Hickson, LaTonya J

AbstractBackgroundExtracorporeal treatments such as hemodialysis and plasma exchange are lifesaving measures in the treatment of drug poisoning. This treatment method generally is not used for severe cutaneous and systemic drug reactions.MethodsHere, we describe three cases wherein hemodialysis therapy was instrumental in reversing the adverse drug reaction.ResultsIn the cases of severe cutaneous drug reactions reviewed, patients presented with linear immunoglobulin A bullous dermatosis, acute generalized exanthematous pustulosis, and toxic epidermal necrolysis. Salvage treatment with hemodialysis therapy drastically influenced the course of disease, resulting in remission.ConclusionsThis novel and highly effective treatment option is not considered in current algorithms for adverse drug reactions. Hence, in addition to the rarity of these reactions, the main limitation of the study is the small number of patients. Hemodialysis can substantially alter the prognosis and, in some cases, be a lifesaving treatment for patients with severe adverse cutaneous drug reaction associated with systemic toxicity.

Atherosclerotic renovascular disease (RVD) reduces renal blood flow (RBF) and GFR and accelerates poststenotic kidney (STK) tissue injury. Preclinical studies indicate that mesenchymal stem cells (MSCs) can stimulate angiogenesis and modify immune function in experimental RVD. We assessed the safety and efficacy of adding intra-arterial autologous adipose-derived MSCs into STK to standardized medical treatment in human subjects without revascularization. The intervention group ( n =14) received a single infusion of MSC (1.0 × 10 5 or 2.5 × 10 5 cells/kg; n =7 each) plus standardized medical treatment; the medical treatment only group ( n =14) included subjects matched for age, kidney function, and stenosis severity. We measured cortical and medullary volumes, perfusion, and RBF using multidetector computed tomography. We assessed tissue oxygenation by blood oxygen level–dependent MRI and GFR by iothalamate clearance. MSC infusions were well tolerated. Three months after infusion, cortical perfusion and RBF rose in the STK (151.8–185.5 ml/min, P =0.01); contralateral kidney RBF increased (212.7–271.8 ml/min, P =0.01); and STK renal hypoxia (percentage of the whole kidney with R2*>30/s) decreased (12.1% [interquartile range, 3.3%–17.8%] to 6.8% [interquartile range, 1.8%–12.9%], P =0.04). No changes in RBF occurred in medical treatment only subjects. Single-kidney GFR remained stable after MSC but fell in the medical treatment only group (−3% versus −24%, P =0.04). This first-in-man dose-escalation study provides evidence of safety of intra-arterial infusion of autologous MSCs in patients with RVD. MSC infusion without main renal artery revascularization associated with increased renal tissue oxygenation and cortical blood flow.

Abstract Obesity is a major risk factor for a number of chronic diseases, including diabetes, cardiovascular diseases, and cancer. Expansion of the adipose mass requires adipocyte precursor cells that originate from multipotent adipose-derived stromal cells (ASCs), which in turn also participate in repair activities. ASC function might decline in a disease milieu, but it remains unclear whether ASC function varies during the development of obesity. We tested the hypothesis that microenvironmental inflammatory changes during development of metabolic disorders in obesity affect ASC function. Domestic pigs were fed with an atherogenic (n = 7) or normal (n = 7) diet for 16 weeks. Abdominal adipose tissue biopsies were collected after 8, 12, and 16 weeks of diet for ASC isolation and immunohistochemistry of in situ ASCs and tumor necrosis factor-α (TNF-α). Longitudinal changes in proliferation, differentiation, and anti-inflammatory functions of ASCs were assessed. At 16 weeks, upregulated TNF-α expression in adipose tissue from obese pigs was accompanied by increased numbers of adipocyte progenitors (CD24+/CD34+) in adipose tissue and enlarged adipocyte size. In vitro, ASCs from obese pigs showed enhanced adipogenic and osteogenic propensity, which was abolished by anti-TNF-α treatment, whereas lean ASCs treated with TNF-α showed enhanced adipogenesis. Furthermore, obese ASCs showed increased senescence compared with lean ASCs, whereas their immunomodulatory capacity was preserved. Adipose tissue inflammation promotes an increase in resident adipocyte progenitors and upregulated TNF-α enhances ASC adipogenesis. Thus, adipose tissue anti-inflammatory strategies might be a novel target to attenuate obesity and its complications. Significance Adipose-derived stromal cell (ASC) function might decline in a disease milieu, but it remains unclear whether ASC function varies during the development of obesity. This study tested the hypothesis that microenvironmental inflammatory changes during development of metabolic disorders in obesity affect ASC function. It was found that ASCs show increased propensity for differentiation into adipocytes, which is partly mediated by upregulated tumor necrosis factor-α (TNF-α), likely in their adipose tissue microenvironment. Furthermore, TNF-α magnified obese ASC senescence, although it did not regulate their anti-inflammatory properties. Thus, adipose tissue inflammation might be a novel therapeutic target to avert ASC maldifferentiation and senescence.

AbstractAimsThe number of elderly persons with end‐stage renal disease is increasing with many requiring hospitalizations. This study examines the causes and predictors of hospitalization in older haemodialysis patients.MethodsWe reviewed hospitalizations of older (≥65 years) incident chronic haemodialysis patients initiating therapy between 1 January 2007 and 31 December 2009 under the care of a single Midwestern United States dialysis provider.ResultsOf 125 patients, the mean age was 76 ± 7 years and 72% were male. At first dialysis, 68% used a central venous catheter (CVC) and 51% were in the hospital. Mean follow‐up was 1.8 ± 1.0 years. At least one hospitalization occurred in 89 (71%) patients and half of all patients were hospitalized once within the first 223 days. Total hospital admission rate was 1.48 per patient year with hospital days totalling 8.54 days per patient year. The three most common reasons for first admission were cardiac (33%), infection (18%) and gastrointestinal (12%). Predictors of future hospitalization included the first dialysis occurring in hospital (hazard ratios (HR) 2.1, 95% CI 1.4–3.3, P = 0.0005) and the use of a CVC at first haemodialysis (HR 2.6, CI 1.6–4.4, P < 0.0001).ConclusionHospitalizations are common in older incident haemodialysis patients. Access preparation and overall burden of illness leading to the initial hospitalization appear to play a role. Identification of additional factors associated with hospitalization will allow for focused interventions to reduce hospitalization rates and increase the value of care.