Beta2-Microglobulin

Among the uremic toxins in the "middle molecule" range, beta2-microglobulin (β2-M) is certainly one of the most frequently studied compounds. Its serum level increases with the progression of chronic kidney disease, to reach very high concentrations in patients with end-stage kidney disease. It is the major protein component of dialysis-related amyloidosis, a dramatic complication which results from high extracellular concentration and posttranslational modification of β2-M and a number of other promoters of amyloid fibril formation and deposition in osteo-articular tissues. Effective removal of β2-M can be achieved with highly effective hemodialysis and hemodiafiltration techniques but predialysis session serum levels cannot be normalized. The prevalence and severity of β2-M amyloidosis appear to have decreased in the last 20 years, although its occurrence may simply be delayed.     

A Systematic Review of the Effectiveness of Contrast Baths

Study DesignSystematic review.IntroductionContrast baths are used as an intervention in hand therapy, yet it is unclear which patients, if any, benefit from this intervention.Purpose of the StudyTo examine the nature and quality of the evidence regarding the use of contrast baths using a systematic review process.MethodsOf a total of 28 clinical research articles on contrast baths, from 1938 forward, ten met the inclusion criteria set by the authors.ResultsThese studies addressed the physiological changes of hot and cold on blood flow, intramuscular temperature, subcutaneous temperature, and the influence of room temperature and age. The subjects included normal/healthy volunteers and patients with a diagnosis of rheumatoid arthritis, diabetes, or foot/ankle injuries. The diversity of conditions, protocols, and outcomes limited the ability to make definitive conclusions on efficacy.ConclusionsThe contrast bath procedure may increase superficial blood flow and skin temperature, though the evidence on the impact on edema is conflicting. No relationship between physiologic effects and functional outcomes has been established.Level of Evidence: 2A     

Total pancreatectomy with islet autotransplantation: an overview

Pain control is one of the most challenging aspects in the management of chronic pancreatitis. Total pancreatectomy can successfully relieve the intractable abdominal pain in these patients but will inevitably result in insulin-dependent diabetes. Islet autotransplantation aims to preserve, as far as possible, the insulin secretory function of the islet cell mass thereby reducing (or even removing) the requirement for exogenous insulin administration after a total pancreactomy. Despite the relatively small number of centres able to perform these procedures, there are important technical variations in the details of their approaches. The aim of this review is to provide details of the current surgical practice for total pancreatectomy combined with islet autotransplantation, and outline the potential advantages and disadvantages of the variations adopted in each centre.     

Impact of type 2 diabetes mellitus on diffuse inflammatory activation of de novo atheromatous lesions: Implications for systemic inflammation

AimsLocal coronary and systemic inflammation is pronounced in patients with diabetes mellitus (DM). Intracoronary thermography detects local inflammation and C-reactive protein (CRP) is a marker of systemic inflammation. We investigated whether or not, in patients with DM, thermal heterogeneity of culprit lesions (CLs) correlates with that of non-culprit lesions (NCLs) and with systemic inflammation.MethodsWe included DM patients who had two angiographically significant lesions and were undergoing percutaneous coronary intervention. We measured the temperature difference (ΔT) between the lesion and proximal vessel wall.ResultsWe included 104 (n = 208 lesions) patients: 32 (n = 64 lesions) had DM and 72 (n = 144 lesions) were non-DM (control group). ΔT was increased in DM in both CLs and NCLs (CLs: DM = 0.12 ± 0.06 °C; no DM = 0.06 ± 0.04 °C; P < 0.01 versus NCLs: DM = 0.13 ± 0.08 °C versus no DM = 0.06 ± 0.05 °C; P < 0.01). Patients with DM had similar ΔT in CLs and NCLs (P = 0.49). A linear correlation was detected between heat production in all lesions and CRP (R = 0.45; P < 0.01), which was attributed to the correlation of ΔT in lesions of patients with DM and CRP (R = 0.32; P < 0.01). In lesions of patients with low CRP, a greater rate of discrepancy was found, as 100% of lesions in patients with DM versus 66.1% of lesions of patients without DM had a high ΔT in one or both lesions (P < 0.01).ConclusionIn patients with DM, local inflammatory activation is diffuse and correlates with systemic inflammation. However, low systemic inflammatory activation does not always predict an increase in local thermal heterogeneity.     

Cytomegalovirus infection and disease in the new era of immunosuppression following solid organ transplantation

Abstract: As the most prevalent pathogen among transplant patients, cytomegalovirus (CMV) affects up to three-quarters of all solid organ transplant recipients. While we have made great strides in preventing CMV infection and disease in the early post-transplant period, late CMV infection and indirect effects due to viral immunomodulation remain problematic. Changing immunosuppression practices, including the increasing use of T-cell depleting induction antibodies, have the potential to affect the risk for CMV infection and disease, even in the face of good prophylactic and preemptive therapy. The purpose of this review article is to discuss the impact of CMV infection on long-term allograft outcomes and to re-evaluate the risks and management strategies for prevention of CMV in the framework of evolving modern immunosuppressive strategies.     

Discordance in HIV-1 viral loads and antiretroviral drug concentrations comparing semen and blood plasma

Objectives

For individuals not on antiretroviral therapy, the risk of heterosexual transmission of HIV appears negligible when blood plasma (BP) viral loads are <1500 HIV‐1 RNA copies/mL. It is not clear whether this observation can be extrapolated to individuals on highly active antiretroviral therapy (HAART). Because of differential tissue penetration, antiretroviral drug concentrations may be sufficient to maintain an undetectable viral load in the BP yet not achieve adequate levels to suppress HIV in the genital tract. Therefore, we wanted to correlate HIV viral loads and drug concentrations in semen plasma (SP) and BP.

Methods

Thirty‐three men were included. All were on combination antiretroviral therapy with an undetectable BP viral load for at least 1 year. Blood and semen samples were collected within 2 h of each other and tested for HIV RNA by the NucliSens QT (bioMerieux, St Laurent, QC, Canada) method; drug concentrations were determined by liquid chromatography tandem mass spectrometry.

Results

Two of the 33 patients (6.1%) with BP viral loads below detection had time‐matched HIV viral loads in SP ≥700 copies/mL. Both patients were on efavirenz, the SP concentrations of which were ≤10% of the levels in BP and well below the minimal therapeutic drug monitoring target concentration required to suppress HIV.

Conclusions

Because, at least in part, of poor drug penetration into the genital tract, an undetectable HIV viral load in the BP does not guarantee an undetectable viral load in semen. In view of this, caution should be taken in concluding that patients on HAART with suppressed viraemia are sexually non‐infectious.