Hemodynamic effects of chronic hemodialysis therapy assessed by pulse waveform analysis

Cardiovascular responses to hemodialysis have been characterized by invasive monitoring techniques. These techniques are not feasible for evaluation of hemodynamic status during dialysis in the outpatient setting. In this study, we used pulse waveform analysis (PWA), a noninvasive tool designed for the ambulatory setting, to assess hemodynamic responses of dialysis treatments in 27 stable subjects with end-stage renal disease receiving chronic hemodialysis. In our population, systolic, diastolic, and pulse pressures were unaffected by dialysis despite the mean fluid removal of 3.0 +/- 0.2 kg. However, using PWA, we observed that stroke volume and cardiac output progressively declined by 17% to 19% (P <.001) with a concomitant increase in systemic vascular resistance by 22% from 1654 +/- 88 to 2020 +/- 121 dynes. sec. cm(-5) (P <.001). Also, we observed a significant reduction in small artery compliance from 4.7 +/- 0.5 to 3.3 +/- 0.4 mL. mm Hg(-1). 100 (P =.01), whereas large artery elasticity was unaffected. These findings suggest that changes in small artery vascular compliance contribute to the elevation in systemic vascular resistance during dialysis. This study confirms that hemodynamic adaptations to the dialysis procedure can be detected using PWA and are consistent with data obtained by invasive monitoring techniques. Furthermore, the observed reduction in vascular compliance in response to dialysis may contribute to the high cardiovascular risk in patients undergoing chronic hemodialysis therapy.     

Incidence and clinical significance of bacteremia and sepsis among cardiac patients treated with intra-aortic balloon counterpulsation pump

In this prospective study, a significant incidence of fever (47%), true bacteremia (15%), and sepsis (12%), were found in 60 cardiac patients treated with an intra-aortic balloon counterpulsation pump. The benefit of antibiotic prophylaxis in this setting should therefore be evaluated.     

Chronic airflow obstruction in Fabry's disease

Seven patients with Fabry's disease, an x-linked sphingolipid storage disorder, were evaluated for the presence and extent of airway obstruction. All were found to have significant obstruction to airflow. In addition, evaluation of their airway epithelial cells obtained by bronchoscopy demonstrated that these cells contained inclusion bodies consistent with deposits of ceramide trihexoside, suggesting that part of their functional obstruction to airflow may be secondary to intrinsic airway disease. Although all of the study population had evidence of airflow obstruction, the impairment was much worse in those who smoked, implying that even mild cigarette smoking is particularly hazardous to patients with Fabry's disease.     

Radiotherapy for benign disease; assessing the risk of radiation-induced cancer following exposure to intermediate dose radiation

Most radiotherapy (RT) involves the use of high doses (>50 Gy) to treat malignant disease. However, low to intermediate doses (approximately 3–50 Gy) can provide effective control of a number of benign conditions, ranging from inflammatory/proliferative disorders (e.g. Dupuytren''s disease, heterotopic ossification, keloid scarring, pigmented villonodular synovitis) to benign tumours (e.g. glomus tumours or juvenile nasopharyngeal angiofibromas). Current use in UK RT departments is very variable. This review identifies those benign diseases for which RT provides good control of symptoms with, for the most part, minimal side effects. However, exposure to radiation has the potential to cause a radiation-induced cancer (RIC) many years after treatment. The evidence for the magnitude of this risk comes from many disparate sources and is constrained by the small number of long-term studies in relevant clinical cohorts. This review considers the types of evidence available, i.e. theoretical models, phantom studies, epidemiological studies, long-term follow-up of cancer patients and those treated for benign disease, although many of the latter data pertain to treatments that are no longer used. Informative studies are summarized and considered in relation to the potential for development of a RIC in a range of key tissues (skin, brain etc.). Overall, the evidence suggests that the risks of cancer following RT for benign disease for currently advised protocols are small, especially in older patients. However, the balance of risk vs benefit needs to be considered in younger adults and especially if RT is being considered in adolescents or children.     

Long‐term effectiveness of recommended boosted protease inhibitor‐based antiretroviral therapy in Europe

Objectives

The aim of the study was to evaluate the long‐term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)‐, darunavir/ritonavir (DRV/r)‐, and lopinavir/ritonavir (LPV/r)‐containing regimens.

Methods

Data were analysed for 5678 EuroSIDA‐enrolled patients starting a DRV/r‐, ATZ/r‐ or LPV/r‐containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART‐naïve subjects (8%) at ritonavir‐boosted protease inhibitor (PI/r) initiation; (2) ART‐experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV‐1 RNA copies/mL; and (3) ART‐experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL. Virological failure (VF) was defined as two consecutive VL measurements >200 copies/mL ≥24 weeks after PI/r initiation. Kaplan–Meier and multivariable Cox models were used to compare risks of failure by PI/r‐based regimen. The main analysis was performed with intention‐to‐treat (ITT) ignoring treatment switches.

Results

The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log‐rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART‐naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment‐experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r‐based ART.

Conclusions

Although confounding by indication and calendar year cannot be completely ruled out, in ART‐experienced subjects the long‐term effectiveness of DRV/r‐containing regimens appears to be greater than that of ATZ/r and LPV/r.