Robert A. Cohen

Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys.

Double negative (DN) T cells are expanded in patients with systemic lupus erythematosus (SLE) and stimulate autoantibody production as efficiently as CD4+ T cells. In this study, we demonstrate that DN T cells from patients with SLE produce significant amounts of IL-17 and IFN-γ, and expand when stimulated in vitro with an anti-CD3 Ab in the presence of accessory cells. Furthermore, IL-17+ and DN T cells are found in kidney biopsies of patients with lupus nephritis. Our findings establish that DN T cells produce the inflammatory cytokines IL-17 and IFN-γ, and suggest that they contribute to the pathogenesis of kidney damage in patients with SLE.

Relationship Between the Prognostic Expectations of Seriously Ill Patients Undergoing Hemodialysis and Their Nephrologists

IMPORTANCEnPatients undergoing hemodialysis have an annual mortality rate exceeding 20%, comparable to many types of cancer. Past research has shown that patients with cancer overestimate their likelihood of survival relative to their physicians, but this relationship has not been examined in patients with noncancer diagnoses. Perceptions of prognosis and transplant candidacy may influence goals of care.nnnOBJECTIVESnTo compare the perceptions of hemodialysis patients and their nephrologists concerning prognosis and the likelihood of transplant; to follow actual survival; and to explore the relationship between patients expectations and their goals of care.nnnDESIGNnWe completed a medical record abstraction to estimate 1-year mortality risk among patients who underwent dialysis at any time from November 1, 2010, through September 1, 2011. We then conducted in-person interviews with eligible patients whose predicted 1-year mortality, based on validated prognostic tools, was at least 20%. We also interviewed their nephrologists. We compared patients and physicians expectations about 1- and 5-year survival and transplant candidacy and measured the association between patients expectations and goals of care. We then followed actual survival using Kaplan-Meier methods.nnnSETTING AND PARTICIPANTSnTwo dialysis units in Boston. Two hundred seven patients undergoing hemodialysis included in the medical record review, with 62 eligible patients interviewed.nnnMAIN OUTCOMES AND MEASURESnPredicted 1-year mortality risk using validated prognostic tools; actual survival; patients and physicians expectations about 1-year survival and likelihood of transplant; and patients goals of care.nnnRESULTSnOf the 207 hemodialysis patients, 72.5% had a predicted 1-year mortality of at least 20%. Of the 80 patients eligible for interview, 62 participated (response rate, 78%). Patients were significantly more optimistic than their nephrologists about 1- and 5-year survival (P < .001 for both) and were more likely to think they were transplant candidates (37 [66%] vs 22 [39%] [P = .008]). Of the 81% of patients reporting a 90% chance or greater of being alive at 1 year, 18 (44%) preferred care focused on extending life, even if it meant more discomfort, compared with 1 (9%) among patients reporting a lower chance of survival (P = .045). Actual survival was 93% at 1 year but decreased to 79% by 17 months and 56% by 23 months.nnnCONCLUSIONS AND RELEVANCEnHemodialysis patients are more optimistic about prognosis and transplant candidacy than their nephrologists. In our sample, patients expectations about 1-year survival were more accurate than those of their nephrologists, but their longer-term survival expectations dramatically overestimated even their 2-year survival rates. Patients prognostic expectations are associated with their treatment preferences. Our findings suggest the need for interventions to help providers communicate effectively with patients about prognosis.

Determinants of retinopathy progression in type 1 diabetes mellitus.

PURPOSEnTo determine the risk factors for retinopathy progression in type 1 (insulin-dependent) diabetes mellitus in a prospective cohort study.nnnSUBJECTS AND METHODSnSubjects were 485 participants in the Sorbinil Retinopathy Trial, a randomized trial of aldose reductase inhibition among patients aged 18 to 56 years with type 1 diabetes mellitus (duration of 1 to 15 years) and no or only mild retinopathy. Retinopathy progression, assessed by seven-field stereoscopic fundus photography, was defined as worsening by two or more levels on a standardized grading scale at the end of follow-up (median, 41 months).nnnRESULTSnThe relative risks for retinopathy progression according to successively greater quintiles of total glycosylated hemoglobin level at baseline, after adjusting for age, diabetes duration, sorbinil assignment, and other variables, were 1.0, 2.0, 1.6, 3.7, and 4.4 (P trend <0.0001). Risk increased with greater baseline diastolic blood pressure: 1.0 for <70 mm Hg, 1.2 for 70 to 79 mm Hg, and 1.8 for > or =80 mm Hg (P for trend = 0.04). Diastolic blood pressure was a significant risk factor for progression in participants with mild baseline retinopathy (P for trend <0.02) but not in those without retinopathy at entry. Systolic blood pressure, by comparison, was not associated with progression. Baseline total cholesterol level was a marginally significant predictor of retinopathy progression when examined as a categorical variable (relative risks for increasing quartiles; 1.0, 1.6, 1.8, 1.9; P for trend = 0.03) but not when it was examined as a continuous variable or when hypercholesterolemic patients were compared with those with normal levels. Furthermore, when cholesterol levels were updated in subsequent visits, it was not a significant predictor of progression, and low density lipoprotein (LDL) cholesterol levels did not predict progression no matter how analyzed. Smoking was not associated with progression of retinopathy.nnnCONCLUSIONSnLevels of hyperglycemia and diastolic blood pressure predicted progression of retinopathy in type 1 diabetes mellitus. We found only a suggestion of an association between total cholesterol level (but not of LDL cholesterol level) and progression of retinopathy; resolution of this issue will require additional studies with larger sample sizes and longer follow-up.

Obstructive sleep apnea oral appliance therapy and severity of condition

OBJECTIVEnThe purpose of this study was to determine whether an oral appliance can effectively treat severe obstructive sleep apnea.nnnDESIGNnThe study was conducted at a tertiary care military facility with an accredited sleep laboratory. Results of the treatment of the first 25 patients with obstructive sleep apnea referred for oral appliance therapy were retrospectively analyzed. Each patient received a mandibular advancement appliance and underwent polysomnography 2 weeks after delivery of the appliance. Patients were divided into two groups: those with slight-to-mild obstructive sleep apnea who had a respiratory disturbance index less than 21, and those with more severe disease. Treatment was considered to be successful if the posttreatment respiratory disturbance index was less than 5.nnnRESULTSnNine (90%) of the 10 patients with slight-to-moderate disease were successfully managed with the oral appliance. Of the 15 patients in the moderate-to-severe group, 9 (60%) were successfully managed.nnnCONCLUSIONnOral appliances have commonly been recommended only for mild obstructive sleep apnea. This study indicates that they may also have a role to play in selected cases in which the condition is more severe. There is a paucity of information about long-term success. This short-term (2-week) study should be followed by others evaluating the effect over longer periods.

T cells and in situ cryoglobulin deposition in the pathogenesis of lupus nephritis

We discuss a 53-year-old woman with systemic lupus erythematosus who presented with vasculitis, hypocomplementemia and nephritis. Although her serum complement 4 (C4) levels were zero, she had four copies of C4 gene. Renal biopsy revealed membranoproliferative glomerulonephritis and the presence of cryoglobulins, detected by electron microscopy, and significant numbers of T cells in the interstitium. Cryoglobulins were considered responsible for the complete consumption of C4 in the serum the levels of which improved gradually after treatment. T cells in the kidney were found to express CD44 and phosphorylated ezrin/radixin/moiesin which explain why they homed to the kidney inappropriately. The contribution of cryoglobulins and T cells in the expression of kidney pathology is discussed.

A Communication Framework for Dialysis Decision-Making for Frail Elderly Patients

Frail elderly patients with advanced kidney disease experience many of the burdens associated with dialysis. Although these patients constitute the fastest-growing population starting dialysis, they often suffer loss of functional status, impaired quality of life, and increased mortality after dialysis initiation. Nephrology clinicians face the challenges of helping patients decide if the potential benefits of dialysis outweigh the risks and preparing such patients for future setbacks. A communication framework for dialysis decision-making that aligns treatment choices with patient goals and values is presented. The role of uncertainty is highlighted, and the concept of a goal-directed care plan is introduced. This plan incorporates a time-limited trial that promotes frequent opportunities for reassessment. Using the communication skills presented, the clinician can prepare and guide patients for the dialysis trajectory as it unfolds.

Male breast cancer following repeated fluoroscopy

A man with cancer of the breast following repeated fluoroscopy for pulmonary tuberculosis is described.

Hemolysis Comparison between the OmniSonics OmniWave Endovascular System and the Possis AngioJet in a Porcine Model

PURPOSEnTo compare the degree of hemolysis generated during use of the ultrasound-based OmniSonics OmniWave Endovascular System and the Possis AngioJet connected to an Xpeedior-6 catheter.nnnMATERIALS AND METHODSnTwelve 64-145-kg Yorkshire pigs were used as the model because their weight, blood volume, and vessel diameters are comparable to that of adult humans. Six pigs were treated with the OmniWave and six with the AngioJet; half of the pigs in each group were treated in the contralateral iliofemoral arteries and half in the ipsilateral iliofemoral veins. Devices were activated for 10 minutes in patent vessels to represent a worst-case scenario for hemolysis generation. Plasma-free hemoglobin (PfHgb) levels, red blood cell counts, white blood cell (WBC) counts, and platelet counts were measured before and after the procedure, and PfHgb levels were measured every 2 minutes during treatment.nnnRESULTSnThe OmniWave generated significantly lower PfHgb levels than the AngioJet (average, 228 vs 1,367 mg/dL; P < .001). The location of activation (arterial vs venous) had no significant effect (P = .575). Compared with OmniWave use, AngioJet use was associated with significantly greater changes from pre- to posttreatment values in WBCs (P = .002), platelets (P = .004), and creatinine (P = .002). AngioJet use was associated with a significant postprocedure decrease in the WBC count (mean, -8,000/microl; 95% confidence interval [CI]: -3,830, -12,170; P = .004) and platelet count (mean, -72,000; 95% CI: -25,000, -120,000; P = .011). With the OmniWave device there were no significant differences between pre- and posttreatment WBC count (P = .127), platelet count (P = .493), and creatinine level (P = .317).nnnCONCLUSIONSnThe OmniWave generated approximately one-sixth of the hemolysis the AngioJet created. In addition, animals treated with the AngioJet exhibited a decrease in WBC and platelet counts.

A Nephrology Fellows’ Communication Skills Course: An Educational Quality Improvement Report

BACKGROUNDnNephrology fellows need expertise navigating challenging conversations with patients throughout the course of advanced kidney disease. However, evidence shows that nephrologists receive inadequate training in this area. This study assessed the effectiveness of an educational quality improvement intervention designed to enhance fellows communication with patients who have advanced kidney disease.nnnSTUDY DESIGNnQuality improvement project.nnnSETTING & PARTICIPANTSnFull-day annual workshops (2013-2014) using didactics, discussion, and practice with simulated patients. Content focused on delivering bad news, acknowledging emotion, discussing care goals in dialysis decision making when prognosis is uncertain, and addressing dialysis therapy withdrawal and end of life. Participants were first-year nephrology fellows from 2 Harvard-affiliated training programs (N=26).nnnQUALITY IMPROVEMENT PLANnStudy assessed the effectiveness of an intervention designed to enhance fellows communication skills.nnnOUTCOMESnPrimary outcomes were changes in self-reported patient communication skills, attitudes, and behaviors related to discussing disease progression, prognostic uncertainty, dialysis therapy withdrawal, treatments not indicated, and end of life; responding to emotion; eliciting patient goals and values; andxa0incorporating patient goals into recommendations.nnnMEASUREMENTSnSurveys measured prior training, pre- and postcourse perceived changes in skills and values, and reported longer term (3-month) changes in communication behaviors, using both closed- and open-ended items.nnnRESULTSnResponse rates were 100% (pre- and postsurveys) and 68% (follow-up). Participants reported improvement in all domains, with an overall mean increase of 1.1 (summed average scores: precourse, 2.8; postcourse, 3.9 [1-5 scale; 5xa0= extremely well prepared]; P<0.001), with improvement sustained at 3 months. Participants reported meaningful changes integrating into practice specific skills taught, such as Ask-Tell-Ask and using open-ended questions.nnnLIMITATIONSnSelf-reported data may overestimate actual changes; small sample size and the programs affiliation with a single medical school may limit generalizability.nnnCONCLUSIONSnA day-long course addressing nephrology fellows communication competencies across the full course of patients illness experience can enhance fellows self-reported skills and practices.

Effect of myo-inositol on renal Na-K-ATPase in experimental diabetes.

The activity of Na-K-ATPase in the kidney is increased by experimental diabetes. Because the kidney is rich in myo-inositol and abnormal inositol metabolism has been implicated in early neural complications of diabetes, we studied the effect of myo-inositol supplementation on Na-K-ATPase activity in renal medullary and cortical homogenates of Sprague-Dawley rats made diabetic with streptozotocin. Myo-inositol (650 mg/kg) was administered by gavage daily for 1 and 2 weeks after induction of diabetes. Medullary Na-K-ATPase (mumol/mg protein/h) was increased at 1 week by approximately 60% in diabetic rats versus control (25.9 +/- 0.07 vs 16.3 +/- 0.7; P less than .01). This increase was completely prevented by myo-inositol supplementation, despite persistent hyperglycemia. At 2 weeks, similar results were seen; medullary Na-K-ATPase activity was increased by 50% in diabetic rats compared with control, and once again myo-inositol prevented this increase. Sorbinil, the aldose reductase inhibitor, was also administered by gavage (20 mg/kg) for 2 weeks and partially prevented the increase in medullary Na-K-ATPase activity (20.0 +/- 0.9; P less than .05). At both 7 and 14 days, Na-K-ATPase activity in the cortex of untreated diabetic rats was also significantly increased compared with nondiabetic control rats and the increase was prevented by myo-inositol or Sorbinil. Myo-inositol or Sorbinil did not reduce Na-K-ATPase activity of nondiabetic control rats, nor did they prevent the increase in medullary Na-K-ATPase in compensatory hypertrophy following uninephrectomy. Myo-inositol content of outer medulla was about five to six times that of cortex, but was unaltered by the diabetic state.(ABSTRACT TRUNCATED AT 250 WORDS)