Compliance of Primary Care Providers With Gout Treatment Recommendations-Lessons to Learn: Results of a Nationwide Survey.

Objectives: Gout is generally managed in the primary health care sector. Compliance of primary care physicians with gout management recommendations has been shown to be insufficient in the past. The primary aims of this study were to assess primary care providers' knowledge regarding gout and to determine if their treatment decisions are influenced by recommendations. Facing considerable variations in postgraduate training options in Austria, we secondly looked for possible knowledge differences between urban and rural areas and eastern and western parts of Austria. Methods: We conducted a survey among 343 primary care physicians in Austria, using a questionnaire consisting of 10 questions on acute, intercritical and general gout management. Gout treatment recommendations served as the therapeutic gold standard. Results: Of the 343 physicians surveyed, 336 completed the questionnaire, leading to a very high return rate of 98%. 289 (86%) physicians were aware of the agreed-upon SUA target (<6 mg/dl). 323 (96.1%) reported change of therapy in case of missing this target. 112 (33.3%) physicians voted for long term ULT. No geographical differences in knowledge regarding gout or its management were revealed, except that colchicine was rated as being a safe medication significantly more often in rural areas (p = 0.035) and in western Austria (p = 0.014). Conclusion: As opposed to former studies, gout knowledge among primary care physicians has improved - however, treatment patterns are still not fully concordant with gout recommendations. Our findings may help to better tailor future postgraduate training to improve primary care physicians' education in gout.

Unplanned reoperation and reintervention after pancreatic resections: an analysis of risk factors.

BACKGROUND: The purpose of the study was to determine the incidence of any unplanned reoperation or reintervention procedure after pancreatic resection and to identify the underlying risk factors. METHODS: A total of 189 consecutive pancreatic resections performed from 2001-2008 were searched for any unplanned reoperation, percutaneous drainage, or angiographic reintervention. A retrospective analysis of a prospectively maintained database, including patient characteristics, comorbidities, details of surgery, specific complications, incidence of reoperation/reintervention, and mortality was performed. RESULTS: Overall rates of reoperation, reintervention, and mortality were 6.3% (12/189), 7.9% (15/189), and 1.6% (3/189), respectively. Four patients underwent reintervention and reoperation, so the combined reoperation/reintervention rate was 12.2% (23/189). Reoperation (P < 0.001) and reintervention (P = 0.002) correlated with mortality. Hemorrhage (relative risk [RR], 58; P = 0.0017) and the combination of hemorrhage and pancreatic fistula (RR, 117; P < 0.0001) were identified as risk factors for unplanned reoperation, hemorrhage (RR, 82; P = 0.005), pancreatic fistula (RR, 42; P < 0.001), and the combination of both complications (RR, 246; P < 0.001) for reoperation and/or reintervention. Other patient- or procedure-related factors did not influence the reoperation and/or reintervention rates significantly. CONCLUSIONS: Pancreatic fistula and hemorrhage are the predominant factors that afford unplanned reoperation/reintervention. Although reporting the incidence of unplanned reoperation will include the most severe postoperative complications, a considerable number of reinterventions are missed. Therefore, in outcome analyses of pancreatic surgery, not only reoperations but also any interventional therapies should be included.

Single incision laparoscopic cholecystectomy (SILC) versus laparoscopic cholecystectomy (LC)-a matched pair analysis.

INTRODUCTION: The aim of our study was to compare single incision laparoscopic cholecystectomy (SILC) and laparoscopic cholecystectomy (LC) with respect to complications, operating time, postoperative pain, use of analgesics, length of stay, return to work, rate of incisional hernia, and cosmetic outcome. METHODS: Sixty-seven patients underwent SILC. Of a cohort of 163 LC operated in the same time period, 67 patients were chosen for a matched pair analysis. Pairs were matched for age, gender, ASA, BMI, acuity, and previous abdominal surgery. In the SILC group, patient characteristics (gender, age, BMI, comorbidities, ASA, previous abdominal surgery, symptomatic cholecystolithiasis, cholecystitis) and perioperative data (surgeon, operation time, conversion rate and cause, intraoperative complications, postoperative complications, reoperation rate, VAS at 24 h, VAS at 48 h, use of analgesics according to WHO class, and length of stay) were collected prospectively. RESULTS: Follow-up in the SILC and LC group was completed with a minimum of 17 and a maximum of 26 months; data acquired were recovery time the patients needed until they were able to get back into the working process, long-term incidence of postoperative hernias, and satisfaction with cosmetic outcome. Operating time was longer for SILC (median 75 min, range 39-168 vs. 63, range 23-164, p = 0.039). There were no significant differences for SILC and LC with regard to postoperative pain measured by VAS at 24 h (median 3, range 0-8 vs. 2, range 0-8, p = 0.224), at 48 h (median 2, range 0-6 vs. 2, range 0-8, p = 0.571), use of analgesics, and length of stay (median 2 days, range 1-9 vs. 2, range 1-11, p = 0.098). There was no major complication in either group. The completion rate of SILC was 85.1% (57 of 67). Although there was a trend towards an earlier return to the working process in patients of the SILC group, this was not significant. The rate of incisional hernias was 1.9% (1/53) in the SILC and 2.1% (1/48) in the LC group indicating no significant difference. Self-assessment of satisfaction with the cosmetic outcome was not judged different by patients in both groups. CONCLUSION: SILC is associated with longer operating time, but equals LC with respect to safety, postoperative pain, use of analgesics, length of stay, return to work, rate of incisional hernia, and cosmetic outcome.

Nitric oxide administration restores the hepatic artery buffer response during porcine endotoxemia.

The hepatic artery buffer response, which is lost during endotoxemia, plays a central role in the autoregulation of liver perfusion. A temporarily decreased synthesis of nitric oxide during early endotoxemia might be responsible for this dysfunction; hence exogenous administration of nitric oxide could reestablish the autoregulation of hepatic blood flow and help prevent hepatic damage later in septic shock. Fifteen pigs were treated with lipopolysaccharide +/- the nitric oxide donor nitroprusside-sodium via the portal vein. Hemodynamics were measured, and serum chemistry and liver biopsies for nitric oxide synthase expression were obtained. Lipopolysaccharide decreased arterial liver perfusion after 5 hours by 38% (p = .012), which was reversed by addition of nitroprusside (8%). Administration of nitroprusside preserved an increase of 28% in hepatic arterial upon portal vein flow reduction (p < .001). Nitroprusside maintained mRNA levels of constitutive nitric oxide synthase in liver tissue which were decreased by lipopolysaccharide (p = .026 vs. p = .114) and tempered the burst in inducible nitric oxide synthase expression at t = 3 hours. The early administration of the nitric oxide donor sodium nitroprusside during endotoxemia is able to reestablish the autoregulatory response of the hepatic artery following reduction of hepatic blood flow. This beneficial effect might help to prevent subsequent hepatic damage in the course of abdominal sepsis.

Antibiotic abscess penetration: fosfomycin levels measured in pus and simulated concentration-time profiles.

The present study was performed to evaluate the ability of fosfomycin, a broad-spectrum antibiotic, to penetrate into abscess fluid. Twelve patients scheduled for surgical or computer tomography-guided abscess drainage received a single intravenous dose of 8 g of fosfomycin. The fosfomycin concentrations in plasma over time and in pus upon drainage were determined. A pharmacokinetic model was developed to estimate the concentration-time profile of fosfomycin in pus. Individual fosfomycin concentrations in abscess fluid at drainage varied substantially, ranging from below the limit of detection up to 168 mg/liter. The fosfomycin concentrations in pus of the study population correlated neither with plasma levels nor with the individual ratios of abscess surface area to volume. This finding was attributed to highly variable abscess permeability. The average concentration in pus was calculated to be 182 +/- 64 mg/liter at steady state, exceeding the MIC(50/90)s of several bacterial species which are commonly involved in abscess formation, such as streptococci, staphylococci, and Escherichia coli. Hereby, the exceptionally long mean half-life of fosfomycin of 32 +/- 39 h in abscess fluid may favor its antimicrobial effect because fosfomycin exerts time-dependent killing. After an initial loading dose of 10 to 12 g, fosfomycin should be administered at doses of 8 g three times per day to reach sufficient concentrations in abscess fluid and plasma. Applying this dosing regimen, fosfomycin levels in abscess fluid are expected to be effective after multiple doses in most patients.

Endoscopic ultrasound guided therapy of benign and malignant biliary obstruction: a case series.

OBJECTIVES: Endoscopic retrograde cholangiography is an established method for treatment of common bile duct stones as well as for palliation of patients with malignant pancreaticobiliary strictures. It may be unsuccessful in the presence of a complex peripapillary diverticulum, prior surgery, obstructing tumor, papillary stenosis, or impacted stones. Percutaneous transhepatic biliary drainage and surgery are alternative methods with a higher morbidity and mortality in these cases. Recently, endoscopic ultrasound (EUS) guided biliary stent placement has been described in patients with malignant biliary obstruction. We describe our experience with this method that was also used for the treatment of cholangiolithiasis for the first time. METHODS: The EUS guided transduodenal puncture of the common bile duct with stent placement was performed in 5 patients. In 2 of these patients, the stents were removed after several weeks and common bile duct stones were extracted. In another patient with gastrectomy, the left intrahepatic bile duct was punctured transjejunally and a metal stent was introduced transhepatically to bridge a distal common bile duct stenosis. RESULTS: Biliary decompression was successful in all 6 patients. No immediate complications occurred. One patient developed a subacute phlegmonous cholecystitis. CONCLUSIONS: Interventional EUS guided biliary drainage is a new technique that allows drainage of the biliary system in benign and malignant diseases when the bile duct is inaccessible by conventional ERCP.

Elevated serum levels of epithelial cell apoptosis-specific cytokeratin 18 neoepitope m30 in critically ill patients.

Apoptosis of the epithelium is deemed to play a pivotal role in the pathogenesis of sepsis. A neoepitope in cytokeratin 18 (CK18), termed M30 neoantigen, becomes available at an early caspase cleavage event during apoptosis of epithelium-derived cells and is not detectable in vital or necrotic epithelial cells. A monoclonal antibody, M30, specifically recognizes a fragment of CK18 cleaved at Asp396 (M30 neoantigen). We used an enzyme-linked immunosorbent assay (ELISA) to measure M30 antigen levels in the sera of 15 septic patients. Healthy humans and critical ill patients suffering from severe trauma served as controls. Mann-Whitney U test was used to calculate significance, and a P value of <0.01 was considered to be statistically significant. Serum levels of the CK18 neoepitope M30 were significantly increased in septic patients (236.88 +/- 47.4 U/L) versus trauma (97.2 +/- 17.1 U/L) and healthy controls (66.9 +/- 9.2 U/L) (P < 0.01 and P < 0.008, respectively). The increased serum level of the CK18 neoepitope in septic patients indicates a heightened apoptotic turnover in epithelial cells as compared with trauma patients and healthy controls. Interestingly, nonsurviving trauma patients exhibited a significant increase in the M30 neoantigen as compared with survivors and healthy controls (P < 0.003 and P < 0.002, respectively). The detection of CK18 neoepitope M30 in the serum might be a useful marker in tracing apoptotic epithelium in septic patients.

Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma.

OBJECTIVE: T1/ST2, a member of the interleukin (IL)-1 receptor superfamily, is predominantly expressed on type-2 T helper (Th2) cells but not Th1 cells, and plays a role in cell proliferation and Th2 immune response. The relation of soluble ST2, Th1-Th2 cytokine profile, and immunoglobulin (Ig) production in sepsis and trauma patients is not well known. DESIGN AND SETTING: Case-control study at a university hospital intensive care unit. PATIENTS: Fifteen patients recruited within 24-48 h of diagnosis of sepsis, 13 trauma patients recruited within 24 h after admission to the ICU, 11 patients who underwent abdominal surgery, and 15 healthy volunteers served as control. MEASUREMENTS AND RESULTS: ELISA was utilized to detect serum soluble ST2, IL-2, IFN-gamma, IL-10, and Ig production. Serum levels of soluble ST2 were significantly increased in septic patients (8420+/-2169 pg/ml) as compared with trauma (2936+/-826 pg/ml), abdominal surgery (1423+/-373 pg/ml), and healthy controls (316+/-72 pg/ml; p<0.001, respectively). These results were accompanied by an increase of IgG1 and IgG2 production, and decrease of IL-2 and IFN-gamma synthesis in septic patients. IL-10 was significantly increased in both septic and trauma patients. CONCLUSIONS: Our results demonstrate that soluble ST2, a marker for Th2 cytokine producing cells, is increased in sepsis and trauma patients, and they provide further evidence for a shift from Th1- to Th2-biased cells.

Continuous therapeutic epinephrine but not norepinephrine prolongs splanchnic IL-6 production in porcine endotoxic shock.

Catecholamines play a central role in the treatment of sepsis-associated hypotension. However, these hormones have also been shown to modulate the lipopolysaccharide (LPS)-induced induction of cytokines such as tumor necrosis factor alpha, interleukin (IL)-10, and IL-6 in vitro and in human endotoxemia. We hypothesized that catecholamines applied therapeutically in septic shock also influence cytokine patterns. We studied the cytokine response in tissues of the splanchnic compartment in a porcine endotoxin shock model up to 4 h. Shock was induced by a short infusion of LPS, and animals were treated either with fluid resuscitation alone or in combination with continuous epinephrine or norepinephrine. Animals, receiving epinephrine therapy, showed a significantly prolonged upregulation of IL-6 mRNA expression at 4 h after LPS application in liver (P = 0.0014), spleen (P < 0.0001), and mesenteric lymph nodes (P = 0.0078) as compared with animals treated with norepinephrine or fluid resuscitation. Serum IL-6 increased over time in all groups. The total concentration of the cytokine (area under the curve) was significantly higher in the epinephrine group as compared with the norepinephrine and fluid resuscitation groups (P = 0.017). The peak of serum tumor necrosis factor alpha at 1 h after LPS application was already significantly reduced by epinephrine, which was only administered at a mean of less than 0.05 microg/kg/min at this time point (P < 0.01). None of the catecholamines had a significant effect on IL-10 serum levels when compared with animals receiving fluid resuscitation alone. Our data suggest that the therapeutic application of epinephrine but not of norepinephrine is associated with a profound effect on the IL-6 response of splanchnic reticuloendothelial tissues.

Surgical treatment of severe acute pancreatitis: timing of operation is crucial for survival.

BACKGROUND: In patients operated on for severe acute pancreatitis (SAP) the impact of the timing of operation on outcome is controversial. MATERIALS AND METHODS: In a retrospective analysis of a prospectively documented database, we studied 250 patients suffering from SAP, who were in need for surgical treatment during their course of disease. RESULTS: From 1982 to 1998, 250 patients with the diagnosis of SAP who required operative treatment were admitted to the intensive care unit (ICU) of a university hospital. The mean APACHE II score on the day of admission was 16.1 (8-35). One hundred eighty-five patients (74%) required reoperation, of whom 111 patients (60%) underwent reoperation on demand and 74 (40%) patients a pre-planned reoperation. Overall mortality was 38.8% (97 patients). In patients who were operated during the first three weeks after onset of disease, mortality was significantly higher than in patients who were operated after three weeks (46% vs. 25%, p < 0.01). Besides patient age (p < 0.05), APACHE II score at admission (p < 0.01), multiple organ dysfunction (p < 0.01), infection of pancreatic necrosis (p < 0.05), surgical control of pancreatic necrosis (p < 0.0001), and the time of surgical intervention (p < 0.05) determined survival significantly. CONCLUSION: Patients who were operated later than three weeks after onset of disease had a significantly better outcome. In patients suffering from SAP who required surgical treatment, the timing of operation is crucial for survival.

Perioperative GLY-GLN infusion diminishes the surgery-induced period of immunosuppression: accelerated restoration of the lipopolysaccharide-stimulated tumor necrosis factor-alpha response.

OBJECTIVE: To investigate whether the administration of different glutamine-containing dipeptides, glycyl-l-glutamine (GLY-GLN) and l-alanyl-l-glutamine, has a differing impact on perioperative immunomodulation. SUMMARY BACKGROUND DATA: Surgery leads to transitory immunosuppression, which is associated with decreased plasma glutamine (GLN) levels and increased susceptibility to infection and sepsis. A useful tool to detect immunocompetence is the ex vivo lipopolysaccharide (LPS)-stimulated tumor necrosis factor alpha (TNF-alpha) secretion in whole blood. METHODS: Forty-five patients undergoing major abdominal surgery were randomized prospectively to receive 0.5 g/kg/24 h GLN dipeptides administered as GLY-GLN or as ALA-GLN or isonitrogenous Vamin (a GLN-free amino acid solution; control group) as a continuous infusion over 72 hours, starting 24 hours before surgery. Blood samples were collected before infusion, at the end of surgery, and 48 hours postoperatively to determine the TNF-alpha release into whole blood stimulated with LPS. Groups were compared by analysis of variance. RESULTS: The groups were comparable in age, gender distribution, and length of operative time. At the end of surgery a significant reduction in ex vivo LPS-stimulated TNF-alpha production was observed in all groups. In patients who received GLY-GLN, the induced TNF-alpha production was restored after 48 hours. CONCLUSIONS: In this study perioperative infusion of GLY-GLN reduced immunosuppression. The effect of GLN-containing dipeptides seems to be different when administered in glycine or alanine form.

Immunomodulatory effects of vasoactive catecholamines.

The immunological side effects of catecholamines have recently gained specific attention in the area of sepsis related research, since stimulation of adrenergic and dopaminergic receptors can lead to a modulation of the cytokine network. Catecholamines alter the production of these immune mediators in peripheral blood cells but also in various tissues such as liver, spleen, lung, heart, kidney and the skin. The sympathetic regulation of cytokines is highly dependent on which type of receptor is stimulated. Whereas ligation of the alpha-adrenoreceptor is associated with predominantly immunostimulating effects (i.e. the induction of TNF alpha and IL-1 beta), stimulation of the beta-adrenoreceptor usually has immunosuppressive consequences (i.e. inhibition of TNF alpha and IL-1 beta, induction of IL-10). In case both receptors are stimulated (i.e. by epinephrine) the beta-adrenoreceptor mediated effects usually dominate those induced by alpha-adrenoreceptor stimulation. Moreover, the adrenergic immunostimulation can be differentially regulated depending on which type of cell or tissue is stimulated. This suggests locoregional effects. Dopaminergic immunomodulation is dominated by immunosuppressive effects, such as the induction of IL-6, the inhibition of TNF alpha, the attenuation of the chemoattractant effect of IL-8 and the inhibition of endothelial adhesion. Catecholamines also alter the number and function of neutrophils and lymphocytes. This again depends on which type of receptor is stimulated. Whereas beta-adrenergic stimulation leads to lymphocytosis, alpha-adrenoreceptors mediate lymphocyte homing. Catecholamine induced neutrophilia involves alpha 1-adrenoreceptor ligation. With respect to neutrophil function, epinephrine increases the respiratory burst. Up to now, most of the available data on catecholamine-induced immunomodulation were obtained in experimental settings. The overwhelming, clear results indicate that this system might have important implications for the pathophysiology of immunological diseases such as septic shock, which are accompanied by increased levels of catecholamines.

How to pass on expertise: pancreatoduodenectomy at a teaching hospital.

Pancreatoduodenectomy (PD) has become a routine procedure. Recent series report perioperative mortality rates of 5% or less, moderate morbidity, and even improved long-term survival. Nevertheless, being one of the most complex abdominal operations, a certain number of surgical procedures (i.e., personal caseload) seems essential for acceptable results. The objectives of this retrospective study were to evaluate whether PD can be safely performed as a teaching operation, and if the personal caseload of the senior surgeon affects morbidity and mortality. A series of 128 consecutive PDs carried out at a large academic teaching hospital were analyzed. The 49 operations performed by 11 residents of the surgical department as teaching operations under supervision of an experienced (senior) surgeon (ES) were compared with operations performed by an ES (group 2, n = 79). Three patients died from non-procedure-related causes (two in group 1). Eleven patients of group 2 had to be reoperated, in contrast to three in group 1 (NS). The total number of complications and number of pancreatic fistulas were comparable in the two groups. Surgeons performing less than one PD per year had significantly more complications. Under direct supervision of an experienced surgeon PD can be performed safely as a teaching operation. A caseload of at least one resection per year seems necessary for consistently good results.

Surgical treatment for severe acute pancreatitis: extent and surgical control of necrosis determine outcome.

In patients operated on for severe acute pancreatitis (SAP), the factors determining outcome remain unclear. From 1986 to 1998 a total of 340 patients with a diagnosis of SAP and in need of operative treatment were admitted to the intensive care unit (ICU) of a university hospital and a secondary care hospital. The mean APACHE II score on the day of admission was 16.1 (range 8-35). All patients required operative therapy. Among the 340 patients, 270 (79.4%) had to be reoperated: 196 patients (72.6%) underwent operative revisions on demand, and 74 (27.4%) patients had preplanned reoperation. The overall mortality was 39.1% (133 patients). Septic organ failure in 126 patients (37.1%) and myocardial infarction or pulmonary embolism in 7 patients (2%) were the causes of death. The patient's age (p < 0.0002), APACHE II scores at admission (p < 0.0001), presence or development of (single or multiple) organ failure (p < 0.002), infection (p < 0.02) and extent (p < 0.04) of pancreatic necrosis, and surgical control of local necrosis (p < 0.0001) significantly determined survival. SAP that requires surgical treatment is associated with high in-hospital mortality. Surgical control of local necrosis is the precondition for survival. Advanced age of the patient, high APACHE II score at admission, development of organ failure, and the extent and infection of pancreatic necrosis influence the outcome.