Descending necrotizing mediastinitis: etiopathogenesis, diagnosis, treatment and long-term consequences-a retrospective follow-up study.

PURPOSE: The primary aim of this retrospective study was to analyze the progression of descending necrotizing mediastinitis (DNM), evaluate the impact of comorbidities on complications and mortality and to observe long-term consequences of DNM on dysphagia and measurements quality of life. DNM is a serious infectious disease that requires multimodal treatment. Current literature varies in conclusions of risk factors, management and outcome of DNM. In addition, little is known about persisting effects on quality of life. METHODS: Retrospective data analysis of 88 patients with DNM representing the largest single-center study. Recording data of patients and diseases as well as clinical progression from 1997 to 2018. Two questionnaires were sent to the participants to measure quality of life and to detect dysphagia. RESULTS: 88 patients were included. The most frequently found pathogen were Streptococcus spp. (52%). 75% of the patients underwent multiple surgeries, mean count of surgical procedures was 4.3 times. 84% received intensive care treatment. Median length of stay on the intensive care unit was 7 days. 51% had pre-existing comorbidities associated with reduced tissue oxygenation (e.g., diabetes). The most common complication was pleural effusion (45%). During the observation period, the mortality rate was 9%. 12 questionnaires could be evaluated. 67% of the participants were affected by dysphagia at the time of the survey. CONCLUSIONS: Descending necrotizing mediastinitis (DNM) is a severe disease requiring an immediate initiation of multimodal treatment. Although quality of life usually isn´t impaired permanently, dysphagia may often persist in patients after DNM.

Multiple Immunostainings with Different Epitope Retrievals-The FOLGAS Protocol.

We describe a sequential multistaining protocol for immunohistochemistry, immunofluorescence and CyTOF imaging for formalin-fixed, paraffin-embedded specimens (FFPE) in the formalin gas-phase (FOLGAS), enabling sequential multistaining, independent from the primary and secondary antibodies and retrieval. Histomorphologic details are preserved, and crossreactivity and loss of signal intensity are not detectable. Combined with a DAB-based hydrophobic masking of metal-labeled primary antibodies, FOLGAS allows the extended use of CyTOF imaging in FFPE sections.

Longitudinal Associations of the Attainment of Developmental Tasks With Psychological Symptoms in Adolescence: A Meta-Analysis.

The present meta-analysis integrates results from 310 longitudinal studies on associations of the attainment of 10 developmental tasks with psychological symptoms (e.g., internalizing or externalizing symptoms, anxiety, and depression). Higher initial success with getting access to a peer group, building friendships, preparing for a future career, body acceptance, as well as developing a personal identity, a value system, and socially responsible behavior predicted lower levels of symptoms at follow-up and stronger declines of symptoms over time when controlling for initial symptom levels. Furthermore, higher initial symptom levels predicted lower attainment of these tasks at follow-up as well as lower progress in task attainment. In contrast, more initial romantic/sexual involvement predicted an increase in symptoms over time, while higher initial symptoms were related to an increase in romantic/sexual involvement. Associations with autonomy varied between different forms of autonomy, while acquisition of a gender role was not related with psychological symptoms.

High Numbers and Densities of PD1+ T-Follicular Helper Cells in Triple-Negative Breast Cancer Draining Lymph Nodes Are Associated with Lower Survival.

Breast cancer tumor draining lymph nodes (TDLNs) display distinct morphologic changes depending on the breast cancer subtype. For triple-negative breast cancers (TNBC), draining LNs display a higher amount of secondary lymphoid follicles, which can be regarded as a surrogate marker for an activated humoral immune response. In the present study, we focus on PD1+ T-follicular helper cells (Tfh) in TDLNs of TNBC, since PD1+ Tfh are drivers of the germinal center (GC) reaction. We quantified PD1+ Tfh in 22 sentinel LNs with 853 GCs and interfollicular areas from 19 patients with TNBC by morphometry from digitalized immunostained tissue sections. Overall survival was significantly worse for patients with a higher number and area density of PD1+ Tfh within GCs of TDLNs. Further, we performed T-cell receptor gamma chain (TRG) analysis from microdissected tissue in the primary tumor and TDLNs. Eleven patients showed the same TRG clones in the tumor and the LN. Five patients shared the same TRG clones in the tumor and the GCs. In two patients, those clones were highly enriched inside the GCs. Enrichment of identical TRG clones at the tumor site vs. the TDLN was associated with improved overall survival. TDLNs are important relays of cancer immunity and enable surrogate approaches to predict the outcome of TNBC itself.

Clinical Significance and Indication for Surgical Treatment of Occult Cervical and Intraglandular Nodal Involvement in Parotid Malignancy.

PURPOSE: Surgical management, including the extent of surgery, for patients with parotid malignant tumors has been challenging. The aims of the present study were to identify the factors associated with survival, estimate the incidence of occult nodal and intraglandular metastases, and determine the predictive influence on overall and disease-free survival, with consideration of the surgical extent. PATIENTS AND METHODS: We implemented a retrospective cohort study and identified incident cases with parotid malignant tumors from 2003 to 2016 at a single quaternary medical care and cancer center. A medical record analysis was performed retrospectively of the patient and histopathologic data. The predictor variables were age; tumor grade; T stage; N stage; facial nerve palsy; perineural, vascular, and lymphovascular invasion; completion parotidectomy; elective neck dissection; and pN0 versus pN+. Overall and disease-free survival were evaluated as primary and secondary outcome variables. Data analysis was performed as a time-to-event analysis (Kaplan-Meier method). RESULTS: A total of 102 patients with parotid carcinoma had undergone surgery from 2003 to 2016 at the University Hospital Freiburg, Germany; 69 patients had undergone completion parotidectomy (total, 36; radical, 33). A total of 13 patients had occult intraparotideal lymph node metastases after elective completion parotidectomy. All the patients who had undergone elective neck dissection and clinically had had no nodal involvement (cN0) had had no pathologic lymph node metastases found (pN0). However, the predictive factors for cervical nodal involvement were high-grade tumors, locally advanced tumors (cT3-cT4), and the presence of intraparotideal nodal metastases. CONCLUSIONS: The rate of occult cervical metastases in the present study was surprisingly low (0%). However, owing to the various predictive factors, elective neck dissection should be performed for high-grade or locally advanced (stage T3-T4) parotid malignoma. Moreover, we highly recommend performing completion parotidectomy for all high-grade tumors and also for locally advanced (stage T3-T4) low-grade tumors, owing to the >12% of occult intraparotideal metastases found in the present study.

Glottic visibility for laryngeal surgery: Tritube vs. microlaryngeal tube: A randomised controlled trial.

BACKGROUND: Good visibility is essential for successful laryngeal surgery. A Tritube with outer diameter 4.4 mm, combined with flow-controlled ventilation (FCV), enables ventilation by active expiration with a sealed trachea and may improve laryngeal visibility. OBJECTIVES: We hypothesised that a Tritube with FCV would provide better laryngeal visibility and surgical conditions for laryngeal surgery than a conventional microlaryngeal tube (MLT) with volume-controlled ventilation (VCV). DESIGN: Randomised, controlled trial. SETTING: University Medical Centre. PATIENTS: A total of 55 consecutive patients (>18 years) undergoing elective laryngeal surgery were assessed for participation, providing 40 evaluable data sets with 20 per group. INTERVENTIONS: Random allocation to intubation with Tritube and ventilation with FCV (Tritube-FCV group) or intubation with MLT 6.0 and ventilation with VCV (MLT-VCV) as control. Tidal volumes of 7 ml kg predicted body weight, and positive end-expiratory pressure of 7 cmH2O were standardised between groups. MAIN OUTCOME MEASURES: Primary endpoint was the tube-related concealment of laryngeal structures, measured on videolaryngoscopic photographs by appropriate software. Secondary endpoints were surgical conditions (categorical four-point rating scale), respiratory variables and change of end-expiratory lung volume from atmospheric airway pressure to ventilation with positive end-expiratory pressure. Data are presented as median [IQR]. RESULTS: There was less concealment of laryngeal structures with the Tritube than with the MLT; 7 [6 to 9] vs. 22 [18 to 27] %, (P < 0.001). Surgical conditions were rated comparably (P = 0.06). A subgroup of residents in training perceived surgical conditions to be better with the Tritube compared with the MLT (P = 0.006). Respiratory system compliance with the Tritube was higher at 61 [52 to 71] vs. 46 [41 to 51] ml cmH2O (P < 0.001), plateau pressure was lower at 14 [13 to 15] vs. 17 [16 to 18] cmH2O (P < 0.001), and change of end-expiratory lung volume was higher at 681 [463 to 849] vs. 414 [194 to 604] ml, (P = 0.023) for Tritube-FCV compared with MLT-VCV. CONCLUSION: During laryngeal surgery a Tritube improves visibility of the surgical site but not surgical conditions when compared with a MLT 6.0. FCV improves lung aeration and respiratory system compliance compared with VCV. TRIAL REGISTRY NUMBER: DRKS00013097.

The TH1 phenotype of follicular helper T cells indicates an IFN-γ-associated immune dysregulation in patients with CD21low common variable immunodeficiency.

BACKGROUND: A subgroup of patients with common variable immunodeficiency (CVID) experience immune dysregulation manifesting as autoimmunity, lymphoproliferation, and organ inflammation and thereby increasing morbidity and mortality. Therefore treatment of these complications demands a deeper comprehension of their cause and pathophysiology. OBJECTIVES: On the basis of the identification of an interferon signature in patients with CVID with secondary complications and a skewed follicular helper T-cell differentiation in defined monogenic immunodeficiencies, we sought to determine the profile of CD4 memory T cells in blood and secondary lymphatic tissues of these patients. METHODS: We quantified TH1/TH2/TH17 CD4 memory T cells in blood and lymph nodes of patients with CVID using flow cytometry, analyzed their function, and correlated all findings to the burden of immune dysregulation. RESULTS: Patients with CVID with immune dysregulation had a skewed memory CD4 T-cell differentiation toward a CXCR3+CCR6- TH1 phenotype both in blood and lymph nodes. Consistent with our phenotypic findings, we observed a higher IFN-γ production in peripheral CD4 memory T cells and lymph node-derived follicular helper T cells of patients with CVID compared with those of healthy control subjects. Increased IFN-γ production was accompanied by a poor germinal center output, an accumulation of T-box transcription factor (T-bet)+ B cells in lymph nodes, and an accumulation of T-bet+CD21low B cells in peripheral blood of affected patients. CONCLUSION: Identification of excessive IFN-γ production by blood and lymph node-derived T cells of patients with CVID with immune dysregulation will offer new therapeutic avenues for this subgroup. CD21low B cells might serve as a marker of this IFN-γ-associated dysregulation.

Experimental Simulation of Clinical Borderline Situations in Temporal Bone Specimens After Ossiculoplasty.

OBJECTIVES: One reason for insufficient hearing improvement with a distinct air-bone gap after ossiculoplasty with implantation of partial or total ossicular replacement prostheses can be the dislocation or minimal shifting of the prosthesis. The aim of this study was the simulation of common clinical borderline situations with minimal shifting of the prosthesis in temporal bone specimens after ossiculoplasty. It was furthermore the goal to identify these specific situations through imaging by cone beam computed tomography (cbCT) and direct visual inspection using the operation microscope. Additionally, the functional status was evaluated using laser-Doppler vibrometry (LDV). DESIGN: We used a total of four temporal bone specimens for this study. A reconstruction with a partial ossicular replacement prostheses was performed in three specimens and with a total ossicular replacement prostheses in one specimen, with good initial acoustic properties. Subsequently, one specific type of prosthesis failure was simulated in each specimen, respectively, by minimally shifting, tilting, or bending the prostheses from their initial positions. These changes were introduced step-by-step until a borderline situation just short of complete acoustic decoupling was reached. Each step was examined using both LDV and cbCT and observed through the operation microscope. RESULTS: LDV was able to quantify the mechanic function of the ossicular chain after most of the manipulation steps by demonstrating the effect of any shifting of the prosthesis on the middle ear transfer function. However, in some situations, the middle ear transfer function was better with a visually more advanced failure of the prosthesis. In addition, cbCT showed most of the steps with excellent resolution and was able to delineate changes in soft tissue (e.g., cartilage covering). CONCLUSION: cbCT seems to be a promising imaging technique for middle ear problems. As cbCT and LDV exhibited slightly different advantages and disadvantages regarding the demonstration of borderline situations, the combination of both techniques allowed for a more precise evaluation of middle ear reconstructions. Knowledge of the specific characteristics of these methods and their possible combination might help otologists and otosurgeons to refine indications for revision surgery and improve their personal patient counseling.

Health-related quality of life in patients with major salivary gland carcinoma.

PURPOSE: To evaluate the health-related quality of life (QOL) in patients with major salivary gland carcinoma (MSGC). METHODS: 45 patients with MSGC completed the University of Washington Quality of Life (UWQOL) questionnaire. Results and factors influencing quality of life were analyzed using Mann-Whitney U test. RESULTS: 24 patients were male, 21 patients were female, and median age was 57 years. 33 patients presented with early stage (UICC stage I or II) cancer. All patients had surgery as initial therapy. The UWQOL domains with the worst results were 'appearance', 'activity' and 'anxiety'. Factors influencing QOL were sex, tumor stage, comorbidities, follow-up time, tumor grade, postoperative radiation therapy and facial nerve dysfunction. CONCLUSIONS: Diagnosis and treatment of MSGC has influence on overall QOL. Postoperative radiation has the greatest impact on QOL. This is one of the largest study evaluating QOL in patients with salivary gland carcinoma using the UWQOL.

Prognostic value of comorbidities in patients with carcinoma of the major salivary glands.

This study aimed at evaluating the influence of comorbidities on outcome and survival in patients with carcinoma of the major salivary glands. Medical records of 109 patients with carcinoma of the major salivary glands treated at a single quaternary medical care and cancer center between 2003 and 2015 were reviewed. Comorbidities were classified according to the Age-Adjusted Charlson Comorbidity Index (ACCI) scoring system. 59 patients were males, 50 were females. Median age was 69 years and the median interval between tumor diagnosis and date of study inclusion was 71 months. Most carcinoma arose in the parotid gland (90 patients), and most patients presented with T 1 (25) or T 2 (37) cancer. Mean ACCI score was 2.9, and the most frequent ACCI score was 4. Mean overall survival was 119 months (ACCI 0-3) and 55 months (ACCI score >4), respectively (p = 0.005). Mean disease-free survival (ACCI 0-3) was 110 and 58 months (ACCI > 4), respectively (p = 0.02). Survival was significantly improved in low grade tumors, lower T and UICC stage and lymph node-negative patients. Sex, age, history of smoking and resection margins had no influence on overall survival. High comorbidity is an independent risk factor on overall and disease-free survival in patients with major salivary gland carcinoma. This is the first study evaluating comorbidity using the ACCI scoring system in this group of patients.

Monitoring micropollutants in the Swist river basin.

Micropollutant pathways were studied for the Swist river basin (Western Germany). The aim was to verify the effectiveness of a monitoring approach to detect micropollutants entering the river. In a separate sewer system, water was frequently found to be contaminated with micropollutants. Improper connections of sewage canals to the stormwater network seemed to be the cause of pollution. Wastewater treatment plants (WWTPs) exerted the largest influence on micropollutants for the receiving river. During a flu outbreak, antibiotics in the Swist stemming from WWTPs increased remarkably. Elevated levels of pharmaceuticals were measured in discharges from a combined sewer overflow (CSO). The study showed that the pharmaceutical load of a CSO was significantly reduced by advanced treatment with a retention soil filter. Painkillers, an anticonvulsant and beta blockers were the most often detected pharmaceuticals in the sewage of urban areas. Herbicides, flame retardants and industrial compounds were also observed frequently. On cropland, Chloridazon and Terbuthylazine compounds were often found in landscape runoff. Fungicides and insecticides were the most frequent positive findings in runoff from orchards. The paper shows that a coherent approach to collecting valid information regarding micropollutants and to addressing relevant pathways as a basis for appropriate management strategies could be established.

Central skull base osteomyelitis: new insights and implications for diagnosis and treatment.

Central skull base osteomyelitis (SBO) is a life-threatening disease originating from ear and from sinonasal infections. The intention of this study was to evaluate contemporary trends in etiology, diagnosis, management, and outcome of SBO and to draw the clinician's attention on this probably underestimated disease. Over a 6-year period we performed this systematic study in an academic quaternary medical care and skull base center including 20 patients (mean age 63.7 years) with central SBO, which is one of the largest series from a single center. In contrast to previous studies we explicitly excluded infections limited to malignant external otitis only but did not restrict central SBO to conditions unrelated to aural pathology. Fifteen patients had otogenic and five sinugenic SBO; four patients had fungal or mixed fungal infections. Pre-existing illnesses altering bone vascularization were detected in 70 % of the patients and had a negative effect on the improvement of cranial nerve palsies that were found in 14 patients. In relation, patients with otogenic SBO more often had local and systemic predisposing factors. Contrary to previous studies 16 patients (80 %) underwent surgical therapy and none of our patients died. A meta-analysis of five recent studies was done and compared with our own data and two previous meta-analyses. The present study highlights several important aspects with major implications for diagnosis and treatment of SBO that have not been adequately addressed as yet. In contrast to the restrictive attitude towards surgery in literature we recommend early and radical operative treatment to reduce its mortality.

Alcohol use among students with and without hearing loss.

We compared alcohol use among adolescents with and without hearing loss. Adolescents with hearing loss reported consuming less alcohol, less binge drinking, fewer episodes of drunkenness, and a higher age at first drunkenness than their hearing peers. Alcohol use did not vary between students who were deaf or hard of hearing or between students with congenital versus acquired hearing loss. Although higher age, male gender, and larger friend networks predicted higher alcohol consumption among adolescents with and without hearing loss, worse grades at school were associated only with alcohol use among hearing students. Lower alcohol use among students with hearing loss when compared with hearing peers was, in part, explained by their lower level of peer-group integration. Although alcohol use is a less serious problem among students with hearing loss, a minority with risky consumption would benefit from interventions aimed at reducing alcohol use.

Increased incidence of adenoidectomy and tonsillectomy in children with renal transplantation.

BACKGROUND: Previous studies have found that pediatric solid organ transplant recipients suffer from adenotonsillar hyperplasia. However, as this condition is also common in normal children, it remains unclear whether the incidence is truly increased. The aim of this study was to compare the incidences of surgery on the adenoids and tonsils of normal children with those receiving renal transplants and to define risk factors in the transplant population. METHODS: Data on 49 consecutive children from a single renal transplant unit were compared to data from a large governmental survey of healthy German children (KiGGS). For analysis of 'survival without operation', controls were matched for gender, region and immigration status (n = 8,650), as well as for age to compare incidence rates (n = 637). RESULTS: The age-matched solid organ transplant recipients had a higher incidence of adenoidectomies [2.3-fold, [95 % confidence interval (CI) for relative risk 1.6-3.3) and a higher incidence of tonsillectomies/tonsillotomies (3.5-fold, 95 % CI 2.1-5.7). The normal peak of adenoidectomies was delayed by 2 years in the pre-school group, and transplanted teenagers showed an extra peak for both operations. Boys and those transplanted at a younger age were significantly more likely to need adenoidectomies. Ciclosporin levels, Epstein-Barr virus and cytomegalovirus infections did not influence the incidence of operations. CONCLUSION: Children receiving renal transplants are at markedly increased risk of adenotonsillar hyperplasia requiring surgery, especially males and young recipients.

Transmucosal core needle biopsy: a novel diagnostic approach to oral and oropharyngeal lesions.

PURPOSE: Oral and oropharyngeal tumors have often been characterized by a deep submucosal growth pattern under an intact mucous membrane. This will be particularly true for lesions of the tongue and could be associated with relevant difficulties regarding diagnosis and treatment planning. We hypothesized that the transoral transmucosal application of a core needle biopsy (CNB) for lesions of the tongue, the base of the tongue, and the floor of the mouth could be of considerable clinical usefulness for many patients. It has only previously been described in single cases and has not yet been separately discussed. MATERIAL AND METHODS: We report on the novel transoral use of CNB during rigid endoscopy with the patient under general anesthesia, with an emphasis on lesions of the tongue. A series of cases and illustrative patients are presented. RESULTS: Transmucosal CNB was accurate and of considerable clinical usefulness in all cases. The relevant advantages of this technique compared with conventional biopsy using biopsy forceps and transmucosal fine needle aspiration are presented. CONCLUSIONS: The transoral transmucosal approach to the submucosal space of the oral cavity and the oropharynx has further extended the field of application of CNB. In selected patients, this CNB approach offers essential diagnostic benefits, in particular, for tumors of the tongue.

Change in psychological problems of adolescents with and without visual impairment.

The present study analyzed change in psychological problems of German adolescents with and without visual impairment across a 2-year interval. A total of 182 adolescents with severe visual impairment and 560 sighted adolescents provided longitudinal data. At the start of the study, adolescents with visual impairment had, on average, elevated scores on all difficulties scales of the Strengths and Difficulties Questionnaire (SDQ) (Goodman R, J Child Psychol Psychiat 38:581-586), 1997 and about 39 % of them scored in the abnormal range of one or more scales as compared to 30.5 % of their sighted peers (p < 0.05). However, between-group differences of emotional and total problems declined over time. While adolescents who are blind and those who have low vision had similar levels of psychological problems, SDQ scores showed less improvement in adolescents with an earlier age at onset of vision loss. In conclusion, a minority of adolescents with visual impairment and with early onset of visual impairment in particular, may benefit from psychological interventions aimed at preventing and reducing psychological problems and increasing the ability to cope with stressors associated with vision loss.

Self-management of patients with tracheostomy in the home setting: a scoping review.

PURPOSE: The aim of this study was to create a model of patient-centered outcomes with respect to self-management tasks and skills of patients with a tracheostomy in their home setting. METHODS: A scoping review using four search engines was undertaken (Medline, CINAHL, PsycINFO, Cochrane Library) to identify studies relevant to this issue and published since 2000. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statements for Scoping Reviews (PRISMA-ScR), the Joanna Briggs Institute (JBI) approach of conducting and reporting a scoping review, and the Participants, Concept, Context (PCC) scheme were employed. The following elements of the framework synthesis study data were screened, and presented based on the self-management model of Lorig and Holman. RESULTS: 34 publications from 17 countries met the criteria for study inclusion: 24 quantitative, 8 qualitative and 2 mixed methods designs. Regarding the dimensions of self-management, 28 articles reported on "managing the therapeutic regimen", 27 articles discussed "managing role and behavior changes", and 16 articles explored "managing emotions". A model of self-management of patients with tracheostomy was developed, which placed the patient in the center, since it is this individual who is completing the tasks and carrying out his or her skill sets. CONCLUSION: This scoping review represents the first comprehensive overview and modeling of the complex self-management tasks and skills required of patients with tracheostomy in their home setting. The theoretical model can serve as a cornerstone for empirical intervention studies to better support this patient-centered outcome for this population in the future.