University Medical Center Hamburg-Eppendorf Research Articles

The Unified Batten Disease Rating Scale (UBDRS): Validation and reliability in an independent CLN3 disease sample.

The neuronal ceroid lipofuscinoses (NCLs) are a group of disorders characterized by neurodegeneration and intracellular accumulation of an auto-fluorescent lipopigment. Together, NCLs represent the most common cause of cerebral neurodegenerative disease in children. CLN3 disease, the classic juvenile-onset form (JNCL) due to mutations in CLN3, is characterized by progressive vision loss, epilepsy, dementia, behavioral difficulties, and motor impairment. The Unified Batten Disease Rating Scale (UBDRS) is a disease-specific rating scale that was developed to assess disease severity in 4 domains: physical, behavior, seizures, and functional capability. Validity and reliability of the UBDRS has been established in a large North American cohort of over 130 individuals. The purpose of this study was to determine whether the UBDRS is valid and reliable when tested in an independent sample. Over the course of one week, 13 individuals with genetically confirmed CLN3 disease were evaluated with the UBDRS by 5 examiners at the University Medical Center Hamburg Eppendorf (UKE). One rater (JWM), one of the developers of the UBDRS, served as the reference standard. The other 4 raters were physicians with expertise in various forms of Batten Disease. After a formal training session, 13 individuals (age 16.5±5.6yrs) were evaluated simultaneous in parallel by the 5 raters. Inter-rater reliability of the Physical subscale was assessed with Intra-class Correlation (ICC) analysis. The relationship between age and severity was assessed and compared to previously published data from the North American cohort. The ICC among the 5 independent raters was 0.92, demonstrating excellent inter-rater reliability. The individual correlations of each UKE rater compared to the reference standard rater were all >0.95. The average UBDRS Physical Subscale score in this sample was 28±21 (mean±SD) with a range from 1 to 61. When evaluated as a function of participant age, the slope was 3.06 points/year (R2=0.66). We have shown excellent interrater reliability for the UBDRS as a clinical rating scale for CLN3 disease in a sample independent from previous work. The results of this study are comparable to those published by Kwon etal., 2011 in a North American cohort showing a slope of 2.86 points per year with a 95% CI of 2.27-3.45 (N=82). Our results demonstrate excellence inter-rater reliability after training a new group of raters and provide additional evidence for construct validity of the UBDRS. The UBDRS is a valid and reliable rating scale that can used by trained raters to assess the severity and rate of progression of CLN3 disease.

Discriminant properties of the Behavioral Pain Scale for assessment of procedural pain-related distress in ventilated children.

Children hospitalized in a pediatric intensive care unit (PICU) are frequently exposed to distressing and painful medical procedures and interventions. There is a lack of clinical scales to measure procedural pain-related distress in ventilated children. The Behavioral Pain Scale (BPS) was initially developed to detect procedural pain incritically ill adults. This study aims to assess the BPS's discriminant properties for measuring procedural pain-related distress in ventilated pediatric patients incorporating two instruments validated for pediatric patients. This prospective exploratory study was performed with ventilated children admitted to the interdisciplinary 14-bed PICU of the University Children's Hospital, University Medical Center Hamburg-Eppendorf, Germany. The nurse in charge and an independent observer simultaneously assessed the patients using German versions of the BPS, the COMFORT-B scale (CBS), and the modified Face, Legs, Activity, Cry, Consolability (mFLACC) scale immediately before and during endotracheal suctioning. We analyzed 170 parallel assessments in n=34 ventilated children. Patients were (mean±SD) 9.5±4.8 years old. Internal consistency for the BPS was excellent (α=0.93). We found a high rater agreement for all clinical scales (BPS: k=0.73, CBS: k=0.80, mFLACC: k=0.71). Strong correlations were identified between BPS and CBS (r=0.89) and BPS and mFLACC (r=0.79). The BPS cutoff values showed likewise excellent results (area under the curve CBS >16: 0.97; mFLACC >2: 0.91). In our population of ventilated children, the BPS was well suited to detect procedural pain-related distress compared with two validated pain scales. Further extensive validation studies should follow to support our findings.

New Insights in the Occurrence of Venous Thromboembolism in Critically Ill Patients with COVID-19-A Large Postmortem and Clinical Analysis.

Critically ill COVID-19 patients are at high risk for venous thromboembolism (VTE), namely deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and death. The optimal anticoagulation strategy in critically ill patients with COVID-19 remains unknown. This study investigated the ante mortem incidence as well as postmortem prevalence of VTE, the factors predictive of VTE, and the impact of changed anticoagulation practice on patient survival. We conducted a consecutive retrospective analysis of postmortem COVID-19 (n = 64) and non-COVID-19 (n = 67) patients, as well as ante mortem COVID-19 (n = 170) patients admitted to the University Medical Center Hamburg-Eppendorf (Hamburg, Germany). Baseline patient characteristics, parameters related to the intensive care unit (ICU) stay, and the clinical and autoptic presence of VTE were evaluated and statistically compared between groups. The occurrence of VTE in critically ill COVID-19 patients is confirmed in both ante mortem (17%) and postmortem (38%) cohorts. Accordingly, comparing the postmortem prevalence of VTE between age- and sex-matched COVID-19 (43%) and non-COVID-19 (0%) cohorts, we found the statistically significant increased prevalence of VTE in critically ill COVID-19 cohorts (p = 0.001). A change in anticoagulation practice was associated with the statistically significant prolongation of survival time (HR: 2.55, [95% CI 1.41–4.61], p = 0.01) and a reduction in VTE occurrence (54% vs. 25%; p = 0.02). In summary, in the autopsy as well as clinical cohort of critically ill patients with COVID-19, we found that VTE was a frequent finding. A change in anticoagulation practice was associated with a statistically significantly prolonged survival time.

Chronic Critical Illness in Patients with COVID-19: Characteristics and Outcome of Prolonged Intensive Care Therapy.

The spread of SARS-CoV-2 caused a worldwide healthcare threat. High critical care admission rates related to Coronavirus Disease 2019 (COVID-19) respiratory failure were observed. Medical advances helped increase the number of patients surviving the acute critical illness. However, some patients require prolonged critical care. Data on the outcome of patients with a chronic critical illness (CCI) are scarce. Single-center retrospective study including all adult critically ill patients with confirmed COVID-19 treated at the Department of Intensive Care Medicine at the University Medical Center Hamburg-Eppendorf, Germany, between 1 March 2020 and 8 August 2021. We identified 304 critically ill patients with COVID-19 during the study period. Of those, 55% (n = 167) had an ICU stay ≥21 days and were defined as chronic critical illness, and 45% (n = 137) had an ICU stay <21 days. Age, sex and BMI were distributed equally between both groups. Patients with CCI had a higher median SAPS II (CCI: 39.5 vs. no-CCI: 38 points, p = 0.140) and SOFA score (10 vs. 6, p < 0.001) on admission. Seventy-three per cent (n = 223) of patients required invasive mechanical ventilation (MV) (86% vs. 58%; p < 0.001). The median duration of MV was 30 (17–49) days and 7 (4–12) days in patients with and without CCI, respectively (p < 0.001). The regression analysis identified ARDS (OR 3.238, 95% CI 1.827–5.740, p < 0.001) and referral from another ICU (OR 2.097, 95% CI 1.203–3.654, p = 0.009) as factors significantly associated with new-onset of CCI. Overall, we observed an ICU mortality of 38% (n = 115) in the study cohort. In patients with CCI we observed an ICU mortality of 28% (n = 46) compared to 50% (n = 69) in patients without CCI (p < 0.001). The 90-day mortality was 28% (n = 46) compared to 50% (n = 70), respectively (p < 0.001). More than half of critically ill patients with COVID-19 suffer from CCI. Short and long-term survival rates in patients with CCI were high compared to patients without CCI, and prolonged therapy should not be withheld when resources permit prolonged therapy.

The use of HCT and/or ACE inhibitors significantly increases the risk of non-melanotic skin cancer in the periocular region

Background/AimsTo investigate a possible association between the use of hydrochlorothiazide (HCT) and/or angiotensin-converting enzyme inhibitors (ACE inhibitors) and the occurrence of periocular non-melanoma skin cancer.MethodsThe files of 929 patients from the University Medical Center Hamburg-Eppendorf who were surgically treated for suspected periocular malignancy were evaluated retrospectively regarding the occurrence of non-melanoma skin cancer and concomitant medication. To be able to put the data in an overall context, we also analyzed age-matched routine data of the DAK-Gesundheit (DAK-G), a nationwide operating German health insurance company.ResultsOf the 929 patient records examined, who underwent surgical excision for suspected non-melanotic malignancy, non-melanocytic skin cancer could actually be determined by histology in 199 patients. In total, 176 patients (103 women, 72 men) had a basal cell carcinoma and 23 patients (16 women, 7 men) suffered from squamous cell carcinoma. The rate of intake of HCT or ACE inhibitors in our patient collective with non-melanotic skin cancer is significantly higher than in the general age-matched population (ORACE: 2.51, p < 0.001; ORHCT: 7.24, p < 0.001, ORBOTH: 4.61, p < 0.001).ConclusionThe rate of intake of HCT or ACE inhibitors is significantly higher in our patient collective with non-melanotic skin cancer compared to the group from the age-matched general population (DAK insured (p < 0.001)) compared to the routine data of the DAK-G. This leads us to the conclusion that taking the medication is associated with an increased risk for non-melanotic skin cancer. We recommend regular skin cancer screening, moderate ordination of photosensitizing medication, but above all comprehensive clarification of possible risks.

Low incidence of COVID-19 in a prospective cohort of patients with liver cirrhosis and hepatocellular carcinoma treated at a tertiary medical center during the 2020 pandemic.

Background and aimsPatients with liver cirrhosis (LC) are considered to be at increased risk for mortality when acquiring SARS-CoV-2 infection and subsequently developing Corona Virus Disease 2019 (COVID-19). During the COVID-19 pandemic, hospitals are regarded as sites with increased risk of infection. Therefore, patient contacts are often limited to urgent indications, which could negatively affect disease monitoring. However, data regarding actual infection rates in cirrhotic patients is limited. The aim of this prospective study was to assess the incidence of COVID-19 in patients with LC with/without hepatocellular carcinoma (HCC) with physical presentation at our University Medical Center.MethodsPatients were enrolled between 1st April and 30th June 2020 at the University Medical Center Hamburg-Eppendorf, Germany. Symptoms of upper airway infection at baseline and presence of SARS-CoV-2 antibodies (IgG/IgM/IgA) were assessed at baseline and follow-up (FU) using an Electro-chemiluminescence immunoassay (Roche Elecsys). FU visits, including liver function test, clinical assessment and symptom questionnaire, were conducted after 6–8 weeks (FU-1) and 6 months (FU-2). Prior to inclusion of the first patient, obligatory face masks and personal distance were implemented as protective measures.ResultsA total of 150 patients were enrolled, 23% (n = 35) also had diagnosis of HCC (median age: 64 years, range: 19–86), 69% were male. Liver function according to Child-Pugh score (CPS) was: CPS A: 46% (n = 62); CPS B: 37% (n = 50); CPS C: 17% (n = 23). Clinical symptoms indicating upper airway infection were present in 53% (n = 77): shortness of breath (n = 40) and coughing (n = 28) were the most frequent. For the 150 patients enrolled, 284 outpatient visits were registered and 33 patients were admitted to the University Medical Center during the follow-up period. After a median of 52 days, n = 110 patients completed FU-1 and n = 72 completed FU-2 after a median of 6.1 months. Only in one patient, an 80-year-old man with stable liver function (CPS A) and advanced HCC, SARS-CoV-2 antibodies were detected at baseline and FU-1, while antibody testing was negative in the remaining patients at baseline, FU-1 and FU-2.ConclusionThe incidence of COVID-19 at our tertiary medical center during the pandemic was low in LC and HCC patients, when simple protective measures were implemented. Therefore, a routine care for patients with chronic liver diseases does not increase the risk of SARS-CoV-2 infection and should be maintained with protective measures.

Low incidence of colonic complications after severe Shiga toxin-producing E. coli O104:H4 infection.

In summer 2011, Shiga toxin producing Escherichia coli (EHEC) serotype O104:H4 caused the most severe EHEC outbreak in Germany to date. The case of a previously recovered patient with symptomatic postinflammatory colonic stenosis following EHEC- infection prompted us to conduct a prospective study to assess the macro- and microscopic intestinal long-term damage in a cohort of patients who had suffered from severe EHEC colitis. Following EHEC infection in 2011, 182 patients were offered to participate in this study between January 2013 and October 2014 as part of the post-inpatient follow-up care at the University Medical Center Hamburg-Eppendorf and to undergo colonoscopy with stepwise biopsies. Prior to colonoscopy, medical history and persistent post-infectious complaints were assessed. Out of 182 patients, 22 (12%) participated in the study, 18 (82%) were female. All patients had been hospitalized due severe EHEC enterocolitis: 20 patients (90%) had subsequently developed hemolytic uremic syndrome (HUS), 16 patients (72%) had additionally required dialysis. On assessment prior to colonoscopy, all patients denied any abdominal complaints before EHEC-infection but 8 (36%) patients reported persistent post-infectious symptoms. According to the ROME IV criteria, 4 (18%) patients met the definition for post-infectious irritable bowel syndrome (PI-IBS). In all patients with persistent symptoms, colonoscopies and histological examination were unremarkable. Only in one symptom-free patient, biopsy revealed a locally limited cryptitis of the caecum, while all patients without complaints had inconspicuous histological and endoscopical findings. Following infection colonic stenosis is a serious but rare long-term complication in patients who had suffered from severe enterocolitis. However, a significant proportion of these patients develop PI-IBS.

Clinical Characteristics, Complications and Outcomes of Patients with Severe Acute Respiratory Distress Syndrome Related to COVID-19 or Influenza Requiring Extracorporeal Membrane Oxygenation-A Retrospective Cohort Study.

Extracorporeal membrane oxygenation (ECMO) represents a viable therapy option for patients with refractory acute respiratory distress syndrome (ARDS). Currently, veno-venous (vv) ECMO is frequently used in patients suffering from coronavirus disease 2019 (COVID-19). VV-ECMO was also frequently utilised during the influenza pandemic and experience with this complex and invasive treatment has increased worldwide since. However, data on comparison of clinical characteristics and outcome of patients with COVID-19 and influenza-related severe ARDS treated with vv-ECMO are scarce. This is a retrospective analysis of all consecutive patients treated with vv/(veno-arterial)va-ECMO between January 2009 and January 2021 at the University Medical Centre Hamburg-Eppendorf in Germany. All patients with confirmed COVID-19 or influenza were included. Patient characteristics, parameters related to ICU and vv/va-ECMO as well as clinical outcomes were compared. Mortality was assessed up to 90 days after vv/va-ECMO initiation. Overall, 113 patients were included, 52 (46%) with COVID-19 and 61 (54%) with influenza-related ARDS. Median age of patients with COVID-19 and influenza was 58 (IQR 53–64) and 52 (39–58) years (p < 0.001), 35% and 31% (p = 0.695) were female, respectively. Charlson Comorbidity Index was 3 (1–5) and 2 (0–5) points in the two groups (p = 0.309). Median SAPS II score pre-ECMO was 27 (24–36) vs. 32 (28–41) points (p = 0.009), and SOFA score was 13 (11–14) vs. 12 (8–15) points (p = 0.853), respectively. Median P/F ratio pre-ECMO was 64 (46–78) and 73 (56–104) (p = 0.089); pH was 7.20 (7.16–7.29) and 7.26 (7.18–7.33) (p = 0.166). Median days on vv/va-ECMO were 17 (7–27) and 11 (7–20) (p = 0.295), respectively. Seventy-one percent and sixty-nine percent had renal replacement therapy (p = 0.790). Ninety-four percent of patients with COVID-19 and seventy-seven percent with influenza experienced vv/va-ECMO-associated bleeding events (p = 0.004). Thirty-four percent and fifty-five percent were successfully weaned from ECMO (p = 0.025). Ninety-day mortality was 65% and 57% in patients with COVID-19 and influenza, respectively (p = 0.156). Median length of ICU stay was 24 (13–44) and 28 (16–14) days (p = 0.470), respectively. Despite similar disease severity, the use of vv/va-ECMO in ARDS related to COVID-19 and influenza resulted in similar outcomes at 90 days. A significant higher rate of bleeding complications and thrombosis was observed in patients with COVID-19.

Sustained Improvement in Health-Related Quality of Life in Patients with Hemophilia A with or without Inhibitors Treated with Fitusiran Prophylaxis

BACKGROUNDFitusiran is an investigational, subcutaneous (SC), prophylactically administered small interfering RNA (siRNA) therapeutic. It targets antithrombin and restores thrombin generation sufficient to rebalance hemostasis in people with hemophilia A or B, with or without inhibitors. Long-term exposure to fitusiran is being studied in a Phase 1/2, 6-year open-label extension study (NCT02554773) in patients with hemophilia (PwH) A or B with or without inhibitors. Improvement in the health-related quality of life (HRQoL) as measured by Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) total score, and specifically in the physical health domain was previously reported by von Mackensen et al. for PwHA with inhibitors (NCT02554773, N=17, von Mackensen et al. Blood 2020;136(1):23-24). This analysis aimed to present HRQoL changes from baseline to last available measure (LAM), as measured by the Haem-A-QoL total score and domains (filtered by actual treatment exposure following 2 voluntary dosing holds) in PwHA, with or without inhibitors, who continued into the Phase 2 open-label extension study.METHODSParticipants who completed the Phase 1 study (NCT02035605) were eligible to participate in Phase 2 long-term exposure study (NCT02554773). All participants received fixed monthly doses of 50 mg (N=9) or 80 mg (N=18) of fitusiran. HRQoL data were collected in 3-month lapse periods. Mean changes from baseline to LAM were calculated for the Haem-A-QoL (total score and domains).RESULTSAs of February 2021, 26 severe and 1 moderate PwHA (13 with, 14 without inhibitors) with mean baseline age (SD) 37.3 (9.7) were treated for up to mean (SD) 33.32 (17.06) months. For the total Haem-A-QoL score and each of 10 domains, mean improvements from baseline to LAM (lower scores denoting better HRQoL) were consistently observed in PwHA (except for the sport & leisure domain that was higher in the non-inhibitor group). Mean estimated reductions (SD) in the Haem-A-QoL total score were -8.33 (13.84) and -9.16 (14.55) while that in the physical health domain score were -13.21 (25.07) and -7.14 (22.80), for PwHA with and without inhibitors respectively (Table 1). When comparing Haem-A-QoL domains in inhibitor to non-inhibitor participants, results suggest a modest favorable trend for non-inhibitor patients (greater reductions in 4 vs 6 domains, respectively).CONCLUSIONSMean improvements in the Haem-A-QoL total scores and 9 out of 10 domains suggest sustained HRQoL improvements in PwHA. Small sample size and outlying results might limit the interpretation. Further research in HRQoL for fitusiran will include a larger population on the new 50 mg every other month dose regimen, and notably Phase III results from NCT03549871 (open-label study in patients switching to fitusiran from previous prophylaxis or bypassing agents) and NCT03754790 (open-label, long-term safety and efficacy study of fitusiran) in various subpopulations. [Display omitted] DisclosuresCano: Sanofi Genzyme: Current Employment, Current equity holder in publicly-traded company; Takeda: Ended employment in the past 24 months. Bartelt-Hofer: Sanofi: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company. Hu: Sanofi: Current Employment. Andersson: Sanofi: Current Employment, Current equity holder in publicly-traded company; WEST advisory committee member: Membership on an entity's Board of Directors or advisory committees. Dasmahapatra: Sanofi: Current Employment, Current equity holder in publicly-traded company. Von Mackensen: Biomarin: Speakers Bureau; Novo Nordisk: Consultancy; Sanofi: Consultancy; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; University Medical Centre Hamburg-Eppendorf: Current Employment; CSL Behring: Speakers Bureau; Chugai/Roche: Membership on an entity's Board of Directors or advisory committees.

A Comparative Outcome Analysis of COVID-19 and Influenza Infection in Patients with Hematological Malignancies

A Comparative Outcome Analysis of COVID-19 and Influenza Infection in Patients with Hematological Malignancies

Treatment of Women with Heavy Menstrual Bleeding with a Combination Therapy of Agnus Castus and Tranexamic Acid - Experiences of a German Single Centre

▪Background:Heavy menstrual bleeding (HMB) is a common gynaecological problem and is the reason for 18-30% of gynaecological visits. In a European study in 4,502 women, 27.2% were diagnosed with HMB (Fraser et al., 2015). On the other hand, HMB is often associated with bleeding disorders (Shankar et al., 2004). The definition of HMB has different perspectives; from a subjective perspective HMB is defined as e excessive menstrual blood loss impacting on women's physical, social, emotional and/or mental quality of life, whereas from an objective perspective it is defined as excessive blood loss >80 ml per cycle (Munro et al., 2012). There are different approaches for treating HMB such as the administration of non-steroidal drugs, Desmopressin, herbal Vitex Agnus Castus (VAC), Tranexamic acid (TXA) or a hormonal therapy; moreover, HMB can also be treated surgically.The aim of this study was to test the efficacy of the specific HMB management used in our center: Women with HMB are treated usually with VAC, which optimizes the relation of estrogen to progesterone in the female body (Yavarikia et al., 2013). VAC can be used without using any hormones (Shahnazi et al, 2016), providing a treatment with a low impact on women's bodies. Additionally, TXA is given during the menstruation due to its antifibrinolytic effect. Furthermore, the “Pictural Blood-Loss-Assessment- Chart” (PBAC Score) is administered to analyze the menstrual blood loss.Methods:Two ad hoc patient-reported questionnaires were developed to test the efficacy of the HMB management in our center The baseline questionnaire includes the following aspects: menarche, duration, regularity, number of sanitary products, pain level, medical background and family history. During the first visit in our center women with HMB filled in the baseline questionnaire. In addition, laboratory tests are done including a comprehensive coagulation test and the examination of iron and hemoglobin levels. Moreover, we presented an application called “My Flow Score” to the patients, which calculates the PBAC score as a result of all entered sanitary products women use during their period. Women are prescribed VAC and/or TXA for the management of their HMB. After four months patients are scheduled for a follow up appointment. At that time they complete the follow-up questionnaire including the following aspects: compliance with the medication or the reason for the non-compliance, health complaints due to the medication, duration of the period, improvement, pain level, PBAC score if the patient did use the APP “My Flow Score” or if not the number of sanitary products. A blood test was taken and the HMB management was adapted to the patients' needs.Results:So far, 100 women with HMB with a median age of 14 years (range 9-50) were enrolled in our study. They had their menarche with a median age of 12 years (range 8-17). Diagnosis of women ranged from iron or folic acid deficiency to different forms of bleeding disorders; with the majority suffering from von Willebrand disease (43/100) followed by iron deficiency (14/100). One fifth of the patients had more than one diagnosis. 1/3 of patients received a treatment for the HMB previously, mainly contraceptives, TXA or VAC. 49% reported anomalies with regard to previous other bleeding; 25.8% had increased hematomas and 19.6% recurrent epistaxis. Most of them reported anomalies already in the family (60.2%). Before treatment women had a median PBAC Score of 169 (range 77-800) and reported a median pain level of 6.5 during menstruation on a scale ranging from 1 (low pain) to 10 (extreme pain). 87/100 women received VCA, of these 75.4% regularly and 85/100 women received TXA, of these 84.6% regularly. 81% of them received a combination of both medicines. Compared to before 28.8% of patients reported shorter duration of menstruation and reduced bleeding with treatment, 11.9% did not experience any improvement; the PBAC score decreased significantly (p<.0001).Conclusions:Although the type of diagnosis in women suffering from HMB had a great variation, these patients had a high disease burden with a relatively high level of pain and a high loss of blood assessed with the PBAC score. Thanks to a combination of VAC and TXA the disease burden in these women could be reduced, especially for the time of menstruation and amount of bleeding. VAC proved to be highly accepted by women due to its low treatment burden. DisclosuresVon Mackensen: University Medical Centre Hamburg-Eppendorf: Current Employment; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy; Novo Nordisk: Consultancy; Biomarin: Speakers Bureau; CSL Behring: Speakers Bureau; Chugai/Roche: Membership on an entity's Board of Directors or advisory committees.

CD19+ B Lymphocytes Are Predictive for Anti-Sars-Cov-2 Vaccination Response in Multiple Myeloma Patients

CD19+ B Lymphocytes Are Predictive for Anti-Sars-Cov-2 Vaccination Response in Multiple Myeloma Patients

Pain persistence and the pain modulatory system: an evolutionary mismatch perspective.

Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany *Corresponding author. Address: Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. Tel.: +49 40 7410 54726. E-mail address: [email protected] (C. Büchel). Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

COVID-19 and seasonal influenza: a comparative analysis in patients with hematological malignancies

The severity and mortality of COVID-19 and seasonal influenza were recently compared in the general population but not in patients with hematological malignancies. We analyzed the clinical courses of 79 patients with hematological malignancies and diagnosis of either SARS-CoV-2 (n = 29) or influenza A or B infections (n = 50) who were admitted or were already under treatment in the Department of Oncology, Hematology and Stem cell Transplantation at the University Medical Center Hamburg-Eppendorf, Germany, between 1 January 2012 and 31 January 2021. For COVID-19, we observed significantly higher rates of acute respiratory distress syndrome with 48% (14/29) compared to 14% (7/50) in the influenza group (p = 0.001) as well as a significantly higher virus-associated 90-day mortality (41% vs. 12%, p = 0.005). Based on our results, we conclude that infections with SARS-CoV-2 are more severe than influenza A or B in patients with hematological malignancies.

Improvement of renal function prior to liver transplantation is not associated with better long-term renal outcome or survival

Introduction and objectivesSince MELD implementation renal impairment in liver transplant (LT) recipients has become of increasing importance. This is the first study evaluating the course of renal function immediately prior to LT as predictor for long-term renal and overall outcome. Patients and methodsIn this retrospective study, 226 adults undergoing LT at the University Medical Center Hamburg-Eppendorf (2011-2015) were included. The impact of renal function over a period of 3 months prior to LT compared to renal function at the day of LT on long-term renal outcome and survival was assessed. ResultsAccording to GFR at day of LT renal function improved (≥1 CKD stage) in 64 patients (28%), remained stable in 144 (64%) or deteriorated in 18 (8%). Improvement of renal function prior to LT did neither significantly affect 90-day (13% vs. 14%, p = 0.83), nor 5-year post-LT mortality (35% vs. 41%, p = 0.57). 50 patients (22%) with hepatorenal syndrome (HRS) received terlipressin prior to LT, but only 18 (37%) showed prolonged stabilization of renal function (improvement ≥1 CKD stage). Response to terlipressin did neither improve 90-day (p=1), 5-year mortality (p = 0.52) nor long-term renal function (p = 0.843). Nevertheless, need for dialysis pre-LT (59% vs. 34%, p = 0.005) and post-LT (62% vs. 17%, p<0.001) was associated with increased 5-year mortality. ConclusionsImprovement of renal function immediately prior to LT, either spontaneously or following terlipressin therapy, did neither ameliorate long-term renal outcome nor survival in LT recipients. Future studies need to clarify the impact of terlipressin in HRS on the transplant waiting time in LT candidates.

High Serum Levels of Wnt Signaling Antagonist Dickkopf-Related Protein 1 Are Associated with Impaired Overall Survival and Recurrence in Esophageal Cancer Patients.

Dickkopf-related protein 1 (DKK1), an antagonist of the canonical Wnt pathway, has received tremendous attention over the past years as its dysregulation is said to be critically involved in a wide variety of gastrointestinal cancers. However, the potential clinical implications of DKK1 remain poorly understood. Although multimodal treatment options have been implemented over the past years, esophageal cancer (EC) patients still suffer from poor five-year overall survival rates ranging from 15% to 25%. Especially prognostic factors and biomarkers for risk stratification are lacking to choose the most beneficial treatment out of the emerging landscape of different treatment options. In this study, we analyzed the serum DKK1 (S-DKK1) levels of 91 EC patients prior to surgery in a single center study at the University Medical Center Hamburg-Eppendorf by enzyme-linked immunosorbent assay. High levels of S-DKK1 could be especially observed in patients suffering from esophageal adenocarcinoma which may promote the hypothesis of a crucial role of DKK1 in inflammation. S-DKK1 levels of ≥5800 pg/mL were shown to be associated with unfavorable five-year survival rates and the presence of CTCs. Interestingly, significantly lower S-DKK1 levels were detected in patients after neoadjuvant treatment, implying that S-DKK1 may serve as a useful biomarker for treatment monitoring. Multivariate analysis identified S-DKK1 as an independent prognostic marker with respect to overall survival in EC patients with a hazard ratio of 2.23. In conclusion, our data implicate a negative prognostic role of DKK1 with respect to the clinical outcome in EC patients. Further prospective studies should be conducted to implement S-DKK1 into the clinical routine for risk stratification and treatment monitoring.

OAB-049: Poor post-vaccination anti-SARS-CoV-2-antibody response in patients with Multiple Myeloma correlates with low CD19+ B-lymphocyte count and anti-CD38 treatment

BackgroundUp to now, only few data are available regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with plasma cell neoplasia. This ongoing observational study aimed to describe the level of post-vaccination anti-SARS-CoV-2-antibodies depending on B lymphocyte count, current therapy, and remission status of patients with multiple myeloma (MM) and related plasma cell dyscrasias, after the first dose of anti-SARS-CoV-2 vaccination.MethodsIn this single-center study, patients aged 18 years and older with a confirmed diagnosis of MM, monoclonal gammopathies of clinical significance (MGCS) or systemic light-chain amyloidosis (AL) who were eligible for Anti-SARS-CoV-2 vaccination according to the International Myeloma Society recommendations were included. Data were collected between January 1st and May 21th, 2021, at the department of oncology and hematology at the University Medical Center Hamburg-Eppendorf, Germany. The primary aim of this study was to evaluate a possible correlation between antibody titers and CD19+ B lymphocyte count and secondary to identify other possible factors influencing immune response. This study is part of the COVIDOUT trial (NCT04779346). Written informed consent was provided by each patient according to local requirements.ResultsA total of 82 patients were included in this study. The median age was 67.5 years (range 40-85 years). 78 patients had MM, 2 MGCS, and 2 AL. Overall, 63 patients were vaccinated with mRNA-based and 19 with vector-based vaccines, respectively. At the time of vaccination, 69 (84.1%) patients were under current anti-myeloma treatment. In total, 34 (41%) patients received anti-CD38-targeting therapies and 52 (63%) patients received IMiD-based therapies. 57 (69.5%) patients were in deep remissions (very good partial remission or better) at the time of vaccination. Assessment of anti-SARS-CoV-2 spike protein antibody titer (SP-AbT) took place on a median of 25 days after the first vaccination (SD ± 11.8). A positive SP-AbT was detected in 23% (17/74) of assessable patients. A cut-off value of ≥ 30 CD19+ B cells/µl was significantly positively correlating with higher SARS-CoV-2 SP-AbT. Individuals with current anti-CD38-antibody treatment showed lower SP-AbT and the likelihood for positive titer results was significantly lower in patients with current anti-CD38 treatment compared to those without. Treatment with immunomodulatory drugs did not harm the development of antibody titers. Furthermore, in multivariable linear regression, higher age and insufficiently controlled disease (≤ partial remission) were significantly negatively correlated with SARS-CoV-2 SP-AbT.ConclusionBased on our results, the majority of myeloma patients respond poorly after receiving the first dose of any anti-SARS-CoV-2 vaccination. Since both low CD19+ B lymphocyte count and CD38-directed therapy negatively impact vaccination response, booster vaccination seems therefore of utter importance.

Low SARS-CoV-2 infection rates and high vaccine-induced immunity among German healthcare workers at the end of the third wave of the COVID-19 pandemic.

In this longitudinal cohort study, we assessed the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) seroconversion rates and analyzed the coronavirus disease 2019 (COVID-19) vaccine-induced immunity of 872 hospital workers at the University Medical Center Hamburg-Eppendorf between May 11 and May 31, 2021. The overall seroprevalence of anti–NC–SARS-CoV-2 antibodies was 4.7% (n = 41), indicating low SARS-CoV-2 infection rates and persistent effectiveness of hospital-wide infection control interventions during the second and third wave of the pandemic. In total, 92.7% (n = 808) out of the entire study cohort, 98.2% (n = 325) of those who had been vaccinated once and all 393 individuals who had been vaccinated twice had detectable anti-S1-RBD-SARS-CoV-2 antibody titers and no significant differences in vaccine-induced immune response were detected between male and female individuals and between different age groups. Vaccinated study participants with detectable anti–NC–SARS-CoV-2 antibody titers (n = 30) developed generally higher anti-S1-RBD-SARS-CoV-2 antibody titers compared to anti–NC–SARS-CoV-2 negative individuals (n = 694) (median titer: 7812 vs. 345 BAU/ml, p < 0.0001). Furthermore, study participants who received heterologous vaccination with AZD1222 followed by an mRNA vaccine showed markedly higher anti-S1-RBD-SARS-CoV-2 antibody titers than individuals who received two doses of an mRNA vaccine or two doses of AZD1222 (median titer: AZD1222/AZD1222: 1069 BAU/ml, mRNA/mRNA: 1388 BAU/ml, AZD1222/mRNA: 9450 BAU/ml; p < 0.0001). Our results indicate that infection control interventions were generally effective in preventing nosocomial transmission of SARS-CoV-2 and that COVID-19 vaccines can elicit strong humoral responses in the majority of a real-world cohort of hospital workers.

The Hamburg register for intravitreal injection therapies (QIVOM)

HintergrundIntravitreale operative Medikamenteneingaben (IVOM) gehören zu den häufigsten medizinischen Prozeduren überhaupt mit ca. 1,5 Mio. Eingriffen in Deutschland pro Jahr. Für diese enorme Versorgungsaufgabe gibt es nur wenige empirische Daten über den Versorgungsprozess und seine klinische und subjektive Wirkung.Material und MethodenEs wird die Entwicklung und der Aufbau des Hamburger Registers für intravitreale Injektionstherapien (QIVOM) detailliert beschrieben. IVOM-Patienten der drei großen Augenkliniken Hamburgs (Asklepios Kliniken Nord-Hamburg und Barmbek, Universitätsklinikum Hamburg-Eppendorf) werden im Rahmen der Routineversorgung mit IVOM zur Studienteilnahme eingeladen. Es werden subjektive Patientenangaben zum Krankheits- und Behandlungserleben erhoben und diese mit den patientenbezogenen medizinischen Parametern elektronisch ergänzt, pseudonymisiert und in einer elektronischen Datenbank erfasst.ErgebnisseVon den ersten 162 Studienpatienten (Alter 41–95 Jahre) war die Behandlungsindikation bei 64% exsudative altersbedingte Makuladegeneration (AMD), bei 22% retinaler Venenverschluss und bei 11% diabetisches Makulaödem. Es ergibt sich ein heterogenes Bild der Erkrankungsschwere und der subjektiven Beeinträchtigung. Eine Sehschärfe von 0,5 und besser wiesen 31,8% der Patienten am behandelten Auge im Vergleich zu 79,1% am Partnerauge auf. Die größte praktische Einschränkung betraf die Lesefähigkeit, bei der über ein Drittel erhebliche Einschränkungen erlebte. Autofahren war immerhin für 62% möglich. Eine Verbesserung der Sehfähigkeit durch IVOM erreichten 45% der Patienten.SchlussfolgerungDie Datenerfassung von patientenseitigen Daten und medizinischer Versorgungsdaten aus den Kliniken stellt den großen Vorteil des neu geschaffenen Registers dar. Die Erweiterung der Datenbasis soll in Zukunft vielfältige weiterführende Erkenntnisse erbringen und zur Qualitätssicherung in der IVOM-Therapie beitragen.

Pelvic lymphadenectomy in vulvar cancer and its impact on prognosis and outcome

BackgroundThe value of pelvic lymphadenectomy (LAE) has been subject of discussions since the 1980s. This is mainly due to the fact that the relation between lymph node involvement of the groin and pelvis is poorly understood and therewith the need for pelvic treatment in general.Patients and MethodsN = 514 patients with primary vulvar squamous cell cancer (VSCC) FIGO stage ≥ IB were treated at the University Medical Center Hamburg-Eppendorf between 1996 and 2018. In this analysis, patients with pelvic LAE (n = 21) were analyzed with regard to prognosis and the relation of groin and pelvic lymph node involvement.ResultsThe majority had T1b/T2 tumors (n = 15, 78.9%) with a median diameter of 40 mm (11–110 mm). 17/21 patients showed positive inguinal nodes. Pelvic nodal involvement without groin metastases was not observed. 6/17 node-positive patients with positive groin nodes also had pelvic nodal metastases (35.3%; median number of affected pelvic nodes 2.5 (1–8)). These 6 patients were highly node positive with median 4.5 (2–9) affected groin nodes. With regard to the metastatic spread between groins and pelvis, no contralateral spread was observed. Five recurrences were observed after a median follow-up of 33.5 months. No pelvic recurrences were observed in the pelvic nodal positive group. Patients with pelvic metastasis at first diagnosis had a median progression-free survival of only 9.9 months and overall-survival of 31.1 months.ConclusionA relevant risk for pelvic nodal involvement only seems to be present in highly node-positive disease, therefore pelvic staging (and radiotherapy) is probably unnecessary in the majority of patients with node-positive VSCC.