Differential Effects of Obesity,Hyperlipidaemia, Dietary Intake and Physical Inactivity on Type I versus Type IV Allergies

Background: Alongside metabolic diseases (esp. obesity), allergic disorders are becoming increasingly prevalent. Since both obesity and allergies are highly impacted by environmental determinants, with this study we assessed the potential link between metabolic implications and two distinct types of allergies. Methods: Using cross-sectional data from the German FoCus cohort, n = 385 allergy cases, either hay fever (=type I allergy, n = 183) or contact allergy (=type IV allergy, n = 202) were compared to age- and sex-matched healthy control subjects (1:1 ratio, in total n = 770) regarding their metabolic phenotype, diet, physical activity, sleep, gut microbial composition, and serum metabolite profile using suitable BMI-adjusted models. Results: Obesity and metabolic alterations were found significantly more prevalent in subjects with allergies. In fact, this relation was more pronounced in contact allergy than hay fever. Subsequent BMI-adjusted analysis reveals particular importance of co-occurring hyperlipidaemia for both allergy types. For contact allergy, we revealed a strong association to the dietary intake of poly-unsaturated fatty acids, particularly α-linolenic acid, as well as the enrichment of the corresponding metabolic pathway. For hay fever, there were no major associations to the diet but to a lower physical activity level, shorter duration of sleep, and an altered gut microbial composition. Finally, genetic predisposition for hyperlipidaemia was associated to both contact allergy and hay fever. Conclusions: Reflected by higher allergy prevalence, our findings indicate an impaired immune response in obesity and hyperlipidaemia, which is differentially regulated in type I and type IV allergies by an unfavourable lifestyle constellation and subsequent microbial and metabolic dysfunctions.     

Predictors of complicated grief among dementia caregivers: a prospective study of bereavement.

OBJECTIVE: Most family caregivers adapt well to the death of their care recipient relative; however, a sizable minority continues to experience postdeath psychiatric morbidity. The purpose of this study was to better understand why some caregivers manifest clinical levels of complicated grief postdeath. This is the first study to prospectively assess predictors of complicated grief among family caregivers of patients with dementia who experience the death of their care recipient. METHOD: The sample of bereaved caregivers is drawn from a larger study of 1,222 family caregivers providing in-home care to their relative with dementia. In-home assessments of caregivers and patients were carried out at baseline and six-month intervals for a total of 18 months. This article is based on the 217 caregivers who experienced the death of their care recipient in the course of the study. Three logistic regression models are tested to identify pre- and postbereavement predictors of complicated grief, including sociodemographic factors, characteristics of the caregiving experience, including participation in a caregiver intervention, other psychiatric morbidities, and medication use. RESULTS: Twenty percent of dementia caregivers evidenced complicated grief along with high levels of depressive symptomatology postdeath. Controlling for sociodemographic factors, caregivers who had high levels of preloss depressive symptoms and burden, reported positive features of the caregiving experience, and were caring for a more cognitively impaired patient were more likely to report clinical levels of complicated grief postloss. In addition, caregivers who were enrolled in a psychosocial caregiver intervention designed to reduce depression and burden reported lower levels of complicated grief. CONCLUSION: This study identifies predictors of complicated grief for which interventions could be developed to not only ease caregiver distress, but also serve as preventive interventions for bereavement. Reducing the burden of active caregiving, treating depression before the death of the loved one and providing supportive psychosocial and skills training caregiver interventions can prevent the emergence of postdeath psychiatric morbidity.     

Quantitative analysis of EBV-specific CD4/CD8 T cell numbers, absolute CD4/CD8 T cell numbers and EBV load in solid organ transplant recipients with PLTD

Post transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients is assumed to be the result of impaired Epstein-Barr Virus (EBV)-specific cellular immunity. We analyzed the absolute CD4 and CD8 T cell counts as well as the EBV-specific CD4 and CD8 T cell responses in relation to EBV load in SOT recipients with PTLD. A prospective, single center study was initiated and 10 immunosuppressed patients with diagnosis of PTLD were analyzed and compared to 3 patients without PTLD (2 SOT recipients with EBV-reactivation, 1 patient with Infectious Mononucleosis) and 6 healthy EBV positive controls. EBV-specific CD8 T cells were enumerated using HLA class I tetramers and the IFN-gamma cytokine secretion assay. EBNA1-specific CD4 T cells were analyzed after protein stimulation and EBV load was quantified by real-time PCR. Absolute CD8 T cell counts were highly variable in all 19 cases analyzed. In contrast, the absolute EBV-specific CD8 T cell count was found to be low in 7/9 patients with PTLD (<5/microl whole blood). These frequencies were similar to absolute EBV-specific CD8 T cell numbers observed in healthy EBV positive donors, but much lower compared to patients with EBV reactivation but no PTLD. Absolute CD4 T cell counts were significantly lower in PTLD patients (mean: 336/microl+/-161 vs. controls 1008/microl+/-424, p=0.0001), with EBNA1-specific CD4 T cell responses being also low, but highly variable. Moreover, low absolute CD4 T cell counts (<230/microl) were associated with an elevated EBV load (>1000 copies/microg DNA). We conclude that SOT recipients with PTLD have an inadequate functional EBV-specific T cell response. Our data suggest that the frequency and function of circulating EBV-specific CD8 T cells are dependent on absolute CD4 T cell counts. Further studies are needed to verify if a low absolute CD4 T cell count presents a risk factor for the development of PTLD in SOT recipients.     

Early Surgery in Prone Position for Associated Injuries in Patients Undergoing Non-operative Management for Splenic and Liver Injuries

Background

In patients undergoing non-operative management (NOM) of blunt splenic and/or liver injuries, no data exist on the safety of same-admission surgery in prone position for concomitant injuries.

Methods

Retrospective study including adult trauma patients with blunt splenic/liver injuries and attempted NOM from 01/2009 to 06/2015 was conducted. Patient and injury characteristics as well as outcomes [failed (f)NOM, mortality] of patients with/without surgery in prone position were compared (‘prone’ vs. ‘non-prone’ group).

Results

A total of 244 patients with blunt splenic/liver injury and attempted NOM were included. Forty patients (16.4%) underwent surgery in prone position on median post-injury day 2.0 [interquartile range (IQR) 3.0]. Surgery in prone position was mostly performed for associated spinal or pelvic injuries. The ISS was significantly higher, and the proportion of patients with high-grade injuries (OIS?≥?3) was significantly less frequent in the ‘prone? group (30.0?±?14.5 vs. 23.9?±?13.2, p?=?0.009 and 27.5 vs. 53.9%, p?=?0.002). In-hospital mortality as well as NOM failure rates were not significantly different between the ‘prone’ and ‘non-prone? group (2.5 vs. 2.9%, p?=?1.000; 0.0 vs. 4.4%, p?=?0.362). Eleven patients with high-grade injuries were operated in prone position at median day 3 (IQR 3.0). None of these patients failed NOM. However, one patient with a grade IV splenic injury required immediate splenectomy after being operated in right-sided position on the day of admission.

Conclusion

In this single-center analysis, surgery in prone position was performed in a substantial number of patients with splenic/liver injuries without increasing the fNOM rate. However, caution should be used in patients with grade IV/V splenic injuries.

     

Genetic fitness and selection intensity in a population affected with high-incidence spinocerebellar ataxia type 1

Spinocerebellar ataxia type 1 (SCA1) is the major and likely the only type of autosomal dominant cerebellar ataxia in the Sakha (Yakut) people of Eastern Siberia. The prevalence rate of SCA1 has doubled over the past 21 years peaking at 46 cases per 100,000 rural population. The age at death correlates closely with the number of CAG triplet repeats in the mutant ATXN1 gene (r = ?0.81); most patients with low-medium (39–55) repeat numbers survived until the end of reproductive age. The number of CAG repeats expands in meiosis, particularly in paternal transmissions; the average total increase in intergenerational transmissions in our cohort was estimated at 1.6 CAG repeats. The fertility rates of heterozygous carriers of 39–55 CAG repeats in women were no different from those of the general Sakha population. Overall, the survival of mutation carriers through reproductive age, unaltered fertility rates, low childhood mortality in SCA1-affected families, and intergenerational transmission of increasing numbers of CAG repeats in the ATXN1 gene indicate that SCA1 in the Sakha population will be maintained at high prevalence levels. The low (0.19) Crow’s index of total selection intensity in our SCA1 cohort implies that this mutation is unlikely to be eliminated through natural selection alone.     

Surgical treatment of symptomatic cerebral cavernous malformations in eloquent brain regions

Background

Despite the increased risk of hemorrhage and deteriorating neurological function of once-bled cerebral cavernous malformations (CM), the management of eloquently located CMs remains controversial.

Methods

All eloquently located CMs (n?=?45) surgically treated between 03/2006 and 04/2011 in our department were consecutively evaluated. Eloquence was characterized according to Spetzler and Martin's definition. The following locations were approached: brainstem, n?=?16; sensorimotor, n?=?8; visual pathway, n?=?7; cerebellum (deep nuclei and peduncles), n?=?7; basal ganglia, n?=?4, and language, n?=?3. Follow-up data was available for 41 patients (91 %) with a median interval of 14 months. Outcomes were evaluated according to the Glasgow outcome and the modified Rankin scale.

Results

Immediately after surgery, 47 % (n?=?21) had a new deficit. At follow-up, 80 % (n?=?36) recovered to at least preoperative status or were better than before surgery, 9 % (n?=?4) exhibited a slight, and 7 % (n?=?3) had a moderate neurological impairment. Only two cases (4 %) with a new permanent severe deficit were observed, both related to dorsal brainstem surgery. The outcome after the surgery of otherwise located brainstem CMs was as beneficial as that for non-brainstem CMs. Patients with initially poor neurological performance fared worse than oligosymptomatic patients.

Conclusions

Despite the high postoperative transient morbidity, the majority improved profoundly during follow-ups. Compared with natural history, surgical treatment should be considered for all eloquent symptomatic CMs. Dorsal brainstem location and poor preoperative neurological status are associated with an increased postoperative morbidity.

     

[<Superscript>11</Superscript>C]choline PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy

Objective  

To evaluate [¹¹C]choline positron emission tomography/computed tomography ([¹¹C]choline PET/CT) for the detection of a biochemical recurrence of prostate cancer after radical prostatectomy.     

Molecular imaging reveals time course of matrix metalloproteinase activity in acute cutaneous vasculitis in vivo

Matrix metalloproteinases (MMPs) play a critical role in various pathological conditions including cutaneous inflammation. Thus far, serial assessment of MMP activity in ongoing inflammation is hampered due to technical limitations. Here, we present an innovative method for longitudinal detection of MMP activity by in vivo imaging. First, we analysed skin sections from patients suffering from leucocytoclastic vasculitis (LcV) and detected a significant MMP signal via immunofluorescence staining. Then, we mimicked LcV in mice in a well‐studied model of immune complex‐mediated vasculitis (ICV). This acute inflammatory process was serially visualized in vivo using the fluorescence‐labelled MMP tracer Cy5.5‐AF443. The deposition of fluorescence‐labelled immune complexes and MMP tracer distribution was visualized repeatedly and non‐invasively by fluorescence reflectance imaging. In correlation with the presence of MMP‐2 and MMP‐9 in immunofluorescence stainings, Cy5.5‐AF443 accumulated in ICV spots in the skin of C57BL/6 mice. This tracer accumulation could also be observed in mice equipped with a dorsal skinfold chamber, where microscopic observations revealed an increased recruitment of fluorescence‐labelled leucocytes during ICV. The specificity of the MMP tracer was supported by (i) analysis of mice deficient in functional β₂‐integrins (CD18^?/?) and (ii) subsequent MMP immunofluorescence staining. These findings let us conclude that MMP accumulation in the acute phase of ICV depends on β₂‐mediated leucocyte recruitment. In summary, we show that MMPs are involved in ICV as determined by Cy5.5‐AF443, a new optical marker to longitudinally and non‐invasively follow MMP activity in acute skin inflammation in vivo.