Depression and anxiety following hematopoietic stem cell transplantation: a prospective population-based study in Germany.

In this prospective multicenter study, we investigated the course of depression and anxiety during hematopoietic stem cell transplantation (HSCT) until 5 years after transplantation adjusting for medical information. Patients were consulted before HSCT (n=239), at 3 months (n=150), 12 months (n=102) and 5 years (n=45) after HSCT. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS). Detailed medical and demographic information was collected. Prevalence rates were compared with an age- and gender-matched control group drawn from a large representative sample (n=4110). The risk of depression before HSCT was lower for patients than for the control group (risk ratio (RR), 0.56; 95% confidence interval (CI), 0.39/0.81). Prevalence rates of depression increased from 12 to 30% until 5 years post HSCT. Anxiety rates were most frequently increased before HSCT (29%, RR, 1.31; 95% CI, 1.02/1.68) and then reached a stable level comparable to the background population (RR 0.83, 95% CI, 0.56/1.22). This study confirms the low levels of depression in the short term after HSCT and identifies depression as a long-term effect. Furthermore, it confirms previous results of heightened anxiety before HSCT. Surveillance of symptoms of anxiety during the short-term phase of HSCT and of depression during the following years is crucial.

Risk of Thrombus Fragmentation during Endovascular Stroke Treatment.

BACKGROUND AND PURPOSE: Periprocedural thrombus fragmentation is a relevant risk in endovascular stroke treatment. Because factors influencing its occurrence are largely unknown, this study addresses a potential relationship between thrombus histology and clot stability. MATERIALS AND METHODS: Eighty-five patients with anterior circulation stroke treated with thrombectomy were included in this retrospective study. The number and location of emboli after retrieving the primary thrombus, the number of maneuvers, and TICI scores were evaluated. H&E and neutrophil elastase staining of retrieved clots was performed, and semiquantitative measurements of thrombus components were correlated with procedural parameters. RESULTS: An inverse correlation between maneuvers required for thrombus retrieval and the number of distal and intermediate emboli was observed (Spearman r, -0.23; P = .032). Younger patients were at higher risk for periprocedural thrombus fragmentation (Spearman r, -0.23; P = .032). Bridging thrombolysis tended to be associated with fewer maneuvers (2 vs 3, P = .054) but more emboli (1 vs 0, P = .067). While no consistent correlation between procedural parameters and red/white blood cells and fibrin-/platelet fractions could be found, higher amounts of neutrophil elastase-positive cells within the thrombus were independently associated with the occurrence of multiple emboli (adjusted OR, 4.6; 95% CI, 1.1-19.7; P = .041) and lower rates of complete recanalization (adjusted OR, 0.3; 95% CI, 0.1-0.9; P = .050). CONCLUSIONS: Younger age, easy-to-retrieve thrombi, and bridging thrombolysis may be risk factors for periprocedural thrombus fragmentation. Findings from standard histologic stains did not provide insight into thrombectomy-relevant thrombus stability. However, higher neutrophil levels in the thrombus tissue were related to an increased risk of periprocedural thrombus fragmentation. This observation aligns with the proposed thrombolytic capacity of neutrophil elastase and points to its potential clinical relevance in the context of stroke thrombectomy.

Investigating the temporal course, relevance and risk factors of fatigue over 5 years: a prospective study among patients receiving allogeneic HSCT.

Although allogeneic hematopoietic stem cell transplantation (HSCT) features severe physical and psychological strain, no previous study has prospectively investigated fatigue beyond 3 years after transplantation. We investigated the temporal course of fatigue over 5 years, compared patients with the general population (GP) and tested for treatment- and complication-related risk factors. Patients were assessed before conditioning (T0, N=239) and at 100-day (T1, N=150), 1-year (T2, N=102) and 5-year (T3, N=45) follow-up. We measured fatigue with the Multidimensional Fatigue Inventory-20. Patients were compared with the GP at T0 and at T3. Global fatigue increased from T0 to T1 (t=3.85, P<0.001), decreased from T1 to T2 (t=-2. 92, P=0.004) and then remained stable (t=0.45, P=0.656). No difference in global fatigue was found between T0 and T3 (t=0.68, P=0.497). Compared with the GP, patients showed higher global fatigue at T0 (t=-6.02, P<0.001) and T3 (t=-2.50, P=0.014). These differences reached meaningful effect sizes (d⩾0.5). Acute and chronic GvHD predicted global fatigue at T1 (γ=0.34, P=0.006) and T2 (γ=0.38, P=0.010), respectively. To conclude, fatigue among allogeneic HSCT patients improves with time, finally returning to pretransplantation levels. However, even after 5 years, the difference from the GP remains relevant. Patients with GvHD are at risk for increased fatigue.

Higher frequencies of HLA DQB1*05:01 and anti-glycosphingolipid antibodies in a cluster of severe Guillain-Barré syndrome.

Few regional and seasonal Guillain-Barré syndrome (GBS) clusters have been reported so far. It is unknown whether patients suffering from sporadic GBS differ from GBS clusters with respect to clinical and paraclinical parameters, HLA association and antibody response to glycosphingolipids and Campylobacter jejuni (Cj). We examined 40 consecutive patients with GBS from the greater Munich area in Germany with 14 of those admitted within a period of 3 months in fall 2010 defining a cluster of GBS. Sequencing-based HLA typing of the HLA genes DRB1, DQB1, and DPB1 was performed, and ELISA for anti-glycosphingolipid antibodies was carried out. Clinical and paraclinical findings (Cj seroreactivity, cerebrospinal fluid parameters, and electrophysiology) were obtained and analyzed. GBS cluster patients were characterized by a more severe clinical phenotype with more patients requiring mechanical ventilation and higher frequencies of autoantibodies against sulfatide, GalC and certain ganglioside epitopes (54 %) as compared to sporadic GBS cases (13 %, p = 0.017). Cj seropositivity tended to be higher within GBS cluster patients (69 %) as compared to sporadic cases (46 %, p = 0.155). We noted higher frequencies of HLA class II allele DQB1*05:01 in the cluster cohort (23 %) as compared to sporadic GBS patients (3 %, p = 0.019). Cluster of severe GBS was defined by higher frequencies of autoantibodies against glycosphingolipids. HLA class II allele DQB1*05:01 might contribute to clinical worsening in the cluster patients.

The Impact of Histological Clot Composition in Embolic Stroke.

PURPOSE: Thrombus composition has been suggested to have a decisive impact on the outcome of patients treated by mechanical thrombectomy because of embolic stroke. The recent development of stent retrievers allows collection and, hence, histopathological analysis of fresh thrombus material. Against this background, the aim of this prospective study was to assess the impact of thrombus composition on mechanical recanalization, clinical outcome and stroke etiology. METHODS: Thirty-four patients suffering from acute ischemic stroke due to occlusion of the distal internal carotid artery/carotid-T, anterior cerebral artery, or middle cerebral arteries were mechanically recanalized, and thrombus material was obtained. Histological thrombus composition was compared with imaging, clinical, and neurointerventional data. RESULTS: The main findings were that a higher percentage of white blood cells (WBCs) in the thrombus was associated with (i) cardioembolic etiology, (ii) extended mechanical recanalization time, and (iii) less favorable recanalization (Thrombolysis in Cerebral Infarction score) and clinical outcome (National Institute of Health Stroke Scale). CONCLUSION: Our results suggest that thrombi with a high WBC fraction are related to more organized thrombi of cardioembolic origin associated with less favorable recanalization and clinical outcome in acute ischemic anterior circulation stroke. WBC-mediated immunological and coagulatory processes may play a key role in thrombus formation and pathogenesis of stroke warranting further investigation.

Fear of recurrence and its impact on quality of life in patients with hematological cancers in the course of allogeneic hematopoietic SCT.

We examined the course and the prevalence of a high fear of cancer recurrence (FCR) in patients undergoing allogeneic PBSC transplantation (hematopoietic SCT (HSCT)) before HSCT (N=239), 100 days after (n=150, and 12 months after allogeneic HSCT (n=102). The Fear of Progression Questionnaire-Short Form (FoP-Q-SF), the EORTC Quality of Life Questionnaire, and the Hospital Anxiety and Depression Scale were used. Pre-HSCT 36% of patients, 100 days after HSCT 24% of patients, and 1 year after HSCT 23% of patients fulfilled the criteria for high FCR (FoP-Q-SF cutoff=34). Being married (b=2.76, P=0.026), female gender (b=4.45, P<0.001) and depression (b=4.44, P<0.001) were significantly associated with FCR at baseline. One hundred days after HSCT, depression significantly predicted FCR (b=6.46, P<0.001). One year following HSCT, female gender (b=6.61, P=0.008) and higher depression were (b=4.88, P=0.004) significant predictors for FCR. Over the three assessment points, patients with high FCR had a significantly lower quality of life compared to patients with low FCR in physical functioning (P=0.019), role functioning (P=0.003), emotional functioning (P<0.001), cognitive functioning (P=0.003), social functioning (P<0.001) and global quality of life (P<0.001). Our data provide evidence that FCR is a prevalent problem in patients with hematological malignancies and has a significant adverse impact on health-related quality of life.

[Radiologically isolated syndrome: multiple sclerosis based solely on MRI findings?]. / Radiologisch-isoliertes Syndrom: Wenn nur das MRT "Multiple Sklerose" sagt.

Incidental brain magnetic resonance imaging (MRI) findings are the result of an increasing usage of MRI in the diagnostic work-up of patients. An adequate assessment of patients in which brain lesions typical for multiple sclerosis (MS) are determined but who have been asymptomatic so far is problematic, especially when Barkhof-Tintoré criteria for spatial dissemination are fulfilled and no other differential diagnosis can be confirmed. This entity, the so-called radiologically isolated syndrome, constitutes a major diagnostic and therapeutic challenge. Two recent studies revealed that a subgroup of patients with radiologically isolated syndrome are at high risk for near-term development of MR-based progression and occurrence of the first clinical event. Hence, the radiologically isolated syndrome has to be classified as a possible preliminary phase of the clinical manifestation of MS in a subgroup of patients and entails in-depth therapeutic considerations. This article covers the current literature for this syndrome and, in the absence of official guidelines, provides a pragmatic diagnostic and therapeutic approach for patient management.

Differential protein abundance and function of UT-B urea transporters in human colon.

Facilitative UT-B urea transporters enable the passage of urea across cell membranes. Gastrointestinal urea transporters are thought to play a significant role in the urea nitrogen salvaging process that occurs between mammalian hosts and their gut bacteria. This study investigated the expression of UT-B urea transporters in different segments of human colon. Immunoblot analysis showed that human colon expressed a 35-kDa glycosylated UT-B protein in the colonic mucosa. The 35-kDa UT-B transporter was predominantly located in plasma membrane-enriched samples (P < 0.001; n = 6), and its expression was greater in the ascending colon compared with the descending colon (P < 0.01; n = 3). At the cellular level, UT-B transporters were located throughout colonocytes situated in the upper portion of the colonic crypts. Bidirectional trans-epithelial urea transport was significantly greater in the ascending colon than the descending colon (P < 0.05; n = 6). In addition, the facilitative urea transporter inhibitor 1,3,dimethylurea significantly reduced urea transport in the ascending colon (P < 0.05; n = 6) but had no effect in the descending colon (NS; n = 6). These results illustrate differential protein abundance of functional UT-B protein in different sections of the human colon, strongly correlating to regions that contain the largest populations of intestinal bacteria. This study suggests an important role for UT-B urea transporters in maintaining the symbiotic relationship between humans and their gut bacteria.

Cognitive function in the acute course of allogeneic hematopoietic stem cell transplantation for hematological malignancies.

The aim of the study was to assess cognitive performance in patients with hematological malignancies before, and 3 months after, allogeneic hematopoietic stem cell transplant (HSCT). A consecutive sample of 39 patients was assessed before admission with a comprehensive neuropsychological test battery and health-related quality-of-life (HRQoL) questionnaires; 19 of these patients were retested around 100 days post HSCT. Test results were compared with normative data and revealed minimal differences at both time points in the level of group-means. One parameter - simple reaction time - was significantly worse (prolonged) at second measurement after HSCT. According to the definition of an impairment score (more than three impaired functions), 26% of patients were classified as impaired before as well as after HSCT. Neuropsychological test results did not vary systematically according to medical variables such as extent of pretreatment, graft-versus-host-disease (GvHD) and kind of conditioning protocol. As a dimension of HRQoL, self-rated cognitive function was in the normal range before and after HSCT. Significant correlations between HRQoL and neuropsychological parameters were related to symptom scales. This study showed impairments of neuropsychological performance for a subgroup of patients before and after allogeneic HSCT. Systematic effects of conditioning, medical variables or self-rated HRQoL could not be observed.

Neuropsychological function in high-risk breast cancer survivors after stem-cell supported high-dose therapy versus standard-dose chemotherapy: evaluation of long-term treatment effects.

BACKGROUND: Studies on cognitive functioning in breast cancer patients point out that a subset of women exhibit chemotherapy-related neuropsychological impairment. Thereby, high-dose therapy may elevate the risk of cognitive dysfunctions. The primary purpose of the study was to evaluate the impact of high-dose versus standard-dose chemotherapy on the late neuropsychological outcome in randomized assigned high-risk breast cancer survivors. Next to focusing prevalence, function specificity and extent of cognitive impairment, the question as to whether doses-dependent group differences occur was investigated. PATIENTS AND METHODS: Twenty-four high-dose and 23 standard-dose patients 5 years, on average, after treatment underwent a comprehensive neuropsychological assessment. In addition, 29 early-stage breast cancer patients matched for age, education and time since treatment were recruited as a comparison group. RESULTS: Global cognitive impairment was observed in 8% of high-dose versus 13% of standard-dose compared with 3% of early-stage breast cancer patients. Compared with normative data, all patient groups performed worse on one attention subtest measuring the simple reaction time (P < 0.001 in each case). By contrast, no significant between-group differences on the late neuropsychological outcome were found. CONCLUSIONS: Five years after treatment, standard-dose patients were slightly, but not significantly, more impaired in cognitive performance than high-dose patients.

[Diabetes mellitus in children under 2 years of age]. / Diabetes mellitus hos barn under to år.

We studied the clinical course in 18 children who were admitted to our department during the time period 1973-87 for onset of diabetes mellitus before two years of age. During these years a total number of 242 diabetics (0-14 years) were admitted from a population of approximately 100,000 children. The 18 cases showed a sex ratio (female/male) of 12/6. In nine cases the duration of symptoms before admittance to hospital was one week or less. The onset of the disease showed no particular seasonal pattern. 13 patients presented with a blood glucose of 25 mmol/l or more. Severe ketoacidosis was observed in nine patients. None of the patients exhibited any well-defined remission period. In the course of the disease, 11 patients had frequent hypoglycemic episodes, nine patients had convulsive attacks, poor metabolic control was evident in five cases, and major psychological problems were frequently encountered. In conclusion, diabetes mellitus in small children can be extremely difficult to manage, both from a medical and a psychosocial point of view. All efforts should be made to support the families of children with this disease.

[Child abuse and neglect: medical aspects]. / Barnemishandling og omsorgssvikt: medisinske aspekter.

Child abuse and neglect is a global problem that effects children of all ages and social classes. The article discusses some of the medical aspects of child abuse. As the presence of "proof" in the form of an obvious physical injury is often lacking, it is of the utmost importance that professional people are sensitive to the signs and symptoms (signals) to which abuse and neglect may be one of many possible diagnoses. Teamwork between the relevant professional groups is essential to solve the problem.

Complex chromosomal rearrangement leading to partial trisomy 22.

We have examined a boy with a peculiar facial appearance and mental retardation. Cytogenetic studies showed 47,XY, monosomy 22, two marker chromosomes, M1 and M2. The karotype is interpreted as functionally partial trisomy 22. Chromosome analyses of both parents and three sibs were normal.

Trisomy 12p syndrome. Evaluation of a family with a t(12;21) (p12.1;p11) translocation with unbalanced offspring.

Two brothers (Nos. 1 and 3), with physical and mental retardation and many other clinical characteristics in common, were both trisomic for 12p(ter leads to 12.1) and monosomic for 21p. Their mother (No. 5), the maternal grandmother (No. 7), aunt (No. 8), and a first-cousin (No. 9) were balanced translocation carriers, 46 rep (12;21) (p12.1;p11). Another cousin (No. 10) had Down syndrome: he had two normal 21 chromosomes in addition to both translocation chromosomes. A sister (No. 2), who died at the age of 1 year without being karyotyped, had several phenotypical features in common with her brothers. Our two cases of trisomy 12p (ter leads to 12.1) were compared with eight cases of trisomy 12p described earlier, and the following common characteristics were found: severe mental and physical retardation; flat and round, broad face with prominent cheeks; flat and broad nasal bridge with short nose; anteverted nostrils and large philtrum; broad and prominent lower lip; low-set or slanting ears, poorly formed with folded helix, prominent antihelix and deep concha; short neck; short sternum; "spade"-shaped fingers, the fifth being short; bilateral genu valgum; bilateral pes planus and talus valgus; increased space between the first and second toes; generalized hypotonia; and certain dermatoglyphic characteristics. An elevated serum lactate dehydrogenase (LDH) was measured in four cases.