The comparison between intratympanic gentamicin prehabilitation and postoperative virtual reality exposure to standard vestibular training in patients with vestibular schwannoma.

OBJECTIVE: Resection of the vestibular schwannoma causes acute peripheral vestibular loss. The process of central compensation starts immediately afterward. The rehabilitation goal is to support this process and restore the quality of life. MATERIALS AND METHODS: In this prospective single-center study, 67 consecutive patients underwent vestibular schwannoma resection (40 females, mean age 52 ± 12 years). The patients were divided into three groups: the prehabilitation with intratympanic gentamicin group, the virtual reality group (optokinetic stimulation via virtual reality goggles in the first ten days after the surgery), and the control group. All patients were examined with objective methods and completed questionnaires before the prehabilitation, before the surgery, at the hospital discharge, and after three months. RESULTS: Intratympanic gentamicin prehabilitation leads ipsilaterally to a significant aVOR reduction in all semicircular canals (p < 0.050), the increase of the unilateral weakness in air calorics (p = 0.026), and loss of cVEMPs responses (p = 0.017). Prehabilitation and postoperative exposure to virtual reality scenes improved the patient's perception of vertigo problems according to Dizziness Handicap Inventory (p = 0.039 and p = 0.076, respectively). These findings conform with the optokinetic testing results, which showed higher slow phase velocities at higher speeds (40 deg/s) in both targeted groups compared to the control group. CONCLUSION: Preoperative intratympanic gentamicin positively affects peripheral vestibular function, influencing balance perception after VS resection. In long-term follow-up, prehabilitation and postoperative exposure to virtual reality improve patients' quality of life in the field of vertigo problems.

Distinct leukocyte populations and cytokine secretion profiles define tumoral and peritumoral areas in renal cell carcinoma.

Renal cell carcinoma (RCC) is a common malignancy frequently diagnosed at the metastatic stage. We performed a comprehensive analysis of the tumor immune microenvironment (TIME) in RCC patients, including the peritumoral tissue microenvironment, to characterize the phenotypic patterns and functional characteristics of infiltrating immune cells. T cells from various compartments (peripheral blood, tumor, peritumoral area, and adjacent healthy renal tissue) were assessed using flow cytometry and Luminex analyses, both before and after T cell-specific stimulation, to evaluate activation status and migratory potential. Our findings demonstrated that tumor-infiltrating lymphocytes (TILs) exhibited heightened cytokine production compared to peritumoral T cells (pTILs), acting as the primary source of cytotoxic markers (IFN-γ, granzyme B, and FasL). CD8+ T cells primarily employed Fas Ligand for cytotoxicity, while CD4+ T cells relied on CD107a. In addition, a statistically significant negative correlation between patient mortality and the presence of CD4+CD107+ pTILs was demonstrated. The engagement with the PD-1/PD-L1 pathway was also more evident in CD4+ and CD8+ pTILs as opposed to TILs. PD-L1 expression in the non-leukocyte fraction of the tumor tissue was relatively lower than in their leukocytic counterparts and upon stimulation, peripheral blood T cells displayed much stronger responses to stimulation than TILs and pTILs. Our results suggest that tumor and peritumoral T cells exhibit limited responsiveness to additional activation signals, while peripheral T cells retain their capacity to respond to stimulatory signals.

HPV testing as an effective triage strategy in the follow-up after fertility-sparing treatment for glandular lesions of the uterine cervix.

OBJECTIVE: The management and surveillance of glandular pre-cancerous lesions of the uterine cervix present distinct challenges compared with squamous lesions, primarily attributed to the lower effectiveness of diagnostic methods such as cytology or colposcopy. This study aimed to investigate the long-term safety of fertility-sparing treatment for adenocarcinoma in situ and microinvasive adenocarcinoma of the cervix, while identifying factors associated with recurrence, with a particular emphasis on the role of human papillomavirus (HPV) testing. METHODS: We retrospectively reviewed data from all patients with histopathologically confirmed adenocarcinoma in situ or microinvasive cervical adenocarcinoma who received treatment at a single center between 2002 and 2023. The study involved the examination of consecutive surgical specimens and the follow-up details. Factors associated with recurrence were assessed in a subgroup of patients with available long-term follow-up data (at least 6 months). RESULTS: In total, 143 patients (112 with adenocarcinoma in situ and 31 with adenocarcinoma) were included in the analysis. Among the 86 patients who underwent fertility-sparing treatment, the recurrence rate was 9% (12% for adenocarcinoma in situ and 4% for adenocarcinoma) during a median follow-up period of 56.6 months (range 7-179). No patients who were HPV negative experienced recurrence during the follow-up period. In contrast, among patients who were HPV positive, the recurrence rate was 38%. Additionally, HPV 16/18 positivity displayed a notable association with a higher risk of recurrence compared with the other high-risk genotypes, although this difference did not reach statistical significance (83% vs 10%; p=0.083, log-rank). CONCLUSION: Our retrospective study demonstrated a significant association between the risk of recurrence and HPV status during the follow-up period. Consequently, long-term follow-up utilizing HPV testing and genotyping appears to be a secure alternative to a hysterectomy.

Does vestibular function correlate with objective MRI findings after vestibular schwannoma surgery?

Objective: Vestibular schwannoma surgery leads to acute unilateral vestibular loss. In some patients, however, the process of post-operatively initiated central compensation proceeds more rapidly than in others. This study aimed to evaluate post-operative vestibular function and correlate it with morphological findings of MRI scans. Methods: The study included 29 patients who underwent surgery for vestibular schwannoma. Vestibular function was analysed post-operatively by video head impulse test (vHIT). Subjective symptoms were evaluated using validated questionnaires. All patients underwent MRI 3 months post-operatively, and the presence of the facial and vestibulocochlear nerves in the internal auditory canal was assessed. Results: The vestibulo-ocular reflex gain measured by the vHIT correlated positively with audiological findings. Subjective perception of vestibular disorder did not correlate with objectively measured vestibular impairment or with MRI findings. Conclusions: After the resection of vestibular schwannoma, some patients may still have preserved vestibular function as measured by vHIT. The preserved function does not correlate with subjective symptoms. Patients with partially deteriorated vestibular function showed lower sensitivity to combined stimuli.

Oncostatin M and Nivolumab Affect the Cytotoxic T-Cell Proportions and the Susceptibility to TRAIL-Induced Death in Non-Leukocyte Cell Subpopulations in Soft Tissue Sarcomas.

INTRODUCTION: Soft tissue sarcomas (STSs) are malignant tumors arising from mesenchymal tissues. Patients with advanced and metastatic STSs have low overall survival rates and relatively limited treatment options. Oncostatin M (OSM) is a pleiotropic cytokine that was shown to carry both pro- and anti-tumorigenic properties in various cancer types. However, the role of OSM in STSs has not yet been elucidated. Moreover, the potential additive effects of combining OSM and anti-PD-1 therapy have not been carried out so far. METHODS: The aim of this study was to determine the effects of in vitro OSM administration on liposarcoma, leiomyosarcoma, and myxofibrosarcoma immune cells isolated from peripheral blood and tumor tissues and the potential cooperative nature of OSM and nivolumab in treating these STSs. We designed a cohort study to explore novel histology-driven therapies in our target STSs. The immune cells were isolated from the peripheral blood and tumors of patients with STS, and the proportions and phenotypes of immune cells were evaluated with flow cytometry after cultivation with therapeutic monoclonal antibodies. RESULTS: The proportion of peripheral CD45+ cells was not affected by OSM but was significantly increased by nivolumab, whereas both treatments had an effect on CD8+ T cells. In tumor tissues, CD8+ T cell and CD45‒ TRAIL+ cell cultures were boosted by nivolumab and significantly enriched by OSM. Our data suggest that OSM may play a role in the treatment of leiomyosarcoma, myxofibrosarcoma, and liposarcoma. CONCLUSION: In conclusion, the biological efficacy of OSM is reflected in the tumor microenvironment rather than in the peripheral blood of the patients in our cohort, and nivolumab could potentiate its mechanism of action in selected cases. Nevertheless, more histotype-tailored studies are needed to fully understand the functions of OSM in STSs.

CCL2, CCL8, CXCL12 chemokines in resectable non-small cell lung cancer (NSCLC).

BACKGROUND: Complex networks of chemokines are part of the immune reaction targeted against tumor cells. Chemokines influence cancer growth. It is unclear whether the concentrations of chemokines at the time of NSCLC (non-small cell lung cancer) diagnosis differ from healthy controls and reflect the extent of NSCLC. AIMS: To compare chemokine concentrations (CCL2, CCL8, CXCL12) in the plasma of patients with resectable NSCLC to those without cancer. To determine whether the chemokine concentrations differ relative to the stage of disease. METHODS: Sixty-nine patients undergoing surgery for proven/suspected NSCLC were enrolled. They underwent standard diagnostic and staging procedures to determine resectability, surgery was performed. Forty-two patients were diagnosed with NSCLC, while 27patients had benign lung lesions and functioned as the control group. Chemokine concentrations in peripheral blood were assessed using ELISA. Parametric statistics were used for the analysis of results. RESULTS: There were no differences in plasma chemokine concentrations in NSCLC patients compared to controls. CXCL12 concentrations correlated positively with tumor extent expressed as clinical stage, (mean values: stage I 5.08 ng/mL, SEM 0.59; stage II and IIIA 7.82 ng/mL; SEM 1.06; P=0.022). Patients with NSCLC stages II+IIIA had significantly higher CXCL12 concentrations than controls (mean values: stage II+IIIA 7.82 ng/mL; SEM 1.06; controls 5.3 ng/mL; SEM 0.46; P=0.017). CONCLUSION: CXCL12 was related to tumor growth and could potentially be used as a biomarker of advanced disease.

Endocrinological aspects of pituitary adenoma surgery in Europe.

Hormone-secreting adenomas are treated in many neurosurgical centers within Europe. The goal of the survey is to understand variance in practice management of pituitary tumors amongst neurosurgical centers. A list of departments performing pituitary surgery was created. The survey consisted of 58 questions. This study focuses on neurosurgical care of hormone-secreting adenomas. For analysis, the departments were divided into four subgroups: academic/non-academic, high-volume/low-volume, "mainly endoscopic/mainly microscopic practice" and geographical regions. Data from 254 departments from 34 countries were obtained. Most centers surgically treat 1-5 hormone-secreting adenomas per year. In prolactinomas this is the case in 194 centers, (76.4%), in GH-secreting adenomas: 133 centers, (52.4%), ACTH-secreting adenomas: 172 centers, (69.8%). Surgery as a primary treatment of prolactinomas is considered in 64 centers (25.2%). In 47 centers (18.8%), GH-secreting microadenomas are often treated pharmacologically first. Debulking surgery for an invasive GH-secreting adenoma in which hormonal remission is not a realistic goal of the surgery and the patient has no visual deficit surgery is always or mostly indicated in 156 centers (62.9%). Routine postoperative hydrocortisone replacement therapy is administered in 147 centers (58.6%). Our survey shows that in most centers, few hormone-secreting adenomas are treated per year. In about 25% of the centers, prolactinoma surgery may be regarded as first-line treatment; in about 20% of the centers, medical treatment is the first-line treatment for GH-secreting adenomas. Pretreatment for ACTH-secreting adenomas is routinely used in 21% of centers. This survey may serve as plea for neurosurgical care centralization of hormone-secreting adenomas.

Pituitary Adenoma Surgery Survey: Neurosurgical Centers and Pituitary Adenomas.

Objective: Pituitary adenoma surgery has evolved rapidly in recent decades. This study aims to determine current practice across a wide range of European neurosurgical centers. Methods: A list of eligible departments performing pituitary adenoma surgery was created. The survey consisted of 58 questions. For analysis, the departments were divided into four subgroups: academic/nonacademic, high-volume/low-volume, "mainly endoscopic/mainly microscopic practice," and geographical regions. Results: Data from 254 departments from 34 countries were obtained. In 108 centers (42.5%), <30 pituitary adenomas were operated per year. Twenty (7.9%) centers performed >100 adenoma surgeries per year. Number of neurosurgeons performing endonasal surgeries are as follows: 1 in 24.9% of centers and 2 in 49.8% of centers. All residents assisted endonasal surgeries in 126 centers (49.8%). In 28 centers (21.1%), all residents performed endonasal surgery under supervision during residency. In 141 centers (56.8%), the endoscopic approach was used in >90% of the surgeries. Regular pituitary board (either weekly or once a month) meetings were held in 147 centers (56.3%). Nonfunctioning adenomas represent >70% of pituitary caseload in 149 centers (58.7%). Conclusions: In our survey, most centers perform less than 100 surgeries for pituitary adenomas. In most centers, pituitary surgeries are performed by one or two neurosurgeons. Residents have a limited exposure to this type of surgery, and the formal pituitary board is not a standard. Nonfunctioning adenomas make up most of surgically treated adenomas. This study can serve as a benchmark for further analyses of pituitary adenoma centers in Europe.

Tumor control and radiobiological fingerprint after Gamma Knife radiosurgery for posterior fossa meningiomas: A series of 46 consecutive cases.

INTRODUCTION: Gamma Knife radiosurgery (GKR) can be a valuable treatment option for posterior cranial fossa meningiomas (PCFM). We retrospectively analyzed outcomes of GKR for PCFM. METHODS: Were included forty-six patients with 47 PCFM. Primary endpoint was tumor control. Secondary endpoint was clinical improvement. Biologically effective dose (BED) was evaluated in relationship to primary and secondary outcomes. Mean marginal dose was 12.4 Gy (median 12, 12-14). Mean BED was 63.6 Gy (median 65, 49.1-88.3). Mean target volume (TV) was 2.21 cc (range 0.3-8.9 cc). RESULTS: Overall tumor control rate was 93.6% (44/47) after mean follow-up of 47.8 months ± 28.46 months (median 45.5, range 6-108). Radiological progression-free survival at 5 years was 94%. Higher pretherapeutic TVs were predictive for higher likelihood of tumor progression (Odds ratio, OR 1.448, 95% confidence interval - CI 1.001-2.093, p = 0.049). At last clinical follow-up, 28 patients (71.8%) remained stable, 10 (25.6%) improved and 1 patient (2.6%) worsened. Using logistic regression, the relationship between BED and clinical improvement was assessed (OR 0.903, standard error 0.59, coefficient 0.79-1.027, CI -0.10; 0.01; p = 0.14). The highest probability of clinical improvement corresponded to a range of BED values between 56 and 61 Gy. CONCLUSION: Primary GKR for PCFM is safe and effective. Higher pretherapeutic TV was predictor of volumetric progression. Highest probability of clinical improvement might correspond to a range of BED values between 56 and 61 Gy, although this was not statistically significant. The importance of BED should be further validated in larger cohorts, other anatomical locations and other pathologies.

What is the current clinical practice in pituitary adenoma surgery in Europe? European Pituitary Adenoma Surgery Survey (EU-PASS) results-technical part.

Pituitary adenoma surgery has evolved rapidly in recent decades, changing clinical practice markedly and raising new challenges. There is no current consensus or guidelines for perioperative care that includes possible complication management. This study aims to determine current practice across European neurosurgical centres. We created a list of eligible departments performing pituitary adenoma surgery based on cooperation with EANS, national neurosurgical societies, and personal communication with local neurosurgeons. We contacted the chairpersons from each department and asked them (or another responsible neurosurgeon) to fill out the survey. The survey consisted of 58 questions. For further analysis, departments were divided into subgroups: "academic"/ "non-academic centre", "high-volume"/"low-volume", "mainly endoscopic"/ "mainly microscopic"/ "mixed practise", and by geographical regions. Data from 254 departments from 34 countries were obtained. The average time to complete the survey was 18 min. Notably, the endoscopic approach is the predominant surgical approach in Europe, used in 56.8% of the centres. In routine cases without intraoperative cerebrospinal fluid leak, high-volume centres are less pedantic with sellar closure when compared with low-volume centres (p < 0.001). On the other hand, when a postoperative cerebrospinal fluid leak occurs, high-volume centres are more active and indicate early reoperation (p = 0.013). Less than 15% of the participating centres perform early postoperative MRI scans. Marked variation was noted among different groups of respondents and some contentious issues are discussed. Such information can encourage useful debate about the reasons for the variations seen and perhaps help develop standardised protocols to improve patient outcomes. A future research focus is to compare European results with other regions.

IL-40: A New B Cell-Associated Cytokine Up-Regulated in Rheumatoid Arthritis Decreases Following the Rituximab Therapy and Correlates With Disease Activity, Autoantibodies, and NETosis.

Background: Interleukin 40 (IL-40) is a newly identified B cell-associated cytokine implicated in humoral immune responses and B cell homeostasis. As B cells play a pivotal role in autoimmunity, we investigated the function of IL-40 in rheumatoid arthritis (RA). Methods: IL-40 expression was determined in the synovial tissue from RA and osteoarthritis (OA) patients. IL-40 was analysed in the serum/synovial fluid of patients with RA (n=50), systemic lupus erythematosus (SLE, n=69), OA (n=44), and healthy controls (HC, n=50). We assessed the changes of IL-40 levels in RA patients following the B cell depletion by rituximab (n=29) or after the TNF inhibition by adalimumab (n=25). We examined the relationship between IL-40, disease activity, autoantibodies, cytokines, and NETosis markers. Effect of IL-40 on synovial fibroblasts was determined. Results: IL-40 was overexpressed in RA synovial tissue, particularly by synovial lining and infiltrating immune cells. The levels of IL-40 were up-regulated in the synovial fluid of RA versus OA patients (p<0.0001). Similarly, IL-40 was increased in the serum of RA patients compared to HC, OA, or SLE (p<0.0001 for all) and decreased after 16 and 24 weeks (p<0.01 and p<0.01) following rituximab treatment. No significant effect of adalimumab on IL-40 was observed. IL-40 levels in RA patients correlated with rheumatoid factor-IgM and anti-cyclic citrullinated peptides (anti-CCP) in the serum (p<0.0001 and p<0.01), as well as in the synovial fluid (p<0.0001 and p<0.001). Synovial fluid IL-40 was also associated with disease activity score DAS28 (p<0.05), synovial fluid leukocyte count (p<0.01), neutrophil attractants IL-8 (p<0.01), MIP-1α (p<0.01), and markers of neutrophil extracellular traps externalization (NETosis) such as proteinase 3 (p<0.0001) and neutrophil elastase (p<0.0001). Synovial fibroblasts exposed to IL-40 increased the secretion of IL-8 (p<0.01), MCP-1 (p<0.05), and MMP-13 (p<0.01) compared to the unstimulated cells. Conclusions: We show the up-regulation of IL-40 in RA and its decrease following B cell depleting therapy. The association of IL-40 with autoantibodies, chemokines, and markers of NETosis may imply its potential involvement in RA development. Moreover, IL-40 up-regulates the secretion of chemokines and MMP-13 in synovial fibroblasts, indicating its role in the regulation of inflammation and tissue destruction in RA.

Myopic Correction with Iris-Fixated Phakic Intraocular Lenses: Twelve-Year Results.

PURPOSE: To evaluate a 12-year follow-up of myopic patients after iris-fixated phakic intraocular lenses (IF pIOLs) implantation. Setting. Ophthalmology Department, Military University Hospital in Prague (Czech Republic). DESIGN: Single-center retrospective cohort study. METHODS: We describe the results of a cohort study that included 85 eyes of 46 myopic patients who underwent implantation of Verisyse myopia, Veriflex, and Verisyse myopia toric (all Abbott Medical Optics, Inc.) intraocular lenses. Refractive functions and adverse events were assessed preoperatively, at 6 months, and 1, 2, 5, and 12 years after IF pIOL implantation. RESULTS: Mean spherical equivalent was measured as -9.37 ± 2.87 D, 0.14 ± 0.61 D, and -0.42 ± 1.08 D, preoperatively, at 6 months and 12 years postoperatively, respectively. There was a significant reduction in the cylinder after surgery. At 12 years postoperatively, 90% of eyes had uncorrected distance visual acuity (UDVA) of 20/40 and 64% of 20/20. The safety index was 1.10 for the whole postoperative follow-up period. We found cataract formation in 3 eyes (3.5%). The endothelial cells loss (EC loss) directly caused by IF pIOL implantation was 6.0%, 8.10%, 12.8%, and 11.9%, at 1, 2, 5, and 12 years, respectively. In our cohort, 95% of eyes lost a higher percentage of EC than would be expected from a physiological loss at 12 years postoperatively. We found a significant negative interaction between preoperative pachymetry and EC loss, indicating that the lower pachymetry leads to a faster decline in endothelial cells density (ECD). IF pIOL re-enclavation was found in 28% of eyes. 7% of subluxations were caused by trauma. The mean time of nontraumatic re-enclavation was 6 years postoperatively. CONCLUSIONS: The study confirmed the advantages of IF pIOL implantation due to rapid visual recovery and stable visual function over the 12-year follow-up and also showed the influence of lower corneal pachymetry regarding EC loss.

Fas-Fas Ligand Interplay in the Periphery of Salivary Gland Carcinomas as a New Checkpoint Predictor for Disease Severity and Immunotherapy Response.

Salivary gland carcinomas (SGCs) are extremely morphologically heterogeneous, and treatment options for this disease are limited. Immunotherapy with immune checkpoint inhibitors (ICIs) represents a revolutionary treatment approach. However, SGCs remain largely resistant to this therapy. An increasing body of evidence suggests that resistance to ICI therapy is modulated by the Fas (CD95)-Fas ligand (FasL, CD178) interplay between tumor cells and immune cells. In this study, we examined the Fas-FasL interplay between tumor cells and tumor-infiltrating immune cells (TIICs) in the center and periphery of SGCs from 62 patients. We found that the Fas-expressing tumor cells accumulated in the center of SGC tumors with increasing tumor stage. Furthermore, this accumulation occurred regardless of the presence of TIICs expressing high levels of FasL. On the contrary, a loss of Fas-expressing TIICs with increasing tumor stage was found in the tumor periphery, whereas FasL expression in tumor cells in the tumor periphery correlated with tumor stage. These data suggest that SGC cells are resistant to FasL-induced apoptosis by TIICs but could utilize FasL to eliminate these cells in high-stage tumors to provide resistance to immunotherapy.

The Periphery of Salivary Gland Carcinoma Tumors Reveals a PD-L1/PD-1 Biomarker Niche for the Evaluation of Disease Severity and Tumor-Immune System Interplay.

The treatment options for patients with advanced salivary gland cancers (SGCs) are limited. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, the response to ICI immunotherapy is largely driven by the immune cell signatures within the tumor tissue and the para-tumoral tissue compartments. To date, there are no data on the expression of programed cell death protein-1/programed cell death protein-ligand 1 (PD-1/PD-L1) in SGC, which may enable the implementation of ICI immunotherapy for this disease. Thus, we performed an immunohistochemical analysis of PD-1 and PD-L1 expression in tumor cells and tumor-infiltrating immune cells (TIICs) in the tumor center and periphery of 62 SGC patients. The tumor periphery showed significantly higher expression of PD-L1 in tumor cells than in TIICs. Moreover, peripheral TIICs had significantly higher PD-1 expression than peripheral tumor cells. PD-1-positive tumor cells were detected exclusively in the tumor center of high-grade tumors, and most importantly, the presence of lymph node (LN) metastases and primary tumor stage significantly correlated with the presence of PD-L1-positive tumor cells in the tumor periphery. The PD-1/PD-L1 molecular signatures in SGC are clustered predominantly in the tumor periphery, reflect disease severity, and may predict the response to ICI immunotherapy in SGC patients.

Are E-cigarette Users a Unique Group of Smokers? Latent Class Analysis of the National Youth Tobacco Survey.

We used data from the 2014 National Youth Tobacco Survey to examine patterns of cigarette smoking behavior and tobacco use. In light of the recent upsurge in e-cigarette use, we modeled current use and future intentions to use vape products along with combustible cigarette smoking and other tobacco products (i.e., cigars, cigarillos, chew, snuff, and dip). Latent class analyses indicated four discrete classes of smokers including a nominally involved class with very modest levels of tobacco product use, a class blending e-cigarette and cigars, a class of youth who predominantly use combustible cigarettes, and a group reporting indiscriminate use of almost all tobacco products excluding chew. Tests of invariance in item response probabilities and latent class proportions showed little variation across race and gender, albeit a new class of combustible cigarette and e-cigarette users emerged when examined by grade. Members of the heavy smoking and tobacco use class were more likely to be male, White, and older. Predictors of class membership included expectancies (perceived benefits of use), perceived harm (risk), media exposure, tobacco dependence, and the desire to quit. Findings are discussed in terms of characterizing risk among already smoking youth and how actionable prevention measures can be incorporated into existing universal and indicated programs that target reducing tobacco use and smoking behaviors.

Assessment of visual sensation, psychiatric profile and quality of life following vestibular schwannoma surgery in patients prehabituated by chemical vestibular ablation.

AIMS: Preoperative chemical vestibular ablation can reduce vestibular symptoms in patients who have gone through vestibular schwannoma resection. The goal of this study was to determine whether chemical vestibular prehabituation influences the patients' post-operative perception of visual stimulation, mental status and quality of life. We also tried to find out whether increases of optokinetic nystagmus, measured by routine electronystagmography, correlate with subjective symptoms. METHODS: We preoperatively administered (2 months prior to surgery) 0.5 - 1.0 mL of 40 mg/mL nonbuffered gentamicin in three intratympanic instillations in 11 patients. Head impulse and caloric tests confirmed reduction of vestibular function in all patients. The control group consisted of 21 patients. Quality of life in both groups was evaluated using the Glasgow Benefit Inventory, the Glasgow Health Status Inventory and the Dizziness Handicap Inventory questionnaires. Visual symptoms and optokinetic sensation were evaluated using a specific questionnaire developed by our team and by measuring gains preoperatively and postoperatively in both groups using routine electronystagmography. The psychological profile was evaluated using the Zung Self-Rating Depression Scale and the Generalised Anxiety Disorder Assessment questionnaires. RESULTS: There were no statistically significant differences between both groups with regards to the results of the questionnaires. Patients who received preoperative gentamicin were less sensitive to visual stimulation (P<0.10) and many of them had a significantly higher gain in the optokinetic nystagmus than the control group in the preoperative stage. CONCLUSION: Pre-treatment with gentamicin helps to lower anxiety levels in patients and improves their general postoperative status. Pre-treated patients are also less sensitive to optokinetic stimulation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03638310.

The impact of co-morbidities on a 6-year survival after methanol mass poisoning outbreak: possible role of metabolic formaldehyde.

Context: The influence of co-morbid conditions on the outcome of acute methanol poisoning in mass poisoning outbreaks is not known.Objective: The objective of this is to study the impact of burden of co-morbidities, complications, and methanol-induced brain lesions on hospital, follow-up, and total mortality.Methods: All patients hospitalized with methanol poisoning during a mass poisoning outbreak were followed in a prospective cohort study until death or final follow-up after 6 years. The age-adjusted Charlson co-morbidity index (ACCI) score was calculated for each patient. A multivariate Cox regression model was used to calculate the adjusted hazards ratio (HR) for death. The survival was modeled using the Kaplan-Meier method.Results: Of 108 patients (mean age with SD 50.9 ± 2.6 years), 24 (54.4 ± 5.9 years) died during hospitalization (mean survival with SD 8 ± 4 days) and 84 (49.9 ± 3.0 years; p = .159) were discharged, including 27 with methanol-induced brain lesions. Of the discharged patients, 15 (56.3 ± 6.8 years) died during the follow-up (mean survival 37 ± 11 months) and 69 (48.5 ± 3.3 years; p = .044) survived. The hospital mortality was 22%, the follow-up mortality was 18%; the total mortality was 36%. Cardiac/respiratory arrest, acute respiratory failure, multiorgan failure syndrome, and arterial hypotension increased the HR for hospital and total (but not follow-up) mortality after adjustment for age, sex, and arterial pH (all p < .05). All patients who died in the hospital had at least one complication. A higher ACCI score was associated with greater total mortality (HR 1.22; 1.00-1.48 95% CI; p = .046). Of those who died, 35 (90%) had a moderate-to-high ACCI. The Kaplan-Meier curve demonstrated that patients with a high ACCI had greater follow-up mortality compared to ones with low (p = .027) or moderate (p = .020) scores. For the patients who died during follow-up, cancers of different localizations were responsible for 7/15 (47%) of the deaths.Conclusions: The character and number of complications affected hospital but not follow-up mortality, while the burden of co-morbidities affected follow-up mortality. Methanol-induced brain lesions did not affect follow-up mortality. Relatively high cancer mortality rate may be associated with acute exposure to metabolic formaldehyde produced by methanol oxidation.

Moderate sensorineural hearing loss is typical for DFNB16 caused by various types of mutations affecting the STRC gene.

INTRODUCTION: Hearing loss is the most frequent sensory disorder and is genetically extremely heterogeneous. By far the most frequent cause of nonsyndromic autosomal recessive hearing loss (AR-NSHL) are biallelic pathogenic mutations in the GJB2 gene causing DFNB1. The worldwide search for the second most common type of AR-NSHL took almost two decades. Recently reported alterations (mostly deletions) of the STRC gene, also named DFNB16, seem to be the second most frequent cause of AR-NSHL. Genetic testing of STRC is very challenging due to the highly homologous pseudogene. Anecdotal evidence from single patients shows that STRC mutations have their typical audiological findings and patients usually have moderate hearing loss. The aim of this study is to discover if audiological findings in patients with biallelic pathogenic mutations affecting STRC have the characteristic features and shape of audiological curves and if there are genotype/phenotype correlations in relation to various types of STRC mutations. METHODS: Eleven hearing loss patients with pathogenic mutations on both alleles of the STRC gene were detected during routine genetic examination of AR-NSHL patients. Audiological examination consisted of pure tone audiometry, stapedial reflexes, tympanometry and otoacoustic emission tests. RESULTS: The threshold of pure tone average (PTA) was 46 dB and otoacoustic emissions were not detectable in these DFNB16 patients. All patients were without vestibular irritation or asymmetry. CONCLUSION: Moderate sensorineural hearing loss is typical for DFNB16-associated hearing loss and there are no significant differences in audiological phenotypes among different types of mutations affecting STRC.

Comparison of bioelectrical impedance analysis and air displacement plethysmography / Comparación de análisis de impedancia bioeléctrica y pletismografía de desplazamiento de aire

The measurement of body composition has become an important component in the diagnosis of health, physical conditioning and nutritional status. The aim of this study was to compare two methods of detecting body composition, bioelectrical impedance and air displacement plethysmography for athletes and non-athletes. Specifically, we compared the parameters as fat mass, fat free mass and the value of basal metabolic rate. A sample size of 52 men (age 26.2 ± 5.4 years) that included a group of mixed martial arts (MMA) fighters (n = 31, age 27.2 ± 5.5 years) and a group of the non-athletes (n =21, age 24.6 ± 5.1 years). Both groups were measured by bioelectrical impedance and air displacement plethysmography. Significant differences in % body fat (p<0.05) and fat-free mass (p<0.05) were noted between bioelectrical impedance and air displacement plethysmography of non-athletes, but there were no significant differences for athletes. Furthermore, there was a significant difference (p<0.001) of basal metabolic rate between bioelectrical impedance and air displacement plethysmography, but the correlation with fat free mass was very strong for both methods. Therefore, the use of bioelectrical impedance and air displacement plethysmography may be useful for detecting changes in body composition, but their accuracy is controversial and for this reason we recommend using only one method and not combining them.

La medición de la composición corporal se ha convertido en un componente importante en el diagnóstico de la salud, el acondicionamiento físico y el estado nutricional. El objetivo de este estudio fue comparar dos métodos para detectar la composición corporal, la impedancia bioeléctrica y la pletismografía de desplazamiento de aire para atletas y no atletas. Específicamente, comparamos los parámetros como masa grasa, masa libre de grasa y el valor de la tasa metabólica basal. Un tamaño de muestra de 52 hombres (edad 26,2 ± 5,4 años) de un grupo de luchadores de artes marciales mixtas (MMA) (n = 31, edad 27,2 ± 5,5 años) y un grupo de no deportistas (n = 21, edad 24,6 ± 5,1 años). Ambos grupos se midieron por impedancia bioeléctrica y pletismografía de desplazamiento de aire. Se observaron diferencias significativas en el porcentaje de grasa corporal (p<0,05) y la masa libre de grasa (p<0,05) entre la impedancia bioeléctrica y la pletismografía de desplazamiento de aire de los no deportistas, sin embargo no hubo diferencias significativas en los atletas. Además, se observó una diferencia significativa (p<0,001) de la tasa metabólica basal entre la impedancia bioeléctrica y la pletismografía de desplazamiento de aire, pero la correlación con la masa libre de grasa fue importante para ambos métodos. Por lo tanto, el uso de la pletismografía de impedancia bioeléctrica y desplazamiento de aire puede ser útil para detectar cambios en la composición corporal, pero su precisión es controvertida por lo que recomendamos usar solo un método y no una combinación de ambos.

Prevalence and distribution of cartilage damage at the metacarpal head level in rheumatoid arthritis and osteoarthritis: an ultrasound study.

OBJECTIVES: To determine the prevalence and distribution of US-detected qualitative cartilage damage at metacarpal heads of patients with RA and hand OA. METHODS: Fifty-two RA patients and 34 patients with hand OA were enrolled. US examination of the metacarpal head cartilage from the II to V finger of both hands was performed. A total of 414 MCP joints in RA and 266 MCP joints in OA patients were scanned with a linear probe up to 22 MHz. Qualitative assessments using a previously described scoring system for cartilage damage were performed. The prevalence and distribution of cartilage damage were analysed. Multivariate regression analysis was used to determine the predictive value of age, gender, BMI, disease duration and the presence of RF and anti-CCP antibodies for US-detected cartilage damage. RESULTS: The metacarpal head cartilage was positive for cartilage damage in 35.7% (148/414) of MCP joints in RA and in 43.6% (116/266) of MCP joints in OA patients. In RA, the hyaline cartilage of the II and III metacarpal heads (bilaterally) was the most frequently affected. In OA, cartilage damage was more homogeneously distributed in all MCP joints. Multivariate regression analysis showed that age and disease duration, but not gender, BMI or autoantibody status, were independent predictors of US-detected cartilage damage in RA. CONCLUSION: Cartilage damage was found in more than one-third of the MCP joints in both RA and OA patients, and in RA patients, the II and III MCP joints were the most damaged.