Relation between long-term steroid treatment after heart transplantation, hypofibrinolysis and myocardial microthrombi generation.

BACKGROUND: Thrombotic complications and transplant coronary artery disease are among the main causes of morbidity and mortality after heart transplantation. A thrombophilic state has been described in transplant recipients, and correlated to immunosuppressive therapy with cyclosporine A or azathioprine, whereas the prothrombotic effects of steroids, even though always given, have never been duly considered. A reduced fibrinolytic capacity due to high levels of PAI-1, the most important inhibitor of plasminogen activators, was suggested to play a role in the development of cardiovascular diseases and transplant coronary artery disease. A severe hypofibrinolytic state secondary to PAI-1 increase has been found in patients with Cushing's disease, and in hypercorticism secondary to long-term steroid treatment after renal transplantation. METHODS: We evaluated plasma clotting and fibrinolytic behaviors in 2 groups of heart transplant patients treated with (26 cases) or without (23 cases) steroids together with cyclosporine A and azathioprine. Twenty-five healthy subjects were studied as normal controls. The following tests were assayed at least 1 year after transplantation: fibrinogen, factor VIII coagulant activity, von Willebrand factor antigen, euglobulin lysis time, tissue plasminogen activator antigen and activity, PAI-1 antigen and activity. In addition, the presence of cardiac microthrombi was evaluated on 2 endomyocardial biopsy specimens obtained in each patient both on day 7 after heart transplantation (first control) and usually 1 year or more later (last control). RESULTS: Plasma levels of fibrinogen, factor VIII and von Willebrand factor were significantly higher in both groups of patients than in normal controls. Fibrinolytic activity was significantly reduced in transplant patients treated with steroids, compared with steroid-free patients and normal controls. In steroid-treated heart transplant recipients, the hypofibrinolytic state was due to a significant and pathological increase in PAI-1 antigen and activity levels. The fibrinolytic impairment was more evident in patients transplanted for ischemic heart disease and treated with steroids than in patients with previous dilated cardiomyopathy and treated either with or without steroids. Myocardial microthrombi were found in 2/49 cases at the first biopsy control, and in 12/49 cases at the last biopsy control after transplantation. This different prevalence was statistically significant (chi2 = 8.33, p = .003). Plasma PAI-1 activity was significantly higher and, as a consequence, euglobulin lysis time was more prolonged in microthrombi-positive patients than in microthrombi-negative ones. Among the 12 transplant recipients who developed cardiac microthrombi, 7 patients were treated with steroids and showed higher PAI-1 levels and more reduced fibrinolytic activity than the 5 steroid-free patients. CONCLUSIONS: Our data confirm the prothrombotic state induced by long-term steroid treatment, characterized by an increase in PAI-1 levels and secondary impairment of fibrinolytic capacity. In heart transplant patients, steroid-related hypofibrinolysis might constitute a further risk factor for transplant coronary artery disease.     

Major bile duct injuries after laparoscopic cholecystectomy: A tertiary center experience

Bile duct injury is a severe and potentially life-threatening complication of laparoscopic cholecystectomy. Several series have described a 0.5% to 1.4% incidence of bile duct injuries during laparoscopic cholecystectomy. The aim of this study was to report on an institutional experience with the management of complex bile duct injuries and outcome after surgical repair. Data were collected prospectively from 40 patients with bile duct injuries referred for surgical treatment to our center between April {dy1998} and December 2003. Prior to referral, 35 patients (87.5%) underwent attempts at surgical reconstruction at the primary hospital. In77.5%of the patients, complex typeE1or typeE2BDIwas found. Concomitant with bile duct injury, seven patients had vascular injuries. Roux-en-Y hepaticojejunostomy was carried out in 33 patients. In two patients, Roux-en-Y hepaticojejunostomy and vascular reconstruction were necessary. Five patients, one with primary nondiagnosed Klatskin tumor, required right hepatectomy. Two patients, both with bile duct injuries and vascular damage, died postoperatively. Because of progressive liver insufficiency, one of them was listed for high-urgency liver transplantation but died prior to intervention. At the median follow-up of 589 days, 82.5% of the patients are in excellent general condition. Seven patients have signs of chronic cholangitis. Major bile duct injuries remain a significant cause of morbidity and even death after laparoscopic cholecystectomy. Because they present a considerable surgical challenge, early referral to an experienced hepatobiliary center is recommended.     

Use of fenoldopam to control renal dysfunction early after liver transplantation.

With the aim of assessing whether fenoldopam can help to preserve renal function after liver transplantation, we randomized 140 consecutive recipients with comparable preoperative renal function to receive fenoldopam 0.1 microg/kg/minute (group F, 46 patients), dopamine 3 microg/kg/minute (group D, 48 patients), or placebo (group P, 46 patients) from the time of anesthesia induction to 96 hours postoperatively. There were no differences between the groups in intraoperative urinary output or furosemide administration (both P =.1). Daily recordings made during the first 4 postoperative days revealed no significant differences in urinary output (P =.1), serum creatinine (P =.5), the incidence of renal insufficiency (P =.7), the need for loop diuretics (P =.9) or vasoactive drugs (P =.8). In comparison with preoperative levels, creatinine clearance at the end of the study in the patients receiving fenoldopam remained substantially unchanged, whereas it decreased by 39 and 12.3%, respectively, in the subjects receiving placebo or dopamine (P <.001); blood cyclosporine A (CsA) levels were similar in the 3 groups (P =.1). Three subjects died in the intensive care unit (1 in each group, P =.9), 2 of them had renal failure. In conclusion, our results confirm the inefficacy of dopamine in preventing or limiting early renal dysfunction after liver transplantation, and suggest that fenoldopam may preserve creatinine clearance by counterbalancing the renal vasoconstrictive effect of CsA, as it has been reported in previous experimental studies.     

Monitoring the performance of residents during training in off-pump coronary surgery

OBJECTIVE: Control charts (eg, cumulative sum charts) plot changes in performance with time and can alert a surgeon to suboptimal performance. They were used to compare performance of off-pump coronary artery bypass surgery between a consultant and four resident surgeons and to compare performance of off-pump coronary artery bypass surgery and conventional coronary artery bypass grafting within surgeons. METHODS: Data were analyzed for consecutive patients undergoing coronary artery bypass grafting who were operated on by one consultant or one of four residents. Conversions were analyzed by intention to treat. Perioperative death or one or more of 10 adverse events constituted failure. Predicted risks of failure for individual patients were derived from the study population. Variable life-adjusted displays and risk-adjusted sequential probability ratio test charts were plotted. RESULTS: Data for 1372 patients were analyzed; 769 of the procedures were off-pump coronary artery bypass operations (56.0%). The consultant operated on 382 patients (293 off-pump, 76.7%), and the residents operated on 990 (474 off-pump, 47.9%). Patients operated on by residents tended to be older, more obese, more likely to require an urgent operation, and more likely to need a circumflex artery graft but less likely to have triple-vessel disease. There were 7 conversions (consultant 5, residents 2). The overall failure rate was 8.5% (9.2% for consultant's operations and 8.2% for residents' operations), including 10 deaths (0.7%). Predicted and observed risks of failure were similar for all five surgeons. After 100 off-pump coronary artery bypass operations, performance was the same or better for the residents as for the consultant. For all surgeons, performance was the same or better for off-pump as for conventional coronary artery bypass grafting. CONCLUSIONS: Off-pump coronary artery bypass surgery can be safely taught to cardiothoracic residents. Implementation of continuous performance monitoring for residents is practicable.     

Abnormalities of the executive control network in multiple sclerosis phenotypes: An fMRI effective connectivity study

The Stroop interference task is a cognitively demanding task of executive control, a cognitive ability that is often impaired in patients with multiple sclerosis (MS). The aim of this study was to compare effective connectivity patterns within a network of brain regions involved in the Stroop task performance between MS patients with three disease clinical phenotypes [relapsing‐remitting (RRMS), benign (BMS), and secondary progressive (SPMS)] and healthy subjects. Effective connectivity analysis was performed on Stroop task data using a novel method based on causal Bayes networks. Compared with controls, MS phenotypes were slower at performing the task and had reduced performance accuracy during incongruent trials that required increased cognitive control. MS phenotypes also exhibited connectivity abnormalities reflected as weaker shared connections, presence of extra connections (i.e., connections absent in the HC connectivity pattern), connection reversal, and loss. In SPMS and the BMS groups but not in the RRMS group, extra connections were associated with deficits in the Stroop task performance. In the BMS group, the response time associated with correct responses during the congruent condition showed a positive correlation with the left posterior parietal → dorsal anterior cingulate connection. In the SPMS group, performance accuracy during the congruent condition showed a negative correlation with the right insula → left insula connection. No associations between extra connections and behavioral performance measures were observed in the RRMS group. These results suggest that, depending on the phenotype, patients with MS use different strategies when cognitive control demands are high and rely on different network connections. Hum Brain Mapp, 37:2293–2304, 2016. © 2016 Wiley Periodicals, Inc.     

Impact of intravesical hyaluronic acid and chondroitin sulfate on bladder pain syndrome/interstitial cystitis

Introduction and hypothesis

Intravesical instillations of hyaluronic acid (HA) and chondroitin sulfate (CS) may lead to regeneration of the damaged glycosaminoglycan layer in interstitial cystitis/bladder pain syndrome (IC/BPS).

Methods

Twenty-two patients with IC/BPS received intravesical instillations (40?ml) of sodium HA 1.6% and CS 2.0% in 0.9% saline solution (IALURIL?, IBSA) once weekly for 8?weeks, then once every 2?weeks for the next 6?months.

Results

The score for urgency was reduced from 6.5 to 3.6 (p?=?0.0001), with a reduction in pain scores from an average of 5.6 to 3.2 (p?=?0.0001). The average urine volume increased from 129.7 to 162?ml (p?p?p?p?Conclusion The treatment appeared to be effective and well tolerated in IC/BPS in this initial experience.     

Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism

Patients with adrenal incidentalomas (AIs) and subclinical hypercortisolism (SH) have increased risk of fracture independent of bone mineral density (BMD) and possibly due to reduced bone quality. The trabecular bone score (TBS) has been proposed as a index of bone microarchitecture. The aim of the study was to investigate TBS in AI. In 102 AI patients, SH was diagnosed in the presence of at least two of the following: (1) urinary free cortisol >70 µg/24 h (193.1 nmol/L); (2) cortisol after 1‐mg dexamethasone suppression test (1‐mg DST) >3.0 µg/dL (82.8 nmol/L); or (3) adrenocorticotropic hormone (ACTH) <10 pg/mL (<2.2 pmol/L). In patients and in 70 matched controls, BMD was measured at lumbar spine (LS) and femur (neck [FN] and total [FT]) by dual X‐ray absorptiometry and TBS was assessed in the region of LS‐BMD; BMD and TBS data were reported as Z‐scores. In patients, vertebral deformities were assessed by radiograph. Patients with SH (n = 34) had lower LS‐BMD (?0.31 ± 1.17), FT‐BMD (?0.29 ± 0.91), and TBS (?3.18 ± 1.21) than patients without SH (n = 68, 0.31 ± 1.42, p = 0.03; 0.19 ± 0.97, p = 0.01; ?1.70 ± 1.54, p < 0.0001, respectively) and controls (0.42 ± 1.52, p = 0.02; 0.14 ± 0.76, p = 0.02; ?1.19 ± 0.99, p < 0.0001, respectively). TBS was inversely correlated with 1‐mg DST (β = ?0.26, t = ?2.79, p = 0.006) regardless of age, LS‐BMD, body mass index (BMI), and gender. The presence of fracture was associated with low TBS alone (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.85–12.42, p = 0.001) and with the cluster low TBS plus low LS‐BMD (OR, 4.37; 95% CI, 1.71–11.4, p = 0.002), after adjustment for age, BMI, and gender. Low TBS plus low LS‐BMD showed a good specificity (79%) for predicting fractures, whereas normal TBS (ie, > ?1.5) plus normal LS‐BMD high specificity (88.1%) for excluding fractures. Finally, TBS predicted the occurrence of a new fracture in 40 patients followed for 24 months (OR, 11.2; 95%CI, 1.71–71.41, p = 0.012) regardless of LS‐BMD, BMI, and age. In SH, bone quality, as measured by TBS, is altered. TBS is useful in detecting AI patients at risk of fractures. © 2012 American Society for Bone and Mineral Research.