Management of Ruptured Brain Arteriovenous Malformations

Intracranial arteriovenous malformations (AVMs) are a common cause of stroke in younger patients, and often present as intracerebral hemorrhages (ICH), associated with 10 % to 30 % mortality. Patients who present with a hemorrhage from an AVM should be initially stabilized according to acute management guidelines for ICH. The characteristics of a lesion including its size, location in eloquent tissue, and high-risk features will influence risk of rupture, prognosis, as well as help guide management decisions. Given that rupture is associated with an increased risk of 6 % re-rupture in the year following the initial hemorrhage, versus 1 % to 3 % predicted annual risk in non-ruptured lesions only, definitive treatment is encouraged after ICH stabilization. A rest period of 2 to 6 weeks after hemorrhage is recommended before definitive treatment to avoid disrupting friable parenchyma and the hematoma. Treatment may consist of endovascular embolization, surgical resection, radiosurgery, or a combination of these three interventions based on the lesion.     

Left ventricular assist device as bridge to recovery for anthracycline-induced terminal heart failure

?2012 Wiley Periodicals, Inc. Anthracycline treatments are hampered by dose-related cardiotoxicity, frequently leading to heart failure (HF) with a very poor prognosis. The authors report a case of a 19-year-old man developing HF after anthracycline treatment for Ewing sarcoma. Despite medical treatment, his condition deteriorated to terminal HF, leading to implantation of a mechanical left ventricular assist device (LVAD). His heart function recovered, allowing explantation of the device 14?months after implantation. Heart transplantation is often contraindicated in the first years after treatment for cancers, and LVAD as "bridge to recovery" may be warranted in similar patients.     

On a heavy path – determining cold plasma-derived short-lived species chemistry using isotopic labelling

Cold atmospheric plasmas (CAPs) are promising medical tools and are currently applied in dermatology and epithelial cancers. While understanding of the biomedical effects is already substantial, knowledge on the contribution of individual ROS and RNS and the mode of activation of biochemical pathways is insufficient. Especially the formation and transport of short-lived reactive species in liquids remain elusive, a situation shared with other approaches involving redox processes such as photodynamic therapy. Here, the contribution of plasma-generated reactive oxygen species (ROS) in plasma liquid chemistry was determined by labeling these via admixing heavy oxygen ¹⁸O₂ to the feed gas or by using heavy water H₂¹⁸O as a solvent for the bait molecule. The inclusion of heavy or light oxygen atoms by the labeled ROS into the different cysteine products was determined by mass spectrometry. While products like cysteine sulfonic acid incorporated nearly exclusively gas phase-derived oxygen species (atomic oxygen and/or singlet oxygen), a significant contribution of liquid phase-derived species (OH radicals) was observed for cysteine-S-sulfonate. The role, origin, and reaction mechanisms of short-lived species, namely hydroxyl radicals, singlet oxygen, and atomic oxygen, are discussed. Interactions of these species both with the target cysteine molecule as well as the interphase and the liquid bulk are taken into consideration to shed light onto several reaction pathways resulting in observed isotopic oxygen incorporation. These studies give valuable insight into underlying plasma–liquid interaction processes and are a first step to understand these interaction processes between the gas and liquid phase on a molecular level.

Cold atmospheric plasmas (CAPs) are promising medical tools producing short-lived reactive species.     

Endoscopic Duodenal–Jejunal Bypass Liner Rapidly Improves Type 2 Diabetes

Background

Bariatric procedures excluding the proximal small intestine improve glycemic control in type 2 diabetes within days. To gain insight into the mediators involved, we investigated factors regulating glucose homeostasis in patients with type 2 diabetes treated with the novel endoscopic duodenal–jejunal bypass liner (DJBL).

Methods

Seventeen obese patients (BMI 30–50 kg/m²) with type 2 diabetes received the DJBL for 24 weeks. Body weight and type 2 diabetes parameters, including HbA_1c and plasma levels of glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon, were analyzed after a standard meal before, during, and 1 week after DJBL treatment.

Results

At 24 weeks after implantation, patients had lost 12.7?±?1.3 kg (p?<?0.01), while HbA_1c had improved from 8.4?±?0.2 to 7.0?±?0.2 % (p?<?0.01). Both fasting glucose levels and the postprandial glucose response were decreased at 1 week after implantation and remained decreased at 24 weeks (baseline vs. week 1 vs. week 24: 11.6?±?0.5 vs. 9.0?±?0.5 vs. 8.6?±?0.5 mmol/L and 1,999?±?85 vs. 1,536?±?51 vs. 1,538?±?72 mmol/L/min, both p?<?0.01). In parallel, the glucagon response decreased (23,762?±?4,732 vs. 15,989?±?3,193 vs. 13,1207?±?1,946 pg/mL/min, p?<?0.05) and the GLP-1 response increased (4,440?±?249 vs. 6,407?±?480 vs. 6,008?±?429 pmol/L/min, p?<?0.01). The GIP response was decreased at week 24 (baseline—115,272?±?10,971 vs. week 24—88,499?±?10,971 pg/mL/min, p?<?0.05). Insulin levels did not change significantly. Glycemic control was still improved 1 week after explantation.

Conclusions

The data indicate DJBL to be a promising treatment for obesity and type 2 diabetes, causing rapid improvement of glycemic control paralleled by changes in gut hormones.     

Management of Anemia in Children Receiving Chronic Peritoneal Dialysis

Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (<10 g/dl or <9.5 g/dl in children older or younger than 2 years, respectively), with significant regional variation; levels were highest in North America and Europe and lowest in Asia and Turkey. Low hemoglobin levels were associated with low urine output, low serum albumin, high parathyroid hormone, high ferritin, and the use of bioincompatible PD fluid. Erythropoiesis-stimulating agents (ESAs) were prescribed to 92% of patients, and neither the type of ESA nor the dosing interval appeared to affect efficacy. The weekly ESA dose inversely correlated with age when scaled to weight but did not correlate with age when normalized to body surface area. ESA sensitivity was positively associated with residual diuresis and serum albumin and inversely associated with serum parathyroid hormone and ferritin. The prevalence of hypertension and left ventricular hypertrophy increased with the degree of anemia. Patient survival was positively associated with achieved hemoglobin and serum albumin and was inversely associated with ESA dose. In conclusion, control of anemia in children receiving long-term PD varies by region. ESA requirements are independent of age when dose is scaled to body surface area, and ESA resistance is associated with inflammation, fluid retention, and hyperparathyroidism. Anemia and high ESA dose requirements independently predict mortality.Almost three decades after the advent of recombinant erythropoietin, the management of renal anemia has become a recent focus of attention and changing paradigms. Whereas correction of hemoglobin (Hb) levels to near-normal has previously been recommended on the basis of association studies linking more severe anemia to morbidity and mortality with dialysis,^1–3 interventional clinical trials consistently demonstrate that near-normalization of Hb increases the risk of vascular events and mortality in adults receiving maintenance hemodialysis and in those with CKD who are not undergoing dialysis.^4–6 This has prompted ongoing reevaluation and revisions of treatment targets in patients exposed to erythropoiesis-stimulating agents (ESAs).⁷The appropriateness of applying treatment recommendations established in adult hemodialysis populations at high cardiovascular risk and adults with CKD to children undergoing dialysis is questionable because cardiovascular events are far less common in children with CKD. Furthermore, two thirds of children requiring dialysis initially opt for peritoneal dialysis (PD), and there are no systematic studies in the adult PD population to inform the optimal Hb target range in these patients. The risk profile of patients receiving PD may differ from that of the hemodialysis setting because of the absence of dialysis-induced intermittent hemoconcentration and lack of contact activation of the complement and coagulation systems.Further aspects to consider in pediatric anemia management are the greater physical activity of children and the need for optimal cognitive functioning at school.^8,9 The significant physiologic variation of the normal Hb range with age¹⁰ and the relative ESA sensitivity that reportedly increases with age during early childhood are also noteworthy.¹¹The registry of the International Pediatric Peritoneal Dialysis Network (IPPN) prospectively collects detailed clinical, biochemical, dialysis, and medication-related information (including ESA types and doses and modalities of iron supplementation) from a substantial number of children undergoing long-term PD around the world. In-depth analysis of this unique database has allowed us to (1) gain insight into the demographic characteristics of renal anemia and its treatment in the pediatric PD population worldwide, (2) explore the relationship between ESA dose requirements and body dimensions, (3) identify factors contributing to ESA resistance in children, and (4) associate anemia control with patient outcomes.     

Longitudinal growth on an everolimus‐ versus an MMF‐based steroid‐free immunosuppressive regimen in paediatric renal transplant recipients

Concerns have been raised that mammalian target of rapamycin inhibitors in pediatric transplant recipients might interfere with longitudinal bone growth by inhibition of growth factor signaling and growth plate chondrocyte proliferation. We therefore undertook a prospective nested, case‐control study on longitudinal growth over 2 years in steroid‐free pediatric renal transplant recipients. Fourteen patients on a steroid‐free maintenance immunosuppressive regimen consisting of low‐dose everolimus (EVR) in conjunction with low‐dose cyclosporine (CsA) were compared to a matched cohort of 14 steroid‐free patients on a standard dose mycophenolate mofetil (MMF) regimen in conjunction with a standard dose calcineurin inhibitor (CNI). The mean change in height standard deviation (SD) score in the first study year was 0.31 ± 0.71 SD score in the EVR group compared to 0.31 ± 0.64 SD score in the MMF group (P = 0.20). For the entire study period of 2 years, the change in height SD score in the EVR group was 0.43 ± 0.81 SDS compared to 0.75 ± 0.85 SDS in the MMF group (P = 0.32). The percentage of prepubertal patients experiencing catch‐up growth, defined as an increase in height SD score ≥0.5 in 2 years, was similar in the EVR group (5/8, 65%) and the MMF group (6/8, 75%; P = 1.00). Longitudinal growth over 2 years in steroid‐free pediatric patients on low‐dose EVR and CsA is not different to that of a matched steroid‐free control group on an immunosuppressive regimen with standard‐dose CNI and MMF. Hence, low‐dose EVR does not appear to negatively impact short‐term growth in pediatric renal transplant recipients.     

Influence of Sport Participation on Community Integration and Quality of Life: A Comparison Between Sport Participants and Non-Sport Participants With Spinal Cord Injury

Background/Objective: To determine whether community integration and/or quality of life (QoL) among people living with chronic spinal cord injury (SCI) are superior among sport participants vs non-sport participants.

Study Design: Cross-sectional study.

Participants/Methods: Persons (n = 90) living in the community with SCI (ASIA Impairment Scale A-D), level C5 or below, > 15 years of age, ≥ 12 months postinjury, and requiring a wheelchair for > 1 hours/day were divided into 2 groups based on their self-reported sport participation at interview: sport participants (n = 45) and non-sport participants (n = 45).

Results: Independent-sample t tests revealed that both Community Integration Questionnaire (CIQ) and Reintegration to Normal Living Index (RNL) total mean scores were higher among sport participants vs nonsport participants (P < 0.05). Significant correlation between CIQ and RNL total scores was found for all participants (Pearson correlation coefficients, P < 0.01). Logistic regression analysis revealed that the unadjusted odds ratio of a high CIQ mean score was 4.75 (95% Cl 1.7, 13.5) among current sport participants. Similarly, the unadjusted odds ratio of a high RNL score was 7.00 (95% Cl 2.3, 21.0) among current sport participants. Regression-adjusted odds ratios of high CIQ and high RNL scores were 1.36 (95% Cl 0.09, 1.45) and 0.15 (95% Cl 0.04, 0.55), respectively. The odds ratio for pre-SCI sport participation predicting post-SCI sport participation was 3.06 (95% Cl 1.23, 7.65).

Conclusions: CIQ and QoL scores were higher among sport participants compared to non-sport participants. There was an association between mean CIQ and RNL scores for both groups. Sport participants were 4.75 and 7.00 times as likely to have high CIQ and QoL scores. Both groups had a similar likelihood of high CIQ and RNL scores after adjusting for important confounders. Individuals who participated in sports prior to SCI were more likely to participate in sports post-SCI.     

Impaired skeletal muscle mitochondrial function in morbidly obese patients is normalized one year after bariatric surgery

BackgroundObesity and type 2 diabetes are associated with impaired skeletal muscle mitochondrial metabolism. As an intrinsic characteristic of an individual, skeletal muscle mitochondrial dysfunction could be a risk factor for weight gain and obesity-associated co-morbidities, such as type 2 diabetes. On the other hand, impaired skeletal muscle metabolism could be a consequence of obesity. We hypothesize that marked weight loss after bariatric surgery recovers skeletal muscle mitochondrial function.MethodsSkeletal muscle mitochondrial function as assessed by high-resolution respirometry was measured in 8 morbidly obese patients (body mass index [BMI], 41.3±4.7 kg/m²; body fat, 48.3%±5.2%) before and 1 year after bariatric surgery (mean weight loss: 35.0±8.6 kg). The results were compared with a lean (BMI 22.8±1.1 kg/m²; body fat, 15.6%±4.7%) and obese (BMI 33.5±4.2 kg/m²; body fat, 34.1%±6.3%) control group.ResultsBefore surgery, adenosine diphosphate (ADP)-stimulated (state 3) respiration on glutamate/succinate was decreased compared with lean patients (9.5±2.4 versus 15.6±4.4 O₂ flux/mtDNA; P<.05). One year after surgery, mitochondrial function was comparable to that of lean controls (after weight loss, 12.3±5.5; lean, 15.6±4.4 O₂ flux/mtDNA). In addition, we observed an increased state 3 respiration on a lipid substrate after weight loss (10.0±3.2 versus 14.0±6.6 O₂ flux/mtDNA; P< .05).ConclusionWe conclude that impaired skeletal muscle mitochondrial function is a consequence of obesity that recovers after marked weight loss.     

Reduced loosening rate and loss of correction following posterior stabilization with or without PMMA augmentation of pedicle screws in vertebral fractures in the elderly

Background

Therapy of vertebral fractures in the elderly is a growing challenge for surgeons. Within the last two decades, the use of polymethylmethacrylate (PMMA) in the treatment of osteoporotic vertebral fractures has been widely established. Besides vertebroplasty and kyphoplasty, the augmentation of pedicle screws with PMMA found widespread use to strengthen the implant–bone interface. Several studies showed an enhanced pullout strength of augmented screws compared to standard pedicle screws in osteoporotic bone models. To validate the clinical relevance, we analyzed postoperative radiologic follow-up data in regard to secondary loss of correction and loosening of pedicle screws in elderly patients.

Materials and methods

In this retrospective comparative study, 24 patients admitted to our level I trauma center were analyzed concerning screw loosening and secondary loss of correction following vertebral fracture and posterior instrumentation. Loss of correction was determined by the bisegmental Cobb angle and kyphosis angle of the fractured vertebra. Follow-up computed tomography (CT) scans were used to analyze the prevalence of clear zones around the pedicle screws as a sign of loosening.

Results

In 15 patients (mean age 76 ± 9.3 years) with 117 PMMA-augmented pedicle screws, 4.3 % of screws showed signs of loosening, whereas in nine patients (mean age 75 ± 8.2 years) with 86 uncemented screws, the loosening rate was 62.8 %. Thus, PMMA-augmented pedicle screws showed a significantly lower loosening rate compared to regular pedicle screws. Loss of correction was minimal, despite poor bone quality. There was significantly less loss of correction in patients with augmented pedicle screws (1.1° ± 0.8°) as compared to patients without augmentation (5° ± 3.8°).

Conclusion

The reinforcement of pedicle screws using PMMA augmentation may be a viable option in the surgical treatment of spinal fractures in the elderly.