Cytogenetic risk grouping by the monosomal karyotype classification is superior in predicting the outcome of acute myeloid leukemia undergoing allogeneic stem cell transplantation in complete remission

We retrospectively analyzed the impact of cytogenetic abnormalities grouped according to the monosomal karyotype (MK) classification or the Southwest Oncology/Eastern Cooperative Oncology Group (SWOG/ECOG) definition in 263 patients with acute myeloid leukemia (AML) who underwent allogeneic stem cell transplantation (alloSCT) in complete remission (CR) at our center. Risk grouping using the MK criteria shows a highly significant difference in 5‐yr overall survival (OS) ranging between 67%, for the most favorable, and 32%, for the poorest risk group (P = 0.001). Although similarly precise in predicting OS, the MK scheme better separates patients with respect to relapse incidence as compared to the SWOG/ECOG grouping (P = 0.0001 vs. P = 0.01). Notably, patients displaying non‐MK abnormalities (MK?) had a 5‐yr relapse incidence identical to those cytogenetically normal (CN), that is 24%. Multivariate analysis revealed that the MK classification is an independent prognosticator and superior in predicting OS (hazard ratios, HR 3.74, P = 0.01) and relapse incidence (HR 3.74, P = 0.005) as compared to the SWOG/ECOG criteria. Finally, subgroup analysis revealed that the prognostic capacity of the MK classification is highly significant in patients treated with standard myeloablative conditioning prior to alloSCT (P = 0.0011 for OS, P = 0.0007 for relapse). In contrast, the MK grouping failed to predict OS or relapse incidence in patients treated with reduced intensity conditioning. Taken together, these results indicate that the MK classification is superior in predicting the overall outcome of patients with AML undergoing alloSCT in CR. Furthermore, our data suggest that the genetic risk profile of MK? and CN patients is mostly overlapping in this setting.     

New and established treatment options for mycosis fungoides and Sézary syndrome – an update

At the time of diagnosis primary cutaneous lymphomas are limited to the skin. T‐cell lymphomas represent at least two thirds of all primary cutaneous lymphomas with mycosis fungoides and Sézary syndrome being the most frequent entities. A precise staging based on clinical, histological, immunohistological and molecular biological criteria is crucial for selecting the appropriate therapy. Since curative treatment is only possible in exceptional cases, the aim of any therapy is to achieve healing of the skin lesions, minimizing relapses, preventing progression and maintaining the quality of life. While in early disease stages skin‐directed therapy is being used, in later stages systemic treatments become more important. This work aims to provide an overview of established and new therapies for the treatment of mycosis fungoides and Sézary syndrome.     

Drug- and Herb-Induced Liver Injury in Clinical and Translational Hepatology: Causality Assessment Methods,Quo Vadis?

Drug-induced liver injury (DILI) and herb-induced liver injury (HILI) are typical diseases of clinical and translational hepatology. Their diagnosis is complex and requires an experienced clinician to translate basic science into clinical judgment and identify a valid causality algorithm. To prospectively assess causality starting on the day DILI or HILI is suspected, the best approach for physicians is to use the Council for International Organizations of Medical Sciences (CIOMS) scale in its original or preferably its updated version. The CIOMS scale is validated, liver-specific, structured, and quantitative, providing final causality grades based on scores of specific items for individual patients. These items include latency period, decline in liver values after treatment cessation, risk factors, co-medication, alternative diagnoses, hepatotoxicity track record of the suspected product, and unintentional re-exposure. Provided causality is established as probable or highly probable, data of the CIOMS scale with all individual items, a short clinical report, and complete raw data should be transmitted to the regulatory agencies, manufacturers, expert panels, and possibly to the scientific community for further refinement of the causality evaluation in a setting of retrospective expert opinion. Good-quality case data combined with thorough CIOMS-based assessment as a standardized approach should avert subsequent necessity for other complex causality assessment methods that may have inter-rater problems because of poor-quality data. In the future, the CIOMS scale will continue to be the preferred tool to assess causality of DILI and HILI cases and should be used consistently, both prospectively by physicians, and retrospectively for subsequent expert opinion if needed. For comparability and international harmonization, all parties assessing causality in DILI and HILI cases should attempt this standardized approach using the updated CIOMS scale.     

Laufbandbasierte Gangreferenzdaten für gesunde Probanden

Background

Clinical gait analysis is an established component in the evaluation of human physiological and pathological gait. Walking speed is one of the most important determinants of kinematic and kinetic parameters, and velocity-specific reference data are thus essential for interpretation of results. The aim of this study was to evaluate kinematic and kinetic gait treadmill data with respect to velocity, gender, height, and body mass.

Subjects and methods

On a dynamometric treadmill, 141 healthy volunteers underwent three trials (30?s per trial) at walking speeds of 2, 4, and 6?km/h. Kinematic and kinetic parameters were obtained using the zebris FDM-TF1.8 Treadmill (zebris Medical GmbH, Isny, Germany).

Results

In 80% (4/5) of the kinematic gait parameters, a significant influence (η² > 0.2) of walking velocity was demonstrated. This ranged from 89% (stance: η² = 0.243) to 98% (stride length: η² = 0.982). Gender effects were observed in two (40%) kinematic gait parameters (stride length: η² = 0.209; cadence: η² = 0.202).

Conclusion

Walking velocity has a large influence on the kinematics of gait on the treadmill. Therefore, clinical analysis of gait parameters should always be related to walking velocity. Use of a standardized velocity is highly recommended in a longitudinal investigation setting.

     

DreKiP – ein ambulantes Therapieprogramm für Kinder und Jugendliche mit Kopfschmerzen

Headaches are a frequent health problem among children and adolescents. The ocurrence of headaches and the resulting impairments in the quality of life and activities of daily living are modulated by biopsychosocial interactions, which necessitate a complex treatment program. The Dresden Childrens Headache Program (DreKiP) is a multidisciplinary therapy program consisting of eight modules for children and adolescents: education, stress relief, relaxation techniques, physical fitness, climbing therapy, art therapy and sensory training. In addition, there are six modules containing parallel workshops for parents. This outpatient program lasts 2–3 months and is performed parallel to the daily and school routine. Therapy groups consist of 6–8 patients in each age group. In total patients receive 15?h and the parents 7?h of therapy. Concomitant with the program, headache-associated data, such as headache frequency, medication use and school absence are documented. So far 32 children and adolescents in groups of 11, 14–15, 14–16, 17 and 17–18 years old completed the program. Of the 32 patients 19 presented with migraine and tension type headache, 6/32 with migraine and 7/32 with tension type headache only. The median number of headache days was 15 per month and 4 official school absence days per month. Preliminary results 6 months after the end of the therapy program showed reduced frequency of headaches in three quarters of our patients. The headache frequency was reduced from an initial median of 15 days per month to a median of 8 days per month after the program. The multidisciplinary program DreKiP improves the use of therapeutic means in children and adolescents with primary headaches. Children and adolescents with headache-related impairment in activities of daily life in school and leisure times constitute the target group of this therapy.     

Whole genome sequencing data used for surveillance of Campylobacter infections: detection of a large continuous outbreak,Denmark, 2019

Background Campylobacter is one of the most frequent causes of bacterial gastroenteritis. Campylobacter outbreaks are rarely reported, which could be a reflection of a surveillance without routine molecular typing. We have previously shown that numerous small outbreak-like clusters can be detected when whole genome sequencing (WGS) data of clinical Campylobacter isolates was applied.AimTyping-based surveillance of Campylobacter infections was initiated in 2019 to enable detection of large clusters of clinical isolates and to match them to concurrent retail chicken isolates in order to react on ongoing outbreaks.MethodsWe performed WGS continuously on isolates from cases (n = 701) and chicken meat (n = 164) throughout 2019. Core genome multilocus sequence typing was used to detect clusters of clinical isolates and match them to isolates from chicken meat.ResultsSeventy-two clusters were detected, 58 small clusters (2–4 cases) and 14 large clusters (5–91 cases). One third of the clinical isolates matched isolates from chicken meat. One large cluster persisted throughout the whole year and represented 12% of all studied Campylobacter cases. This cluster type was detected in several chicken samples and was traced back to one slaughterhouse, where interventions were implemented to control the outbreak.ConclusionOur WGS-based surveillance has contributed to an improved understanding of the dynamics of the occurrence of Campylobacter strains in chicken meat and the correlation to clusters of human cases.