University Medical Center Hamburg Research Articles

Need for individualized counseling regarding psoriasis systemic therapy in women of childbearing age: analysis of the PsoFem study at the University Medical Center Hamburg.

For patients with moderate-to-severe psoriasis and current childbearing/pregnancy, the choice of therapy is limited. The present study compared the disease burden and treatment choices in women of childbearing age (WoCBA) with and without a current wish for pregnancy. Female patients aged 18 to 45 years, with moderate-to-severe psoriasis vulgaris, were consecutively recruited. The patients reported on sociodemographic/reproductive characteristics and quality of life impairments. The physicians assessed disease severity, comorbidities, and current treatment(s). Both patients' and dermatologists' perceptions of shared decision-making for the current systemic treatment were surveyed. Participants were 145 WoCBA with psoriasis: 73 were pregnant or reported a desire to conceive (group CB+) and 72 reported no wish to have (more) children (group CB-). Patients without childbearing wishes were older and often had previous children; no significant differences in clinical features or quality of life impairments were found. A significantly higher proportion of patients in the CB+ group were prescribed tumor necrosis factor alpha blockers, particularly certolizumab pegol. This treatment option was associated with previous children and the desire to conceive, but not with disease variables. Family planning was more often discussed and considered in the clinical decision for the CB+ group, but patient-doctor agreement for shared decision-making was fair-to-moderate. The small sample size prevented comparative analyses between patients planning a pregnancy in the short- vs long-term future. In addition, specific variables related to the decision-making process for the current therapy need to be assessed and examined in more detail in further research. For WoCBA with childbearing wishes, tumor necrosis factor alpha blockers were most frequently prescribed, in accordance with current guidelines/recommendations. Decision-making for continuing or changing systemic therapy during pregnancy must take into account medication specificities and the vulnerable stages in pregnancy, as well as the limited amount of pregnancy-compatible drugs.

Pregnancy & cardiovascular disease: the PREG-CVD-HH registry.

Cardiovascular disease (CVD) remains the leading cause of death in pregnant and peripartal women in western countries. Physiological changes during pregnancy can lead to cardiovascular complications in the mother; women with pre-existing heart disease may not tolerate these changes well, increasing their susceptibility to adverse cardiovascular outcomes during pregnancy. The aim of this study is to characterize pregnancy-induced changes in cardiac function, biomarker concentrations and cardiovascular outcomes in women with CVD during pregnancy at a tertiary care hospital in Germany. The PREG-CVD-HH study is a prospective single-center observational study of pregnant women with prevalent CVD treated at the University Medical Center Hamburg, Germany and currently includes 63 women with congenital or acquired heart disease and ten women from the general population included as controls. Participants underwent baseline assessment and dedicated comprehensive echocardiography. Biomarkers N-terminal pro B-type natriuretic peptide (NT-proBNP), MR-proadrenomedullin (MRproADM) and high-sensitivity cardiac troponin I (hs-cTnI) were measured serially throughout pregnancy and until 6 and 12 months postpartum. A maternal cardiac event was defined as death due to cardiovascular cause, arrhythmia, heart failure or hospitalization for other cardiac intervention. Mean maternal age was 34 years. A majority had a congenital heart disease (N=41), 10 patients developed pregnancy-associated CVD (e.g., preeclampsia, peripartum cardiomyopathy) and 12 women had known acquired heart disease (e.g., valvular disease, arrhythmia, cardiomyopathy). New-onset heart failure was observed in 14.1% of patients (N=9). Five patients developed arrhythmia and three patients developed preeclampsia. About 21.2% of patients were hospitalized due to cardiovascular events. Death from any or cardiovascular cause did not occur over the study period. Left and right ventricular global longitudinal strain (LV GLS, RV GLS) showed a transient worsening in the third trimester and peripartum period. NT-proBNP ranges broadened during the pregnancy and tended to progressively decrease postpartum in women with CVD. Hs-cTnI levels tended to trend upwards during pregnancy in patients with CVD, however, the hs-cTnI levels remained consistently low throughout pregnancy. In our cohort, pregnancy was associated with a transient increase in cardiac biomarkers and worsening of cardiac function during the third trimester and peripartum. These temporal changes reversed at 6-12 months postpartum, potentially due to decreased cardiac load, fluid shifts and hormonal changes. Overall, data on reference ranges in echocardiographic and biomarker measurements in the pregnant cardiac population are limited and require further investigation. Albeit one third of our cohort was deemed at high and highest maternal risk during pregnancy, there was no maternal death. We recommend that women with CVD receive preconceptional counselling and ongoing management by a specialized "Pregnancy Heart Team" to optimize care and, potentially, maternal outcomes.

Sequential Conditioning With FLAMSA Does Not Improve Outcomes of Allogeneic Stem Cell Transplantation in Chronic Myelomonocytic Leukemia Patients

As with myelodysplastic syndromes (MDS), effective treatment options for Chronic myelomonocytic leukemia (CMML) are limited, and the optimal treatment approach remains undefined. Allogeneic stem cell transplantation (allo-SCT) is potentially curative therapy for patients with CMML. Sequential conditioning with FLAMSA was initially developed for refractory acute myeloid leukemia (AML) and has since been applied in the treatment of MDS and CMML. Data on optimal allo-SCT conditioning in CMML Patients is scarce. This retrospective study from the Department of Stem Cell Transplantation at the University Medical Center Hamburg, Germany, compared allo-SCT outcomes in CMML patients across three conditioning regimes: Thiotepa-Busulfan (TB), Sequential FLAMSA-Busulfan Fludarabine (FLAMSA-FB), and Treosulfan-Fludarabine (Treo-Flu). Sixty-nine consecutive patients with CMML who underwent allo-SCT between the years 2006-2022 were included in the study. Twenty-two received TB, 27 received FLAMSA-FB, and 20 received Treo-Flu conditioning. Transplant sources included matched related donors (MRD, 8 patients), mismatched related donors (MMRD, 8 all in the TB group), matched unrelated donors (MUD, 31), and mismatched unrelated donors (MMUD, 22) with significant group variations (p<0.001). Most patients received anti-T lymphocyte Globulin (ATLG) for graft versus host disease (GVHD) prophylaxis (TB 68%, FLAMSA-FB 93%, Treo-Flu 85%, p=0.08). CPSS-Molecular score was comparable between the groups. One TB patient experienced primary graft failure, but engraftment times were comparable across the groups. Although not statistically significant, the TB group showed a trend towards improved 3-year OS rates (80%) compared to FLAMSA-FB (37%) and Treo-Flu (55%) (p=0.05). The TB group also displayed significantly higher 3-year PFS rates (80%) compared to FLAMSA-FB (33%) and Treo-Flu (both 39%), (p=0.02). No significant differences were observed in 3-year non-relapse mortality (NRM) across the TB (20%), FLAMSA-FB (30%), and Treo-Flu (26%) groups (p=0.8). Interestingly, no TB patients relapsed at 3 years, contrasting with the FLAMSA-FB (41%) and Treo-Flu groups (30%, p=0.02). Lastly, cumulative incidences of acute and chronic GVHD were similar across groups. Our analysis suggests FLAMSA-FB does not improve transplant outcomes, however TB represents the preferred conditioning regimen for CMML patients undergoing allo-SCT. It demonstrates notable advantages in relapse prevention and leads to improved OS and PFS compared to FLAMSA-FB and Treo-Flu protocols.

Alcohol consumption in cancer patients receiving psycho-oncologic care analysis of socio-demographic, health-related and cancer-related factors.

The carcinogenic effects of alcoholic beverages and the negative impact of alcohol consumption on cancer progression and treatment outcomes are well established in oncology research. Many cancer patients experience significant psychological distress, often manifesting as elevated levels of depression and anxiety. In the general population, alcohol consumption is commonly used as a coping mechanism for such distress. For cancer patients facing substantial psychological challenges, psycho-oncology care is available to help manage their symptoms and the overall impact of their condition. However, there is limited understanding of the alcohol consumption patterns in this particularly vulnerable group of patients, as well as the disease-related factors that may influence their drinking behavior. This study aims to examine the prevalence of potentially risky alcohol consumption in cancer patients receiving psycho-oncology care and to identify sociodemographic, health-related, and psychosocial factors associated with alcohol consumption after cancer diagnosis. By understanding drinking patterns and the factors associated with them, we aim to promote healthier behaviors and enhance treatment outcomes for cancer patients receiving psycho-oncology care. A consecutive sample of 1.225 patients from the psycho-oncology outpatient clinic of the University Medical Center Hamburg Eppendorf (UKE) was analyzed with regard to their alcohol consumption behavior using the Alcohol Use Disorders Identification Test-Consumption Items (AUDIT-C). Self-report questionnaires were employed to assess sociodemographic, health-related, and cancer-specific information. For statistical analysis, multiple linear regression was utilized. In the sample of cancer patients receiving psycho-oncology support one in six of both female and male patients showed risky alcohol drinking behavior (e.g. AUDIT-C above three for women and four for men). In the analysis (R-Square: 0.056) male gender (regression coefficient B 0.686, 95% CI: 0.453-0.919) and patientsreporting a higher physical health-related quality of life (SF8-PCS) (B 0.021, 95% CI: 0.011-0.032) were associated with higher levels of alcohol consumption, whereas having children (B -0.481, 95%CI: -0.700- -0.262) was associated with lower alcohol consumption. With regard to cancer type, a single-factor analysis of variance with gender as the centered covariate showed that patients with gastrointestinal cancer had had lower average consumption levels compared to the groups of patients with breast cancer, melanoma, genitourinary cancer, and lymphoma. Also, patients with sarcoma had lower average consumption levels than patients with lymphoma. The results allow to identify patient characteristics and cancer types associated with higher or lower alcohol consumption levels and higher likelihood of risky consumption behavior in this sample of cancer patients receiving psycho-oncological support. Cancer patients are particularly susceptible to the hazardous effects of alcohol consumption. The results of this study help to identify cancer patients at risk of worsening prognosis due to alcohol consumption and to develop intervention programs to minimize alcohol consumption in this group.

Unmasking inadequate healthcare: Laser hair removal for transfemme adults in Germany

Background Facial and body hair alterations are crucial for some transfemme individuals. To date, no data on the healthcare quality of permanent hair removal for transfemme adults are available for Germany. Aims To analyze the financial and psychological distress, treatment satisfaction, and health service situation of transfemme individuals in Germany seeking laser hair removal. Methods This study was designed as a prospective cross-sectional clinical trial including adults from the routine cohort of the Laser Department at the University Medical-Center Hamburg. The Brief Symptom Inventory-18 (BSI-18) and a self-developed, structured questionnaire were applied. Results In total, 80 transfemme people were included with a mean age of 30.3 years (SD 8.5; range: 19–56). Among respondents, 96.3% identified as female and 3.7% as nonbinary. Participants experienced significant burden in daily life, relationships, and work due to facial hair. BSI-18 results indicate great psychological distress. Laser hair removal was received with high satisfaction. The time from referral for laser hair removal to the initial consultation at the Laser Department was 4 months (IQR 4). Approval for cost coverage from health insurance after the first consultation took 4 months (SD 4.3). 40.0% received direct cost coverage approval by the health insurance, 34.5% received approval after opposition, with over 20% not receiving any cost coverage approval. Conclusion Unwanted facial and body hair has a massive impact on transfemme adults’ psychosocial and mental well-being. The current insurance framework indicates an insufficient healthcare situation of those individuals in Germany.

Sequential Conditioning Does Not Improve Outcomes of Allogeneic Stemcell Transplantation in CMML Patients

Background: Allogeneic stem cell transplantation (SCT) is potentially curative therapy for patients with CMML. Data on optimal allo-SCT conditioning in CMML Patients is scarce. Methods: This retrospective study from the Department of Stem Cell Transplantation at the University Medical Center Hamburg, Germany, compared allo-SCT outcomes in CMML patients across three conditioning regimes: Thiotepa-Busulfan (TB), Sequential FLAMSA-Busulfan Fludarabine (FLAMSA-FB), and Treosulfan-Fludarabine (Treo-Flu). TB consisted of Thiotapa ( 5mg/Kg; a total dose of 10mg/Kg) on day -6 and -5 and Busulfan (3.2mg/Kg; total dose 6.4mg/Kg or 9.6mg/Kg) on days -4 and -3 or -4 to -2. FLAMSA-FB regimen consists of fludarabine (30 mg/m 2 ; total dose 120 mg/m 2 ), amsacrine (100 mg/m 2 ; total dose 400 mg/m 2 ), and cytarabine (1 g/m 2 ; total dose 4 g/m 2 ) therapy from days -11 to minus -8, followed by a three-day interval without therapy and Busulfan from day -4 to -2 with a total dose of 6.4mg/Kg and Fludarabine on day -4 and -3 (30 mg/m 2, total dose 60mg/m 2 ).Treo-Flu regimen consisted of Treosulfan (12 g/m 2 , total dose 36 mg/m 2 ) on days-6 to -4 and fludarabine (30 mg/m 2 ; total dose 150 mg/m 2 ) on days -6 to -2. Results Sixty-nine consecutive patients with CMML who underwent allo-SCT between the years 2006-2022. Twenty-two received TB, 27 received FLAMSA-FB, and 20 received Treo-Flu conditioning. Transplant sources included matched related donors (MRD, 8 patients), mismatched related donors (MMRD, 8 from TB), matched unrelated donors (MUD, 31), and mismatched unrelated donors (MMUD, 23) with significant group variations (p&amp;lt;0.001). Most Patients received ATLG for GVHD prophylaxis (TB 68%, FLAMSA-FB 93%, Treo-Flu 85%, p=0.08). Regarding CPSS-mol scores, the TB group exhibited a significantly higher proportion of high (46%) and intermediate-2 scores (32%) than FLAMSA-FB (11% high, 7% intermediate-2) and Treo-Flu (40% high, 20% intermediate-2) (p=0.001). One TB patient experienced primary graft failure, but engraftment times were comparable across groups. Although not statistically significant (p=0.07), the TB group showed a trend towards improved 3-year OS rates (84%) compared to FLAMSA-FB (37%) and Treo-Flu (49%). The TB group also displayed significantly higher 3-year PFS rates (79%) compared to FLAMSA-FB and Treo-Flu (both 30%), (p=0.03). (Figure 1) No significant differences were observed in 3-year non-relapse mortality (NRM) across the TB (17%), FLAMSA-FB (30%), and Treo-Flu (26%) groups (p=0.7). Interestingly, no TB patients relapsed at 3 years, contrasting with the FLAMSA-FB (41%) and Treo-Flu groups (43%, p=0.02). Lastly, cumulative incidences of acute GVHD grade II-IV (TB 41%, FLAMSA-FB 35%, Treo-Flu 30%, p=0.75) and all-grade chronic GVHD (TB 50%, FLAMSA-FB 65%, Treo-Flu 40%, p=0.35) were similar across groups. Conclusion Our study suggests that sequential conditioning with FLAMSA-FB does not improve Transplant outcomes in patients undergoing allo-SCT for CMML.

The Impact of Anti-T-Lymphocyte-Globulin Dosing on Gvhd in Matched Sibling Allogeneic Stemcell Transplantation

Introduction: Due to the graft versus tumor effect allogeneic stem cell transplantation (allo-SCT) is a curative strategy for hematological malignancies. However, its benefits are offset by non-related mortality (NRM) primarily from graft-versus-host-disease (GVHD). In vivo T-cell depletion (TCD) with Anti-T-Lymphocyte globulin (ATLG) can reduce GVHD. Although lower ATLG doses may compromise the immunosuppression effects, higher ATLG doses may offset its benefit by decreasing antiviral and graft-versus-malignancy effect by depletion of donor effector T cells. Even though the use of ATLG in allo-SCT is well established, however, data on optimal ATLG dosing in the setting of matched sibling donor (MSD) -allo-SCT is scarce. Methods: In this retrospective study conducted at the Department of stem cell transplantation, University Medical Center Hamburg Eppendorf (UKE) we aim to compare the transplant outcomes between recipients of 15 mg/Kg vs 30 mg/Kg ATLG as T-cell depletion in Patients undergoing allo-SCT from MRD. Results: In the study, 109 sequential patients (ATLG 15, n=72; ATLG 30, n=37) underwent allo-SCT between the years 2018 and 2022 from MSD for hematological conditions. PBSC was the primary stem cell source in both cohorts (ATLG-15, 99%; ATLG-30, 92%; p=0.08). In the ATLG-15 group, 13% received TBI versus none in the ATLG-30 group (p=0.025). The MAC regimen was utilized in 65% of ATLG-15 patients, compared to 27% in ATLG-30 (p&amp;lt;0.001). The most prevalent disease was AML in ATLG-15 (54%) and PMF in ATLG-30 (54%, p&amp;lt;0.001). More ATLG-15 patients were transplanted in CR (43%) than in ATLG-30 (16%, p=0.02). All ATLG-15 patients had ECOG0-1 status, against 90% in ATLG-30 (p=0.007). The median age at transplant was similar, 58 and 56 years in ATLG-15 and ATLG-30, respectively (p=0.99). All other Patients donor and transplant characteristics were comparable between the two groups. One patient died prior to engraftment and three patients had primary graft failure in the ATLG-15 group, all remaining patients successfully engrafted. The ATLG-15 cohort showed an earlier leukocyte engraftment (median 11 days, range 9-19, p=0.001) and a tendency towards quicker platelet engraftment (median 12 days, range 8-107, p=0.06) compared to the other group's medians of 13 days (range 8-16) and 17 days (range 3-130), respectively. Grade II-IV aGVHD at day 100 was 36% in the ATLG-15 group compared to 23% in the ATLG-30 group (p=0.45). A trend towards lower 2-year moderate/severe cGVHD was observed in the ATLG-15 group (48% vs 36%, p=0.08). The ATLG-15 group showed a trend towards higher 2-year OS (84% vs 72%, p=0.06), however this trend disappeared on multivariate analysis (MVA) (HR 0.853 [95%CI 0.319, 2.283]; p=0.75) no other factor affected OS on MVA. The 2-year PFS was similar across both groups (ATLG-15, 63%; ATLG-30, 60%; p=0.5). On MVA only TBI had a significant effect on PFS (HR 0.310 [95%CI, 0.101, 0.957], p=0.04), none of the other factors significantly affected PFS. There was a trend for Lower NRM in the ATLG-30 group (at 1 Yr, 0% vs 11%, p=0.09), while the two-year relapse incidences were comparable (ATLG-15, 7%; ATLG-30, 14%; p=0.2). Conclusion: Acknowledging the retrospective nature of our study, however our results show that a higher ATLG dose may reduce incidence of chronic GVHD in Patients undergoing allo-SCT from MSD, however our findings should be confirmed in larger prospective studies.

Health behaviors of people with multiple sclerosis and its associations with MS related outcomes: a German clinical cohort.

Health behaviors in persons with multiple sclerosis (pwMS) have been associated with MS-related disease outcomes. The aim of the study was to gain knowledge about current patient health behaviors in a convenience sample representative for pwMS presenting to a large university-based outpatient clinic and to investigate associations between modifiable risk factors with physical impairment, quality of life (QoL) and cardiovascular comorbidities. A questionnaire was administered at the MS Outpatient Clinic of the University Medical Center Hamburg Eppendorf asking for health behaviors regarding dietary habits assessed with the German adaptation of the validated Spanish short Diet Quality Screener (sDQS), level of physical activity assessed with the Godin Leisure Time Questionnaire (GLTEQ) and tobacco smoking. Participants were asked to report cardiovascular comorbidities using items from the Self-Report Comorbidity Questionnaire for Multiple Sclerosis. Additionally, cardiovascular risk factors like blood pressure, height and weight (to calculate BMI) and waist circumference were measured. MS specific clinical data, e.g., disease course, duration, disability and MS-specific QoL were collected from the clinical database. Descriptive analyses were performed and multivariate regression analyses for complete cases were carried out for each of the three outcome variables including all mentioned modifiable risk factors (dietary behavior, smoking, physical activity and BMI) as independent variables. In this sample of 399 pwMS the mean age was 42 years (SD 12.8) with a mean disease duration since diagnosis of 7.4 years (SD 8.4) and a mean EDSS of 2.8 (SD 1.9). 24% were current smokers, 44% were insufficiently physically active and 54% did not follow a healthy dietary pattern. 49% of this relatively young clinical population was overweight and 27% reported one or more cardiovascular comorbidities. Most modifiable risk factors showed no convincing associations with MS-related disease outcomes in the multiple regression analyses. This clinical cohort of pwMS shows a high prevalence of critical health behaviors and comorbidities and emphasizes the need for monitoring, education and assistance for behavior change in this population.

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.

Post-Transplant MRD Negativity on Day +100 Predicts Outcomes for Pre-Transplant Relapsed/Refractory AML Patients

IntroductionPatients with relapsed/refractory (r/r) AML have in general a dismal prognosis. Allogeneic stem cell transplantation (allo-SCT) provides a curative approach for these patients, however the overall survival (OS) remains still low achieving 20-40%. Though post-transplant minimal residual disease (MRD) monitoring has been shown to be predictive for development of post-transplant relapses and lower survival, data focusing on pre-transplant relapsed/refractory AML patients is scarce. In this study, we investigated the impact of achieving MRD negativity on day +100 for relapses and survival for this high risk patients.Patients and MethodsWe analyzed post-transplant outcomes for pre-transplant r/r AML patients depending on their post-transplant MRD status at day +100. The day +100 was chosen concerning the possibility of early post-transplant interventions (e.g. tapering of immunosuppression or administration of donor lymphocytes).Fifty six consecutive adult patients (≥18 years old) with r/r AML (median age 58, range 20-76; male, n=34, 61%) who underwent allo-SCT (first, n=44, 79%; second, n=12, 21%) between 2015-2020 at the Department for Stem Cell Transplantation at the University Medical Center Hamburg (Germany) were included. The MRD was assessed on day +100 using multiparameter flow cytometry according to “different from normal” strategy.The patients experienced rather primary refractory disease (64%), secondary/therapy-related AML (55%) and abnormal cytogenetics (59%) at diagnosis. The median pre-transplant blast count was 25% (6-91%). A number of 29 patients (52%) showed blasts in peripheral blood. Myeloablative conditioning was used in 31 (55%) patients, whereas 25 (45%) patients received reduced intensity regimens. A number of 29 patients (52%) received a FLAMSA-based conditioning. Post-transplant donor lymphocyte infusions as well as other treatment were given to 13 (23%) and 17 (30%) patients, respectively.ResultsThe median follow up was 20 months (range 4-66). Forty patients (71%) achieved MRD negativity on day +100 and 16 (29%) remained MRD positive. The 2-year OS, LFS, relapses and NRM at 2 years for day +100 MRD negative patients were: 76% (95% CI: 60-87%), 59% (95% CI: 41-75%), 31% (95% CI: 17-50%) and 8% (95% CI: 3-19%), respectively. The 2-year OS, LFS, relapses and NRM at 2 years for day +100 MRD positive patients were: 35% (95% CI: 17-59%, p=p=0.001), 23% (95% CI: 9-46%, p<0.0001), 70% (95% CI: 45-87%, p=0.0002) and 6% (95% CI: 1-28%, p=0.88), respectively.Several factors were evaluated for possible association with day +100 MRD negativity (Table 1). There were no significant associations. Further, the incidence of acute (grade II-IV) GvHD at 100 days was not significantly different between the day 100 MRD positive und negative patients.Following factors had impact on post-transplant outcomes in multivariate analysis: presence (no vs yes) of peripheral blasts prior to allograft (OS: HR 0.3, 95% CI: 0.1-0.9, p=0.03; LFS: HR 0.4, 95% CI: 0.1-0.9, p=0.03; relapses: HR 0.4, 95% CI: 0.1-0.99, p=0.048; NRM: HR 0.5, 95% CI: 0.2-1.3, p=0.17), FLAMSA vs other preparative regimens (OS: HR 0.4, 95% CI: 0.1-0.93, p=0.03; LFS: HR 0.4, 95% CI: 0.2-0.98, p=0.04; relapses: HR 0.4, 95% CI: 0.2-1.0, p=0.05; NRM: HR 0.4, 95% CI: 0.2-1.0, p=0.06), and day +100 MRD (negative vs positive) (OS: HR 0.3, 95% CI: 0.1-0.7, p=0.009; LFS: HR 0.2, 95% CI: 0.1-0.6, p=0.001; relapses: HR 0.2, 95% CI: 0.1-0.4, p=0.0001; NRM: HR 0.2, 95% CI: 0.1-0.5, p=0.0006).ConclusionsPost-transplant MRD detection plays predictive role in pre-transplant r/r AML patients and may help to define possible candidates for early post-transplant interventions. DisclosuresNo relevant conflicts of interest to declare.

Slow-Release Oral Morphine May Help Patients With OUD

Back to table of contents Previous article Next article Clinical & ResearchFull AccessSlow-Release Oral Morphine May Help Patients With OUDTerri D'ArrigoTerri D'ArrigoSearch for more papers by this authorPublished Online:21 Jun 2021https://doi.org/10.1176/appi.pn.2021.5.10AbstractPotential benefits include improved mental health and less intravenous drug use.Slow-release oral morphine may be an effective treatment for people with opioid use disorder (OUD) who experience adverse events or unsatisfactory results with other forms of medication treatment, suggests a study in the Journal of Substance Abuse Treatment. The study also found that patients who took slow-release oral morphine drank less alcohol and reported an improvement in their mental and physical health.Slow-release oral morphine may benefit patients with OUD for whom other treatments are unsatisfactory, says Kirsten Lehmann, M.P.H.Carina Haeusler“We know that all available medications, despite their effectiveness, can cause unwanted symptoms like adverse effects, and it often occurs that patients are using additional psychotropic substances. To counteract an unsatisfactory course of treatment, we need a therapy tailored to the patient’s conditions,” said lead author Kirsten Lehmann, M.P.H., a scientific assistant at the Centre for Interdisciplinary Addiction Research of Hamburg University at the University Medical Center Hamburg–Eppendorf in Germany.Lehmann and her colleagues analyzed data from 180 adults with OUD from 23 outpatient treatment centers in Germany, where slow-release oral morphine is approved for OUD treatment. (It is not approved for treating OUD in the United States.) The patients had been taking medication treatment, such as racemic methadone, levomethadone, buprenorphine, or diamorphine for an average of seven years and had decided to switch to slow-release oral morphine because they were not satisfied with their current treatment. After 12 months, 60.6% were still being treated with slow-release oral morphine. The majority of those who stopped taking slow-release oral morphine switched back to their previous form of medication treatment.An analysis of the patients’ mental health using the German version of the Brief Symptom Inventory-18 and the Global Severity Index revealed that symptoms of depression, anxiety, and somatization improved in patients with those conditions. Patients also reported improved physical health on the Opiate Treatment Index–Health Symptom Scale, a checklist of 50 symptoms that people with OUD often experience.Roughly 24% of patients experienced adverse events over 12 months. However, only 31% of those adverse events were documented as having a possible, probable, or certain relationship to slow-release oral morphine.A subset of 113 patients reported their prior 30-day substance use at several points throughout the study. From baseline to 12 months, the average number of days they used heroin in the previous 30 days dropped from 4.9 to 1.4, and the average number of days they used substances intravenously dropped from 2.7 to .02. The average number of days they used alcohol in the previous 30 days dropped from 6.4 to 4.0. Their scores on visual analog scales, which measure heroin cravings, decreased from 34.8 at baseline to 13.6 at 12 months.Lehmann noted that the study did not add any interventions that could have affected the results. “Thus, the observed improvements in mental and physical health, alcohol consumption, and illegal drug use may be attributed primarily to [slow-release oral morphine],” she said.This study was supported by an unrestricted grant from Mundipharma Deutschland GmbH & Co. KG. ■ “Substitution Treatment for Opioid Dependence With Slow-Release Oral Morphine: Retention Rate, Health Status, and Substance Use After Switching to Morphine” is posted here. ISSUES NewArchived

Prediction of Nociception in Children Using the Nociceptive Flexion Reflex Threshold and the Bispectral Index-A Prospective Exploratory Observational Study.

The prediction of patient responses to potentially painful stimuli remains a challenge in PICUs. We investigated the ability of the paintracker analgesia monitor (Dolosys GmbH, Berlin, Germany) measuring the nociceptive flexion reflex threshold, the cerebral sedation monitor bispectral index (Medtronic, Dublin, Ireland), the COMFORT Behavior, and the modified Face, Legs, Activity, Cry, Consolability Scale scores to predict patient responses following a noxious stimulus. Single-center prospective exploratory observational study. Fourteen-bed multidisciplinary PICU at the University Children's Hospital, University Medical Center Hamburg Eppendorf, Germany. Children on mechanical ventilation receiving analgesic and sedative medications. Noxious stimulation by way of endotracheal suctioning. Two independent observers assessed modified Face, Legs, Activity, Cry, Consolability and COMFORT Behavior Scales scores during noxious stimulation (n = 59) in 26 patients. Vital signs were recorded immediately before and during noxious stimulation; bispectral index and nociceptive flexion reflex threshold were recorded continuously. Mean prestimulation bispectral index (55.5; CI, 44.2-66.9 vs 39.9; CI, 33.1-46.8; p = 0.007), and COMFORT Behavior values (9.5; CI, 9.2-13.2 vs 7.5; CI, 6.7-8.5; p = 0.023) were significantly higher in observations with a response than in those without a response. Prediction probability (Pk) values for patient responses were high when the bispectral index was used (Pk = 0.85) but only fair when the nociceptive flexion reflex threshold (Pk = 0.69) or COMFORT Behavior Scale score (Pk = 0.73) was used. A logistic mixed-effects model confirmed the bispectral index as a significant potential predictor of patient response (p = 0.007). In our sample of ventilated children in the PICU, bispectral index and nociceptive flexion reflex threshold provided good and fair prediction accuracy for patient responses to endotracheal suctioning.

A Resident-Led Virtual Journal Club to Educate Pediatric Residents About Coronavirus Disease 2019.

A Resident-Led Virtual Journal Club to Educate Pediatric Residents About Coronavirus Disease 2019.

Lower Levels of Transaminases but Higher Levels of Serum Creatinine in Patients with Acute Hepatitis E in Comparison to Patients with Hepatitis A.

In patients with hepatitis E virus (HEV) infections, extrahepatic, particularly renal and hematological manifestations, are increasingly reported in the medical literature but have never been studied compared to a control cohort. We retrospectively analyzed medical records of consecutive patients that were diagnosed with acute hepatitis E (AHE) (n = 69) or acute hepatitis A (AHA) (n = 46) at the University Medical Center Hamburg Eppendorf from January 2009 to August 2019 for demographical, clinical, and laboratory information. Patients with AHE had significantly lower median levels of ALAT (798 U/L) and total bilirubin (1.8 mg/dL) compared to patients with AHA (2326 U/L; p < 0.001 and 5.2 mg/dL; p < 0.001), suggesting a generally less severe hepatitis. In contrast, patients with AHE had significantly higher median serum creatinine levels (0.9 mg/dL vs. 0.8 mg/dL; p = 0.002) and lower median estimated glomerular filtration rate (eGFR) (91 mL/min/1.73 m2 vs. 109 mL/min/1.73 m2; p < 0.001) than patients with AHA. Leucocyte, neutrophil and lymphocyte count, hemoglobin, platelets, red cell distribution width (RDW), neutrophil to lymphocyte ratio (NLR), and RDW to lymphocyte ratio (RLR) did not differ between patients with AHE and those with AHA. Our observations indicate that renal but not hematological interference presents an underrecognized extrahepatic feature of AHE, while inflammation of the liver seems to be more severe in AHA.

First person – Lena Marie Westermann

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Lena Marie Westermann is first author on ‘Imbalanced cellular metabolism compromises cartilage homeostasis and joint function in a mouse model of mucolipidosis type III gamma’, published in DMM. Lena Marie is an MD student in the lab of Dr Sandra Pohl at University Medical Center Hamburg-Eppendorf, Hamburg, Germany, investigating bone and connective tissue phenotypes in lysosomal storage disorders.

Response to growth hormone in patients with RNPC 3 mutations

Corrigendum7 September 2020Open Access Response to growth hormone in patients with RNPC3 mutations Gabriel Á Martos-Moreno Gabriel Á Martos-Moreno Search for more papers by this author Lourdes Travieso-Suárez Lourdes Travieso-Suárez Search for more papers by this author Jesús Pozo-Román Jesús Pozo-Román Search for more papers by this author María T Muñoz-Calvo María T Muñoz-Calvo Search for more papers by this author Julie A Chowen Julie A Chowen Search for more papers by this author Mikko J Frilander Mikko J Frilander Search for more papers by this author Luis A Pérez-Jurado Luis A Pérez-Jurado Search for more papers by this author Federico G Hawkins Federico G Hawkins Search for more papers by this author Jesús Argente Jesús Argente orcid.org/0000-0001-5826-0276 Search for more papers by this author Gabriel Á Martos-Moreno Gabriel Á Martos-Moreno Search for more papers by this author Lourdes Travieso-Suárez Lourdes Travieso-Suárez Search for more papers by this author Jesús Pozo-Román Jesús Pozo-Román Search for more papers by this author María T Muñoz-Calvo María T Muñoz-Calvo Search for more papers by this author Julie A Chowen Julie A Chowen Search for more papers by this author Mikko J Frilander Mikko J Frilander Search for more papers by this author Luis A Pérez-Jurado Luis A Pérez-Jurado Search for more papers by this author Federico G Hawkins Federico G Hawkins Search for more papers by this author Jesús Argente Jesús Argente orcid.org/0000-0001-5826-0276 Search for more papers by this author Author Information Gabriel Á Martos-Moreno, Lourdes Travieso-Suárez, Jesús Pozo-Román, María T Muñoz-Calvo, Julie A Chowen, Mikko J Frilander, Luis A Pérez-Jurado, Federico G Hawkins and Jesús Argente EMBO Mol Med (2020)12:e13132https://doi.org/10.15252/emmm.202013132 This article corrects the following: Response to growth hormone in patients with RNPC3 mutations06 June 2018 PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info The authors recently noticed that one of the reported mutations, chr1:104093621C>A/p.P474T, was incorrectly listed as c.1320C>A at the cDNA level. The correct mutation is c.1420C>A; the nomenclature at the protein level was correct. This genetic variant is correctly listed in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/587367/), has an allele frequency of 0.00003185 in gnomAD (https://gnomad.broadinstitute.org/variant/1-104093621-C-A?dataset=gnomad_r2_1) and has been reported in a second family with growth hormone deficiency due RNPC3 dysfunction (Verberne et al, 2020). References Verberne EA, Faries S, Mannens MMAM, Postma AV, van Haelst MM (2020) Expanding the phenotype of biallelic RNPC3 variants associated with growth hormone deficiency. Am J Med Genet A https://doi.org/10.1002/ajmg.a.61632Wiley Online LibraryWeb of Science®Google Scholar Previous ArticleNext Article Read MoreAbout the coverClose modalView large imageVolume 12,Issue 9,07 September 2020This month's cover highlights the article Characterization of circulating breast cancer cells with tumorigenic and metastatic capacity by Claudia Koch, Andra Kuske, Klaus Pantel and colleagues. New estrogen receptor‐positive breast cancer cell line CTC‐ITB‐01 enables functional studies of circulating tumor cells. Cytoplasmatic keratin (orange) and nuclear estrogen receptor (green) protein expression in CTC‐ITB‐01 cells. DAPI nuclear staining (blue). (Scientific image by Claudia Koch et al., Institute of Tumor Biology, University Medical Center Hamburg, Eppendorf, Hamburg, Germany) Volume 12Issue 97 September 2020In this issue ReferencesRelatedDetailsLoading ...

Allogeneic stem cell transplantation for myelofibrosis patients aged ≥65 years.

Myelofibrosis (MF) is a disease of elderly with median age of 65years at diagnosis. Allogeneic stem cell transplantation (ASCT) currently is the only potentially curative option, although associated with treatment-related morbidity and mortality. Development of reduced intensity conditioning (RIC) regimens enabled transplant to be performed successfully in older patients. To evaluate outcome of transplantation among elderly patients (≥65years), we conducted retrospective analysis of results in 45 patients transplanted between 2002 and 2018 at the University Medical Center Hamburg. Median age at ASCT was 67years (r: 65-74). The majority of patients (n=43) received busulfan plus fludarabine RIC regimen and were classified as DIPSS intermediate-2 or high risk at time of transplantation. After a median follow-up of 4years, 6-year estimated progression-free survival and overall survival were 60% and 64%, respectively. Cumulative incidence of non-relapse mortality was 21% at 1year. Cumulative incidence of relapse at 6years was 10%. Patients with Sorror score 3 or less had a significant better survival (73% vs 25%, P=.009). Reduced intensity conditioning regimen followed by ASCT in older patients with myelofibrosis is a curative treatment option. Outcome is more favorable in patients with no or minimal comorbidities.

High Cure Rate By Allogeneic Stem Cell Transplantation for Myelofibrosis Patients Aged 65 or Older

IntroductionMyelofibrosis (MF) is predominantly a disease of the elderly with a median age of 65 years at diagnosis. Allogeneic stem cell transplantation (ASCT), which is associated with substantial treatment-related morbidity and mortality, is the only potentially curative option so far. The development of reduced intensity conditioning (RIC) regimens has enabled transplant to be performed successfully in older patients. To evaluate the outcome of transplantation among elderly patients, we conducted a retrospective analysis of results in 46 patients, aged 65 years or older, who were transplanted between 2002 and 2018 at the University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.Patients and methodsRetrospective data from 46 patients with primary or secondary MF, who underwent ASCT, were collected. Median age at ASCT was 67 years (r: 65-74). 76% of patients were classified as MF-3 according to the WHO criteria. DIPSS risk status was intermediate-1 in 4% of patients, intermediate-2 in 61% and high in 33%. 70% of patients had mutation in JAK2, 17% in CALR and 9% in MPL. All patients received peripheral blood stem cell (PBSC) as graft source. Stem cell donor was related in 9% of patients, unrelated in 91%; 74% of patients had a completely HLA-matched donor, whereas 26% had at least 1 allele or antigen mismatch. 85% of patients received busulfan 10 mg/kg orally (or 8 mg/kg intravenously) plus fludarabine (150 mg/m2) reduced intensity conditioning regimen, whereas 15% received myeloablative conditioning with busulfan 16 mg/kg orally (or 12.8 mg/kg intravenously) plus fludarabine (150 mg/m2). 96% of the patients received anti-T-lymphocyte globulin (Grafalon®, Neovii, Germany) at a cumulative dose of 30 mg/kg for matched related donor (MRD) transplants and 60 mg/kg for matched/mismatched unrelated donor (MUD/MMUD) transplants. Further GVHD prophylaxis consisted of cyclosporine A and mycophenolate from day +1 to +28.ResultsEngraftment rate was 94%, with a median time to neutrophil engraftment of 13 days (r: 10-19). Two patients (4%) experienced primary graft failure (PGF), one received a second ASCT with successful engraftment, while the other had further PGF after second ASCT and died of infection after third ASCT. Platelet engraftment rate was 87% and was reached in a median time of 21 days (r: 10-293). Five patients (11%) developed secondary poor graft function and four received CD34+ selected PBSC boost, two achieving complete remission (CR) and one obtaining CR with incomplete platelet recovery (CRp).52% of patients experienced acute GVHD grade I to IV, while the overall rate of chronic GVHD was 56%, which was moderate disease in 24% and severe disease in 13%.After a median follow-up of 4 years, 6-year estimated progression-free survival (PFS) and overall survival (OS) were 60% (95% CI: 42-78) and 64% (95% CI: 48-80), respectively. In the univariate analysis, male donor sex was the only significant factor for improved OS and PFS at 6 years (P=.001 and P=.003, respectively). A positive impact on OS was observed for mutation in CALR (P=.05), as previously reported. Interestingly, survival was not significantly different in patients aged 65-70 years compared with those aged 71-74 years.Cumulative incidence of non-relapse mortality (NRM) was 29% at 4 years (95% CI: 13-45). Major causes of death were infections (n=4) and GVHD (n=3). The only significant factor for lower NRM in the univariate analysis was male donor sex vs female (NRM 17% vs 58%, P=.004). No NRM occurred in CALR-mutated patients (p=0.00).Cumulative incidence of relapse at 6 years was 10% (95% CI: 0-22): one patient durably restored molecular response after early tapering of cyclosporine, one died because of GVHD without any further treatment, one achieved a long-lasting CR after donor lymphocytes infusions (DLI), while two patients underwent a second ASCT after DLI alone in one case and DLI plus azacitidine in the other, with long-term CR in the former.ConclusionOur results show that RIC regimen followed by allogeneic stem cell transplantation in older patients with myelofibrosis is a curative treatment option. These results are encouraging for older MF patients with minimal comorbidities. In addition to Hematopoietic cell transplantation-specific comorbidity index (HCT-CI), a comprehensive geriatric assessment could be a useful tool for a better selection of patients with the aim to further reduce NRM. DisclosuresNo relevant conflicts of interest to declare.

Traumatic brain injury in high versus low falls in young children and adolescents: a retrospective analysis.

OBJECTIVE So-called low falls are gaining interest in traumatology. To date, there are no studies on low versus high falls in the pediatric population. The aim of the current analysis was to characterize the symptoms, diagnostics, and injuries associated with high versus low falls and to examine the effect of fall height on injuries and outcome in the context of current guideline-based recommendations. METHODS After obtaining study approval from the local ethics committee, the authors reviewed the data for patients ages 5-17 years who had been consecutively treated at either hospital associated with the University Medical Center Hamburg in the period from January 2009 to August 2014 for diagnoses including traumatic brain injury (TBI). Retrospective analysis of the electronic patient charts was performed to obtain data on demographics; accident mechanism; initial neurological status with respect to consciousness, symptoms, and Glasgow Coma Scale score; radiological studies; diagnoses; length of stay; all intracranial procedures; and Glasgow Outcome Scale (GOS) score. RESULTS Sixty-five fall-related TBIs among 380 patients were identified; 26 patients fell from a height of 3 m or more and 28 fell from a height under 3 m (height undocumented in 11 cases). Patients who fell from ≥ 3 m were 22 times more likely than those who fell from < 3 m to undergo spiral CT studies in the emergency room (p = 0.05). In addition, there was a 7.4 times greater chance of undergoing cranial CT (p = 0.02). There were significantly more noncerebral injuries requiring surgery in patients who fell from ≥ 3 m versus those who fell from < 3 m (p = 0.007). There was no difference in the frequency of neurosurgical procedures performed between low and high groups. Follow-up ranged from 0 to 92 months (mean 12.5 months, median 0 months). There was no significant difference in good (GOS score 4-5) and poor (GOS score 1-3) outcomes between high and low falls (p = 0.208). CONCLUSIONS Low falls can be associated with intracranial hemorrhages requiring ICU monitoring and/or surgery. The authors encourage intensive monitoring and CT scans based on clinical presentation, not on fall height.

6. FACT OR ARTIFACT? BENEFITS AND LIMITATIONS OF ADVANCED NEUROIMAGING METHODS FOR PSYCHOSIS

Overall : Neuroimaging tools introduced the ability to non-invasively search for pathological signatures in the brains of subjects suffering from psychosis. In fact, with almost any neuroimaging modality there are studies that report the identification of abnormalities in the brains of schizophrenia subjects. The abundance of findings made it much clearer that brain abnormalities are common and expected in mental disorders. However, the quantity of findings, and especially their inconsistence across studies also raise questions as to the source of these abnormalities. Are they signifying a complicated range of pathologies and interactions? Or do they reflect auxiliary changes that are not directly related to the root, or the etiology of the disorder?In addition, these inconsistencies raise technical questions such as are our tools sufficiently sensitive to reliably identify brain abnormalities in psychosis? And, to what extent are our tools sensitive to misinterpretation and to artifacts, which may explain some of the group differences found when comparing psychotic populations with controls? Emerging imaging modalities attempt to address these concerns by improving the specificity, i.e., the ability to relate identified abnormalities with underlying pathologies. At the same time analysis must carefully pay attention to common physiological sources of artifacts, such as subject motion, blood flow, brain metabolism, partial volume, etc.This symposium will bring together five leading neuroimagers from 4 continents, who will present paradigm-shifting state of the art in their field, while providing critical cautionary remarks regarding the shortcomings of these methods, as well as recommendations for proper use in the context of psychosis studies. Speakers are:1) Prof. Jennifer Caughlin, M.D. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University. She will present state of the art in TSPO-PET acquisition and analysis, and its potential for the evaluation of neuroinflammation in schizophrenia.2) Prof. Ofer Pasternak, Ph.D. Departments of Psychiatry and Radiology, Harvard Medical School. He will present recent advances in diffusion MRI, and how microstructural imaging may inform the study of psychosis.3) Prof. Christoph Mulert, M.D. Department of Psychiatry and Psychotherapy. University medical center Hamburg, Germany. He will present new approaches for EEG acquisitions combined with fMRI that may shed light on neuronal activity.4) Prof. Helen Juan Zhou, Ph.D. Neuroscience & Behavioural Disorders Programme, Duke-Nus Medical School, Singapore. She will present the emerging field of connectomics and its potential application to study functional and structural brain networks in schizophrenia.The discussant will be Prof. Christos Pantelis, M.D. Department of Psychiatry, University of Melbourne, Australia. Dr. Pantelis will complement the panel by bringing in a more clinical point of view, informed of the needs in psychiatric neuroimaging. The panel will also benefit from his vast experience across all imaging modalities.This symposium is designed to provide information and considerations that can be essential for psychosis researchers before considering the application of advanced imaging tools. We will describe the main and unique findings that were provided by each modality, towards a discussion of how far are imaging studies from leading to a breakthrough in the understanding of the pathophysiology of psychosis or its treatment.