University Hospital Frankfurt Research Articles

Predictive value of a novel digital risk calculator to determine early patient outcomes after major surgery: a proof-of-concept pilot study

BackgroundA structured risk assessment of patients with validated and evidence-based tools can help to identify modifiable factors before major surgeries. The Protego Maxima trial investigated the value of a new digitized risk assessment tool that combines tools which can be easily used and implemented in the clinical workflow by doctors and qualified medical staff. The hypothesis was that the structured assessment and risk-grouping is predictive of short-term surgical quality reflected by complications and overall survival.MethodsThe Protego Maxima Trial was a prospective cohort analysis of patients undergoing major surgery (visceral, thoracic, urology, vascular and gynecologic surgeries) as key inclusion criterion and the absence of an acute or acute on chronically decompensated pulmo-cardiovascular decompensation. Patients were risk-scored with the software (The Prehab App) that includes a battery of evidence-based risk assessment tools that allow a structured risk assessment. The data were grouped to predefined high and low risk groups and aggregate and individual scores. The primary outcome was to validate the predictive value of the RAI score and the TUG for overall survival in the high and low risk groups. Secondary outcomes were surgical outcomes at 90-days after surgery (overall survival, Clavien-Dindo (CD) 1–5 (all complications), and CD 3–5 (major complications)). The study was carried out in accordance with the DIN ISO 14,155, and the medical device regulation (MDR) at Frankfurt University Hospital between March 2022 and January 2023.ResultsIn total 267 patients were included in the intention to treat analysis. The mean age was 62.1 ± 12.4 years. Patients with a RAI score > 25 and/or a timed up and go (TUG) > 8 s had a higher risk for mortality at 90 days after surgery. The low-risk group predicted beneficial outcome and the high-risk group predicted adverse outcome in the ROC analysis (Area Under the Curve Receiver Operator Characteristics: AUROC > 0.800; p = 0.01). Risk groups (high vs. low) showed significant differences for 90-day survival (99.4% vs. 95.5%; p = 0.04) and major complications (16.4% vs. 32.4%; p < 0.001).ConclusionThe proof-of-concept trial showed that a risk assessment with ‘The Prehab App’ may be viable to estimate the preoperative risk for mortality and major complications before major surgeries. The overall performance in this initial set of data indicated a certain reliability of the scoring and risk grouping, especially of the RAI score and the TUG. A larger data set will be required to proof the generalizability of the risk scoring to every subgroup and may be fostered by artificial intelligence approaches.Trial registrationEthics number: 2021-483-MDR/MPDG-zuständig monocentric; The Federal Institute for Pharmaceuticals and Medical Devices/BfArM, reference number: 94.1.04-5660-13655; Eudamed: CIV-21-07-0307311; German Clinical Trial Registry: DRKS 00026985.

Influence of aberrant right hepatic artery on survival after pancreatic resection for ductal adenocarcinoma of the pancreatic head.

The presence of an aberrant right hepatic artery (aRHA), arising from the superior mesenteric artery, is a common variant of the liver vascular anatomy. Considering that tumor spread occurs along vessels, the question arises, whether the presence of an aRHA influences the oncologic outcome after resection for cancer of the pancreatic head. Patients with ductal adenocarcinoma of the pancreatic head, who underwent resection from 2011 to 2020 at the Frankfurt University Hospital, Germany, were analyzed retrospectively. Surgical records and computed tomography imaging were reviewed for the presence of aRHA. Overall and disease-free survival as well as hepatic recurrence were analyzed according to the presence of aRHA. aRHA was detected in 21 out of 145 patients (14.5%). The median overall survival was 26 months (95%CI 20.8-34.4), median disease-free survival was 12.1 months (95%CI 8.1-17.3). There was no significant difference in overall survival (26.1 versus 21.4 months, adjusted hazard ratio 1.31, 95%CI 0.7-2.46, p = 0.401) or disease-free survival (14.5 months versus 12 months, adjusted hazard ratio 0.98, 95%CI 0.57-1.71, p = 0.957) without and with aRHA. The hepatic recurrence rate was 24.4.% with conventional anatomy versus 30.8% with aRHA (adjusted odds ratio 1.36, 95%CI 0.3-5.38, p = 0.669). In the multivariable analysis, only lymphatic vessel invasion was an independent prognostic factor for hepatic recurrence. The presence of an aRHA does not seem to influence the long-term survival and hepatic recurrence after resection for ductal adenocarcinoma of the pancreatic head.

The clinical relevance of fractional curettage in the diagnostic management of primary endometrial cancer.

Hysteroscopy and fractional curettage are commonly utilized techniques for the diagnosis of postmenopausal abnormal uterine bleeding (AUB) 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. This retrospective study encompassed a cohort of 84 patients diagnosed with T1-stage endometrial cancer (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. 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-Chi-square test, while for multivariate analyses and regression modeling, the Kaplan-Meier method and Cox regression models were respectively employed. The median age of patients with pT2-stage EC was 64 years (range: 38 to 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 endocervical curettage (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 (PFS). 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). The retrospective design of the study, as well as a small number of patients. 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 endometrial cancer.

Terlipressin therapy is associated with increased risk of colonisation with multidrug-resistant bacteria in patients with decompensated cirrhosis.

Patients with cirrhosis are susceptible to develop bacterial infections that trigger acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Infections with multidrug-resistant organisms (MDRO) are associated with deleterious outcome. MDRO colonisation frequently proceeds MDRO infections and antibiotic therapy has been associated with MDRO colonisation. The aim of the study was to assess the influence of non-antibiotic medication contributing to MDRO colonisation. Three hundred twenty-four patients with AD and ACLF admitted to the ICU of Frankfurt University Hospital with MDRO screening were included. Regression models were performed to identify drugs associated with MDRO colonisation. Another cohort (n = 129) from Barcelona was included to validate. A third multi-centre cohort (n = 203) with metagenomic sequencing data of stool was included to detect antibiotic resistance genes. A total of 97 patients (30%) were identified to have MDRO colonisation and 35 of them (11%) developed MDRO infection. Patients with MDRO colonisation had significantly higher risk of MDRO infection than those without (p = 0.0098). Apart from antibiotic therapy (odds ratio (OR) 2.91, 95%-confidence interval (CI) 1.82-4.93, p < 0.0001), terlipressin therapy in the previous 14 days was the only independent covariate associated with MDRO colonisation in both cohorts, the overall (OR 9.47, 95%-CI 2.96-30.23, p < 0.0001) and after propensity score matching (OR 5.30, 95%-CI 1.22-23.03, p = 0.011). In the second cohort, prior terlipressin therapywas a risk factor for MDRO colonisation (OR 2.49, 95% CI 0.911-6.823, p = 0.075) and associated with risk of MDRO infection during follow-up (p = 0.017). The validation cohort demonstrated that antibiotic inactivation genes were significantly associated with terlipressin administration (p = 0.001). Our study reports an increased risk of MDRO colonisation in patients with AD or ACLF, who recently received terlipressin therapy, while other commonly prescribed non-antibiotic co-medications had negligible influence. Future prospective trials are needed to confirm these results.

Heterogeneity of small duct- and large duct-type intrahepatic cholangiocarcinoma.

The histological subtype of intrahepatic cholangiocarcinoma (iCCA) is associated with different mutational characteristics that impact clinical management. So far, data are lacking on the presence of small duct iCCA (SD-iCCA) and large duct iCCA (LD-iCCA) in a single patient. The aim of the current study was to determine the presence and degree of intratumoural heterogeneity of SD- and LD-iCCA features in different tumour regions. All patients treated with surgically resected iCCA at Frankfurt University Hospital between December 2005 and March 2023 were retrospectively analysed. Histomorphological features of SD- and LD-iCCA were evaluated by an expert hepatobiliary pathologist. Tissue samples suspicious for subtype heterogeneity were further investigated. Immunohistochemistry for N-cadherin, S100P, MUC5AC, MUC6, TFF1 and AGR2 and mutational profiling with the Illumina TruSight Oncology 500 (TSO500) assay were performed separately for the SD- and LD-iCCA regions. Of 129 patients with surgically resected iCCA, features of either SD- or LD-iCCA were present in 67.4% (n = 87) and 24.8% of the patients (n = 32), respectively; 7.8% (n = 10) had histomorphological features of both SD- and LD-iCCA, seven patients (5.4%) of which had sufficient formalin-fixed, paraffin-embedded tissue for further analysis. Heterogeneity of both subtypes could be confirmed with immunohistochemistry. In five of seven (71.4%) patients, molecular profiling revealed intratumoural differences in genetic alterations between the SD- and LD-iCCA region. In one patient, a BRAF mutation (p.V600E) was found in the SD-iCCA but not in the LD-iCCA region of the tumour. A marked portion of patients with iCCA exhibits both SD- and LD-iCCA in different tumour regions. In case of the presence of histopathological heterogeneity, mutational profiling should be considered to avoid missing therapeutically relevant genetic alterations.

First person – Tanja Müller

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Tanja Müller is first author on ‘ The neuronal transcription factor MEIS2 is a calpain-2 protease target’, published in JCS. Tanja conducted the research described in this article while a PhD student in Prof. Dr Dorothea Schulte's lab at the Institute of Neurology (Edinger Institute), University Hospital Frankfurt, Germany. She is now a postdoc and co-lead of the Translational Neurooncology Junior Group in the lab of Dr Ann-Christin Hau at the Translational Neurooncology Group at the University Hospital Frankfurt, Germany. Her current research focuses on the identification of invasion-promoting genes in high-grade glial tumors.

P046 Real-world data on the treatment with Mirikizumab in a mostly biological-experienced Ulcerative colitis cohort

Abstract Background Mirikizumab was approved for treating Ulcerative colitis (UC) in May 2023. However, real-world data, especially in biological-experienced patients, is scarce. We aimed to determine the treatment efficacy and persistence of Mirikizumab in mostly treatment-experienced UC patients. Methods All patients treated for UC in the Inflammatory Bowel Disease (IBD) outpatient clinic of the University Hospital Frankfurt from 07/23-11/23 were analyzed retrospectively. Data on clinical (Simple Clinical Colitis Activity Index (SCCAI)) and biochemical disease activity (fecal calprotectin (FC)), as well as patient history, were collected. Patients were followed up for at least 12 weeks. Results Seventeen patients with UC were included. Sixteen patients had already received at least one biological agent before starting Mirikizumab. Twelve patients were exposed to ≥ 2 biological agents, and four patients to ≥ 4 biological agents before starting Mirikizumab. One patient received Mirikizumab as a first-line treatment. 4 patients were treated with Ustekinumab before the therapy with Mirikizumab. Nine patients received oral steroids as a concomitant treatment. The median SCCAI at the time of the first infusion/start of induction was 7. We report a reduction in clinical disease activity from 7 to 5 based on the preliminary data of the SCCAI. Biochemical disease activity was assessed with FC levels. The median FC level at the start of the induction was 557.5. At week 8, the median FC level was 513 based on 7 out of 17 patients reached week eight until November 2023. Intravenous induction therapy was extended in 2 of 17 patients. There was no report of adverse events. Conclusion We report preliminary real-world data on the evidence and efficacy of Mirikizumab. In our interim analysis, Mirikizumab is an effective and safe treatment in biological-experienced UC patients.

P1088 Real-world data on the treatment with Upadacitinib in a biological-experienced Crohn's disease cohort

Abstract Background Upadacitinib was approved for the treatment of Crohn's disease in June 2023. However, real-world data, especially in biological-experienced patients, is scarce. We aimed to determine the treatment efficacy and persistence of Upadacitinib in treatment-experienced Crohn's disease (CD) patients Methods All patients treated for Crohn's disease in the IBD outpatient clinic of the University Hospital Frankfurt from 06/23-11/23 were retrospectively analyzed. Data on clinical (Harvey-Bradshaw index (HBI)) and biochemical disease activity (fecal calprotectin FC), as well as patient history, were collected. Patients were followed up for at least 12 weeks. Results Twenty patients with CD were included. All patients had already received at least one biological agent before starting upadacitinib. Six patients reported extraintestinal manifestations, most commonly arthralgia. Five patients had stenosis of the terminal/neoterminal ileum, and one patient underwent surgery during Upadacitinib induction. Five patients had preexisting fistulae; four reported fistulae activity at treatment initiation. The median Harvey-Bradshaw Index was 11. We report an HBI reduction after induction (8.5). The median FC level at induction was 719 ug/g. After the induction, the median FC was 216 ug/g. Nineteen of the twenty patients completed the induction period of 12 weeks at the time of this interim analysis. All patients continued with 30mg of Upadacitinib post-induction. The most common adverse event was acne. No significant changes in the patients' lipid status were observed. Conclusion We report preliminary real-world data on the treatment with upadacitinib. In our interim analysis, Upadacitinib is an effective and safe treatment in biological-experienced CD patients.

Mechanical ventilation as a major driver of COVID-19 hospitalization costs: a costing study in a German setting

BackgroundWhile COVID-19 hospitalization costs are essential for policymakers to make informed health care resource decisions, little is known about these costs in western Europe. The aim of the current study is to analyze these costs for a German setting, track the development of these costs over time and analyze the daily costs.MethodsAdministrative costing data was analyzed for 598 non-Intensive Care Unit (ICU) patients and 510 ICU patients diagnosed with COVID-19 at the Frankfurt University hospital. Descriptive statistics of total per patient hospitalization costs were obtained and assessed over time. Propensity scores were estimated for length of stay (LOS) at the general ward and mechanical ventilation (MV) duration, using covariate balancing propensity score for continuous treatment. Costs for each additional day in the general ward and each additional day in the ICU with and without MV were estimated by regressing the total hospitalization costs on the LOS and the presence or absence of several treatments using generalized linear models, while controlling for patient characteristics, comorbidities, and complications.ResultsMedian total per patient hospitalization costs were €3,010 (Q1 – Q3: €2,224—€5,273), €5,887 (Q1 – Q3: €3,054—€10,879) and €21,536 (Q1 – Q3: €7,504—€43,480), respectively, for non-ICU patients, non-MV and MV ICU patients. Total per patient hospitalization costs for non-ICU patients showed a slight increase over time, while total per patient hospitalization costs for ICU patients decreased over time. Each additional day in the general ward for non-ICU COVID-19 patients costed €463.66 (SE: 15.89). Costs for each additional day in the general ward and ICU without and with mechanical ventilation for ICU patients were estimated at €414.20 (SE: 22.17), €927.45 (SE: 45.52) and €2,224.84 (SE: 70.24).ConclusionsThis is, to our knowledge, the first study examining the costs of COVID-19 hospitalizations in Germany. Estimated costs were overall in agreement with costs found in literature for non-COVID-19 patients, except for higher estimated costs for mechanical ventilation. These estimated costs can potentially improve the precision of COVID-19 cost effectiveness studies in Germany and will thereby allow health care policymakers to provide better informed health care resource decisions in the future.

Differences in characteristics between patients from Egypt and Germany presenting with lacunar stroke

Despite the enormous health burden of lacunar stroke, data from low- and middle-income countries on lacunar stroke characteristics and its comparison with that of high-income countries are scarce. Thus, we aimed to investigate and compare the variable characteristics and vascular status in patients from Egypt and Germany suffering lacunar stroke. Two cohorts of lacunar stroke patients from Ain Shams University Hospital, Egypt and Goethe University Hospital Frankfurt, Germany were retrospectively collected between January 2019 and December 2020 and analyzed for demographics, risk factors, mode of presentation, neuroimaging features, treatment protocols and outcomes. MRI showed a different distribution pattern of lacunar strokes between cohorts, detecting posterior circulation lacunar infarctions preponderantly in patients from Egypt and anterior circulation lacunar infarctions preponderantly in patients from Germany. Complementary MR/CT angiography revealed a significantly higher proportion of intracranial and combined intracranial and extracranial arterial stenosis in patients from Egypt than in patients from Germany, suggesting differences in pathological processes. Younger age, higher NIHSS on admission, and posterior circulation lacunar infarction were predictors of Egyptian origin, whereas hypertension was a predictor of German origin. Our results support the idea of clinical and neuroimaging phenotype variations in lacunar stroke, including different sources of lacunar stroke in patients of different populations and geographical regions. This implies that guidelines for management of lacunar stroke might be tailored to these differences accordingly.

Investigation of acquired dysfibrinogenaemia in adult patients with sepsis using fibrinogen function vs. concentration ratios: a cross-sectional study.

Inherited or acquired molecular abnormalities form a clinically heterogeneous group of fibrinogen disorders called dysfibrinogenaemia. Apart from a pediatric case report and in contrast to other clinical conditions, acquired dysfibrinogenaemia has not been previously reported in septic patients. In an observational cohort study, 79 adult septic patients were investigated for the presence of acquired dysfibrinogenaemia at the time of their admission to the intensive care unit (ICU) of the University Hospital Frankfurt. Following established recommendations, fibrinogen clotting activity vs. antigen ratios were analyzed using Clauss fibrinogen, prothrombin-derived fibrinogen, and radial immunodiffusion (RID) fibrinogen concentration. Prothrombin-derived fibrinogen levels were highest (527 ± 182 mg/dL) followed by Clauss fibrinogen (492 ± 209 mg/dL) and radial immunodiffusion fibrinogen (426 ± 159 mg/dL). Very few cases demonstrated hypofibrinogenaemia making overt disseminated intravascular coagulation (DIC) unlikely in the cohort investigated. Clauss/RID fibrinogen ratios were lower (1.17 ± 0.19) compared to prothrombin time-derived/RID ratios (1.35 ± 0.33). Using the Clauss/RID dataset, 21% of patients (16/76 patients) demonstrated values below a threshold ratio for suspected acquired dysfibrinogenaemia arbitrarily set at 1.0. In contrast, prothrombin-derived ratios were below the threshold in only 7% (4/58 patients). The results point to the presence of acquired dysfibrinogenaemia in part of adult septic patients. If confirmed in further studies, this may form part of a specific laboratory signature of a sepsis-associated coagulation phenotype.

The influence of epidural anesthesia in pregnancies with scheduled vaginal breech delivery at term: a hospital-based retrospective analysis

Abstract Introduction Epidural anesthesia is a well-established procedure in obstetrics for pain relief in labor and has been well researched as it comes to cephalic presentation. However, in vaginal intended breech delivery less research has addressed the influence of epidural anesthesia. The Greentop guideline on breech delivery states that there’s little evidence and recommends further evaluation. Objective The aim of this study was to compare maternal and neonatal outcomes in vaginally intended breech deliveries at term with and without an epidural anesthesia. Design This study was a retrospective cohort study. Sample This study included 2122 women at term with a singleton breech pregnancy from 37 + 0 weeks of pregnancy on and a birth weight of at least 2500 g at the obstetric department of University hospital Frankfurt from January 2007 to December 2018. Methods Neonatal and maternal outcome was analyzed and compared between women receiving “walking” epidural anesthesia and women without an epidural anesthesia. Results Fetal morbidity, measured with a modified PREMODA score, showed no significant difference between deliveries with (2.96%) or without (1.79%; p = 0.168) an epidural anesthesia. Cesarean delivery rates were significantly higher in deliveries with an epidural (35 vs. 26.2%, p = 0.0003), but after exclusion of multiparous women, cesarean delivery rates were not significantly different (40.2% cesarean deliveries with an epidural vs. 41.5%, p = 0.717). As compared to no epidurals, epidural anesthesia in vaginal delivery was associated with a significantly higher rate of manual assistance (33.8 versus 52.1%) and a longer duration of birth (223.7 ± 194 versus 516.2 ± 310 min) (both p &lt; 0.0001)". Conclusion Epidural anesthesia can be offered as a safe option for pain relief without increasing neonatal or maternal morbidity and mortality. Nevertheless, it is associated with a longer birth duration and manually assisted delivery.

Trends and Differences in Status Epilepticus Treatment of Children and Adults Over 10 Years: A Comparative Study of Medical Records (2012-2021) from a University Hospital in Germany.

Over the last decade, significant advancements have been made in status epilepticus (SE) management, influenced by landmark trials such as ESETT and RAMPART. The objectives of this study were to explore the evolution of drug treatments for patients with SE, to investigate its association with outcomes and mortality, and to evaluate differences in treatment patterns between adults and children for a potential shift in medication trends due to the above mentioned trials. The medical records of patients with SE treated at University Hospital Frankfurt between 2012 and 2021 were evaluated for medication trends and outcomes. Children and adults were analyzed separately and jointly. This study included 1151 SE episodes in 1021 patients (mean age = 53.3 ± 28.3 years; 52.5 % female [n = 533]). The overall percentage of patients with SE treated prehospital was stable over the last decade. More than half (53.6 %) of children were treated prehospital, compared with less than one-third (26.7 %) of adults. Prehospital midazolam use increased over time, while diazepam use decreased. Lorazepam was the most commonly used benzodiazepine in hospitals in 2012-2013, used in 40.8 % of all episodes. However, its use declined to 27.2 % in 2020-2021, while midazolam use increased to 44.0 %. While the use of older antiseizure medications (ASMs) such as phenobarbital (p = 0.02), phenytoin (p < 0.001), and valproate (p < 0.001) decreased, the use of newer ASMs such as levetiracetam and lacosamide significantly increased (p < 0.001). Propofol and continuous midazolam infusion remained the most used third-line therapy drugs. Overall mortality was 16.5 % at discharge and 18.9 % at 30 days. Mortality rates did not change between 2012 and 2021. Midazolam has become the preferred benzodiazepine in pre- and in-hospital settings, both in children and adults. The same applies to the increased use of levetiracetam and lacosamide over time in children and adults, while phenobarbital, phenytoin, and valproate use decreased. Continuous midazolam infusion and propofol remain the most frequently used anesthetic drugs. Mortality and outcome remain stable despite changes in medication patterns.

Analysis of Mould Exposure of Immunosuppressed Patients at a German University Hospital.

Moulds are ubiquitous components of outdoor and indoor air and local conditions, temperature, humidity and season can influence their concentration in the air. The impact of these factors on mould exposure in hospitals and the resulting risk of infection for low to moderately immunocompromised patients is unclear. In the present retrospective analysis for the years 2018 to 2022, the monthly determined mould contamination of the outdoor and indoor air at the University Hospital Frankfurt am Main is compared with the average air temperature and the relative humidity. Mould infections (Aspergillus spp., Mucorales) of low to moderately immunosuppressed patients of a haematological-oncological normal ward were determined clinically according to the criteria of the European Organisation for Research and Treatment of Cancer (EORTC, Brussels, Belgium) and of the National Reference Centre for Surveillance of Nosocomial Infections (NRC-NI, Berlin, Germany). The data revealed that in the summer months (May-October), increased mould contamination was detectable in the outdoor and indoor air compared to the winter months (November-April). The mould levels in the patient rooms followed the detection rates of the outdoor air. Two nosocomial Aspergillus infections, one nosocomial Mucorales (Rhizopus spp.) infection (according to both NRC-NI and EORTC criteria) and five Aspergillus spp. infections (according to EORTC criteria) occurred in 4299 treated patients (resulting in 41,500 patient days). In our study, the incidence density rate of contracting a nosocomial mould infection (n = 3) was approximately 0.07 per 1000 patient days and appears to be negligible.

Enhancing HIV Patient Support Through Telehealth: Exploring Design Solutions.

In recent years, telemedicine has advanced significantly, offering new possibilities for improving healthcare and patient outcomes. This paper presents a telemedicine app for HIV patients, developed using a human-centered design approach. Designed to meet the diverse and specific needs of Pre-Exposure Prophylaxis (PrEP) users and Late Presenters (LP), the app is part of the COMTRAC-HIV Project at the University Hospital Frankfurt. Through interviews with HIV experts and healthcare professionals, initial design solutions were derived. The paper explores the app's design process, core functionalities, and future directions, aiming to provide comprehensive support for individuals living with HIV.

P16.09.B NEUROGENIC DYSPHAGIA IN MENINGEOSIS NEOPLASTICA PATIENTS

Abstract BACKGROUND Meningeosis neoplastica (MN) occurs in 5-10 % of all cancers and is characterized by diffuse seeding of tumor cells in the cerebrospinal fluid (CSF) and meninges. Common clinical symptoms suggestive of MN include headache, cranial nerve (CN) deficits, psychiatric symptoms as well as paresthesia. Neurogenic dysphagia (ND) has been suggested a rare MN symptom resulting from affection of CN IX and X. The aim of this work was to investigate frequency, severity and pattern of malfunction of ND due to MN as well as to assess its impact on the rate of pneumonia and overall survival. MATERIAL AND METHODS The database of the Institute of Neurooncology of the University Hospital Frankfurt was screened for patients with MN diagnosed between March 2009 and July 2021 who received a systematic dysphagia assessment (DA). DA comprised a standardized clinical swallowing examination as well as an additional fiber optic endoscopic evaluation of the swallowing act (FEES) in case of suspected aspiration. Severity of dysphagia and extent of oral impairment were systematically recorded. In addition to demographics, clinical diagnoses, underlying cancer and treatment, information on radiological imaging including presence of contrast-enhancing lesions was collected. RESULTS A total of 262 patients with a diagnosis of MN were detected, 69 of whom (52 % women, mean age 61 ± 14 years) were included for further analysis. Underlying cancers included lung cancer (16 cases, 23 %), breast cancer (15, 22 %), as well as lymphoma and melanoma (each 7 cases, 10%). The remaining 24 patients suffered from cancer entities (ovarian cancer, gastrointestinal tumors or cancers of unknown primary). 46 patients (66.6 %) were diagnosed with ND, 15 of these patients required a feeding tube (FOIS 1-3). Dysphagic patients had an increased risk of pneumonia (p&amp;lt;0.001) and a shorter survival time compared to non-dysphagic patients (p=0.003). Affection of the cranial nerves affected CN V (n=6), CN VII (n=22), CN IX (n=21), CN X (n=7) and CN XII (n=12). There was no significant correlation between the presence of an ND and the above-mentioned cranial nerve deficits. CONCLUSION The results of this study show that ND is a common symptom in patients with MN and can also occur independently of paresis of CN IX and X. In addition, the presence of ND is associated with a higher rate of pneumonia and a shorter survival time. Therefore, patients with suspected or confirmed MN should receive a systematic dysphagia assessment. In addition, the presence of MN should also be considered in the differential diagnosis of unclear neurogenic dysphagia.

Active Autophagy Is Associated with Favorable Outcome in Patients with Surgically Resected Cholangiocarcinoma.

Data on the impact of autophagy in primary cholangiocarcinoma (CCA) remain scarce. Here, we therefore investigated the role of active autophagy and its impact on survival in CCA patients. All CCA patients who underwent surgical resection with curative intent between 08/2005 and 12/2021 at University Hospital Frankfurt were evaluated. Autophagic key proteins were studied by immunohistochemistry. iCCA processed for gene expression profiling of immune-exhaustion gene sets was used for an autophagy approach in silico. Active autophagy was present in 23.3% of the 172 CCA patients. Kaplan-Meier curves revealed median OS of 68.4 months (95% CI = 46.9-89.9 months) and 32.7 months (95% CI = 23.6-41.8 months) for active and non-active autophagy, respectively (p ≤ 0.001). In multivariate analysis, absence of active autophagy (HR = 2, 95% CI = 1.1-3.5, p = 0.015) was an independent risk factor for OS. Differential-expression profiling revealed significantly upregulated histone deacetylases (HDAC) mRNA in patients showing non-active autophagy. In line with this, pan-acetylated lysine was significantly more prominent in CCA patients with ongoing autophagy (p = 0.005). Our findings strengthen the role of active autophagy as a prognostically relevant marker and a potential therapeutic target.

Obstetric anesthesia from the beginning to the end: opportunities and challenges.

Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany Correspondence to Vanessa Neef, MD, University Hospital Frankfurt, Goethe University Frankfurt, Germany. E-mail: [email protected]

Editorial introductions.

Current Opinion in Anesthesiology was launched in 1988. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of anesthesiology is divided into 16 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Vanessa NeefVanessa NeefDr Vanessa Neef, MD graduated in medicine from Johannes Gutenberg University Mainz, Germany. In 2015, she achieved her doctoral degree at the Department of Anaesthesiology, University Medical Centre Mainz, Germany. Currently, Dr Neef is working on a consultant level at the department of Anaesthesiology, Intensive Care Medicine and Pain Therapy at the University Hospital Frankfurt, Germany (Director: Professor K. Zacharowski, MD PhD ML FRCA FESAIC), where she also completed her residency. Since 2021, she is Section Head for Obstetrics and Gynaecology within the Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy at University Hospital Frankfurt, Germany. Dr Neef did her habilitation in 2022 at the Goethe-University Frankfurt, Germany. In 2022 she also achieved an MBA in economics in medicine from the University in Erlangen-Nürnberg, Germany. She is a member of the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) and the Professional Association of German Anaesthesiologists (BDA). Her research interest is on perioperative medicine including Patient Blood Management, evidence-based medicine, patient safety and outcomes research in perioperative medicine. She has published several journal articles in national and international journals as well as book chapters, mainly in the field of Patient Blood Management. Dr Vanessa Neef has been involved on a voluntary basis at the School Health Screening by the Ministry of Health and Bureau of Public Health of the Republic of Palau, Micronesia. Christiane BeckChristiane BeckDr Christiane Beck is the leading senior consultant at the Clinic of Anesthesiology and Intensive Care Medicine at Hannover Medical School. She has studied medicine at the University of Göttingen, Germany, Johannesburg, South Africa, and Madison, USA and received her degree in 1997 from the University of Göttingen, Germany. She completed her anesthesiology residency training in 2003 and is a certified anesthesiologist, intensivist and emergency physician. She achieved her doctoral degree at the Centre for Radiologic Diagnostics, University of Göttingen, Germany in 2000. Dr Christiane Beck habilitated in 2021 at the Hannover Medical School, Germany. Besides clinical duties, she implemented and coordinates to date preoperative fasting guidelines for children and is co-author of the actual ESAIC Fasting Guideline and coordinator of the German fasting guidelines on this subject. She is specialized in pediatric anesthesia, anesthesia for complex congenital cardiac surgery and transplant surgery in children and is invited to numerous conferences as a speaker on these topics. She is member of the German Society of Anesthesiology and Intensive Care Medicine (DGAI), the Professional Association of German Anesthesiologists (BDA), the European Society of Anesthesiology and Intensive Care Medicine (ESAIC) the Scientific Working Group for Pediatric Anesthesia and since 2021 Speaker of the Scientific Working Group for Pediatric Cardiac Anesthesia of the German Society of Anesthesiology. Her focus is on the research of pediatric anesthesia. She coordinated a national study on preoperative fasting in children for the Scientific Working Group for Pediatric Anesthesia and is part of the research group of Prof. Robert Sümpelmann. She has published several journal articles and book chapters mainly on the field of pediatric anesthesia. She is a passionate mentor for trainees and early career junior residence in building a clinical or scientific career. Dr Christiane Beck has been involved on a voluntary basis as the leading anesthetist to pediatric cardiac missions to Moldova, Bosnia Herzegovina, Cyprus and Romania. She is in close contact and support to an innovative project MOHKI – the mobile kinderherzen clinic of the kinderherzen association (kinderherzen - Fördergemeinschaft deutscher Kinderherzzentren e.V.) to provide excellent medical infrastructure for cardiac missions in low-income countries. She is board member of the Kinderherzen-scholarship, founded in 2022, by the kinderherzen association (kinderherzen - Fördergemeinschaft deutscher Kinderherzzentren e.V.) and the Dr Andreas Urban foundation to promote young specialist in the field of pediatric heart medicine. Wolfgang BuhreWolfgang BuhreWolfgang Buhre is Anaesthesiologist and Medical Director of the Division of Anesthesiology, Perioperative Medicine, Emergency Medicine, and Critical Care Medicine at Maastricht University Medical Centre (MumC), The Netherlands. He is also Professor of Anesthesiology at Maastricht University, The Netherlands. At Maastricht, he is a member of the School Council and a research fellow in the School of Mental Health and Neurosciences (MhenS) and an associated research fellow in the Care and Public health Research Institute (CAPHRI), Maastricht University. He earned his medical degree at the University of Göttingen, Germany. He completed his residency training at the same University and is trained in intensive care medicine and pain medicine. His areas of research are outcome research, artificial intelligence, and modern technology to support decision making in clinical practice. Wolfgang Buhre is leading the Research Mentorship Program of the European Society of Anaesthesiology and Intensive Care Medicine (ESAIC). Moreover, he is coordinating investigator in the Academic Research Organization of ESAIC and serves within the society also as industrial liaison member for the Academic research organization (A-CRO).

Is Olfactory Testing a Useful Diagnostic Tool to Identify SARS-CoV-2 Infections Early? A Cross-Sectional and Longitudinal Analysis.

Genesis and the prognostic value of olfactory dysfunction (OD) in COVID-19 remain partially described. The objective of our study was to characterize OD during SARS-CoV-2 infection and to examine whether testing of OD may be a useful tool in clinical practice in order to early identify patients with SARS-CoV-2 infection. Olfactory function assessment was objectively carried out using the u-Smell-it® test. In a cross-sectional study part, we evaluated this test in a control cohort of SARS-CoV-2 negative tested patients, who attended the University Hospital Frankfurt between May 2021 and March 2022. In a second longitudinal study part, sensitivity and specificity of OD was evaluated as a diagnostic marker of a SARS-CoV-2 infection in Frankfurt am Main, Germany in SARS-CoV-2 infected patients and their close contacts. Among 494 SARS-CoV-2 negative tested patients, OD was detected in 45.7% and was found to be significantly associated with the male gender (p < 0.001), higher age (p < 0.001), cardiovascular and pulmonary comorbidities (p < 0.001; p = 0.03). Among 90 COVID-19 positive patients, OD was found in 65.6% and was significantly associated with male gender and positive smoking status (p = 0.04 each). Prevalence and severity of OD were significantly increased in infections with the Delta variant (B.1.617.2) compared to those with the Omicron variant (BA.1.1.529). Diagnostic sensitivity and specificity of OD for diagnosis of SARS-CoV-2 infection were 69% and 64%, respectively. OD is common in COVID-19 negative and positive tested patients with significantly different prevalence rates observed between different variants. Diagnostic accuracy of OD is not high enough to implement olfactory testing as a tool in diagnostic routine to early identify patients with a SARS-CoV-2 infection.