[Hypertrophy of lingual tonsil following tonsillectomy and correlation with BMI]. / Zungengrundhyperplasie nach Tonsillektomie und Korrelation mit dem BMI.

OBJECTIVE: The hyperplasia of the lingual tonsil is a rare and at the same time potentially dangerous change in the area of the upper respiratory tract. The pathogenesis of the lingual tonsillar hyperplasia is still largely unknown. In this study, we investigated if there is a compensatory lingual tonsil hyperplasia after tonsillectomy. MATERIAL AND METHODS: 300 patients were examined consecutively in the ENT clinic of the Hannover Medical School. In the context of indirect laryngoscopy, the lingual tonsil, the visibility of the larynx and its subregions were assessed according to a scheme. The data were then evaluated depending on the status of the palatal tonsils. In addition, the body mass index (BMI) was determined and compared with the results of laryngoscopy. RESULTS: Out of 300 patients, 89 (29.6%) were in condition after bilateral tonsillectomy. In the total population, a greatly enlarged lingual tonsil was only detectable in 14 cases (4.6%). Of these 14 patients, 4 had a history of tonsillectomy. In patients with severe lingual tonsil hyperplasia the mean BMI was 27.3 compared to 24.4 in patients with a normal lingual tonsil. CONCLUSION: In our population the incidence of severe lingual tonsil hyperplasia is 4.7%. We couldn't prove s a connection between a condition after tonsillectomy and compensatory lingual hyperplasia statistically. However, there was a significant relationship between BMI and lingual tonsil hyperplasia.

Acute disease induced cognitive dysfunction in older patients - an unrecognized syndrome.

BACKGROUND: It is unknown, how many older hospitalized patients experience cognitive changes independently from delirium. METHODS: In this retrospective study, cognitive function was assessed with the Montreal Cognitive Assessment on admission and discharge in 103 acute care geriatric hospital patients. RESULTS: Mean age was 80.8 ± 7.3 years. The total MoCA score on admission was 17.8 (±4.5) and at discharge 17.7 (±4.4). The mean difference of the total MoCA score was - 0.1 (±3.5). 12 (11.7%) patients suffered from delirium. 46 (44.7%) patients experienced significant changes of cognitive function <- 2 or > 2 MoCA points without delirium. There was no significant association between delirium during hospital stay and the prevalence and magnitude of changes in total MoCA score. CONCLUSION: Cognitive changes frequently occur during acute disease of geriatric patients independently from delirium. We propose the term "acute disease induced cognitive dysfunction" (ADICD) for this entity. TRIAL REGISTRATION: German Clinical trial register (DRKS-ID: DRKS00025157 on 28.04.2021).

Proteome profile of patients with excellent and poor speech intelligibility after cochlear implantation: Can perilymph proteins predict performance?

Modern proteomic analysis and reliable surgical access to gain liquid inner ear biopsies have enabled in depth molecular characterization of the cochlea microenvironment. In order to clarify whether the protein composition of the perilymph can provide new insights into individual hearing performance after cochlear implantation (CI), computational analysis in correlation to clinical performance after CI were performed based on the proteome profile derived from perilymph samples (liquid biopsies). Perilymph samples from cochlear implant recipients have been analyzed by mass spectrometry (MS). The proteins were identified using the shot-gun proteomics method and quantified and analyzed using Max Quant, Perseus and IPA software. A total of 75 perilymph samples from 68 (adults and children) patients were included in the analysis. Speech perception data one year after implantation were available for 45 patients and these were used for subsequent analysis. According to their hearing performance, patients with excellent (n = 22) and poor (n = 14) performance one year after CI were identified and used for further analysis. The protein composition and statistically significant differences in the two groups were detected by relative quantification of the perilymph proteins. With this procedure, a selection of 287 proteins were identified in at least eight samples in both groups. In the perilymph of the patients with excellent and poor performance, five and six significantly elevated proteins were identified respectively. These proteins seem to be involved in different immunological processes in excellent and poor performer. Further analysis on the role of specific proteins as predictors for poor or excellent performance among CI recipients are mandatory. Combinatory analysis of molecular inner ear profiles and clinical performance data using bioinformatics analysis may open up new possibilities for patient stratification. The impact of such prediction algorithms on diagnosis and treatment needs to be established in further studies.

SEVTAR-A multicenter randomized controlled trial to investigate the impact of prophylactic endoluminal placed vacuum sponge for prevention of anastomotic leakage after low rectal resections.

Background: Low anterior resection for rectal cancer is commonly associated with a diverting stoma. In general, the stoma is closed 3 months after the initial operation. The diverting stoma reduces the rate of anastomotic leakage as well as the severeness of a potential leakage itself. Nevertheless, anastomotic leakage is still a life-threatening complication and might reduce the quality of life in the short and long term. In case of leakage, the construction can be converted into a Hartmann situation or it could be treated by endoscopic vacuum therapy or by leaving the drains. In recent years, endoscopic vacuum therapy has become the treatment of choice in many institutions. In this study, the hypothesis is to be evaluated, if a prophylactic endoscopic vacuum therapy reduces the rate of anastomotic leakage after rectal resections. Methods: A multicenter parallel group randomized controlled trial is planned in as many as possible centers in Europe. The study aims to recruit 362 analyzable patients with a resection of the rectum combined with a diverting ileostoma. The anastomosis has to be between 2 and 8 cm off the anal verge. Half of these patients receive a sponge for 5 days, and the control group is treated as usual in the participating hospitals. There will be a check for anastomotic leakage after 30 days. Primary end point is the rate of anastomotic leakages. The study will have 60% power to detect a difference of 10%, at a one-sided alpha significance level of 5%, assuming an anastomosis leakage rate of 10%-15%. Discussion: If the hypothesis proves to be true, anastomosis leakage could be reduced significantly by placing a vacuum sponge over the anastomosis for 5 days. Trial registration: The trial is registered at DRKS: DRKS00023436. It has been accredited by Onkocert of the German Society of Cancer: ST-D483. The leading Ethics Committee is the Ethics Committee of Rostock University with the registration ID A 2019-0203.

Comparison of FORTA, PRISCUS and EU(7)-PIM lists on identifying potentially inappropriate medication and its impact on cognitive function in multimorbid elderly German people in primary care: a multicentre observational study.

OBJECTIVES: Our study aimed to assess the frequency of potentially inappropriate medication (PIM) use (according to three PIM lists) and to examine the association between PIM use and cognitive function among participants in the MultiCare cohort. DESIGN: MultiCare is conducted as a longitudinal, multicentre, observational cohort study. SETTING: The MultiCare study is located in eight different study centres in Germany. PARTICIPANTS: 3189 patients (59.3% female). PRIMARY AND SECONDARY OUTCOME MEASURES: The study had a cross-sectional design using baseline data from the German MultiCare study. Prescribed and over-the-counter drugs were classified using FORTA (Fit fOR The Aged), PRISCUS (Latin for 'time-honoured') and EU(7)-PIM lists. A mixed-effect multivariate linear regression was performed to calculate the association between PIM use patients' cognitive function (measured with (LDST)). RESULTS: Patients (3189) used 2152 FORTA PIM (mean 0.9±1.03 per patient), 936 PRISCUS PIM (0.3±0.58) and 4311 EU(7)-PIM (1.4±1.29). The most common FORTA PIM was phenprocoumon (13.8%); the most prevalent PRISCUS PIM was amitriptyline (2.8%); the most common EU(7)-PIM was omeprazole (14.0%). The lists rate PIM differently, with an overall overlap of 6.6%. Increasing use of PIM is significantly associated with reduced cognitive function that was detected with a correlation coefficient of -0.60 for FORTA PIM (p=0.002), -0.72 for PRISCUS PIM (p=0.025) and -0.44 for EU(7)-PIM (p=0.005). CONCLUSION: We identified PIM using FORTA, PRISCUS and EU(7)-PIM lists differently and found that PIM use is associated with cognitive impairment according to LDST, whereby the FORTA list best explained cognitive decline for the German population. These findings are consistent with a negative impact of PIM use on multimorbid elderly patient outcomes. TRIAL REGISTRATION NUMBER: ISRCTN89818205.

Non-random relations in drug use expressed as patterns comprising prescription and over-the-counter drugs in multimorbid elderly patients in primary care: Data of the exploratory analysis of the multicentre, observational cohort study MultiCare.

BACKGROUND: The elderly population deals with multimorbidity (three chronic conditions) and increasinged drug use with age. A comprehensive characterisation of the medication - including prescription and over-the-counter (OTC) drugs - of elderly patients in primary care is still insufficient. OBJECTIVES: This study aims to characterise the medication (prescription and OTC) of multimorbid elderly patients in primary care and living at home by identifying drug patterns to evaluate the relationship between drugs and drug groups and reveal associations with recently published multimorbidity clusters of the same cohort. METHODS: MultiCare was a multicentre, prospective, observational cohort study of 3189 multimorbid patients aged 65 to 85 years in primary care in Germany. Patients and general practitioners were interviewed between 2008 and 2009. Drug patterns were identified using exploratory factor analysis. The relations between the drug patterns with the three multimorbidity clusters were analysed with Spearman-Rank-Correlation. RESULTS: Patients (59.3% female) used in mean 7.7 drugs; in total 24,535 drugs (23.7% OTC) were detected. Five drug patterns for men (drugs for obstructive pulmonary diseases (D-OPD), drugs for coronary heart diseases and hypertension (D-CHD), drugs for osteoporosis (D-Osteo), drugs for heart failure and drugs for pain) and four drug patterns for women (D-Osteo, D-CHD, D-OPD and drugs for diuretics and gout) were detected. Significant associations between multimorbidity clusters and drug patterns were detectable (D-CHD and CMD: male: ρ = 0.376, CI 0.322-0.430; female: ρ = 0.301, CI 0.624-0.340). CONCLUSION: The drug patterns demonstrate non-random relations in drug use in multimorbid elderly patients and systematic associations between drug patterns and multimorbidity clusters were found in primary care.

Anticholinergic drug burden according to the anticholinergic drug scale and the German anticholinergic burden and their impact on cognitive function in multimorbid elderly German people: a multicentre observational study.

OBJECTIVES: The aims of our study were to examine the anticholinergic drug use and to assess the association between anticholinergic burden and cognitive function in the multimorbid elderly patients of the MultiCare cohort. SETTING: MultiCare was conducted as a longitudinal cohort study in primary care, located in eight different study centres in Germany. PARTICIPANTS: 3189 patients (59.3% female). PRIMARY AND SECONDARY OUTCOME MEASURES: Baseline data were used for the following analyses. Drugs were classified according to the well-established anticholinergic drug scale (ADS) and the recently published German anticholinergic burden (German ACB). Cognitive function was measured using a letter digit substitution test (LDST) and a mixed-effect multivariate linear regression was performed to calculate the influence of anticholinergic burden on the cognitive function. RESULTS: Patients used 1764 anticholinergic drugs according to ADS and 2750 anticholinergics according to the German ACB score (prevalence 38.4% and 53.7%, respectively). The mean ADS score was 0.8 (±1.3), and the mean German ACB score was 1.2 (±1.6) per patient. The most common ADS anticholinergic was furosemide (5.8%) and the most common ACB anticholinergic was metformin (13.7%). The majority of the identified anticholinergics were drugs with low anticholinergic potential: 80.2% (ADS) and 73.4% (ACB), respectively. An increasing ADS and German ACB score was associated with reduced cognitive function according to the LDST (-0.26; p=0.008 and -0.24; p=0.003, respectively). CONCLUSION: Multimorbid elderly patients are in a high risk for using anticholinergic drugs according to ADS and German ACB score. We especially need to gain greater awareness for the contribution of drugs with low anticholinergic potential from the cardiovascular system. As anticholinergic drug use is associated with reduced cognitive function in multimorbid elderly patients, the importance of rational prescribing and also deprescribing needs to be further evaluated. TRIAL REGISTRATION NUMBER: ISRCTN89818205.

First results of electrode reimplantation and its hypothetical dependence from artificial brain maturation.

BACKGROUND: After introducing the first Cochlear Implants also in children theses are grown with electrical intracochlear stimulation and subsequent auditory cortical development. Over the meantime the positioning of the electrode was changed orientated on the development of electrode design, ability to insert atraumatic and on the widening of the indications towards highfrequency deafness. METHODS: In this pilot study we analysed five prelingually deafened patients implanted as child in the late 90's and had a reimplantation 2016 or later. We compared CT and DVT (cone beam CT) scans of the temporal bone and measured the insertion angle, the cochlear coverage, the total length of the electrode in the cochlea and the distance of the first active electrode to the round window. Moreover, we compared their speech understanding before and after reimplantation. RESULTS: The results show a lowering in the insertion angle, the cochlear coverage, the total length of the electrode in the cochlea, in the distance of the first active electrode to the round window and in the speech understanding after reimplantation. CONCLUSION: These results show a difference in the depth of insertion while the speech understanding is not significantly improving in this group-although the technology is advanced. The influence of auditory maturation with CI in these patients will be discussed.

Pandemia e fronteiras: o primeiro ano no Brasil / Nota Técnica n. 26 (Dirur) : Pandemia e fronteiras : o primeiro ano no Brasil

Nesta NT, a abordagem se voltará ao período que compreende desde os primeiros casos e óbitos no país, até 30 de novembro de 2020. Terá como objetivo retomar algumas hipóteses levantadas na NT nº 16 (Pêgo et al., 2020), elaborada com base em informações até 15 de abril de 2020, e avançar na prospecção de tendências. Encontra-se organizada em cinco seções, sendo a primeira esta introdução. Na segunda, serão atualizadas a leitura da posição do país no contexto geral da pandemia, a análise dos números registrados e a distribuição de casos e óbitos no território. A terceira discorrerá sobre os impactos do fechamento das fronteiras com os países limítrofes, particularmente em relação aos arranjos transfronteiriços. Na quarta seção, a abordagem particularizará as relações transfronteiriças e vulnerabilidades dos povos indígenas frente à Covid-19. A NT será finalizada, em sua quinta seção, com algumas considerações sínteses ou complementares.

Oito meses de pandemia no Brasil: medidas para o enfrentamento federativo e perspectivas com as vacinas / Nota Técnica n. 21 (Dirur) : Oito meses de pandemia no Brasil : medidas para o enfrentamento federativo e perspectivas com as vacinas

Nesta NT, a abordagem se voltará ao período que compreende desde os primeiros casos e óbitos no país até 30 de novembro de 2020. Terá como objetivo retomar algumas hipóteses levantadas na NT n° 16/2020 (Pêgo et al., 2020), elaborada com base em informações até 15 de abril de 2020, e avançar na prospecção de tendências. Encontra-se organizada em cinco seções, sendo a primeira esta introdução. Na segunda seção, será atualizada a análise das medidas e decisões das esferas de governo, federal e estaduais, no enfrentamento à Covid-19 e das medidas econômicas dos estados, segundo grandes regiões, culminando com os números sobre a evolução dos óbitos nas Unidades da Federação (UF). A terceira seção está dedicada à vulnerabilidade socioespacial e ao direito à moradia durante a pandemia, com ênfase nas precárias condições de enfrentamento em regiões carentes das periferias metropolitanas. Na quarta seção, a análise se volta ao enfrentamento da Covid-19 por meio do desenvolvimento de vacinas e de agentes terapêuticos, abordando sucintamente as reincidências pandêmicas. Na quinta e última seção, estarão as considerações finais.

Pandemia e fronteiras: oito meses em evolução no Brasil / Nota Técnica n. 22 (Dirur): Pandemia e fronteiras: oito meses em evolução no Brasil

Nesta NT, a abordagem se voltará ao período que compreende desde os primeiros casos e óbitos no país, até 30 de novembro de 2020. Terá como objetivo retomar algumas hipóteses levantadas na NT nº 16 (Pêgo et al., 2020), elaborada com base em informações até 15 de abril de 2020, e avançar na prospecção de tendências. Encontra-se organizada em cinco seções, sendo a primeira esta introdução. Na segunda, serão atualizadas a leitura da posição do país no contexto geral da pandemia, a análise dos números registrados e a distribuição de casos e óbitos no território. A terceira discorrerá sobre os impactos do fechamento das fronteiras com os países limítrofes, particularmente em relação aos arranjos transfronteiriços. Na quarta seção, a abordagem particularizará as relações transfronteiriças e vulnerabilidades dos povos indígenas frente à Covid-19. A NT será finalizada, em sua quinta seção, com algumas considerações sínteses ou complementares.

Ansiedade materna odontológica e experiência de cárie dentária em crianças de 7 a 13 anos de idade: um estudo transversal / Maternal dental anxiety and dental caries experience in children aged 7 to 13 years: a cross-sectional study

Objetivo: o objetivo deste estudo foi investigar se a ansiedade materna odontológica está associada à experiência de cárie dentária da criança. Métodos: este estudo transversal foi realizado com crianças entre 7 a 13 anos de idade. A coleta de dados consistiu na aplicação de um questionário às mães e exame clínico nas crianças. A ansiedade odontológica materna foi avaliada pela Modified Dental Anxiety Scale. A experiência de cárie dentária foi avaliada por meio do índice CPO-D/CEO-D. A análise multivariada, bruta e ajustada, foi realizada pelo teste de Regressão de Poisson com variância robusta para testar o efeito das variáveis independentes no desfecho (Razão de Prevalência, Intervalo de Confiança de 95%). Um nível de significância de 5% foi adotado. Resultados: participaram 85 díades mãe/criança. Em torno de 32% das mães apresentaram moderado/alto grau de ansiedade odontológica. A experiência de cárie foi associada à idade da criança (p = 0,001), à percepção materna da saúde bucal da criança (p = 0,017) e à ansiedade materna odontológica (p = 0,001). Após os ajustes, a ansiedade materna odontológica permaneceu associada à experiência de cárie da criança. Crianças filhas de mães ansiosas apresentaram 23% maior prevalência de experiência de cárie dentária quando comparadas aquelas crianças filhas de mães não ansiosas. Conclusão: em crianças de 7 a 13 anos de idade, a ansiedade materna odontológica foi associada à experiência de cárie da criança.(AU)

Aim: to investigate if maternal dental anxiety is associated eith dental caries experience in children. Methods: this cross-sectional study was performed in children aged 7-13 years. Data collection included in a questionnaire applied to mothers and in a clinical examination in children. Maternal dental anxiety was measured using the Modified Dental Anxiety Scale. Dental caries was assessed through dmft/DMFT Index. Multivariate analyses, crude and adjusted, using Poisson Regression model with robust variance in order to test asssociation between maternal dental anxiety and dental caries experience (Prevalence Ratio, 95% Confidence Interval). A significance level of 5% was adopted. Results: na overall of 85 dyades mothers/ children particpated. About 32% of mothers presented moderate/high level of dental anxiety. Dental caries was associated to child's age (p = 0,001), maternal perception abut oral health of children (p = 0,017) and to maternal dental anxiety (p = 0,001). After adjustments, maternal dental anxiety was associated to dental caries experience. Children from anxious mothers presented 23% higher prevalence of dental caries experience than those whose mothers did not present anxiety. Conclusion: in children aged 7 to 13 years, maternal dental anxiety was associated to dental caries experience.(AU)

Pandemia e fronteiras brasileiras: análise da evolução da Covid-19 e proposições / Nota Técnica n. 16 (Dirur): Pandemia e fronteiras brasileiras: análise da evolução da Covid-19 e proposições / Português

Esta nota técnica (NT) tem como objetivo analisar a trajetória da pandemia após cruzar as fronteiras do território brasileiro, avaliar as medidas adotadas para sua contenção e encaminhar sugestões. Este estudo terá como grande questão norteadora responder de que forma o Brasil se preparou para enfrentar esse evento global, tendo exemplos de medidas empreendidas por países que já enfrentavam a então epidemia do Sars-COV-2, e que ações desencadeou, com particular atenção ao papel de suas fronteiras. Nesse sentido, serão destacadas as principais medidas adotadas e apontadas aquelas que necessitam de uma maior adequação à realidade local e regional na fronteira brasileira, diante da propagação exponencial do vírus no país. Para tanto, serão consideradas informações sistematizadas pelo Ministério da Saúde (MS), pela Organização Mundial da Saúde (OMS) e pela Fundação Oswaldo Cruz (Fiocruz) em suas análises sobre o processo e na orientação das medidas a serem tomadas em relação ao que se pode chamar de a grande crise humanitária desde o início deste século.

Successful Treatment of Delayed Methotrexate Clearance Using Glucarpidase Dosed on Ideal Body Weight in Obese Patients.

Delayed methotrexate (MTX) elimination after treatment with high-dose (HD) MTX may result in life-threatening toxicities as well as acute kidney injury (AKI). Treatment includes administration of glucarpidase, an enzyme that rapidly inactivates MTX. Dosing of glucarpidase is based on body weight; however, recommendations for dosage adjustments in obese patients are lacking. We describe three obese adult patients (body mass index [BMI] range 31-43 kg/m2 ) who received HD-MTX following all precautions for its treatment. Although peak MTX concentrations were within the expected range (308-368 µmol/L), MTX concentrations after 24 hours or later were markedly increased (97, 52, and 19 µmol/L, respectively). Two patients experienced AKI. After a single intravenous dose of glucarpidase 4000 units (50 units/kg on the basis of ideal body weight [IBW]) was administered to each patient 38, 46, and 60 hours, respectively, after the start of MTX, MTX concentrations dropped quickly to 1.37, 0.07, and 0.03 µmol/L, respectively, and further decreased steadily. Over time, clinical status and renal function improved in all patients. Glucarpidase is a highly hydrophilic molecule with a volume of distribution of 3.6 L, representing the intravascular volume of an adult. Therefore, we used IBW for glucarpidase dose calculations, allowing us to reduce the dose that would have been determined by using total body weight. This approach resulted in a rapid decrease of MTX serum concentrations and may reduce treatment costs of this highly expensive drug.

Thymus-resident memory CD8+ T cells mediate local immunity.

The thymus is a primary lymphoid organ responsible for production and selection of T cells. Nonetheless, mature T cells and in particular activated T cells can reenter the thymus. Here, we identified memory CD8(+) T cells specific for lymphocytic choriomeningitis virus or vaccinia virus in the thymus of mice long-time after the infection. CD8(+) T cells were mainly located in the thymic medulla, but also in the cortical areas. Interestingly, virus-specific memory CD8(+) T cells in the thymus expressed the cell surface markers CD69 and CD103 that are characteristic of tissue-resident memory T cells in a time-dependent manner. Kinetic analyses and selective depletion of peripheral CD8(+) T cells by antibodies further revealed that thymic virus-specific memory CD8(+) T cells did not belong to the circulating pool of lymphocytes. Finally, we demonstrate that these thymus-resident virus-specific memory CD8(+) T cells efficiently mounted a secondary proliferative response, exhibited immediate effector functions and were able to protect the thymus from lymphocytic choriomeningitis virus reinfection. In conclusion, the present study not only describes for the first time virus-specific memory CD8(+) T cells with characteristics of tissue-resident memory T (T(RM)) cells in a primary lymphoid organ but also extends our knowledge about local T-cell immunity in the thymus.

Human milk banking-facts and issues to resolve.

The number of human milk banks is increasing worldwide. Although the beneficial effects of feeding premature infants with their mother's milk are well documented, less is known about the effects of feeding these infants with pasteurized donor milk. We propose a randomized trial comparing the effects of a 100% human milk-based diet (human milk supplemented with a human milk-derived fortifier) and a diet (partially) based on bovine milk. In theory, human milk has a beneficial effect on various aspects of human physiology, most of which become apparent after infancy. We therefore propose an extensive follow-up program that takes this aspect into consideration. Other issues concerning the practice of human milk banks need to be addressed as well as optimization of the feeding strategies for preterm infants.