Outcome of simultaneous liver-kidney transplantation in highly sensitized,crossmatch-positive patients

BACKGROUND: In simultaneous liver-kidney transplantation (SLKT), the liver has been described to protect the kidney from rejection, and acceptable results are possible despite a pretransplant positive crossmatch. At our center, 21 SLKT have been performed since 1993, 2 of them against a positive crossmatch. OBJECTIVES: In this study we retrospectively analyzed two cases of SLKT after positive pretransplant crossmatch. METHODS: Two highly sensitized women (30 and 52 years) with hepatic cirrhosis VHC on hemodialysis after a first KT failure were assessed. Pretransplant panel reactive antibodies (PRA) by complement dependent cytotoxicity NIH (CDC) were 81% and 99% respectively. Both patients received a SLKT. CM was performed at pretransplant and 24 and 48 hours posttransplant by CDC and by flow cytometry with double labeling with CD3-PE and antihuman IgG-FITC. Patients received ATG, cyclosporine, and prednisone therapy. RESULTS: CM was positive pretransplant by CDC and flow cytometry. At 48 hours, CDC became almost negative (10%-20% mortality) and flow cytometry became negative. One of the patients experienced an episode of acute rejection at 10 days posttransplant that resolved with steroid pulses. Both patients presently have working grafts 26 and 24 months posttransplant (Cr, 1.1 and 1.5 mg/dL; GOT, 34 and 14 IU/L; GTP, 29 and 12 IU/L; GGT, 9 and 66 IU/L). CONCLUSIONS: Our experience suggests that a positive crossmatch is not an absolute contraindication for SLKT. Good graft and patient survival rates are possible even among highly sensitized patients.     

Colorectal Polyps in Carriers of the APC I1307K Polymorphism

PURPOSE The probability of colorectal cancer is moderately increased among carriers of the APC I1307K polymorphism. However, it is not known if endoscopic surveillance of this high-risk group is warranted. The prevalence of polyps and adenomas in specimens of colorectal cancer who are carriers and noncarriers of the APC I1307K polymorphism is compared. METHOD Prevalence of adenomatous polyps in the pathology specimens of the study participants, stratified by their APC I1307K polymorphism status, was studied in 900 consecutive cases of colorectal cancer diagnosed in northern Israel between 1998 and 2002, within the framework of a population-based, case-controlled study (MECC Study). RESULTS The APC I1307K mutation was detected in 78 colorectal cancer cases (8.7 percent) of the study population. Prevalence was higher among Ashkenazi Jews (11.2 percent) than among non-Ashkenazi Jews (2.7 percent) or Arabs (3.1 percent). After adjustment for age, APC I1307K carriers were significantly more likely than noncarriers to have polyps in their surgical specimen (51.3 percent vs. 32.6 percent, P = 0.002). Adenomas with a tubular component (either tubular adenomas or tubulovillous adenomas), but not villous adenomas, were significantly more frequent among carriers (37.2 percent vs. 23.6 percent, P = 0.005). CONCLUSION Together with former evidence of I1307K being a risk factor for colorectal cancer, these data suggest that colonoscopic surveillance for colorectal adenomas and cancer may be warranted in I1307K carriers, even in the absence of other identifiable risk factors. Supported by the National Institutes of Health grant RO1-CA81488 to S.B.G. and G.R.     

Active tuberculosis in inflammatory bowel disease patients under treatment from an endemic area in Latin America

BACKGROUNDThere has been an increase in cases of inflammatory bowel disease (IBD) in recent years. There is also greater access and availability of immunosuppressive and biological agents, which increase the risk of opportunistic infection despite improving the quality of life and promoting mucosal healing. Tuberculosis (TB) remains a public health problem, and it has a high incidence in several countries. Therefore, knowledge of the risk of developing TB in patients with IBD is important.AIMTo evaluate the risk of active TB in patients with IBD under treatment from an endemic area in Latin America.METHODSA standard questionnaire included demographic variables, clinical aspects of IBD disease, history of active TB during treatment, active TB characteristics and evolution, initial screening and results and time from the start of anti-tumor necrosis factor alpha (TNFα) to TB development.RESULTSAzathioprine, anti-TNFα and the combination of these two drugs were associated with a higher risk of active TB incidence. The TNFα blockers increased the relative risk of developing active TB compared to other treatments. All four multivariable models showed that the use of TNFα blockers alone or in combination with azathioprine was an important risk factor for the incidence of active TB. After adjustment for sex, age, type of IBD and latent TB, anti-TNFα with azathioprine increased the relative risk to 17.8 times more than conventional treatment. Late TB, which was diagnosed 3 mo after the start of anti-TNFα, was the most frequent.CONCLUSIONTreatment with anti-TNFα increased the risk of active TB in IBD patients from an endemic area in Latin America. This risk was increased when anti-TNFα was combined with azathioprine. The time from the beginning of the treatment to the active TB diagnosis suggests a new TB infection.     

Postural orthostatic tachycardia syndrome associated with multiple sclerosis

BackgroundThe aim of this study was to determine if there is a difference in the frequency of postural orthostatic tachycardia syndrome (POTS) in patients with multiple sclerosis (MS) compared to patients with symptoms of orthostatic intolerance and with no evidence of MS or other neurological illness.MethodsWe analyzed data gathered from 293 patients who underwent the head-up tilt table test protocol. Group 1 included prospectively analyzed 112 with MS and group 2 included retrospectively analyzed 181 patients who were evaluated because of symptoms of orthostatic intolerance, and with no evidence of MS or other neurological illness. If POTS was identified the head-up tilt table test was repeated and supine as well as standing serum epinephrine and norepinephrine were determined.ResultsPOTS was identified in 39 patients: 21 (19%) in the MS group comparing to 18 (10%) in the non MS group (p = 0.035). There was no difference between groups in the occurrence of POTS associated syncope (p = 0.52). There was no difference between groups in the epinephrine or norepinephrine in supine and standing positions. While both standing epinephrine and norepinephrine levels were significantly higher compared to levels in the supine position in the non MS group, only standing norepinephrine levels were significantly higher in the MS group.ConclusionsThe results of this study suggest that POTS is associated with MS.     

Guiding Breast-Conserving Surgery in Patients After Neoadjuvant Systemic Therapy for Breast Cancer: A Comparison of Radioactive Seed Localization with the ROLL Technique

Background

Radioguided occult lesion localization (ROLL) with technetium-99 m colloid (ROLL-^99mTc) is commonly used to perform breast-conserving surgery in patients with nonpalpable breast tumors. Radioactive seed localization is a relatively new technique that localizes the tumor with a radioactive iodine-125 (¹²⁵I) seed. The feasibility and outcome of these techniques after neoadjuvant systemic treatment has not been widely investigated.

Methods

All patients treated with neoadjuvant systemic treatment between 2007 and 2010 in the Netherlands Cancer Institute who underwent breast-conserving surgery with the ROLL-^99mTc technique (n = 83) or with ¹²⁵I seed localization (n = 71) were analyzed. The weight of the resected specimen, the margins, and the percentage of patients requiring a second surgical intervention as a result of positive margins were assessed.

Results

Patient and tumor characteristics and systemic treatment regimens were comparable between both groups. The median weight of the resected specimen (53 vs. 48 g), the median smallest margin (3.5 vs. 3.0 mm), and the risk for additional surgery for incomplete resections (7 vs. 8 %) did not differ significantly between patients treated with the ROLL-^99mTc technique and ¹²⁵I seed localization.

Conclusions

The ROLL-^99mTc technique and ¹²⁵I seed localization demonstrate comparable results when used to perform breast-conserving surgery after neoadjuvant systemic treatment. Because ¹²⁵I seed localization does not require additional radiological localization shortly before surgery, it simplifies surgery scheduling. Therefore, we prefer ¹²⁵I seed localization to perform breast-conserving surgery after neoadjuvant systemic treatment.     

Youth survival: addressing the role of promoting the acquisition of the prosocial triad and other survival skills in youth

This article addresses the issue of teaching youth skills that will help them to maximize opportunities and positive consequences and minimize exposure to negative consequences in their lives. These skills will allow them to mature into mentally healthy, productive members of society. Essential skills that are critical to allow this maturational process include developing prosocial skills; the ability to recognize, discriminate the level of threat, and use strategies to avoid danger; and the ability to adapt to the changing demands of his or her environment.     

In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system

In this study, the in vivo hypoglycemic effect of a donut-shaped polyanion salt (NH₄)₁₄[Na@P₅W₃₀O₁₁₀]·31H₂O {NaP₅W₃₀} and its Ag-containing derivative K₁₄[Ag@P₅W₃₀O₁₁₀]·22H₂O·6KCl {AgP₅W₃₀}, as well as their hepatotoxicity and nephrotoxicity, was evaluated. In the screening hypoglycemic study, Wistar albino rats with streptozotocin induced diabetes were treated intraperitoneally with three single doses (5, 10, and 20 mg per kg per b.w.) of both investigated polyoxotungstates. The blood glucose levels, measured before and after 2, 4 and 6 h polyoxotungstate application, showed that both studied compounds induced the most pronounced and time dependent glucose lowering effects at the doses of 20 mg kg⁻¹. Thus, daily doses of 20 mg kg⁻¹ were administered to Wistar albino rats orally for 14 days in further toxicity examinations. The serum glucose concentration and biochemical parameters of kidney and liver function, as well as a histopathological analysis of kidney and liver tissues were evaluated 14 days after the polyoxotungstate administration. Both investigated compounds did not induce statistically significant alterations of the serum glucose and uric acid concentrations, as well as some of the liver function markers (serum alanine and aspartate aminotransferases, and alkaline phosphatase activities). However, the significant decrease in serum total protein and albumin concentrations and the increase in biochemical parameters of renal function – serum urea (up to 63.1%) and creatinine concentrations (up to 23.3%) were observed for both polyoxotungstates. In addition, the detected biochemical changes were in accordance with kidney and liver histhopathological analysis. Accordingly, the hepatotoxic and nephrotoxic effects of these potential antidiabetic polyoxotungstates could be considered as mild.

Study of the in vivo hypoglycemic effect, hepatotoxicity and nephrotoxicity of a donut-shaped polyanion salt (NH₄)₁₄[Na@P₅W₃₀O₁₁₀]·31H₂O {NaP₅W₃₀} and its Ag-containing derivative K₁₄[Ag@P₅W₃₀O₁₁₀]·22H₂O·6KCl {AgP₅W₃₀}.