Comorbid symptoms occurring during acute low-tone hearing loss (AHLH) as potential predictors of Meniere's disease

Acute low-tone sensorineural hearing loss (ALHL) is a type of idiopathic sudden sensorineural hearing loss. ALHL is rarely a solitary condition but rather co-occurs with vertigo and tinnitus, being an element of contemporary diagnostic criteria for Meniere's disease (MD). The goal of our present study was to determine the value of ALHL for the early diagnosis of MD in patients presenting in the emergency room with AWL as a main complaint. The files of 106 patients with ALHL who were admitted to the emergency room over the period of 7 years and 104 patients with acute high- tone sensorineural hearing loss (AHHL) from the same period were included in this retrospective study. Forty ALHL patients presented with recurrent episode of hearing loss and 66 remaining patients presented with ALHL for the first time. Of the latter group, 25 patients gave consent for the follow-up. First, we analyzed the difference in the occurrence of tinnitus and vertigo between the ALHL and AHHL groups. In patients with ALHL, the incidence of vertigo with tinnitus and the number of recurrent episodes were statistically higher than in patients with AHHL. Next, we focused on the ALHL follow-up group (25 patients). In that group, two patients had all MD symptoms at presentation, 18 had ALHL and tinnitus and five ALHL only. Of 18 patients with ALHL and tinnitus at admission, five developed vertigo and thus the triad of Meniere's disease. None of the five patients with AHLH as a sole symptom developed MD during the follow-up time but four of them have developed tinnitus. Patients with recurrent ALHL had significantly higher incidence of MD than the patients with first episode. We conclude that some patients who present with ALHL and concomitant tinnitus or have recurrent episodes of ALHL are more likely to develop Meniere's disease than these patients, who present with ALHL as a sole symptom. Nonetheless, we recommend otological follow-up for all patients presenting with ALHL

Incidence and survival of HNSCC patients living with HIV compared with HIV-negative HNSCC patients

Purpose: The aim was to analyze the incidence and survival of patients living with HIV (PLWH) with head and neck squamous cell carcinoma (HNSCC) and to compare with a control group of HIV-negative HNSCC patients. Methods: Clinicopathological data and predictors for overall survival (OS) and disease-free survival (DFS) were investigated (2009-2019). Results: 50 of 5151 HNSCC patients (0.97%) were PLWH, and 76% were smokers. Age <= 60 years, HIV-PCR <= 50 copies, CD4 cells <= 200/mm(3), cART treatment, T and UICC classification, oral cavity and nasal/paranasal sinuses, and therapy were significantly associated with OS in univariate analysis. In the multivariate analysis, only age and HIV-PCR independently predicted OS. The OS of the 50 PLWH was not significantly altered compared with the 5101 HIV-negative controls. However, OS and DFS were significantly inferior in advanced tumor stages of PLWH compared with an age-matched control group of 150 HIV-negative patients. Conclusions: PLWH were diagnosed with HNSCC at a significantly younger age compared to HIV-negative patients. Taking into account patient age at initial diagnosis, both OS and DFS rates in PLWH are significantly worse compared with a matched control group of HIV-negative patients in advanced tumor stages UICC III/IV. The prognosis (OS) is improved when taking cART treatment, the HIV viral load is undetectable and CD4 count is high

Perturbations of mesenchymal stromal cells after allogeneic hematopoietic cell transplantation predispose for bone marrow graft- versus-host-disease

Functional impairment of the bone marrow (BM) niche has been suggested as a major reason for prolonged cytopenia and secondary graft failure after allogeneic hematopoietic cell transplantation (alloHCT). Because mesenchymal stromal cells (MSCs) serve as multipotent progenitors for several niche components in the BM, they might play a key role in this process. We used collagenase digested trephine biopsies to directly quantify MSCs in 73 patients before (n = 18) and/or after alloHCT (n = 65). For the first time, we demonstrate that acute graft-versus-host disease (aGvHD, n = 39) is associated with a significant decrease in MSC numbers. MSC reduction can be observed even before the clinical onset of aGvHD (n = 10). Assessing MSCs instantly after biopsy collection revealed phenotypic and functional differences depending on the occurrence of aGvHD. These differences vanished during ex vivo expansion. The MSC endotypes observed revealed an enhanced population of donor-derived classical dendritic cells type 1 and alloreactive T cells as the causing agent for compartmental inflammation and MSC damage before clinical onset of aGvHD was ascertained. In conclusion, MSCs endotypes may constitute a predisposing conductor of alloreactivity after alloHCT preceding the clinical diagnosis of aGvHD

Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation

Background The role of allogeneic hematopoietic cell transplantation (alloHCT) in acute myeloid leukemia (AML) with mutated IDH1/2 has not been defined. Therefore, we analyzed a large cohort of 3234 AML patients in first complete remission (CR1) undergoing alloHCT or conventional chemo-consolidation and investigated outcome in respect to IDH1/2 mutational subgroups (IDH1 R132C, R132H and IDH2 R140Q, R172K). Methods Genomic DNA was extracted from bone marrow or peripheral blood samples at diagnosis and analyzed for IDH mutations with denaturing high-performance liquid chromatography, Sanger sequencing and targeted myeloid panel next-generation sequencing, respectively. Statistical as-treated analyses were performed using R and standard statistical methods (Kruskal–Wallis test for continuous variables, Chi-square test for categorical variables, Cox regression for univariate and multivariable models), incorporating alloHCT as a time-dependent covariate. Results Among 3234 patients achieving CR1, 7.8% harbored IDH1 mutations (36% R132C and 47% R132H) and 10.9% carried IDH2 mutations (77% R140Q and 19% R172K). 852 patients underwent alloHCT in CR1. Within the alloHCT group, 6.2% had an IDH1 mutation (43.4% R132C and 41.4% R132H) and 10% were characterized by an IDH2 mutation (71.8% R140Q and 24.7% R172K). Variants IDH1 R132C and IDH2 R172K showed a significant benefit from alloHCT for OS (p = .017 and p = .049) and RFS (HR = 0.42, p = .048 and p = .009) compared with chemotherapy only. AlloHCT in IDH2 R140Q mutated AML resulted in longer RFS (HR = 0.4, p = .002). Conclusion In this large as-treated analysis, we showed that alloHCT is able to overcome the negative prognostic impact of certain IDH mutational subclasses in first-line consolidation treatment and could pending prognostic validation, provide prognostic value for AML risk stratification and therapeutic decision making

Real-world experience of CPX-351 as first-line treatment for patients with acute myeloid leukemia

Abstract To investigate the efficacy and toxicities of CPX-351 outside a clinical trial, we analyzed 188 patients (median age 65 years, range 26–80) treated for therapy-related acute myeloid leukemia (t-AML, 29%) or AML with myelodysplasia-related changes (AML-MRC, 70%). Eighty-six percent received one, 14% two induction cycles, and 10% received consolidation (representing 22% of patients with CR/CRi) with CPX-351. Following induction, CR/CRi rate was 47% including 64% of patients with available information achieving measurable residual disease (MRD) negativity (<10−3) as measured by flow cytometry. After a median follow-up of 9.3 months, median overall survival (OS) was 21 months and 1-year OS rate 64%. In multivariate analysis, complex karyotype predicted lower response (p = 0.0001), while pretreatment with hypomethylating agents (p = 0.02) and adverse European LeukemiaNet 2017 genetic risk (p < 0.0001) were associated with lower OS. Allogeneic hematopoietic cell transplantation (allo-HCT) was performed in 116 patients (62%) resulting in promising outcome (median survival not reached, 1-year OS 73%), especially in MRD-negative patients (p = 0.048). With 69% of patients developing grade III/IV non-hematologic toxicity following induction and a day 30-mortality of 8% the safety profile was consistent with previous findings. These real-world data confirm CPX-351 as efficient treatment for these high-risk AML patients facilitating allo-HCT in many patients with promising outcome after transplantation

Diagnostics and therapy of nasal obstruction - Evaluation of conventional and development of innovative methods

Die Atmung über die Nase ist der einzig physiologische Atemweg. Für die chronische Rhinosinusitis, das Asthma bronchiale und das obstruktive Schlafapnoesyndrom ist in Übersichtsarbeiten und bevölkerungsbasierten Studien die Einschränkung der respiratorischen Funktion der Nase als bedeutende assoziierte Erkrankung nachgewiesen worden Die Analyse der klinischen und experimentellen Diagnostik- und Therapieverfahren bei eingeschränkter respiratorischer Funktion der Nase spielt damit eine vordringliche Rolle. In dieser Arbeit wurden ausgewählte klinische und experimentelle Diagnostik und Therapieverfahren der häufigsten Ursachen der eingeschränkten respiratorischen Funktion wie allergische Rhinitis, Hypertrophie der Conchae nasales inferiores und Nasenseptumperforation vorgestellt

Zusammenhang zwischen Umweltlärmbelästigung und Lärmempfindlichkeit

Die hohe Inzidenz von 300 bis 400 Herzinfarkten pro 100000 Personen der Bevölkerung in Deutschland pro Jahr zeigt die hohe gesundheitspolitische Bedeutung der Vorsorge. Die Betrachtung des Lärms als möglicher Kofaktor bei der Pathogenese des Herzinfarktes beziehungsweise des plötzlichen Herztodes bildete den Schwerpunkt der epidemiologischen Lärmstudie in Berlin. Die vorliegende Arbeit beschäftigte sich dabei vorwiegend mitdem Zusammenhang zwischen der Lärmempfindlichkeit und der Lärmbelästigung durch STrassenverkehrslärm. In den Analysen wurde die Korrelation zwischen beiden Variablen und die mögliche Beeinflussung dieser Korrelation durch soziodemografische Faktoren bestimmt. Im Rahmen einer Fall-Kontroll-Studie wurden für den Zeitraum von zwei Jahren die Angaben von 2235 Probanden ausgewertet. Die Datenerhebung fand im Rahmen eines circa einstündigen Interviews im Krankenhaus statt. Die Gruppe der Fälle bildeten die Patienten mit akuten Herzinfarkt. Die Kontrollgruppe setzteThe high incidence of heart attacks in Germany (approximately 300 to 400 cases for every 100000 people) emphasises the importance of heart attack prevention as a public health issue.Consequently, an epidemiologic study investigating chronic noise as a cofactor of the pathogenesis of the heart attack or sudden heart death is being conducted at the Charite University Hospital, Berlin. This thesis describes the relation between noise annoyance through road traffic noise and noise sensitivity as part of the aforementioned study. The correlations were determined by analysis between both variables while taking into account the possible influence of socialogical factors such as age, sex, lifestyle.To this end, data from 2235 persons were evaluated in a case-control-study within a two year period. Collection and evaluation of the data took place in the hospital and included a 1 hour 1 interview with the subjects. The subjects were taken from a pool of patients with current acute heart attacks, defined as having a acute heart attack within the period of two to ten days previous to the interview. Surgical patients without current heart complications were used as the control study group. Noise annoyance in the daytime and noise sensitivity had a little correlation of rp = 0,23. Correlation was rp = 0,19 between noise annoyance in the nighttime and noise sensitivity. 19 percent of variations of noise annoyance in the daytime were explained by noise sensitivity, sex, income and marital status in a multivariate analysis. 18 percent of variations noise annoyance in the nighttime were explained by noise sensitivity, age and education. 17 percent of variations were explained by noise annoyance and all socialogical factors in the case of dependence of noise sensitivity. There is a significant, but only little correlation between noise sensitivity and noise annoyance. An independent and separate inspection of both factors should be made in clinical studies of heart and circulation diseases, which include noise sensitivity and noise annoyance

Methods for Testing the Subjective Visual Vertical during the Chronic Phase of Menière’s Disease

The subjective visual vertical (SVV) evaluates the function of the utricle, which, in patients with Meniere's disease (MD), can be affected by endolymphatic hydrops. This study aimed to determine the SVV in MD patients during the chronic phase of illness compared to healthy participants. The second aim was to compare the SVV measurement tools: the analog bucket test, digital bucket test, and C-SVV© goggles. The SVV scores differed significantly between MD patients and the control group for the analog bucket test (p < 0.001) and the C-SVV® goggles (p = 0.028), but no significance was shown when using the digital bucket test (p = 0.062). When comparing the analog bucket test and the C-SVV® goggles applying the calculated threshold (1.125 degrees in analog bucket test, 2.5 degrees in C-SVV® goggles), the bucket test showed higher accuracy (bucket test 73.84%, C-SVV® goggles 69.23%). When examining the influence of betahistine on SVV scores, there were no statistically significant differences in both the analog bucket test and C-SVV© goggles. We conclude that SVV test can be used as an additional tool to evaluate utricle function during the chronic phase of MD and that the analog bucket test produces the most reliable results. The intake of betahistine does not influence the perception of SVV

Incidence and survival of HNSCC patients living with HIV compared with HIV-negative HNSCC patients

Purpose!#!The aim was to analyze the incidence and survival of patients living with HIV (PLWH) with head and neck squamous cell carcinoma (HNSCC) and to compare with a control group of HIV-negative HNSCC patients.!##!Methods!#!Clinicopathological data and predictors for overall survival (OS) and disease-free survival (DFS) were investigated (2009-2019).!##!Results!#!50 of 5151 HNSCC patients (0.97%) were PLWH, and 76% were smokers. Age ≤ 60 years, HIV-PCR ≤ 50 copies, CD4 cells ≤ 200/mm!##!Conclusions!#!PLWH were diagnosed with HNSCC at a significantly younger age compared to HIV-negative patients. Taking into account patient age at initial diagnosis, both OS and DFS rates in PLWH are significantly worse compared with a matched control group of HIV-negative patients in advanced tumor stages UICC III/IV. The prognosis (OS) is improved when taking cART treatment, the HIV viral load is undetectable and CD4 count is high

Impaired DNA double-strand break repair and effective radiosensitization of HPV-negative HNSCC cell lines through combined inhibition of PARP and Wee1

Objectives: In head and neck squamous cell carcinoma (HNSCC), tumors negative for Human Papillomavirus (HPV) remain a difficult to treat entity and the morbidity of current multimodal treatment is high. Radiotherapy in combination with molecular targeting could represent suitable, less toxic treatment options especially for cisplatin ineligible patients. Therefore, we tested dual targeting of PARP and the intra-S/G2 checkpoint through Wee1 inhibition for its radiosensitizing capacity in radioresistant HPV-negative HNSCC cells. Materials and methods: Three radioresistant HPV-negative cell lines (HSC4, SAS, UT-SCC-60a) were treated with olaparib, adavosertib and ionizing irradiation. The impact on cell cycle, G2 arrest and replication stress was assessed through flow cytometry after DAPI, phospho-histone H3 and γH2AX staining. Long term cell survival after treatment was determined through colony formation assay and DNA double-strand break (DSB) levels were assessed through quantification of nuclear 53BP1 foci in cell lines and patient-derived HPV± tumor slice cultures. Results: Wee1 and dual targeting induced replication stress but failed to effectively inhibit radiation-induced G2 cell cycle arrest. Single as well as combined inhibition increased radiation sensitivity and residual DSB levels, with the largest effects induced through dual targeting. Dual targeting also enhanced residual DSB levels in patient-derived slice cultures from HPV-negative but not HPV+ HNSCC (5/7 vs. 1/6). Conclusion: We conclude that the combined inhibition of PARP and Wee1 results in enhanced residual DNA damage levels after irradiation and effectively sensitizes radioresistant HPV-negative HNSCC cells. Ex vivo tumor slice cultures may predict the response of individual patients with HPV-negative HNSCC to this dual targeting approach