Diagnostik und Therapie der auditorischen Synaptopathie/Neuropathie

Pathological auditory brainstem responses (lack of responses, elevated thresholds and perturbed waveforms) in combination with present otoacoustic emissions are typical audiometric findings in patients with a hearing impairment that particularly affects speech comprehension or complete deafness. This heterogenous group of disorders first described as “auditory neuropathy” includes dysfunction of peripheral synaptic coding of sound by inner hair cells (synaptopathy) and/or of the generation and propagation of action potentials in the auditory nerve (neuropathy). This joint statement provides prevailing background information as well as recommendations on diagnosis and treatment. The statement focuses on the handling in the german language area but also refers to current international statements.     

Aktuelle Leitlinien zur interventionellen Mammadiagnostik

Minimally invasive diagnostic procedures for the breast under mammography, ultrasound, and magnetic resonance guidance have led to a higher specificity of imaging techniques and a decrease in open biopsy of the breast. The percutaneous approach is more cost and time effective and reduces morbidity compared with open biopsy. The “Step-3-guideline for early breast cancer detection in Germany” represents the first national guidelines for a nationwide, quality assured, early breast cancer detection program, including recommendations for minimally invasive breast diagnostics. Indications for ultrasound guided vacuum biopsy of the breast are summarized in the “Consensus on the use and technique of vacuum-assisted sonographic breast biopsy” by the Study Group on Minimally Invasive Breast Interventions (AG MiMi) of the German Society of Senology (DGS).     

Strahlentherapie des Schilddrüsenkarzinoms

Zusammenfassung Beim differenzierten Schilddrüsenkarzinom besteht bei nicht Organkapsel überschreitendem Tumorwachstum und adäquater Operation keine Indikation zur postoperativen Bestrahlung. Bei Patienten mit Organkapsel überschreitendem Wachstum wird nach vollständiger Resektion der Nutzen einer zusätzlichen perkutanen Radiotherapie kontrovers diskutiert. Die MSDS-Studie (Multizenterstudie Differenziertes Schilddrüsenkarzinom), die eine Randomisierung genau zu dieser Fragestellung durchführte, musste aufgrund der mangelnden Rekrutierung vorzeitig beendet werden. Beim anaplastischen Schilddrüsenkarzinom wird die vollständige Resektion angestrebt. Die postoperative Bestrahlung ist dann obligat. Bei Therapieprotokollen mit zusätzlicher Adriamycingabe konnten erhöhte lokale Kontroll- und Überlebensraten beobachtet werden. Bei medullärem Schilddrüsenkarzinom und inkompletter Tumorresektion geht eine additive Radiotherapie mit einer verbesserten lokalen Kontrolle einher. Bei nicht Radiojod speichernden Metastasen des Schilddrüsenkarzinoms wird die Radiotherapie im Bereich des Knochens bei Schmerzen, Frakturgefahr oder Myelonkompression eingesetzt.     

Moderne immuntherapeutische Ansätze für die Behandlung von Lungen- und Kopf-Hals-Tumoren

Zusammenfassung Multimodale Therapiestrategien, die Chirurgie, Strahlen- und Chemotherapie kombinieren, haben die Behandlungsergebnisse bei Tumoren der Lunge und der Kopf-Hals Region verbessert. Die Ergänzung des Therapiespektrums um weitere Ansätze, die sich in der Wirkungsweise und möglichst durch reduzierte Toxizität von den konventionellen unterscheiden, erscheint jedoch zur Erzielung weiterer Fortschritte notwendig. Eine neue Generation immunologischer passiver (antikörperbasierter) und auch aktiver (Vakzinierungs-) Strategien erscheint aussichtsreich und befindet sich gegenwärtig in der klinischen Prüfung. Die Untersuchung der optimalen zeitlichen Sequenz in Kombination mit den konventionellen Therapieverfahren und die Individualisierung der Therapie auf Basis genomischer/proteomischer Daten muss die klinische Integration begleiten.     

Therapieprinzipien beim Lokalrezidiv des Rektumkarzinoms

The aim of treatment in isolated locally recurrent rectal cancer is R0 resection, which is possible in 30%. Because of the high rate of surgical complications after repeat surgery in the pelvis, preoperative staging has to be precise to estimate the extent and location of the recurrent rectal cancer. After exclusion of distant metastases, surgery should be considered following preoperative radiochemotherapy if possible. When a curative treatment concept is not indicated, radiotherapy is the best treatment choice. This paper presents various tabularised summaries about therapeutic strategies in isolated locally recurrent rectal cancer.     

Shallow WGS of individual CTCs identifies actionable targets for informing treatment decisions in metastatic breast cancer

Background We report copy-number profiling by low-pass WGS (LP-WGS) in individual circulating tumour cells (CTCs) for guiding treatment in patients with metastatic breast cancer (MBC), comparing CTC results with mutations detected in circulating tumour DNA (ctDNA) in the same blood samples.Methods Across 10 patients with MBC who were progressing at the time of blood sampling and that had >20 CTCs detected by CellSearch^®, 63 single cells (50 CTCs and 13 WBCs) and 16 cell pools (8 CTC pools and 8 WBC pools) were recovered from peripheral blood by CellSearch^®/DEPArray™ and sequenced with Ampli1 LowPass technology (Menarini Silicon Biosystems). Copy-number aberrations were identified using the MSBiosuite software platform, and results were compared with mutations detected in matched plasma cfDNA analysed by targeted next-generation sequencing using the Oncomine™ Breast cfDNA Assay (Thermo Fisher).Results LP-WGS data demonstrated copy-number gains/losses in individual CTCs in regions including FGFR1, JAK2 and CDK6 in five patients, ERBB2 amplification in two HER2-negative patients and BRCA loss in two patients. Seven of eight matched plasmas also had mutations in ctDNA in PIK3CA, TP53, ESR1 and KRAS genes with mutant allele frequencies (MAF) ranging from 0.05 to 33.11%. Combining results from paired CTCs and ctDNA, clinically actionable targets were identified in all ten patients.Conclusion This combined analysis of CTCs and ctDNA may offer a new approach for monitoring of disease progression and to direct therapy in patients with advanced MBC, at a time when they are coming towards the end of other treatment options.Subject terms: Prognostic markers, Breast cancer     

Feasibility Study and Clinical Impact of Incorporating Breast Tissue Density in High-Risk Breast Cancer Screening Assessment

Breast tissue density (BTD) is known to increase the risk of breast cancer but is not routinely used in the risk assessment of the population-based High-Risk Ontario Breast Screening Program (HROBSP). This prospective, IRB-approved study assessed the feasibility and impact of incorporating breast tissue density (BTD) into the risk assessment of women referred to HROBSP who were not genetic mutation carriers. All consecutive women aged 40–69 years who met criteria for HROBSP assessment and referred to Genetics from 1 December 2020 to 31 July 2021 had their lifetime risk calculated with and without BTD using Tyrer-Cuzick model version 8 (IBISv8) to gauge overall impact. McNemar’s test was performed to compare eligibility with and without density. 140 women were referred, and 1 was excluded (BRCA gene mutation carrier and automatically eligible). Eight of 139 (5.8%) never had a mammogram, while 17/131 (13%) did not have BTD reported on their mammogram and required radiologist review. Of 131 patients, 22 (16.8%) were clinically impacted by incorporation of BTD: 9/131 (6.9%) became eligible for HROBSP, while 13/131 (9.9%) became ineligible (p = 0.394). It was feasible for the Genetics clinic to incorporate BTD for better risk stratification of eligible women. This did not significantly impact the number of eligible women while optimizing the use of high-risk supplemental MRI screening.     

选择性头部降温对胎羊缺血性脑损伤纹状体神经元凋亡和星形胶质细胞增殖的影响

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体神经元凋亡和星形胶质细胞增殖的影响。方法胎羊于妊娠117~124d时通过双侧颈动脉阻塞30min造成双侧脑缺血损伤,损伤后将胎羊随机分为:损伤组(n=10)、2h低温组(损伤后2h开始亚低温治疗,n=7)和6h低温组(损伤后6h开始亚低温治疗,n=8),另设正常对照组(n=5)。通过冷循环水进行选择性头部降温,取脑组织用免疫组化法检测胎羊纹状体caspase-3(半胱天冬氨酸酶-3),GFAP(胶质纤维酸性蛋白)和PCNA(增殖细胞核抗原)的表达。结果①纹状体神经元凋亡:正常对照组中,caspase-3表达极少(11.00±13.77),损伤组caspase-3免疫阳性细胞为177.70±48.69,明显增加(P=0.000),损伤后2h治疗组(54.14±39.44,P=0.000)和损伤后6h治疗组(122.43±52.36,P=0.017)均能减少caspase-3免疫阳性细胞。②纹状体星形胶质细胞增殖:与正常对照组(163.40±21.98)相比,缺血性脑损伤组的GFAP免疫阳性细胞明显增多(433.25±66.69,P=0.000),损伤后2h开始亚低温治疗(219.50±35.31,P=0.000)和损伤后6h开始亚低温治疗(272.50±86.20,P=0.000)均能减少GFAP免疫阳性细胞。③纹状体PCNA阳性细胞的表达:在正常对照组中,PCNA免疫阳性细胞较少,为153.40±12.46,缺血性脑损伤组的PCNA免疫阳性细胞明显增多(353.70±45.60,P=0.000),损伤后2h开始亚低温治疗(187.14±26.26,P=0.000)和损伤后6h开始亚低温治疗(230.25±67.46,P=0.000)均能减少PCNA免疫阳性细胞。结论亚低温可以抑制纹状体神经元的凋亡和星形胶质细胞的增殖,该作用可能为选择性头部降温的脑保护作用机制之一。     

Weisheitszähne — Stationär behandlungsbedürftige Komplikationen

Background

In view of the conflicting guidelines issued by national and international scientific societies, debate about the indications for prophylactic extraction of wisdeom teeth is ongoing. This prospective study was therefore set up to explore the complications associated with wisdom teeth and requiring in-patient treatment.

Patients and Methods

From January /2003 to December 2003, 21 subjects were admitted for treatment of complications associated with wisdom teeth. The medical history was recorded for each of these patients, as were the cause and type of the complications. The parameter used to quantify the severity of any infections was the CRP, and the overall clinical complexity level of each case was assessed by the length of stay in hospital (and the duration of intensive care if this had been necessary). The characteristics of patients in the group with postoperative complications were compared to those of patients with complications attributable to pericoronitis. Moreover, complications in patients who had undergone prophylactic extraction of wisdom teeth that had not been causing any symptoms were compared with those in patients whose wisdom teeth had been extracted because of morbidity.

Results

Overall, 18 deep-space infections (15 abscesses, 2 inflammatory infiltrations, 1 case of phlegmonous cellulitis), 2 mandibular fractures and 1 lingual nerve injury were noted within 1 year. The complications resulted from surgical procedures in 15 of the 21 cases, while in 6 they had their origin in pericoronitis. Extensive surgery or intensive care was required only for patients with postoperative complications. The length of stay in hospital was significantly greater for patients with postoperative complications (p= 0.007, U-test). However, 9 of these 15 patients reported preoperative episodes of infection. Thus, more than two thirds of the complications could be traced back to wisdom teeth that were causing symptoms.

Conclusion

In our clinic’s catchment area, infectious complications were more frequent and more severe and required more intensive and longer treatment in hospital than complications arising from pericoronitis. However, complications of prophylactic extraction of wisdom teeth were decidedly less frequent than direct or indirect complications of extraction of symptomatic teeth. Thus, our data tend to support the concept of elective extraction of wisdom teeth with the aim of preventing serious infections.