Altered microperfusion at the rectal stump is predictive for rectal anastomotic leak

PURPOSE: The aim of this study was to evaluate the reliability of intraoperative laser-Doppler measurements in predicting the occurrence of anastomotic leak in patients with colorectal cancer undergoing stapled straight anastomosis to the rectum. METHODS: A prospective study was undertaken on 55 patients with rectal cancer or distal sigmoid cancer programmed for elective curative surgery. In all patients transmural colonic blood flow was measured by laser-Doppler flowmetry technique before bowel manipulation (baseline measurement) and after vascular ligation and division. Comorbidities at admission, intraoperative events, associated surgical procedures, and clinical outcome were tested for any association with anastomotic leak. RESULTS: Postoperative mortality was 1.8 percent (1/55 patients), and the overall morbidity was 21.3 percent. Anastomotic leak occurred in eight patients (14.5 percent). After colonic division a blood flow reduction at the rectal stump was observed in 42 patients (76.3 percent) as compared with baseline measurement. The mean rectal stump flow reduction was 6.2 percent in patients without anastomotic leak, whereas in patients who developed anastomosis breakdown it was 16 percent (P<0.001). Mean proximal stump flow reduction was 5.1 percent in the uncomplicated patients, whereas in patients who had an anastomosis breakdown it was 12.9 percent (P<0.01). A positive linear correlation was found between decrease in blood flow and rate of anastomotic leak. CONCLUSION: Blood flow reduction at the rectal stump is associated with an increased risk of anastomotic leak.Presented in part at the XVII Biennial Congress of the International Society of University Colon and Rectal Surgeons, Malmö, Sweden, June 7 to 11, 1998.     

Autoantibody-mediated cardiac arrhythmias: mechanisms and clinical implications

Cardiac arrhythmias, including conduction defects and tach- yarrhythmias, represent an important source of morbidity and mortality in industrialized countries. Among the different pathophysiological mechanisms involved in the arrhythmogenesis, an inappropriate activation of the immune system represents a field of recent increasing interest. In fact, a large amount of studies suggest that specific autoantibody may be significantly involved in the pathogenesis of cardiac arrhythmias not only in the course of systemic autoimmune disease, but also in a number of rhythm disorders currently classified as “idiopathic.” Although the strongest evidence concerns the relationship between anti-Ro/SSA antibodies and the development of congenital heart block in foetus and newborn, other specific autoantibodies demonstrated the aptitude to affect directly the myocardial tissue, thus producing interference in its bioelectric activity thereby leading to rhythm disorders, also life-threatening. The identification of an immunological autoantibody-mediated mechanism opens new perspectives in the treatment and prevention of cardiac arrhythmias in such patients, including the use of immunosuppressive agents and/or the removal of autoantibodies by immuno-adsorption technique. Returned for 1. revision: 17 September 2007 1. Revision received: 24 September 2007     

Effectiveness of theophylline prophylaxis of renal impairment after coronary angiography in patients with chronic renal insufficiency

Contrast media can lead to renal impairment that results in longer hospitalization and increased mortality. Adenosine is a crucial mediator of contrast-induced nephropathy (CIN; an increase in serum creatinine of >or=0.5 mg/dl within 48 hours). Therefore, it was the purpose of our study to investigate whether the adenosine antagonist theophylline reduces the incidence of CIN after coronary angiography. We also characterized risk factors for CIN after coronary angiography. One hundred patients with serum creatinine concentrations of >or=1.3 mg/dl randomly received 200 mg IV theophylline or placebo 30 minutes before coronary angiography (amount of contrast medium >or=100 ml). Patients who received theophylline and the controls were comparable with regard to baseline creatinine levels (means +/- SD) (1.65 +/- 0.41 vs 1.72 +/- 0.69 mg/dl) and the amount of contrast medium received (235 +/- 89 vs 261 +/- 139 ml). Theophylline significantly reduced the incidence of CIN (4% vs 20%, p = 0.0138). With placebo, creatinine significantly increased at 12 (1.82 +/- 0.79 mg/dl, p = 0.0057), 24 (1.90 +/- 0.86 mg/dl, p = 0.0001), and 48 hours (1.90 +/- 0.89 mg/dl, p = 0.0007) after administration of contrast medium. With pretreatment with theophylline, mean creatinine only increased 24 hours after contrast medium administration (1.70 +/- 0.40 mg/dl, p = 0.029), but was stable 12 hours (1.65 +/- 0.43 mg/dl, p = 0.99) and 48 hours after contrast medium administration (1.65 +/- 0.41 mg/dl, p = 0.99). The following parameters were significantly associated with contrast-induced renal impairment: Cigarroa quotient >5 (contrast medium [milliters] x serum creatinine/body weight [kg]), elevated troponin T, >300 ml of contrast medium, and emergency angiography. In conclusion, theophylline reduces the incidence of CIN in patients with chronic renal insufficiency undergoing coronary angiography. It should be used especially in patients receiving large amounts of contrast medium, and in patients with a Cigarroa quotient of >5 and/or elevated troponin T levels.     

GLUT-1 overexpression: Link between hemodynamic and metabolic factors in glomerular injury?

Mesangial matrix deposition is the hallmark of hypertensive and diabetic glomerulopathy. At similar levels of systemic hypertension, Dahl salt-sensitive but not spontaneously hypertensive rats (SHR) develop glomerular hypertension, which is accompanied by upregulation of transforming growth factor beta1 (TGF-beta1), mesangial matrix expansion, and sclerosis. GLUT-1 is ubiquitously expressed and is the predominant glucose transporter in mesangial cells. In mesangial cells in vitro, GLUT-1 overexpression increases basal glucose transport, resulting in excess fibronectin and collagen production. TGF-beta1 has been shown to upregulate GLUT-1 expression. We demonstrated that in hypertensive Dahl salt-sensitive (S) rats fed 4% NaCl (systolic blood pressure [SBP]: 236+/-9 mm Hg), but not in similarly hypertensive SHR (SBP: 230+/-10 mm Hg) or their normotensive counterparts (Dahl S fed 0.5% NaCl, SBP: 145+/-5 mm Hg; and Wistar-Kyoto, SBP: 137+/-3 mm Hg), there was an 80% upregulation of glomerular GLUT-1 protein expression (P< or =0.03). This was accompanied by a 2.7-fold upregulation of TGF-beta1 protein expression in glomeruli of DSH compared with DSN rats (P=0.02). TGF-beta1 expression was not upregulated and did not differ in the glomeruli of Wistar-Kyoto and SHR rats. As an in vitro surrogate of the in vivo hemodynamic stress imposed by glomerular hypertension, we used mechanical stretching of human and rat mesangial cells. We found that after 33 hours of stretching, mesangial cells overexpressed GLUT-1 (40%) and showed an increase in basal glucose transport of similar magnitude (both P< or =0.01), which could be blocked with an anti TGF-beta1-neutralizing antibody. These studies suggest a novel link between hemodynamic and metabolic factors that may cooperate in inducing progressive glomerular injury in conditions characterized by glomerular hypertension.     

Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity: The CECCY Trial

Background

Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with β-blockers remains controversial.

Ca2+ mobilization induced by ouabain in thymocytes involves intracellular and extracellular Ca2+ pools

Immune dysfunction has been reported in hypertensive rats, and circulating levels of ouabain are increased in some experimental models of hypertension. Ouabain is an inhibitor of the Na+/K+-ATPase capable of diverse effects on cells of the immune system, but its mode of action on these cells is still unknown. The levels of cytoplasmic calcium ions play an important role in cell signaling, and ouabain may induce an increase in intracellular calcium indirectly through the Na+/Ca2+ exchanger. The current work examined the possibility that this drug could be exerting its effects on thymocytes through calcium mobilization and an increase in the cytosolic calcium concentration. Intracellular calcium was evaluated by using Balb-c mouse thymocytes loaded with FURA-2. Both intracellular and extracellular calcium pools were mobilized by ouabain (3 to 1000 nmol). The influx of extracellular calcium depended on the Na+/Ca2+ exchanger and on voltage-dependent calcium channels, as it was inhibited by amiloride and benzamil, consistent with the inhibition of the Na+/K+ pump. In addition, the increase of calcium from intracellular stores was extremely rapid. Furthermore, an increase in cytosolic calcium levels was obtained with the combination of ouabain and thapsigargin, which was greater than that seen with either drug alone. Our data suggest that low concentrations of ouabain may be acting on thymocytes through a mechanism different from the traditional inhibition of the Na+/K+-ATPase, as the cytosolic calcium rise was partly dependent on the release from intracellular stores.     

Dilutional hyponatremia in patients with cirrhosis and ascites

OBJECTIVES: To analyze the predisposing factors, modifications of vasoactive systems, and prognosis of patients with cirrhosis and hyponatremia. PATIENTS AND METHODS: Fifty-four patients with hyponatremia (serum sodium level of <130 mEq/L after 5 days of hyponatremic diet and no diuretic therapy). Twenty cirrhotic patients served as controls. We measured plasma renin activity and levels of plasma aldosterone, norepinephrine, and antidiuretic hormone. Follow-up identified the development of hepatorenal syndrome and death. RESULTS: A higher percentage of patients with hyponatremia had decreased liver size, higher levels of plasma renin activity, and higher serum concentrations of aldosterone and norepinephrine. Renal insufficiency was detected in 31 of them (57%). Precipitating factors (hemorrhage or infections) were detected in 27 patients (50%). Incidence of hepatorenal syndrome and death were higher in patients with spontaneous development of hyponatremia (n = 23 [85%] and n = 25 [93%], respectively) than in patients with precipitating factors (n = 15 [56%] and n = 12 [44%], respectively) and cirrhotic controls (n = 1 [5%] and n = 5 [25%], respectively) (P<.001). Results of multivariate analysis showed that Child-Pugh index, presence of hepatocarcinoma, and serum concentration of urea were associated with mortality. After excluding those patients with kidney failure at the time of admission, only Child-Pugh index and norepinephrine concentrations were independent predictors of mortality. CONCLUSIONS: Hyponatremia is an alteration in patients with advanced liver disease. Although survival is significantly reduced in patients with spontaneous development of hyponatremia, a reduced sodium concentration cannot be considered as a independent predictor of the risk for death.     

Hemophagocytic lymphohistiocytosis associated with Leishmania: A hidden passenger in endemic areas

IntroductionHemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome characterized by excessive immune activation. We analyzed the presentation, diagnosis and prognosis of our cohort of HLH-Leishmania cases.MethodsWe studied HLH cases in patients over 14 years of age in the province of Granada (Spain), from January 2008 to November 2019.ResultsIn this study, Leishmania was the predominant trigger of adult HLH in our region. There were no differences in the clinical-analytical presentation between HLH triggered by Leishmania and those initiated by a different cause. RT-PCR was the best tool to identify Leishmania as the trigger of HLH, given that the other microbiological tests showed low sensitivity to detect the parasite in our HLH-Leishmania cases.ConclusionA comprehensive search for Leishmania is mandatory in HLH cases. Based on our findings, we propose that RT-PCR for Leishmania in bone marrow samples must be included in HLH differential diagnostic protocols.     

Successful treatment of autoimmune hepatitis and idiopathic thrombocytopenic purpura with the monoclonal antibody, rituximab: case report and review of literature.

Rituximab, a chimeric monoclonal anti-CD20 antibody, has shown activity in several autoimmune disorders. We describe a case of a 52 years old female who was diagnosed with idiopathic thrombocytopenic purpura and concomitant autoimmune hepatitis (AIH), both non-responsive to steroids. She was subsequently treated with rituximab, which resulted in a rapid increase in her platelet count and an unexpected normalization of her hepatic biochemical tests. Both her platelet count and her hepatic biochemical tests remained normal for over 5 months. In this case, rituximab showed an impressive clinical response for the treatment of AIH, and it may be considered as an alternative treatment in patients who do not respond to corticosteroid therapy. Prospective randomized studies in AIH are needed to validate this observation.