of miR21, miR146a, and miR155 in TSC lesions (cortical tubers and subependymal giant cell astrocytomas, SEGAs). We observed an increased expression of miR21, miR146a, and miR155 in TSC tubers compared with control and perituberal brain tissue. Expression was localized in dysmorphic neurons, giant cells, and reactive astrocytes and positively correlated with IL-1ß expression. In addition, cultured human astrocytes and SEGA-derived cell cultures were used to study the regulation of the expression of these miRNAs in response to the proinflammatory cytokine IL-1ß and to evaluate the effects of overexpression or knockdown of miR21, miR146a, and miR155 on inflammatory signaling. IL-1ß stimulation of cultured glial cells strongly induced intracellular miR21, miR146a, and miR155 expression, as well as miR146a extracellular release. IL-1ß signaling was differentially modulated by overexpression of miR155 or miR146a, which resulted in pro- or anti-inflammatory effects, respectively. This study provides supportive evidence that inflammation-related microRNAs play a role in TSC. In particular, miR146a and miR155 appear to be key players in the regulation of astrocyte-mediated inflammatory response, with miR146a as most interesting anti-inflammatory therapeutic candidate.

Role of apoptosis-related miRNAs in resveratrol-induced breast cancer cell death.

Breast cancer is the most frequently diagnosed cancer in women, and one of the leading causes of cancer-related deaths worldwide. Recent evidences indicate that dietary agents such as resveratrol may inhibit cancer progression through modulation of microRNAs (miRNAs). We demonstrate that resveratrol regulates apoptotic and cell cycle machinery in breast cancer cells by modulating key tumor-suppressive miRNAs including miR-125b-5p, miR-200c-3p, miR-409-3p, miR-122-5p and miR-542-3p. Resveratrol-mediated miRNA modulation regulates key anti-apoptotic and cell cycle proteins including Bcl-2, X-linked inhibitor of apoptosis protein and CDKs, which are critical for its activity. Modulating miRNAs with mimics or inhibitors further validated a key role for miR-542-3p in MCF-7 and miR-122-5p in MDA-MB-231 breast cancer cell death in response to resveratrol. In conclusion, this study reveals novel miRNAs modulated by resveratrol that have a key role in breast cancer cell death.

Interpreting pre-operative mastoid computed tomography images: comparison between operating surgeon, radiologist and operative findings.

OBJECTIVES: This study aimed to compare the interpretations of temporal bone computed tomography scans by an otologist and a radiologist with a special interest in temporal bone imaging. It also aimed to determine the usefulness of this imaging modality. METHODS: A head and neck radiologist and an otologist separately reported pre-operative computed tomography images using a structured proforma. The reports were then compared with operative findings to determine their accuracy and differences in interpretations. RESULTS: Forty-eight patients who underwent pre-operative computed tomography scans in a 30-month period were identified. Six patients were excluded because complete operative findings had not been recorded. Positive and negative predictive values and accuracy of the anatomical and pathological findings were calculated for 42 patients by both reporters. The accuracy was found to be less than 80 per cent, except for identification of the tegmen and lateral semicircular canal erosion. Overall, there was no significant difference in interpretations of computed tomography scans between reporters. There was a slight difference in interpretation for tympanic membrane retraction, facial canal erosion and lateral semicircular canal fistula and/or erosion. CONCLUSION: Pre-operative computed tomography scanning of the temporal bone is useful for predicting anatomy for surgical planning in patients with chronic otitis media, but its reliability remains questionable.

Are head bandages really required after middle-ear surgery? A systematic review.

OBJECTIVE: A systematic review was performed to evaluate the role and effectiveness of head bandages after routine elective middle-ear surgery. METHODS: Studies that compared the effectiveness of head bandage use after elective middle-ear surgery (e.g. myringoplasty, mastoidectomy and cochlear implantation) were identified using the following databases: Ovid Medline and Embase, the Ebsco collections, the Cochrane Library, PubMed, and Google Scholar. An initial search identified 71 articles. All titles and abstracts were reviewed. Thirteen relevant articles were inspected in more detail; of these, only five met the inclusion criteria. These included three randomised, controlled trials, one retrospective case series and one literature review. RESULTS: The three randomised, controlled trials (level of evidence 1b) showed no statistically significant differences in post-operative outcomes (in terms of complications) associated with head bandage use in middle-ear surgery. This finding was supported by the retrospective case series involving patients undergoing cochlear implantation. CONCLUSION: Current available evidence shows no advantage of head bandage use after middle-ear surgery. Head bandages may not be required after routine, uncomplicated middle-ear surgery.

Differential expression and clinical significance of three inflammation-related microRNAs in gangliogliomas.

PURPOSE: miR21, miR146, and miR155 represent a trio of microRNAs which has been shown to play a key role in the regulation of immune and inflammatory responses. In the present study, we investigated the differential expression and clinical significance of these three miRNAs in glioneuronal tumors (gangliogliomas, GGs) which are characterized by prominent activation of the innate immune response. METHODS: The expression levels of miR21, miR146, and miR155 were evaluated using Taqman PCR in 34 GGs, including 15 cases with sufficient amount of perilesional cortex. Their expression was correlated with the tumor features and the clinical history of epilepsy. In addition, in situ hybridization was used to evaluate their cellular distribution in both tumor and peritumoral cortex. RESULTS: Increased expression of miR146a was observed in both tumor and peritumoral cortex compared to control samples. miR146a was detected in both neuronal and astroglial cells. Tumor and peritumoral miR146a expression was negatively correlated with frequency of seizures and the density of activated microglial cells. Neuronal and astroglial expression was observed for both miR21 and miR155 with increased expression of miR21 within the tumor and miR155 in the peritumoral region. Negative correlations were observed between the miRNA levels and the expression of putative targets within the astroglial component of the tumor. CONCLUSION: We report a differential regulation of three miRNAs, known to be related to inflammation, in both tumor and peritumoral cortex of patients with GG. Moreover, our findings suggest a functional relationship between miR146a expression and epilepsy, either directly in epileptogenesis or as modulation of seizure activity.

Primary otological manifestations of granulomatosis with polyangiitis: a case series.

OBJECTIVES: A primary otological presentation of granulomatosis with polyangiitis is rare. We present four cases of granulomatosis with polyangiitis with different otological manifestations. CASE REPORT: A literature review of granulomatosis with polyangiitis cases presenting to otolaryngologists was undertaken. A case series review of four patients presenting within a 12-month period was also performed. One patient had serous otitis media which worsened after myringotomy. Two patients presented with acute ear infection and facial palsy and one with acute mastoiditis. All were positive for antineutrophilic cytoplasmic antibody, and three had positive findings upon histological analysis. CONCLUSION: When acute supposed ear infections fail to respond to treatment (antibiotics or surgery), rarer causes of the symptoms should be considered. By reporting this case series, we aim to improve the early diagnosis of granulomatosis with polyangiitis to enable timely treatment and prevent systemic involvement.

Normothermic ex vivo perfusion provides superior organ preservation and enables viability assessment of hearts from DCD donors.

The shortage of donors in cardiac transplantation may be alleviated by the use of allografts from donation after circulatory death (DCD) donors. We have previously shown that hearts exposed to 30 min warm ischemic time and then flushed with Celsior supplemented with agents that activate ischemic postconditioning pathways, show complete recovery on a blood-perfused ex vivo working heart apparatus. In this study, these findings were assessed in a porcine orthotopic heart transplant model. DCD hearts were preserved with either normothermic ex vivo perfusion (NEVP) using a clinically approved device, or with standard cold storage (CS) for 4 h. Orthotopic transplantation into recipient animals was subsequently undertaken. Five of six hearts preserved with NEVP demonstrated favorable lactate profiles during NEVP and all five could be weaned off cardiopulmonary bypass posttransplant, compared with 0 of 3 hearts preserved with CS (p < 0.05, Fisher's exact test). In conclusion, DCD hearts flushed with supplemented Celsior solution and preserved with NEVP display viability before and after transplantation. Viability studies of human DCD hearts using NEVP are warranted.

Control of eight predominant Eimeria spp. involved in economic coccidiosis of broiler chicken by a chemically characterized essential oil.

AIM: To control eight most predominant Eimeria spp. involved in the economic disease of coccidiosis in broiler chicken, by a chemically characterized essential oil of eucalyptus and peppermint. METHODS AND RESULTS: The experimental design consisted of 160 day-old-broiler chicks, divided into four equal groups (G1 , G2 , G3 and G4 ), with 40 birds per group. Each group was divided into four equal subgroups. Birds in G1 were deprived of essential oil treatment and of Eimeria challenge. Birds in G2 were unchallenged, and administered the essential oil in drinking water at 0.69 ml kg(-1) body weight. Birds in G3 were untreated with essential oil, and each of its four subgroups was challenged at a different age (14, 21, 28 and 35 days). Birds in G4 were treated with essential oil, and challenged in the same manner as for G3 . Equal number of birds from all subgroups (n = 10) were sacrificed at the sixth day after the time allocated for each challenge. The 6 day incubation period post challenge resulted in respective mean per cent weight increase in G2 and G1 birds equivalent to 57.8 and 53.1% (P < 0.05). In addition, the essential oil improved the per cent weight increase in challenged birds (54.6%) compared to the challenged-untreated birds (18.6%) (P < 0.05). The mean feed conversion, mortality, intestinal lesion scores and oocyst counts were significantly reduced in the challenged-treated birds compared to the challenged-untreated birds (P < 0.05). CONCLUSIONS: The results support the hypothesis of using the essential oils of eucalyptus and peppermint to control the most prevalent Eimeria spp. involved in coccidiosis of broiler chicken, helping in improvement of their production, alleviation of lesions and reduction in intestinal oocyst counts. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides information about the possibility of using this blend of essential oil as a coccidiostat for the protection of broiler chickens against the prevalent eight Eimeria spp. of coccidiosis.

Expression of neurodegenerative disease-related proteins and caspase-3 in glioneuronal tumours.

AIMS: Recent evidence supports the activation of mechanisms underlying cellular ageing and neurodegeneration in developmental lesions associated with epilepsy. The present study examined the ongoing cell injury and vulnerability to neuronal degeneration in glioneuronal tumours (GNT). METHODS: We evaluated a series of GNT (n = 31 gangliogliomas, GG and n = 30 dysembryoplastic neuroepithelial tumours, DNT). Sections were processed for immunohistochemistry using markers for the evaluation of caspase-3 and neurodegeneration-related proteins/pathways and their expression was correlated with the tumour features and the clinical history of epilepsy. RESULTS: Both GG and DNT specimens contained caspase-3-positive cells. In GG, expression of activated caspase-3 was negatively correlated the with the BRAF V600E mutation status. We also observed an abnormal expression of death receptor-6 and ß-amyloid precursor protein (APP). Moreover, dysplastic neurones expressed p62, phosphorylated (p)TDP43 and pTau. Double labelling experiments showed colocalization of phosphorylated S6 (marker of mammalian target of rapamycin, mTOR, pathway activation) with pTau and p62. In GG, neuronal p62 expression was positively correlated with pS6. The immunoreactivity score (IRS) of caspase-3, APP, DR6, p62 and pTDP43 were found to be significantly higher in GG than in DNT. Expression of APP, DR6, pTau (in GG and DNT) and caspase-3 (in GG) positively correlated with duration of epilepsy. In GG, the expression of neuronal caspase-3, DR6 and glial p62 was associated with a worse postoperative seizure outcome. CONCLUSIONS: Our observations in GNT provide evidence of premature activation of mechanisms of neurodegeneration which are associated with the clinical course of epilepsy in patient with GG.

Increasing the tolerance of DCD hearts to warm ischemia by pharmacological postconditioning.

Donation after circulatory death (DCD) offers a potential additional source of cardiac allografts. We used a porcine asphyxia model to evaluate viability of DCD hearts subjected to warm ischemic times (WIT) of 20­40 min prior to flushing with Celsior (C) solution. We then assessed potential benefits of supplementing C with erythropoietin, glyceryl trinitrate and zoniporide (Cs), a combination that we have shown previously to activate ischemic postconditioning pathways. Hearts flushed with C/Cs were assessed for functional, biochemical and metabolic recovery on an ex vivo working heart apparatus. Hearts exposed to 20-min WIT showed full recovery of functional and metabolic profiles compared with control hearts (no WIT). Hearts subjected to 30- or 40-min WIT prior to C solution showed partial and no recovery, respectively. Hearts exposed to 30-min WIT and Cs solution displayed complete recovery, while hearts exposed to 40-min WIT and Cs solution demonstrated partial recovery. We conclude that DCD hearts flushed with C solution demonstrate complete recovery up to 20-min WIT after which there is rapid loss of viability. Cs extends the limit of WIT tolerability to 30 min. DCD hearts with ≤30-min WIT may be suitable for transplantation and warrant assessment in a transplant model.