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.     

Impaired in vitro growth of PHA induced T lymphocyte colonies in hemodialyzed renal failure patients

Summary Using an in vitro method that allows the study of the colony forming capacity of phytohemagglutinin stimulated peripheral blood T lymphocytes, we have detected an impaired T cell colony formation in hemodialyzed renal failure patients. By contrast a near normal pattern of responses was observed in patients treated with a conservative therapy. The poor in vitro T cell responsiveness of hemodialyzed patients was not corrected by supplementing the cultures with an adherent cell contitioned medium prepared from normal donors. We conclude that an intrinsic defect of the T cell colony forming capacity exists in hemodialyzed patients.     

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.     

Centenarians and supercentenarians: a black swan. Emerging social,medical and surgical problems

Background

Five percent of all patients with breast cancer have distant metastatic disease at initial presentation. Because metastatic breast cancer is considered to be an incurable disease, it is generally treated with a palliative intent. Recent non-randomized studies have demonstrated that (complete) resection of the primary tumor is associated with a significant improvement of the survival of patients with primary metastatic breast cancer. However, other studies have suggested that the claimed survival benefit by surgery may be caused by selection bias. Therefore, a randomized controlled trial will be performed to assess whether breast surgery in patients with primary distant metastatic breast cancer will improve the prognosis.

Design

Randomization will take place after the diagnosis of primary distant metastatic breast cancer. Patients will either be randomized to up front surgery of the breast tumor followed by systemic therapy or to systemic therapy, followed by delayed local treatment of the breast tumor if clinically indicated. Patients with primary distant metastatic breast cancer, with no prior treatment of the breast cancer, who are 18 years or older and fit enough to undergo surgery and systemic therapy are eligible. Important exclusion criteria are: prior invasive breast cancer, surgical treatment or radiotherapy of this breast tumor before randomization, irresectable T4 tumor and synchronous bilateral breast cancer. The primary endpoint is 2-year survival. Quality of life and local tumor control are among the secondary endpoints. Based on the results of prior research it was calculated that 258 patients are needed in each treatment arm, assuming a power of 80%. Total accrual time is expected to take 60 months. An interim analysis will be performed to assess any clinically significant safety concerns and to determine whether there is evidence that up front surgery is clinically or statistically inferior to systemic therapy with respect to the primary endpoint.

Discussion

The SUBMIT study is a randomized controlled trial that will provide evidence on whether or not surgery of the primary tumor in breast cancer patients with metastatic disease at initial presentation results in an improved survival.

Trial registration

NCT01392586.     

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.     

Beating heart ischemic mitral valve repair and coronary revascularization in patients with impaired left ventricular function

OBJECTIVE: The aim of this study is to evaluate in a cohort of patients with impaired left ventricular (LV) function and ischemic mitral valve regurgitation (MVR), the effects of on-pump/beating heart versus conventional surgery in terms of postoperative mortality and morbidity and LV function improvement. MATERIALS AND METHODS: Between January 1993 and February 2001, 91 patients with LVEF between 17% and 35% and chronic ischemic MVR (grade III-IV), underwent MV repair in concomitance with coronary artery bypass grafting (CABG) Sixty-one patients (Group I) underwent cardiac surgery with cardioplegic arrest, and 30 patients (Group II) underwent beating heart combined surgery. Aortic valve insufficiency was considered a contraindication for the on-pump/beating heart procedure. Mean age in Group I was 64.4 +/- 7 years and in Group II, 65 +/- 6 years (p = 0.69). RESULTS: The in-hospital mortality in Group I was 8 (13%) patients versus 2 (7%) patients in Group II (p > 0.1). The cardiopulmonary bypass (CPB) time was significantly higher in Group I (p < 0.001). In Groups I and II, respectively (p > 0.1), 2.5 +/- 1 and 2.7 +/- 0.8 grafts per patient were employed. Perioperative complications were identified in 37 (60.7%) patients in Group I versus 10 (33%) patients in Group II (p = 0.025). Prolonged inotropic support of greater than 24 hours was needed in 48 (78.7%) patients (Group I) versus 15 (50%) patients (Group II) (p = 0.008). Postoperative IABP and low cardiac output incidence were significantly higher in Group I, p = 0.03 and p = 0.027, respectively. Postoperative bleeding greater than 1000 mL was identified in 24 patients (39.4%) in Group I versus 5 (16.7%) in Group II (p = 0.033). Renal dysfunction incidence was 65.6% (40 patients) in Group I versus 36.7% (11 patients) in Group II (p = 0.013). The echocardiographic examination within six postoperative months revealed a significant improvement of MV regurgitation fraction, LV function, and reduced dimensions in both groups. The postoperative RF was significantly lower in Group II patients 12 +/- 6 (%) versus 16 +/- 5.6 (%) in Group I (p = 0.001). The 1, 2, and 3 years actuarial survival including all deaths was 91.3%, 84.2%, and 70% in Group I and 93.3%, 87.1%, and 75% in Group II (p = ns). NYHA FC improved significantly in all patients from both groups. CONCLUSION: We conclude that patients with impaired LV function and ischemic MVR may undergo combined surgery with acceptable mortality and morbidity. The on/pump beating heart MV repair simultaneous to CABG offers an acceptable postoperative outcome in selected patients.     

Right living donor liver transplantation: an option for adult patients: single institution experience with 74 patients

OBJECTIVE: To present an institutional experience with the use of right liver grafts in adult patients and to assess the practicability and efficacy of this procedure by analyzing the results. SUMMARY BACKGROUND DATA: Living donor liver transplantation (LDLT) for the pediatric population has gained worldwide acceptance. In the past few years, LDLT has also become feasible for adult patients due to technical evolution in hepatobiliary surgery and increased experience with reduced-size and split-liver transplants. Nevertheless, some graft losses remain unexplained and are possibly due to unrecognized venous outflow problems. METHODS: From April 1998 to September 2002, we performed 74 right LDLTs (segments 5-8). The 74 donors were selected from 474 candidates according to standard protocol. The median age of the donors was 35 years (range 18-58 years) and 51 years (range 18-64 years) in recipients. Standard and extended indications for transplantation were considered. Over the period reported, technical modifications in the bile duct anastomosis (duct-to-duct, end-to-end, or end-to-side) and a new graft implantation technique that provides maximized venous outflow, leading to outcome improvement, were developed. RESULTS: 64.9% of patients had liver cirrhosis and 35.1% had malignancy. While 44 donors (59.5%) presented an uneventful postoperative course, 27% minor (pleural effusion, pneumonia, venous thrombosis, wound infection, incisional hernia) and 13.5% major (biliary leakage, death of a donor due to unrecognized hereditary liver disease, and consecutive liver insufficiency) complications were documented. In recipients, 23% biliary complications and 6.8% hepatic artery thrombosis occurred. The overall patient and graft survival rate after 1 year was 79.4% and 75.3%, respectively. In cases with extended indication, the patient survival rate was 74% and the graft survival rate 68% at 12 months. Using technical modifications in the last 10 recipients, including 2 critically decompensated cirrhotics, the survival rate was 100% at a median follow-up of 3.5 months. CONCLUSIONS: In our transplant program, living donor liver transplantation has become a standard option in the adult patient population. The critical issue of this procedure is donor morbidity. Technical improvements in the harvesting and implantation of right grafts can also offer hope to patients with challenging forms of end-stage liver disease or malignant liver tumors.