Aquaporin-2 (AQP2) Urinary Excretion and Assumption of Water with Different Mineral Content in Healthy Subjects

The aquaporin-2 (AQP2) plays a key role in AVP-induced absorption of water, and its urinary excretion is related to its function. We aimed to test if the assumption of water with different mineral content can modify the expression of AQP2, leading to a change in AQP2 urinary concentration, in 20 healthy young subjects. Each subject received an oral water load (LM or HM) of 250 mL/hour for four hours, and several variables were measured. Plasmatic osmolality after water assumption was significantly reduced with no differences after the low (LM) or the high mineral (HM) water load. Urinary osmolality and plasmatic vasopressin concentration were significantly reduced after an assumption of both kinds of water. However, serum vasopressin was lower after HM water assumption than after LM. AQP2 urinary excretion was significantly reduced after water assumption with respect to the basal level and it was lower after LM than after HM water assumption. The different mineral content of water was investigated as a factor contributing to the development of hypertension. Considering that AQP2 can play a role in pathogenesis of hypertension, our demonstration that AVP-mediated AQP2 urinary excretion is strictly influenced by the consumption of water with different mineral content suggests a new, interesting field of investigation related to the link between blood pressure alterations and nutritional habits.     

Incidence and Consequence of Close Margins in Patients with Ductal Carcinoma-In Situ Treated with Mastectomy: Is Further Therapy Warranted?

Background

The impact of close margins in patients with ductal carcinoma-in situ (DCIS) treated with mastectomy is unclear; however, this finding may lead to a recommendation for postmastectomy radiotherapy (PMRT). We sought to determine the incidence and consequences of close margins in patients with DCIS treated with mastectomy.

Methods

The records of 810 patients with DCIS treated with mastectomy from 1996 through 2009 were reviewed. Clinical and pathologic factors were analyzed with respect to final margin status. Median follow-up was 6.3 years.

Results

Overall, 94 patients (11.7 %) had close margins (positive, n = 5; negative but ≤1 mm, n = 54; 1.1–2.9 mm, n = 35). Independent risk factors for close margins included multicentricity, pathologic lesion size ≥1.5 cm, and necrosis, but not age, use of skin-sparing mastectomy, or immediate reconstruction (p > 0.05). Seven patients received PMRT, and none had a locoregional recurrence (LRR). Among the remaining 803 patients, the 10-year LRR rate was 1 % (5.0 % for margins ≤1 mm, 3.6 % for margins 1.1–2.9 mm, and 0.7 % for margins ≥3 mm [p < 0.001]). The 10-year rate of contralateral breast cancer was 6.4 %. On multivariate analysis, close margins was the only independent predictor of LRR (p = 0.005).

Conclusions

Close margins occur in a minority of patients undergoing mastectomy for DCIS and is the only independent risk factor for LRR. As the LRR rate in patients with close margins is low and less than the rate of contralateral breast cancer, PMRT is not warranted except for patients with multiple close/positive margins that cannot be surgically excised.     

High-Efficiency Postdilution Online Hemodiafiltration Reduces All-Cause Mortality in Hemodialysis Patients

Retrospective studies suggest that online hemodiafiltration (OL-HDF) may reduce the risk of mortality compared with standard hemodialysis in patients with ESRD. We conducted a multicenter, open-label, randomized controlled trial in which we assigned 906 chronic hemodialysis patients either to continue hemodialysis (n=450) or to switch to high-efficiency postdilution OL-HDF (n=456). The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular mortality, all-cause hospitalization, treatment tolerability, and laboratory data. Compared with patients who continued on hemodialysis, those assigned to OL-HDF had a 30% lower risk of all-cause mortality (hazard ratio [HR], 0.70; 95% confidence interval [95% CI], 0.53–0.92; P=0.01), a 33% lower risk of cardiovascular mortality (HR, 0.67; 95% CI, 0.44–1.02; P=0.06), and a 55% lower risk of infection-related mortality (HR, 0.45; 95% CI, 0.21–0.96; P=0.03). The estimated number needed to treat suggested that switching eight patients from hemodialysis to OL-HDF may prevent one annual death. The incidence rates of dialysis sessions complicated by hypotension and of all-cause hospitalization were lower in patients assigned to OL-HDF. In conclusion, high-efficiency postdilution OL-HDF reduces all-cause mortality compared with conventional hemodialysis.In the last decades, renal replacement therapy with hemodialysis has become a standard of care for patients with ESRD. Despite continuous improvement, annual mortality among these patients ranges between 15% and 25%.^1,2 Hemodialysis techniques are based on the ability of molecules to diffuse across a semipermeable membrane, which allows adequate clearance of low molecular weight particles. To increase the clearance of middle-to-large molecules, synthetic membranes with high water permeability (high-flux membranes) were introduced years ago. The anticipated benefit of high-flux over low-flux hemodialysis on patient survival was not confirmed in the Hemodialysis (HEMO) study.³ However, the Membrane Permeability Outcome (MPO) study,⁴ as well as a post hoc analysis in diabetic patients, showed that high-flux hemodialysis improved long-term survival in patients with hypoalbuminemia.Clearance of middle-to-large molecules can be increased by combining diffusive and convective transport through hemodiafiltration. The introduction of online hemodiafiltration (OL-HDF) using ultrapure dialysate as the source of the replacement fluid has allowed the convective volume to be increased and has reduced the cost of the procedure.⁵ Randomized studies with limited sample sizes and nonrandomized studies have shown that OL-HDF improves hemodynamic stability and response to erythropoietic-stimulating agents (ESAs) and reduces the incidence of hemodialysis-associated amyloidosis and chronic inflammation.^6–11 The effect of OL-HDF on patient survival is derived from noncontrolled studies. The European Dialysis Outcomes and Practice Pattern Study was associated with a mortality risk reduction of 35% in patients treated with high-efficiency hemodiafiltration compared with those treated with conventional hemodialysis.¹² These results were confirmed in other noncontrolled studies conducted in several European countries,^13–15 although two recent, randomized studies failed to show differences in patient survival^16,17In 2007, the Catalonian Health Authorities approved a specific additional reimbursement for OL-HDF to dialysis care providers and the Catalonian Society of Nephrology promoted this randomized study (On-Line Hemodiafiltration Survival Study, or Estudio de Supervivencia de Hemodiafiltración On-Line [ESHOL]) to compare the effect of OL-HDF over hemodialysis on patient survival.¹⁸     

Primary Cutaneous Posttransplant Lymphoproliferative Disorders in Solid Organ Transplant Recipients: A Multicenter European Case Series

Primary cutaneous posttransplant lymphoproliferative disorders (PTLD) are rare. This retrospective, multicenter study of 35 cases aimed to better describe this entity. Cases were (re)‐classified according to the WHO‐EORTC or the WHO 2008 classifications of lymphomas. Median interval between first transplantation and diagnosis was 85 months. Fifty‐seven percent of patients had a kidney transplant. Twenty‐four cases (68.6%) were classified as primary cutaneous T cell lymphoma (CTCL) and 11 (31.4%) as primary cutaneous B cell PTLD. Mycosis fungoides (MF) was the most common (50%) CTCL subtype. Ten (90.9%) cutaneous B cell PTLD cases were classified as EBV‐associated B cell lymphoproliferations (including one plasmablastic lymphoma and one lymphomatoid granulomatosis) and one as diffuse large B cell lymphoma, other, that was EBV‐negative. Sixteen (45.7%) patients died after a median follow‐up of 19.5 months (11 [68.8%] with CTCL [6 of whom had CD30⁺ lymphoproliferative disorders (LPD)] and 5 [31.2%] with cutaneous B cell PTLD. Median survival times for all patients, CTCL and cutaneous B cell PTLD subgroups were 93, 93, and 112 months, respectively. Survival rates for MF were higher than those for CD30⁺ LPD. The spectrum of primary CTCL in organ transplant recipients (OTR) is similar to that in the general population. The prognosis of posttransplant primary cutaneous CD30⁺ LPD is worse than posttransplant MF and than its counterpart in the immunocompetent population. EBV‐associated cutaneous B cell LPD predominates in OTR.     

LIGHT/HVEM/LTβR Interaction as a Target for the Modulation of the Allogeneic Immune Response in Transplantation

The exchange of information during interactions of T cells with dendritic cells, B cells or other T cells regulates the course of T, B and DC‐cell activation and their differentiation into effector cells. The tumor necrosis factor superfamily member LIGHT (homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes) is transiently expressed upon T cell activation and modulates CD8 T cell‐mediated alloreactive responses upon herpes virus entry mediator (HVEM) and lymphotoxin β receptor (LTβR) engagement. LIGHT‐deficient mice, or WT mice treated with LIGHT‐targeting decoy receptors HVEM‐Ig, LTβR‐Ig or sDcR3‐Ig, exhibit prolonged graft survival compared to untreated controls, suggesting that LIGHT modulates the course and severity of graft rejection. Therefore, targeting the interaction of LIGHT with HVEM and/or LTβR using recombinant soluble decoy receptors or monoclonal antibodies represent an innovative therapeutic strategy for the prevention and treatment of allograft rejection and for the promotion of donor‐specific tolerance.     

Study of Bone Mass in Young Daughters of Women With Fracture of the Distal End of the Radius

The main aim was to assess whether young and healthy daughters of women with fractures of the distal end of the radius (DER) had less bone mass than the control group. In an observational study of cases and controls (1:1), the daughters of women with fractures of DER (96) were selected at the age of reaching the peak of bone mass and compared with a control group (91). All women underwent medical history, analytical determinations, and densitometry. In the case group, we found lower bone mass values at the spine and femoral neck than the control group. We also found a lower bone mass at the hips of daughters of women with 1 or more osteoporotic fractures associated with DER and at the lumbar spine in those whose mothers had densitometric osteoporosis. In conclusion, young daughters of women with fractures of DER had lower levels of bone mass density, with a possible “location-specific” occurrence based on the presence of 1 or more osteoporotic fractures associated with DER or on the presence of maternal densitometric osteoporosis.