Hyposensitisation to wasp venom in six hours

Eleven patients with a history of anaphylaxis, positive reactions to skin tests, and specific IgE antibody to wasp venom underwent hyposensitisation in a six hour procedure. No general reactions occurred. Complement activation and proteinuria could not be shown. The patterns of specific IgE, IgG1, and IgG4 were as described in other procedures--namely, IgE increased sharply and then decreased; IgG1 and IgG4 increased steadily and then decreased--but increase and decrease came earlier. Challenge by a stinging insect at least four weeks after treatment proved complete protection. The skin reactivity two years later showed an unpredictable pattern.     

Driving performance during word generation--testing the function of human brain lateralization using fTCD in an ecologically relevant context

It has been hypothesized that cerebral lateralization of function enhances cognitive performance. Evidence was found in birds and fish. However, recent research in humans did not support this hypothesis. We aimed to replicate and extend these findings for single- and dual-task performance in an ecologically relevant task. We combined a word generation task which is assumed to be primarily processed in the left hemisphere with a driving task which is assumed to be primarily processed in the right hemisphere. For each task the individual strength and direction of hemispheric lateralization was assessed by using functional transcranial Doppler sonography (fTCD). For each subject (36 right-handed, 35 nonright-handed) performance was measured in the two single-tasks and in the dual-task condition. On average, subjects showed a left hemisphere bias for the word generation task, a right hemisphere bias for the driving task and dual-task interference. Within subjects, lateralization of language and driving were statistically independent.In accordance with earlier studies, the results show no indication of a positive effect of strength of lateralization on performance in single-tasks or dual-task efficiency. We also found no advantage of a typical compared to an atypical or a contralateral compared to an ipsilateral lateralization pattern. In right-handers, but not in nonright-handers, we even found a negative relationship between strength of lateralization and dual-task efficiency for atypically lateralized subjects. This further supports the suggestion that lateralization does not enhance cognitive performance in humans.     

Adrenocortical carcinoma: A population-based study on incidence and survival in the Netherlands since 1993

BackgroundThe reported annual incidence of adrenocortical carcinoma (ACC) is 0.5–2.0 cases per million individuals. Updated population-based studies on incidence are lacking. The aim of this nationwide survey was to describe the incidence and survival rates of ACC in the Netherlands. Secondary objectives were to evaluate changes in both survival rates and the number of patients undergoing surgery.MethodsAll ACC patients registered in the Netherlands Cancer Registry (NCR) between 1993 and 2010 were included. Data on demographics, stage of disease, primary treatment modality and survival were evaluated.ResultsIncluded were 359 patients, 196 of whom were female (55%). Median age at diagnosis was 56 years (range 1–91). The 5-year age-standardised incidence rate decreased from 1.3 to 1.0 per one million person-years. Median survival for patients with stage I–II, stage III and stage IV disease was 159 months (95% confidence interval (CI) 93–225 months), 26 months (95% CI: 4–48 months) and 5 months (95% CI: 2–7 months), respectively (P < 0.001). Improvement in survival was not observed, as reflected by the lack of association between survival and time of diagnosis. The percentage of patients receiving treatment within 6 months after diagnosis increased significantly from 76% in 1993–1998 to 88% in 2005–2010 (P = 0.047), mainly due to an increase in surgery for stage III–IV patients.ConclusionThese nationwide data provide an up-to-date survey of the epidemiology of ACC in the Netherlands. A trend towards a decreasing overall incidence rate was observed. Survival rates did not change during this period despite an increased number of surgical procedures.     

Dusted Community: Piloting a Virtual Peer-to-Peer Support Community for People with an Asbestos-Related Diagnosis and Their Families

Individuals with an asbestos-related diagnosis and their carers face burdens including debilitating and life-limiting physical symptoms and medico-legal stressors. Feelings of social isolation are common. Increasing social connectedness can lead to increased feelings of personal empowerment and may inhibit chronic stress responses. The authors report on the development, via a process of participatory action research, of an online peer-to-peer support group, and the first 30-day test phase of this virtual community. Initial indications are that individuals with an asbestos-related diagnosis and their carers can benefit, in psychosocial terms, from membership of an on-line support group comprised of experientially similar others.     

Nephrotoxicity after PRRT with <Superscript>177</Superscript>Lu-DOTA-octreotate

Purpose

After peptide receptor radionuclide therapy (PRRT), renal toxicity may occur, particular in PRRT with ⁹⁰Y-labelled somatostatin analogues. Risk factors have been identified for increased probability of developing renal toxicity after PRRT, including hypertension, diabetes and age. We investigated the renal function over time, the incidence of nephrotoxicity and associated risk factors in patients treated with PRRT with [¹⁷⁷Lu-DOTA⁰,Tyr³]-Octreotate (¹⁷⁷Lu-Octreotate). Also, radiation dose to the kidneys was evaluated and compared with the accepted dose limits in external beam radiotherapy and PRRT with ⁹⁰Y-radiolabelled somatostatin analogues.

Methods

The annual decrease in creatinine clearance (CLR) was determined in 209 Dutch patients and the incidence of grade 3 or 4 renal toxicity (according to CTCAE v4.03) was evaluated in 323 patients. Risk factors were analysed using a nonlinear mixed effects regression model. Also, radiation doses to the kidneys were calculated and their association with high annual decrease in renal function were analysed.

Results

Of the 323 patients, 3 (1 %) developed (subacute) renal toxicity grade 2 (increase in serum creatinine >1.5?–?3.0 times baseline or upper limit of normal). No subacute grade 3 or 4 nephrotoxicity was observed. The estimated average baseline CLR (±?SD) was 108?±?5 ml/min and the estimated average annual decrease in CLR (±?SD) was 3.4?±?0.4 %. None of the risk factors (hypertension, diabetes, high cumulative injected activity, radiation dose to the kidneys and CTCAE grade) at baseline had a significant effect on renal function over time. The mean absorbed kidney dose in 228 patients was 20.1?±?4.9 Gy.

Conclusion

Nephrotoxicity in patients treated with ¹⁷⁷Lu-octreotate was low. No (sub)acute grade 3 or 4 renal toxicity occurred and none of the patients had an annual decrease in renal function of >20 %. No risk factors for renal toxicity could be identified. Our data support the idea that the radiation dose threshold, adopted from external beam radiotherapy and PRRT with ⁹⁰Y-labelled somatostatin analogues, does not seem valid for PRRT with ¹⁷⁷Lu-octreotate.

     

Correction of ankle valgus by hemiepiphysiodesis using the tension band principle in patients with multiple hereditary exostosis

Background

Ankle valgus is a common deformity in patients with multiple hereditary exostoses (MHE) and a potential risk factor for early degenerative arthritis. In children, medial hemiepiphysiodesis of the distal tibia is a relatively simple surgical technique used to correct this deformity. We present here the first results of applying this procedure using the eight-Plate guided growth system (eight-Plate) for growth guidance.

Methods

Between 2006 and 2011 we performed hemiepiphysiodesis of the distal medial tibia in 30 ankles of 18 children with MHE using the eight-Plate. Weight-bearing total leg radiographs were obtained preoperatively, during follow-up and at the time of implant removal or when the distal tibial physis had closed. The lateral distal tibia angle (LDTA) was measured and fibular shortening assessed using the Malhotra classification. To evaluate the effect of hemiepiphysiodesis, we correlated the LDTA with age.

Results

The mean age at time of surgery was 12.6 (range 9.5–15.0) years, and the mean preoperative LDTA was 76.9° (range 68.5°–83.5°). During follow-up, the implant was removed in 12 extremities and the physis had closed in 18 extremities. The mean LDTA at the time of implant removal or at closure of the physis was 83.6° (range 76.5°–90.0°). Mean correction of LDTA was 6.9° after a mean follow-up period of 22 (range 3–43) months. During follow-up, no changes in the Malhotra classification were found in any of the patients. Correction of the valgus deformity of the ankle was significantly correlated (r = ?0.506) (p = 0.004) with age in all patients.

Conclusion

Temporary medial hemiepiphyseodesis of the distal tibia seems to be an effective strategy for correcting ankle valgus in children with MHE. Timing of the intervention is, however, of importance. Hemiepiphyseodesis alone has no effect on the Malhotra classification.

Level of evidence

IV, retrospective review.

     

A multicentre evaluation of the guidelines for the use of cyclosporin A in severe psoriasis

Background Controversy still exists as lo whether a dosage scheme for the treatment of severe psoriasis with cyclosporin A (CsA) should start with low dosages (3 mg/kg/day) or rather with high dosages (5 mg/kg/day). Aims In this open prospective multi-centre trial guidelines for the use of CsA in psoriasis beginning with low dosages were evaluated. A secondary aim of the study was to elucidate factors predicting efficacy of CsA treatment. Methods Efficacy and tolerability of CsA were evaluated monthly during 16 weeks in 86 patients (56 males, 30 females, mean age 43,0 ± 14,9 years) suffering from chronic severe plaque-type psoriasis, not responding to topical therapy (mean PASI 18.0 ± 8.1). All patients started with 3 mg/kg/day. Patients were defined as responders with a PASI reduction > 25% at month 1, ≥ 25% at month 1, ≥ 60% at month 3 and ≥ 70% at month 4. When a patient was a failure, the dose was increased by 1 mg/kg/day lo a maximum of 5 mg/kg/day. Results A gradual mean PASI reduction of 38%. 59%, 72% to 76% was reached with a mean CsA dose of 3.0, 3.2, 3.5, and 3.6 mg/kg/day at weeks 4, 8, 12 and 16. respectively. At the end of the study period, 39 patients were still on 3, 24 patients were on 4 and 15 patients were on 5 mg/kg/day. Due to subjective side-effects 6 patients dropped out on 3 mg/kg/day and 2 on 4 mg/kg/day. Diastolic and systolic blood pressure and creatinine levels were stable. Overall, CsA was relatively well tolerated. Absence of previous therapies, low baseline PASI and failure at week 4 were predictive for higher drop-out and failure rate and lower PASI at the end of study. Conclusions This study shows that a significant proportion of severe psoriasis patients can be treated with 3 mg/kg/day CsA with good tolerability and excellent clinical results. It is concluded that a treatment scheme with an optimal risk-benefit ratio should start with low dosages of CsA (3 mg/kg/day).