Late recurrences of Cushing's disease after initial successful transsphenoidal surgery

CONTEXT: Few studies have systematically analyzed the long-term recurrence rates of Cushing's disease after initial successful transsphenoidal surgery. SETTING: This was a retrospective review of patients treated at the University of Virginia Medical Center. PATIENTS: A total of 215 subjects with Cushing's disease who underwent initial transsphenoidal surgery for resection of a presumed pituitary microadenoma from 1992-2006 were included. MAIN OUTCOME MEASURES: Remission and recurrence rates of Cushing's disease were examined. Recurrence was defined as an elevated 24-h urine free cortisol with clinical symptoms consistent with Cushing's disease. RESULTS: Of the 215 patients who underwent transsphenoidal surgery for Cushing's disease, surgical remission was achieved in 184 (85.6%). The mean length of follow-up was 45 months. Actuarial recurrence rates of Cushing's disease after initially successful transsphenoidal surgery at 1, 2, 3, and 5 yr were 0.5, 6.7, 10.8, and 25.5%, respectively. Among the 184 patients who achieved remission, 32 (17.4%) patients followed for more than 6 months ultimately had a recurrence of Cushing's disease. The median time to recurrence was 39 months. Immediate postoperative hypocortisolemia (serum cortisol < or = 2 microg/dl within 72-h surgery) was achieved in 97 (45.1%) patients. Patients who had postoperative serum cortisol of more than 2 microg/dl were 2.5 times more likely to have a recurrence than patients who had serum cortisol less than or equal to 2 microg/dl (odds ratio = 2.5; 95% confidence interval 1.12-5.52; P = 0.022). CONCLUSIONS: A quarter of the patients with Cushing's disease who achieve surgical remission after transsphenoidal surgery, recur with long-term follow-up. This finding emphasizes the need for continued biochemical and clinical follow-up to ensure remission after surgery.     

Influence of Liver Histopathology on Transaminitis Following Total Pancreatectomy and Autologous Islet Transplantation

Background

In type 1 diabetics undergoing allogenic islet transplants, transaminitis and portal vein thrombosis (PVT) after transhepatic portal infusion of islets may be related to infusion pressure and the purity of islets. Complications of intraoperative portal infusion of islets in patients with chronic pancreatitis undergoing a total pancreatectomy (TP) and autologous islet transplant (AIT) and the relationship to liver histopathology have not been examined.

Aim

The purpose of this study was to examine complications of intraportal infusion of autologous islets after TP.

Methods

Data on 26 TP-AIT patients were analyzed.

Results

Infusion of islets [mean 304,473 ± 314,557 islet equivalents, median volume 300 mL (50–600)] resulted in mean postinfusion PV pressure of 9.15 ± 10.09 cmH₂O which correlated with infused islets equivalents (r ² = 33.6, P = 0.002) and volume (r ² = 30.4, P = 0.005). Of 23 patients undergoing liver biopsy, 8 (35 %) were normal, 10 (43 %) had steatosis, and 5 (22 %) periportal fibrosis. Peak alanine aminotransferase (ALT; median 1 day after infusion) differed among the three histologic groups (P = 0.025). The difference in ALT was statistically significant between steatosis (showed the greatest increase) and the other two groups, but not between the normal and fibrosis groups. No correlation was found between the portal pressure increase at infusion and other variables. Two patients that developed PVT on day 1 had the highest infusion pressures; a third occurred on day 5.

Conclusion

Preexisting liver pathology is a contributing factor in the rise in liver enzymes but does not correlate with development of PV thrombosis.     

Searching for Genes That Matter in Acute Kidney Injury: A Systematic Review

Background and Objectives: Identifying patients who may develop acute kidney injury (AKI) remains challenging, as clinical determinants explain only a portion of individual risk. Another factor that likely affects risk is intrinsic genetic variability. Therefore, a systematic review of studies was performed that related the development or prognosis of AKI to genetic variation.Design, setting, participants, and measurements: MEDLINE, EMBASE, HuGEnet, SCOPUS, and Web of Science were searched for articles from 1950 to Dec 2007. Two independent researchers screened articles using predetermined criteria. Studies were assessed for methodological quality via an aggregate scoring system.Results: The 16 included studies were of cohort or case-cohort design and investigated 35 polymorphisms in 21 genes in association with AKI. Fifteen gene-gene interactions were also investigated in four separate studies. Study populations were primarily premature infants or adults who were critically ill or postcardiac bypass patients. Among the studies, five different definitions of AKI were used. Only one polymorphism, APO E e2/e3/e4, had greater than one study showing a significant impact (P < 0.05) on AKI incidence. The mean quality score of 5.8/10 (range four to nine), heterogeneity in the studies, and the dearth of studies precluded additional meta-analysis of the results.Conclusions: Current association studies are unable to provide definitive evidence linking genetic variation to AKI. Future success will require a narrow consensus definition of AKI, rigorous epidemiologic techniques, and a shift from a priori hypothesis-driven to genome-wide association studies.Acute kidney injury (AKI) is a complex disorder manifested by a rapid loss of renal function that results in retention of metabolic waste products (1). The incidence of AKI has steadily increased over the past decade, and while mortality has fallen with advances in renal replacement therapy (RRT), AKI still confers significant morbidity and mortality (2–4). In-hospital mortality for patients who develop AKI ranges from 20% to 28%; for those requiring RRT, mortality ranges from 28% to 33% (3,4). As such, the ability to identify high-risk patients and potentially prevent AKI becomes crucial.The current literature maintains that a patient''s risk for AKI depends on a combination of acute insults and chronic co-morbidities. Acute risk factors include volume depletion, exposure to nephrotoxic agents, surgery, and sepsis (5–8). Chronic risk factors include age, chronic kidney disease (CKD), diabetes, and congestive heart failure (8,9). However, models using these traditional risk factors remain inadequate (5,6,10–12). Two patients with identical clinical risk factors often react differently to the same insult; one may suffer no harm while the other may require RRT. Furthermore, we remain unable to predict who will progress to chronic dialysis and who will recover.Consequently, there are likely to be clinically unobservable risk factors that contribute to one''s susceptibility to AKI. Our understanding of epithelial, vascular, and immune responses in kidney injury makes it likely that genetic variability in regulatory elements of these responses plays a major role in determining one''s risk of AKI. This has been seen in other complex diseases, such as the discovery of a single nucleotide polymorphism (SNP) in complement factor H as a risk factor for macular degeneration (13). In AKI, genetic variation in inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6) have recently been proposed as risk factors (11,14–17). This is due to the role of inflammatory mediators in the pathophysiology of AKI, especially with ischemia and sepsis (1,18,19). Genetic variations of vasomotor regulatory proteins, such as angiotensin converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS), have also been investigated given the importance of vascular reactivity in the pathogenesis of AKI (11,18,20–22).However, it remains difficult to ascertain which polymorphisms are truly associated with AKI (23). False positive reports are common in genetic association studies, and the plausibility of an association is highly dependent on the quality of the studies involved (24). Therefore, we conducted this systematic review to evaluate the quality of published studies on genetic associations with AKI and to ascertain if the current evidence demonstrates any polymorphism to be conclusively associated with AKI.     

Efficacy of 3% Saline Vs. Conivaptan in Achieving Hyponatremia Treatment Goals

Hyponatremia is the most common electrolyte abnormality encountered in clinical practice, but its optimal management is still evolving. While guidelines for infusion rates of hypertonic saline (HS) have been introduced, there is a risk of underestimating the response in serum sodium concentration after therapy. Guidelines also have evaluated the use of vasopressin receptor antagonists as alternatives or supplements to standard therapies. This single-center retrospective study from The Methodist Hospital (TMH) compared the effect of HS and conivaptan intervention in the management of 49 patients with hyponatremia from January 2009 through November 2010. Demographics, volume status, medical history, medication data, and serum sodium concentration correction over 48 hours were analyzed. No significant difference was noted with regard to age, ethnicity, gender, volume status, use of medications known to cause hyponatremia, or comorbidities. Baseline serum sodium concentration was not significantly different between HS (120.5 ± 3.8 mEq/L) and conivaptan (118.3 ± 6.7 mEq/L) groups. Regardless of whether the patient was euvolemic or hypervolemic, no significant difference was noted in serum sodium concentration at 4, 12, 24, or 48 hours after initiation of treatment or in frequency of over-correction between groups. This study compares the effect of HS to conivaptan intervention in the management of hyponatremia. No significant differences were identified in adherence to treatment guidelines. Further, based on this small retrospective study, neither agent poses a significant risk of over-correction at 4, 24, or 48 hours of therapy.     

Antimicrobial activity of a novel catheter lock solution

Intravascular catheter-associated bloodstream infections significantly increase rates of morbidity and hospital costs. Microbial colonization and development of biofilms, which are known to be recalcitrant to antibiotic therapy, often lead to the loss of otherwise patent vascular access systems. We evaluated a new taurolidine- and citrate-based catheter lock solution (Neutrolin; Biolink Corporation, Norwell, Mass.) for its activity against planktonic microbes, antimicrobial activity in a catheter model, and biofilm eradication activity. In studies of planktonic microbes, after 24 h of contact, 675 mg of taurolidine-citrate solution per liter caused > 99% reductions in the initial counts of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Entercoccus faecalis. A solution of 13,500 mg/liter was cidal for Candida albicans. Ports and attached catheters inoculated with 50 to 600 CFU of these bloodstream isolates per ml were locked with heparin or the taurolidine-citrate solution. After 72 h, there was no growth in the taurolidine-citrate-treated devices but the heparin-treated devices exhibited growth in the range of 6 x 10(2) to 5 x 10(6) CFU/ml. Biofilms were developed on silicone disks in modified Robbins devices with broth containing 6% serum (initial counts, 10(6) to 10(8) CFU/cm(2)). The axenic biofilms were treated for 24 h with taurolidine-citrate or heparin. Taurolidine-citrate exposure resulted in a median reduction of 4.8 logs, whereas heparin treatment resulted in a median reduction of 1.7 logs (P < 0.01). No significant differences in the effects of the two treatments against P. aeruginosa and C. albicans were observed. These findings suggest that taurolidine-citrate is a promising combination agent for the prevention and treatment of intravascular catheter-related infections.