Long-term effects of pollen allergoid tyrosine-adsorbed subcutaneous immunotherapy on allergic rhinitis and asthma.

BACKGROUND: Allergen immunotherapy (AIT) may have a long-term disease-modifying effect. The aim of this study was to demonstrate the long-term effects of pollen allergoid tyrosine-adsorbed subcutaneous AIT on allergic rhinitis (AR) and asthma (AA) in clinical practice. METHODS: This retrospective study, funded by an AIT manufacturer, analysed the impact of AIT on AR progression and onset of need for AA medication, using a German database covering ~35% of national prescriptions during 2008-2020. Anonymized prescription data of AR patients aged 5-65 years treated with grass or tree pollen AIT between 2009 and 2013 and followed for at least 2 years after AIT cessation were compared with matched control patients with seasonal AR. RESULTS: 181,496 patients received AIT prescriptions. 5959 fulfilled the inclusion criteria. The median AIT treatment duration was 1092 days and the follow-up duration was 6.4 years. Less patients treated with AIT received prescriptions for symptomatic AR medication in the follow-up versus controls (AIT: OR: 0.37; 95% Confidence Interval (CI) 0.34, 0.40; p < .001, tyrosine-adsorbed AIT: OR: 0.27; 95% CI 0.20, 0.35 p < .001). Less asthmatic patients under AIT received prescriptions for AA medications versus controls (AIT: OR: 0.48; 95% CI 0.41, 0.55; p < .001, tyrosine-adsorbed AIT: OR: 0.48; 95% CI 0.29, 0.79; p = .004). AR and AA medication prescriptions for AIT patients were reduced in the follow-up versus baseline and controls (AIT: AR: 20.0%; 1.5 vs. 0.2 prescriptions; AA: 29.1%; 2.0 vs. 0.6 prescriptions, p < .001; tyrosine-adsorbed AIT: AR: 24.2%, 1.4 vs. 0.2 prescriptions; AA: 35.6%, 2.1 vs. 0.6 prescriptions, p < .001). The probability of AA medication onset in non-asthmatic patients during follow-up was reduced for AIT patients compared to controls (OR: 0.77, 95% CI 0.66, 0.90; p = .001). All endpoints were significant for children/adolescents and adults in stratified analyses. CONCLUSIONS: We found evidence for long-term effects up to 9.5 years for tyrosine-adsorbed AIT.

AM-301, a barrier-forming nasal spray, versus saline spray in seasonal allergic rhinitis: A randomized clinical trial.

RATIONALE: Saline nasal sprays are frequently used in the management of seasonal allergic rhinitis (SAR) for the cleansing and clearing of aeroallergens from the nasal cavity. Also using a drug-free approach, AM-301 nasal spray is forming a thin film barrier on the nasal mucosa to prevent contact with allergens, trap them, and facilitate their discharge. A clinical trial compared the efficacy, safety, and tolerability of AM-301 and saline spray in SAR. METHODS: A total of 100 patients were randomized 1:1 to self-administer AM-301 or saline 3 × daily for 2 weeks. Primary efficacy endpoint: reduction in mean daily reflective Total Nasal Symptom Score (rTNSS). Secondary efficacy endpoints: reduction in mean instantaneous TNSS and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), global impression of efficacy. Safety and tolerability: adverse events, relief medication use, symptom-free days, global impression of tolerability. RESULTS: AM-301-treated patients achieved a significantly lower rTNSS than the saline group (LS square means difference -1.1, 95% CI -1.959 to -0.241, p = .013) with improvement observed across all individual nasal symptoms. Likewise, all secondary endpoints showed statistical significance in favor of AM-301; for example, quality of life was significantly improved overall (p < .001) as well as for each individual RQLQ domain. Both treatments showed similarly good safety and tolerability. With AM-301, fewer patients used relief medication and more enjoyed symptom-free days compared to saline treatment. CONCLUSIONS: AM-301 was more effective than saline in improving SAR nasal symptoms and related quality of life while offering similar tolerability, demonstrating the benefits of a barrier approach.

Real-world data show sustained therapeutic effects of dupilumab in chronic rhinosinusitis with nasal polyps (CRSwNP) over 3 years.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent chronic inflammatory condition affecting the nose and paranasal sinuses, posing a significant socio-economic impact with substantial challenges in management. Biologics targeting type 2 inflammation such as dupilumab, have emerged as promising options. This study addresses a critical knowledge gap by comprehensively evaluating the 3-year impact of sustained dupilumab therapy in CRSwNP. METHODS: A multicentric, retrospective collection of real-world data from five tertiary referral centers in Germany was conducted, enrolling 150 adult patients. The study investigated patient-reported outcomes, disease-specific indices and clinical measures, focusing on therapeutic response persistence, adverse events, and factors influencing treatment continuity. RESULTS: Results indicate significant improvements in clinical parameters from baseline (n = 150) with sustained effectiveness after 36 months (n = 138) as indicated in mean score ± standard deviation. Dupilumab treatment significantly improved overall disease-related impairment (VAS score: 7.5 ± 2.5 to 1.6 ± 1.3) and rhinosinusitis symptoms (SNOT-22: 59.4 ± 19.4 to 18.0 ± 15.0). Nasal Polyp Scores (NPS) decreased (5.3 ± 1.8 to 0.7 ± 1.1), and olfactory function improved (3.2 ± 2.5 to 8.4 ± 2.8), with three out of four patients achieving normosmia or hyposmia after 36 months. An "Excellent" treatment response according to EUFOREA23 criteria was observed in 76.5% of patients after 36 months. Sixteen patients discontinued Dupilumab, 12 permanently. Adverse events totaled 69 in 48 patients, commonly self-limiting. CONCLUSION: The study highlights the enduring effectiveness and lack of habituation to dupilumab after a sustained therapy of 3 years, providing valuable insights into its long-term therapeutic implications for CRSwNP patients.

Primary results of the AGO-Zervix-1 Study: A prospective, randomized phase III study to compare the effects of paclitaxel and topotecan with those of cisplatin and topotecan in the treatment of patients with recurrent and persistent cervical cancer.

BACKGROUND: Before the era of immunotherapies and antibody-drug conjugates, there were limited chemotherapeutic options for patients with recurrent and metastatic cervical cancer. Combination therapies with cisplatin have shown some superiority over monotherapy. This study examined platinum-free treatment regimens, comparing a combination of topotecan and paclitaxel (TP) with topotecan and cisplatin (TC) in patients with recurrent or metastatic cervical cancer, with or without prior platinum-based treatment. METHODS: The AGO-Zervix-1 Study (NCT01405235) is a prospective, randomized phase III study in which patients were randomly assigned at a 1:1 ratio to treatment within the control arm with topotecan (0.75 mg/m2) on days 1-3 and cisplatin (50 mg/m2) on day 1 every 3 weeks and in the study arm topotecan (1.75 mg/m2) and paclitaxel (70 mg/m2) on days 1, 8, and 15 every 4 weeks or treatment. The primary study aim was overall survival; progression-free survival, toxicity, and quality of life were secondary aims. The interim and final analysis is here reported after recruitment of 173 of 312 planned patients. RESULTS: Median overall survival in the TP arm was 9.6 months, compared with 12.0 months in the TC arm (log-rank test, P = 0.33). Median progression-free survival rates were 4.4 months with TP and 4.2 months with TC (log-rank test, P = 0.47). Leukopenia and nausea/vomiting were more frequent in the cisplatin-containing arm. Otherwise, toxicity profiles were comparable. There were no differences in FACT-G-assessed quality of life. CONCLUSION: Platinum-based combination chemotherapy remains the standard of care chemotherapy regimen for patients with recurrent or metastatic cervical cancer.

The Clinical Relevance of Fractional Curettage in the Diagnostic Management of Primary Endometrial Cancer.

OBJECTIVE: Hysteroscopy and fractional curettage are commonly utilized techniques for the diagnosis of postmenopausal abnormal uterine bleeding and histopathological verification of primary endometrial cancer (EC). This study delves into the clinical significance of procuring preoperative endocervical tissue in conjunction with corpus fractions through fractional curettage. DESIGN: This retrospective study encompassed a cohort of 84 patients diagnosed with T1 stage EC and 55 patients diagnosed with T2 stage EC, who underwent primary treatment between the years 2011 and 2021 at the University Hospital Frankfurt or Jung-Stilling Hospital Siegen. MATERIALS, SETTING, METHODS: Among the postoperative T2 stage EC patients, a stratification was performed based on preoperative endocervical curettage (ECC) results obtained through fractional curettage. Categorical and continuous variables were compared utilizing the Pearson χ2 test, while for multivariate analyses and regression modeling, the Kaplan-Meier method and Cox regression models were respectively employed. RESULTS: The median age of patients with pT2 stage EC was 64 years (range: 38-85). A predominant majority of these patients exhibited the endometrioid subtype of EC (90.9%). Upon conducting comparative analysis between groups, a notably higher frequency of laparotomies was observed (p = 0.002) among patients in whom preoperatively detected positive ECC was evident. The detection performance of fractional curettage in identifying positive ECC yielded a sensitivity of 70.9% and a specificity of 73.8%. In multivariate analysis, age at diagnosis (p = 0.022), positive ECC observed during fractional curettage (p = 0.036), and the FIGO stage (p = 0.036) emerged as prognostic determinant for progression-free survival. Independent prognostic factors for overall survival (OS) were age at diagnosis (p = 0.003), positive ECC (p = 0.008), histological grading (p = 0.016), and the FIGO stage (p = 0.022). A significant difference in OS was evident between patients characterized by preoperative negative ECC and those displaying positive ECC (81.8 vs. 59.5 months, p = 0.019). LIMITATIONS: Limitations include the retrospective design of the study as well as a small number of patients. CONCLUSIONS: Preoperative determination of endocervical involvement of primary T2 stage EC could be a prognostic indicator in decision-making to treat EC. The conduct of prospective trials is necessary to definitively establish the routine application and associated benefits of fractional curettage in the context of primary EC.

Postoperative Reproductive Outcomes in Patients with Endometriosis-Associated Infertility: A Single-Center Retrospective Study.

OBJECTIVES: Endometriosis is a chronic inflammatory disease known to contribute to infertility. Laparoscopic excision of endometriotic lesions represents a standard treatment modality for symptomatic women. Our study aims to assess the potential benefits of laparoscopic excision of endometriosis in patients experiencing infertility associated with the condition, as well as to define the clinical factors that may impact the cumulative pregnancy rate. DESIGN: In this retrospective analysis, a total of 102 patients with endometriosis-related infertility were enrolled. MATERIALS, SETTING, METHODS: All participants underwent reproductive surgery and were then categorized into two groups: those who conceived were assigned to group A, while those who did not were assigned to group B. The correlation between clinical factors and pregnancy rate was assessed using the log-rank test, and both univariate and multivariate analyses were conducted utilizing the Cox regression model. RESULTS: The median age of the patients was 33.5 years, with a median follow-up duration of 70 months. Throughout the study period, 71 patients (69.6%) conceived (group A), while the remaining 31 patients (30.4%) did not conceive (group B), irrespective of the use of Assisted-Reproduction Technologies. The Cox regression model revealed that factors such as the duration of infertility, presence of deep infiltrating endometriosis, bowel endometriosis, rASRM stages, pelvic adhesions, and recurrent disease negatively impacted postoperative conception rates. Conversely, complete excision and coagulation of endometriotic lesions, as well as ablation of ovarian endometriomas, emerged as independent positive predictive factors for postoperative clinical pregnancy. LIMITATIONS: Limitations of this study is retrospective design of the study, as well as a small number of patients. CONCLUSIONS: Complete excision of endometriosis during reproductive surgery may yield a positive effect and optimize the likelihood of pregnancy in patients with endometriosis-related infertility.

Status quo and future directions of digitalization in gynecology and obstetrics in Germany: a survey of the commission Digital Medicine of the German Society for Gynecology and Obstetrics.

PURPOSE: Digitalization plays a critical role and is beginning to impact every part of the patient journey, from drug discovery and data collection to treatment and patient-reported outcomes. We aimed to evaluate the status quo and future directions of digital medicine in the specialty of gynecology and obstetrics in Germany. METHODS: An anonymous questionnaire was distributed via the German Society of Gynecology and Obstetrics newsletter in December 2022. The questionnaire covered the domains baseline demographic information, telemedicine, digital health applications (DIGAs), and future expectations. RESULTS: In all, 91 participants completed the survey. Median age was 34 years; 67.4% (60 of 89) were female and 32.6% (29 of 89) were male. About 10% (9 of 88) have prescribed DIGAs to date and 14% (12 of 86) offer telemedical appointments. Among those who do not use digital medicine, very few plan to do so in the near future. Reasons include missing software interfaces, lack of time to try out new things, lack of knowledge, lack of monetary compensation (66.3%), and employee concerns. A majority agreed that digitalization will help to save time and improve patient care and that intelligent algorithms will aid clinicians in providing patient care to women. CONCLUSIONS: The status quo and future directions of digital medicine in gynecology and obstetrics in Germany are characterized by contradicting expectations regarding the benefits of digital medicine and its actual implementation in clinical routine. This represents an important call to action to meet the requirements of modern patient care.

[Enhanced quality of documentation for biologic therapy of chronic rhinosinusitis through structured digital reporting and indication?] / Qualitätssteigerung der Dokumentation zur Biologikatherapie der chronischen Rhinosinusitis durch digitale, strukturierte Befunderhebung und Indikationsstellung?

BACKGROUND: With targeted inhibition of type 2 inflammation, biologics represent the standard add-on therapy for inadequately controlled severe forms of chronic rhinosinusitis with nasal polyps (CRSwNP). Despite standardization with paper-based checklists, the documentation of medical history and current findings pertinent to indication criteria are a significant challenge for physicians. Through development of an application based on structured reporting, the current study aimed to improve documentation quality and simplify the decision-making process. Previously available paper checklists served as a comparison. METHODS: For this study, a digital incremental tool was programmed to record current findings and check for fulfilment of indication criteria. The tool was compared with other checklists in terms of completeness, time required, and readability. RESULTS: A total of 20 findings were collected for each of the three documentation options and included in the analysis. Documentation with the two paper-based checklists had comparable information content: 17.5 ± 5.1/21.7 ± 7.6 points out of a maximum of 43 points; p > 0.05. Documentation using the digital application led to a significant increase in information content compared to all paper-based documentation. The average score was 38.25 ± 3.7 (88.9% of maximum; p < 0.001). On average, user satisfaction was high (9.6/10). Use of the digital application was initially more time consuming, but as more cases were documented, the time taken improved significantly. CONCLUSION: In the future, structured reporting using apps could replace paper-based reporting for the indication of biologic therapy in CRSwNP patients and offer additional benefits in terms of data quality and traceability of results. The increasing volume of documentation in the future, the progress of digitalization, and the possibility of networking between individual centers make introduction of the app in the near future both likely and economical.

[Results of a survey on the current management of chronic rhinosinusitis with nasal polyps in Germany]. / Ergebnisse einer Umfrage zur aktuellen Behandlung der chronischen Rhinosinusitis mit nasalen Polypen.

INTRODUCTION: With a prevalence of 0.55% to 4%, chronic rhinosinusitis with nasal polyps (CRSwNP) is a relevant part of the daily work of German otolaryngologists. The aim of the questionnaire-based data collection was to assess the current treatment status of CRSwNP in Germany. MATERIAL AND METHODS: For this purpose, 24 questions within an anonymized online questionnaire were sent to all German ENT departments. RESULTS: Of 160 contacted ENT departments, 50 participated in the survey (31.3%). Among these, 76% performed more than 100 sinus surgeries annually and 38% treated more than 50 patients with biologics. Saline irrigations (80%) and intranasal glucocorticoids (GCS, 96%) were the most common conservative therapies. Systemic GCSs (52%) and intranasal GCS irrigation (20%) were less common. 80% of departments used biologics in the therapy of CRSwNP with an overall preference for dupilumab (70%). For therapy of aspirin intolerance, biologics (52%) were preferred to aspirin desensitization (26%). Prior to treatment with biologics clinical workup included the nasal polyp score (90%), the SNOT-22 questionnaire (84%), surrogate markers of type 2 inflammation (60%-72%), and computer tomography (50%). Final treatment success was assessed after 24 weeks (50%). CONCLUSION: Mostly, the responding departments followed German and European recommendations for diagnosis and therapy of CRSwNP. Therapy with biologics is widely used. The value of preoperative systemic GCS and the frequent performance of CT before initiation of therapy with a biologic should be debated in regard to its currently widespread use.

[Medical clinical diagnostics for indoor mould exposure - Update 2023 (AWMF Register No. 161/001)]. / Medizinisch klinische Diagnostik bei Schimmelpilzexposition in Innenräumen ­ Update 2023 (AWMF-Register-Nr. 161/001).

This article is an abridged version of the updated AWMF mould guideline "Medical clinical diagnostics in case of indoor mould exposure - Update 2023", presented in July 2023 by the German Society of Hygiene, Environmental Medicine and Preventive Medicine (Gesellschaft für Hygiene, Umweltmedizin und Präventivmedizin, GHUP), in collaboration with German and Austrian scientific medical societies, and experts. Indoor mould growth is a potential health risk, even if a quantitative and/or causal relationship between the occurrence of individual mould species and health problems has yet to be established. There is no evidence for a causal relationship between moisture/mould damage and human diseases, mainly because of the ubiquitous presence of fungi and hitherto inadequate diagnostic methods. Sufficient evidence for an association between moisture/mould damage and the following health effects has been established for: allergic respiratory diseases, allergic rhinitis, allergic rhino-conjunctivitis, allergic bronchopulmonary aspergillosis (ABPA), other allergic bronchopulmonary mycosis (ABPM), aspergilloma, Aspergillus bronchitis, asthma (manifestation, progression, exacerbation), bronchitis (acute, chronic), community-acquired Aspergillus pneumonia, hypersensitivity pneumonitis (HP; extrinsic allergic alveolitis (EEA)), invasive Aspergillosis, mycoses, organic dust toxic syndrome (ODTS) [workplace exposure], promotion of respiratory infections, pulmonary aspergillosis (subacute, chronic), and rhinosinusitis (acute, chronically invasive, or granulomatous, allergic). In this context the sensitizing potential of moulds is obviously low compared to other environmental allergens. Recent studies show a comparatively low sensitization prevalence of 3-22,5 % in the general population across Europe. Limited or suspected evidence for an association exist with respect to atopic eczema (atopic dermatitis, neurodermatitis; manifestation), chronic obstructive pulmonary disease (COPD), mood disorders, mucous membrane irritation (MMI), odor effects, and sarcoidosis. (iv) Inadequate or insufficient evidence for an association exist for acute idiopathic pulmonary hemorrhage in infants, airborne transmitted mycotoxicosis, arthritis, autoimmune diseases, cancer, chronic fatigue syndrome (CFS), endocrinopathies, gastrointestinal effects, multiple chemical sensitivity (MCS), multiple sclerosis, neuropsychological effects, neurotoxic effects, renal effects, reproductive disorders, rheumatism, sick building syndrome (SBS), sudden infant death syndrome, teratogenicity, thyroid diseases, and urticaria.The risk of infection posed by moulds regularly occurring indoors is low for healthy persons; most species are in risk group 1 and a few in risk group 2 (Aspergillus fumigatus, A. flavus) of the German Biological Agents Act (Biostoffverordnung). Only moulds that are potentially able to form toxins can be triggers of toxic reactions. Whether or not toxin formation occurs in individual cases is determined by environmental and growth conditions, water activity, temperature and above all the growth substrates.In case of indoor moisture/mould damage, everyone can be affected by odor effects and/or mood disorders.However, this is not an acute health hazard. Predisposing factors for odor effects can include genetic and hormonal influences, imprinting, context and adaptation effects. Predisposing factors for mood disorders may include environmental concerns, anxiety, condition, and attribution, as well as various diseases. Risk groups to be protected particularly regarding infection risk are immunocompromised persons according to the classification of the German Commission for Hospital Hygiene and Infection Prevention (Kommission für Krankenhaushygiene und Infektionsprävention, KRINKO) at the Robert Koch-Institute (RKI), persons suffering from severe influenza, persons suffering from severe COVID-19, and persons with cystic fibrosis (mucoviscidosis); with regard to allergic risk, persons with cystic fibrosis (mucoviscidosis) and patients with bronchial asthma must be protected. The rational diagnostics include the medical history, physical examination, and conventional allergy diagnostics including provocation tests if necessary; sometimes cellular test systems are indicated. In the case of mould infections, the reader is referred to the specific guidelines. Regarding mycotoxins, there are currently no useful and validated test procedures for clinical diagnostics. From a preventive medical point of view, it is important that indoor mould infestation in relevant magnitudes cannot be tolerated for precautionary reasons.For evaluation of mould damage in the indoor environment and appropriate remedial procedures, the reader is referred to the mould guideline issued by the German Federal Environment Agency (Umweltbundesamt, UBA).

The role of a digital twin in supporting criminal investigations - a case report about a possible abuse.

As part of a comprehensive analysis, this case report presents a possible case of child maltreatment that can serve as a basis for forensic and medical examiner investigations. This case concerns the death of an infant who was approximately two months old. During a routine examination by the pediatrician at the end of May 2021, the child was found to have a normal head circumference of 31 cm. No other abnormalities were noted. On June 19, 2021, the child died, and an autopsy revealed a head circumference of 44 cm and a subdural hematoma as the cause of death. Questions arose as to who might have abused the child and when. The only evidence was a low-quality cell phone video taken by the child's parents on June 13, 2021, six days before the child's death, in which the child could be seen lying on a pillow. It was necessary to determine whether the child in this video already had an unnatural head circumference. This study presents a novel workflow that demonstrates how to analyze and deal with low quality video to answer questions like the above. The workflow demonstrates the creation of 3D scenes from digital image and video material. These 3D scenes can be used for object measurement and to support forensic and medical investigations. In the present case, where only low quality smartphone images were available, the presented workflow was used to create a 3D scene of the child lying on the pillow. In this 3D scene, it was possible to determine the child's head circumference. These measurements support the findings of the medical examiner (dated June 24, 2021) and confirm the suspicion that possible child abuse had already taken place on June 13, 2021. The innovative approach makes it possible to identify evidence of possible abuse based on a specific point in time, in this case the child's private footage. It also demonstrates the potential of 3D scene reconstruction in complex forensic and medical scenarios.

Therapy Response and Survival among Patients with Gynecologic Tumors Treated with Transarterial Chemoperfusion and Transarterial Chemoembolization.

Background and Objectives: This study aimed to evaluate the tumor response relating to and survival benefit of transarterial chemoperfusion (TACP) and transarterial chemoembolization (TACE) in the treatment of patients with unresectable gynecologic tumors who are intolerant of or have a suboptimal response to chemotherapy and radiotherapy. Materials and Methods: Between January 2000 and October 2023, 75 patients diagnosed with gynecologic tumors underwent 213 TACP and 154 TACE procedures. Of these, 33 patients were treated with TACP, 20 were treated with TACE, and 22 received a combination of both therapies. A retrospective evaluation of local tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) was conducted, and survival rates were determined using the Kaplan-Meier estimator. Results: Of the total 75 patients, 50 (67%) maintained a stable course of disease until the completion of therapy, 10 (13%) had a partial response, 2 (3%) had a complete response following thermal ablation, and 13 (17%) experienced progression. Furthermore, a 6% reduction in the sum of the longest diameters and an 8% reduction in tumor volume were observed. The median overall survival was 16.15 months, while the median progression-free survival was 13.19 months. Conclusions: TACP and TACE are potential treatment options for local tumor control in patients with unresectable gynecologic tumors who are intolerant of or show a poor response to chemotherapy and radiotherapy. However, further investigation and adjustment of treatment protocols are required to improve therapy response and survival outcomes.

Limited Reimbursement and Underuse of Digital Healthcare Concepts Are Major Barriers to Clinical Allergological Care in Germany.

INTRODUCTION: Allergic diseases represent a broad spectrum of high-prevalence, chronic conditions that remain underdiagnosed and undertreated. The aims of this interdisciplinary, questionnaire-based, non-interventional study were to identify and analyze potential barriers to clinical allergological care in Germany. METHODS: All hospitals listed in the German hospital register involved in the treatment of allergological patients (n = 899) were invited to participate. The study yielded a response rate of 52.1% (n = 468). RESULTS: Overall, 88.5% of clinics agreed that allergological care in Germany needs improvement, especially in terms of reimbursement for diagnostics and therapy. More than 80% of participating clinics reported that the decreased availability of test substances and the time-intensity of allergological testing represent relevant barriers. For dermatology and pulmonology, the former is the strongest barrier, while for pediatric and ENT clinics, time-intensity is regarded as the strongest barrier. The availability of good therapy and appropriate guidelines present no barriers to allergological care. Regarding the use of digital healthcare concepts, a very large majority of clinics (n = 352; 91.4%) do not offer video consultations or the use of health applications in patient care. CONCLUSION: In conclusion, we have identified several structural barriers to allergological care in Germany. Reimbursement and the use of digital healthcare concepts in German clinics providing allergological care need improvement. Based on the results of this study, there is an urgent need for researchers and policymakers to further investigate and support allergology departments in their clinical work and in their implementation of digital healthcare concepts.

Interventional oncological treatment of breast cancer liver metastasis (BCLM): single center long-term evaluation over 26 years using thermoablation techniques like LITT, MWA and TACE in a multimodal application.

The purpose of the study is to retrospectively evaluate the development and technological progress in local oncological treatments of patients with breast cancer liver metastasis (BCLM) using LITT (laser interstitial thermotherapy), MWA (microwave ablation) and TACE (transarterial chemoembolization) ablation techniques in a multimodal application. The study uses data generated between 1993 and 2020. Therapy results were evaluated using the Kaplan-Meier survival estimate, Cox proportional hazard regression and log-rank test. Cox regression analysis showed that the different treatment methods are statistically significant predictors of survival of patients. Median survival times for groups treated with LITT (212 patients) and LITT + TACE (215 patients) were 2.2 years and 2.1 years respectively; median survival times for groups treated with MWA (17 patients) and MWA + TACE (143 patients) were 5.6 and 2.4 years respectively. For LITT only treatments, the 1-, 3- and 5-year survival probability scored 80%, 37%, 22%. Results for combined LITT + TACE treatments were 76%, 34% and 15%. In group MWA, the 1-/3-/5-year survival probability rates were calculated as 89%, 89%, 89% (however, they should be interpreted carefully due to a relatively small sample size of n = 17 patients). Group MWA + TACE offered values of 77%, 38% and 22%. A separate group of 549 patients was analyzed with TACE monotherapy treatment. The estimated median survival time in this group was 0.8 years. The 1-/3-/5-year survival probability rates were 37%, 8% and 4%. Treatments with combined MWA and MWA + TACE resulted in the best median survival time estimations in this study.

The non-apoptotic function of Caspase-8 in negatively regulating the CDK9-mediated Ser2 phosphorylation of RNA polymerase II in cervical cancer.

Cervical cancer is the fourth most frequently diagnosed and fatal gynecological cancer. 15-61% of all cases metastasize and develop chemoresistance, reducing the 5-year survival of cervical cancer patients to as low as 17%. Therefore, unraveling the mechanisms contributing to metastasis is critical in developing better-targeted therapies against it. Here, we have identified a novel mechanism where nuclear Caspase-8 directly interacts with and inhibits the activity of CDK9, thereby modulating RNAPII-mediated global transcription, including those of cell-migration- and cell-invasion-associated genes. Crucially, low Caspase-8 expression in cervical cancer patients leads to poor prognosis, higher CDK9 phosphorylation at Thr186, and increased RNAPII activity in cervical cancer cell lines and patient biopsies. Caspase-8 knock-out cells were also more resistant to the small-molecule CDK9 inhibitor BAY1251152 in both 2D- and 3D-culture conditions. Combining BAY1251152 with Cisplatin synergistically overcame chemoresistance of Caspase-8-deficient cervical cancer cells. Therefore, Caspase-8 expression could be a marker in chemoresistant cervical tumors, suggesting CDK9 inhibitor treatment for their sensitization to Cisplatin-based chemotherapy.

Current landscape of hospital information systems in gynecology and obstetrics in Germany: a survey of the commission Digital Medicine of the German Society for Gynecology and Obstetrics.

PURPOSE: Hospital information systems (HIS) play a critical role in modern healthcare by facilitating the management and delivery of patient care services. We aimed to evaluate the current landscape of HIS in the specialty of gynecology and obstetrics in Germany. METHODS: An anonymous questionnaire was distributed via the German Society of Gynecology and Obstetrics newsletter in December 2022. The questionnaire covered the domains baseline demographic information, satisfaction with daily use, satisfaction with implementation, and degree of digitization. RESULTS: Ninety-one participants completed the survey. Median age was 34 years; 67.4% (60 of 89) were female, and 32.6% (29 of 89) were male. Of the survey participants, 47.7% (42 of 88) were residents, 26.1% (23 of 91) senior physicians, and 9.1% (8 of 88) medical directors. The degree of digitization of clinical documentation is mainly mixed digital and paper-based (64.0%, 57 of 89) while 16.9% (15 of 89) operate mainly paper-based. The current HIS has been in use on average for 9 years. The median number of different software systems used in daily routine is 4. About 33.7% (30 of 89) would likely or very likely recommend their current HIS to a colleague. CONCLUSIONS: The current landscape of HIS in gynecology and obstetrics in Germany is characterized by a high heterogeneity of systems with low interoperability and long service life; thus, many healthcare professionals are not satisfied. There is both a need to enhance and an interest in modernizing the technological infrastructure to meet today's requirements for patient care.

Randomized, placebo-controlled study on efficacy, safety and tolerability of drug-induced defibrinogenation for sudden sensorineural hearing loss: the lessons learned.

PURPOSE: Disturbance of cochlear microcirculation is discussed as final common pathway of various inner ear diseases. Hyperfibrinogenemia causing increased plasma viscosity is a possible factor for a critical reduction of cochlear blood flow that might lead to sudden sensorineural hearing loss (SSHL). The aim was to determine the efficacy and safety of drug-induced defibrinogenation by ancrod for SSHL. METHODS: Double-blind, randomized, placebo-controlled, multicenter, parallel group, phase II (proof-of-concept) study (planned enrollment: 99 patients). Patients received an infusion of ancrod or placebo (day 1) followed by subcutaneous administrations (day 2, 4, 6). Primary outcome was the change in pure tone audiogram air conduction average until day 8. RESULTS: The study was terminated early due to slow recruiting (31 enrolled patients: 22 ancrod, 9 placebo). A significant improvement of hearing loss was registered in both groups (ancrod: - 14.3 dB ± 20.4 dB, - 39.9% ± 50.4%; placebo: - 22.3 dB ± 13.7 dB, - 59.1% ± 38.0%). A statistically significant group-difference was not detected (p = 0.374). Placebo response of 33.3% complete and 85.7% at least partial recovery was observed. Plasma fibrinogen levels were reduced significantly by ancrod (baseline: 325.2 mg/dL, day 2: 107.2 mg/dL). Ancrod was tolerated well, no adverse drug reaction was of severe intensity, no serious adverse events occurred. CONCLUSION: Ancrod reduced fibrinogen levels that support its mechanism of action. The safety profile can be rated positively. Since the planned number of patients could not be enrolled, no efficacy conclusion can be drawn. The high rate of placebo response challenges clinical trials for SSHL and needs to be considered in future investigations. Trial registrations This study was registered in the EU Clinical Trials Register, EudraCT-No. 2012-000066-37 at 2012-07-02.

Characteristics of smell and taste disorders depending on etiology: a retrospective study.

PURPOSE: This study investigates the impact of etiology on the epidemiologic profile, disease severity, type of treatment and therapy outcome in smell and taste disorders. METHODS: This is a retrospective analysis of 270 patients that presented with a smell or taste disorder in a specialized, tertiary care center. An established questionnaire was used to collect data from patients and physicians. Olfactometry was performed with the Sniffin' Sticks test kit, while gustometry was performed by taste strips. RESULTS: Post-traumatic etiology was associated with young age (median 46 years) and male sex, and showed the most severe degrees of smell loss compared to other etiologies (64.3% anosmia). Postinfectious causes occurred more frequently in females (77.3%) and correlated with a history of pharyngeal surgery, suggesting a vulnerability for virally mediated sensory dysfunction following adenoid/tonsil removal. Parosmia also correlated with both postinfectious etiology (62.5%) and female sex. In sinunasal etiology, the presence of nasal polyps worsened the overall olfactory test score by approximately 50%. In particular, smell threshold and discrimination were reduced, while smell identification was not significantly impacted by nasal polyp obstruction. Sinunasal dysfunction was the only etiology to show significant improvement after therapy (73.9% improved). Finally, we could establish good correlations between the subjective impairment and objective dysfunction for each sensory modality. CONCLUSION: Each etiology of chemosensory dysfunction shows particular distributions of variables like sex, age, comorbidities and operations, disease severity, sensory threshold, discrimination and identification. This paper offers a detailed account of the correlations between the cause and the characteristics of smell and taste loss.

Nasal residence time and rheological properties of a new bentonite-based thixotropic gel emulsion nasal spray - AM-301.

OBJECTIVE: The present work provides characterization of rheological properties of a new bentonite-based thixotropic gel emulsion nasal spray (AM-301), its nasal residence time, distribution, safety and tolerability. SIGNIFICANCE: The nasal epithelium is a portal of entry for allergens and primary infection by airborne pathogens. Non-pharmacological interventions, which enhance physical and biological barriers, protect against allergens and pathogens without drug-related side effects. AM-301 has shown promising efficacy and safety in the nasal epithelium against viruses (in vitro) and pollen (clinical). METHODS: Technical part (i) spray characterization was performed with a validated droplet size distribution method; evaluation of the rheological properties of the formulation was performed by a validated amplitude sweep method and a validated oscillation, rotation, oscillation; Clinical part (ii) nasal and oropharyngeal endoscopy were used to provide a semi-quantitative evaluation of distribution and residence time of fluorescein-labelled AM-301 in the nose and oropharynx of healthy volunteers; (iii) tolerability and safety. RESULTS: (i) The non-Newtonian rheological properties of the formulation allow AM-301 to be sprayed and then to revert to a gel to prevent run-off from the nasal cavity; (ii) the formulation remains on the inferior turbinate, septum and oropharynx of volunteers for up to 210 min and on the middle turbinate for up to 60 min; two nasal sprays provide no substantial benefit over a single application with regards to coverage or retention; (iii) the spray is well tolerated. CONCLUSIONS: Single dose spray delivery of AM-301 provides extended coverage of the nasal mucosa up to the inferior turbinates.

Current situation of allergological health care at German hospitals.

BACKGROUND: Allergic medical care in Germany is organized on an interdisciplinary basis. An overview of the current care situation is necessary to manage and improve interdisciplinary cooperation. METHODS: Between January and February 2022, questionnaires were sent online and by mail to chief physicians of inpatient clinical departments to which most allergological diseases are assigned (dermatology, otorhinolaryngology [ENT], pulmonology, pediatrics, environmental/occupational medicine, gastroenterology; n = 899). RESULTS: The response rate was 52.1%. Allergology departments of dermatology, ENT and pulmonology were predominantly located in metropolitan areas (> 100,000 inhabitants), whereas responses of pediatric departments were mostly from smaller towns. 76.8% of the respondents reported existing interdisciplinary treatment plans with other specialties. Pediatric and pulmonology clinics stated disproportionately few interdisciplinary treatment concepts with dermatology and ENT clinics, especially in smaller cities with < 100,000 inhabitants. Diagnosis and therapy of allergic rhinitis were performed in particular by the departments of ENT, asthma mainly by the pulmonology departments. Care of other allergological diseases was most frequently reported by chief physicians of dermatology and pediatrics. CONCLUSIONS: In metropolitan areas, participating departments provide allergology care in a cooperative manner. A large spectrum of care is covered in cooperation with dermatological clinics. In more rural areas, cooperation is rarer; here, mainly pediatric departments provide allergological care, which may explain the more limited range of services compared to metropolitan areas.