Fractional excretion of electrolytes and neutrophil gelatinase-associated lipocalin as early biomarkers of acute kidney injury in dogs with acute pancreatitis

Objectives: To determine if fractional excretion of urinary electrolytes and neutrophil gelatinase-associated lipocalin could detect different degrees of kidney injury in dogs with naturally occurring acute pancreatitis. Materials and Methods: We included dogs with acute pancreatitis. Dogs with a history of kidney disease, urinary tract infection, dogs which received potentially nephrotoxic drugs and dogs managed with haemodialysis were excluded. Acute kidney injury was diagnosed if there was an acute onset of clinical signs, haemato-chemical results compatible with acute kidney injury. Students or staff-owned dogs were selected to build the healthy group. Results: The study population was composed of 53 dogs: acute pancreatitis with AKI (n=15), acute pancreatitis alone (n=23), and healthy dogs (n=15). In dogs with acute pancreatitis and AKI, all the FEs of urine electrolytes were significantly higher than dogs with acute pancreatitis alone and healthy ones. Dogs with acute pancreatitis alone had higher uNGAL/uCr than healthy dogs (median 54 ng/mg vs. 0.1 ng/mg) and lower compared to AP-AKI patients (54 ng/mg vs 209 ng/mg). Clinical Significance: Some fractional excretion of electrolytes are increased acute kidney injury dogs, however their role in the early detection of renal injury in acute pancreatitis dogs remains doubtful. On the contrary, urinary neutrophil gelatinase-associated lipocalin had higher concentrations in dogs with acute pancreatitis with or without acute kidney injury compared to healthy controls, suggesting that it may be used as an early marker of renal tubular damage in acute pancreatitis dogs

Small bowel obstruction due to metastasis of cutaneous melanoma: 7-years after primary diagnosis.

Aim of study: Metastatic involvement of the small bowel by melanoma is rare. The average time from the excision of the primary cutaneous melanoma to the occurrence of intestinal metastases tends to be between 3 and 5 years; one case of recurrence after 15 years is described. The most common kind of lesion is polypoid: this can cause intussusception and intestinal occlusion. We report a case of intestinal occlusion by an ileal metastasis of a melanoma occurred 7 years earlier. Materials and Methods: Case Report: The patient was a 57-year-old female who was admitted to our hospital for persistent abdominal pain and sub-occlusion. The patient's past medical history included cutaneous malignant melanoma 7 years before and lobular breast adenocarcinoma 10 years before. During the previous three months, she had intermittent abdominal pain and a weight loss of about 7 kg. Abdominal-US, EGDS and colonoscopy were all negative for pathologic findings. During the hospital stay, a CT enterography revealed lower intestinal intussusception, and enlarged lymph nodes both in the abdominal cavity and in the retroperitoneum. Intraoperatively we found an ileal invagination due to a polypoid mass of the ileal tract. Segmental ileal resection was performed; wide mesenteric lymph node dissection was not possible because of large and extended retroperitoneal lymphadenopathies. Histological examination showed epithelioid and spindle tumor cells with obvious cytoplasmic melanin deposition. Immunohistochemical staining revealed that tumor cells were positive for S-100, HMB-45 and vimentin, confirming the diagnosis of melanoma. Main results and conclusions: Appearance of GI metastases is reported up to 15 years after the inital diagnosis of melanoma. Reported clinical signs and symptoms generally include chronic abdominal pain, occult or gross bleeding and, as in this case, weight loss. Aspecificity of symptoms may impede early diagnosis and treatment of the disease. As in this case, where curative surgery is impossible because of the extent of disease, metastatic tumor resection or GI tract bypass surgery is recommended to relieve symptoms or avoid future complications. Early diagnosis of metastases requires adequate imaging (CT) and prolonged follow up

FACTORS PREDICTING MORBIDITY AND MORTALITY AFTER SURGERY FOR COMPLICATED ACUTE DIVERTICULITIS: A SINGLE CENTER EXPERIENCE

Introduzione Complicated acute diverticulitis (CAD) occurs in approximately 10 to 25 percent of patients affected by diverticular disease and a surgical treatment is often necessary. Postoperative morbidity and mortality are still high, up to 40% of cases in patients with generalized peritonitis. The purpose of this study is to identify predictive prognostc factor for postoperative morbidity and mortality in patients requiring surgical intervention for CAD. Pazienti e metodi From September 2011 to May 2015 170 patients underwent surgical intervention for diverticular disease in our unit. Of these, 119 patients required urgent surgery for complicated acute diverticulitis (CAD). Pre-, intra- and postoperative findings were collected in a prospective database. Multivariate analysis with logistic regression was performed to find out independent predictive factors for postoperative morbidity and mortality. Statistical analysis was made with SPSS v.13.0 and significance was considered with p value < 0.05. Risultati There were 56 males and 63 females with mean age of 68 \ub1 15 years. 100 patients (84.0%) were at first hospital admission for diverticular disease and in 16 cases (13.4%) the disease was localized at right colon or ceacum. A stomy was required in 84 patients (70.6%) and postoperative morbidity rate was 52,9% according Clavien\u2013Dindo Classification. Anyway only 10.9% of patients were affected by grade III or IV complication with a mortality rate of 16.8%. At multivariate analysis the presence of a postoperative medical complication was the only predictive factor for mortality (OR 10.3; 95%CI 2.1-51.3 p=0.004) while the presence of COPD and purulent or fecal peritonitis were not statistically significant (OR 3.3; 95%CI 0.9-12.2 p=0.073 and OR 3.1 95%CI 0.8-11.6 p=0.099 respectively). For postoperative morbidity the logistic regression showed that patients 6575 years and with ASA score > 2 were independently associated with postoperative morbidity (OR 2.8; 95%CI 1.1-7.2 p=0.028 and OR 5.3 95%CI 2.0-13.9 p=0.001 respectively). The same factors were independent prognostic factor associated with medical complication with OR 3.0; 95%CI 1.1-7.8 p=0.028 and OR 6.5 95%CI 2.0-21.3 p=0.002 respectively. Multivariate analysis of factor predicting surgical morbidity showed that age 6575 was the only predictive factor for postoperative surgical morbidity (OR 3.1; 95%CI 1.1-8.8 P=0.027). Conclusioni In our experience the majority of patients who require surgery for CAD are at the first episode of acute diverticulitis. Medical complication after surgery for CAD is the only factor associated with mortality while surgical complications do not seem to have the same weight. Age 6575 years and ASA score >2 are independent predictive factors for postoperative medical complications while only age seems to have a significant effect on surgical morbidity

SHORT TERM RESULTS OF ELECTIVE COLON RESECTIONS FOR UNCOMPLICATED DIVERTICULAR DISEASE

Introduzione Indications for elective surgery in diverticular disease are sill debated and recent findings suggest a conservative approach since most patients present complicated diverticulitis as the first manifestation of diverticular disease. In our study we analyze the result in term of postoperative morbidity and mortality in patiets who underwent elective surgery for diverticular disease. Pazienti e metodi From September 2011 to May 2015 we perfomerd 170 surgical interventions for diverticular disease in our unit. Of these, 51 resection were performed in elective setting. Pre-, intra- and postoperative findings were collected in a prospective database. Multivariate analysis with logistic regression was performed to find out independent predictive factors for postoperative events. Statistical analysis was made with SPSS v.13.0 and significance was considered with p value < 0.05. Risultati Male:Female ratio was 1:1 with mean age of 59\uf0b114 years. 44 patients was younger than 75 years. 54.9% of patients had one or more comorbidities and 12 patients (23.5%) had ASA score >2. Most patients had only one previous hospital admission (28 patients, 54.9&) while 9 patients reported two or more admissions. 2 patient underwent surgery for the development of colo-vescical or colovaginal fistula and 2 patient for paracolic or pelvic abscess refractory to medical therapy. In 70.6% (36 patients) of cases a laparoscopic approach was performed with a conversion rate of 16.7%. No postoperative in-hospital mortality was recorded. Postoperative complication rate was 31.4% (16 patients) according Clavien-Dindo Classification. Anyway 14 patients had grade I or II complication with mild clinical impairment. Multivariate analysis did not find any independent predictive factor for overall and surgical complications. On the other hand presence of diabetes mellitus (DM) and ASA score > 2 was associated with increased risk of medical complication (OR 16.7; 95%CI 1.1-259.9 P=0.044 and OR 8.5; 95%CI 1.1-62.6 P=0.036 respectively). A T-test was performed to compare mean of postoperative stay within the two variables. Patients with ASA score > 2 were found to have longer postoperative stay respect to those with ASA score 1-2 (13,5 vs 8,4 P=0.008). No significant difference was found in patients with or without DM (9.0 vs 9.6 P=0.818). Conclusioni In our experience, elective surgery for diverticular disease can be performed safely and often with mini-invasive approach, with accetable rate of significant postoperative event. Anyway we need powerful studies providing strong evidence to identify patients who could really take advantage of elective surgical intervention

Cloning, Expression and Physico-Chemical Characterization of a New Di-Heme Cytochrome c from Shewanella baltica OS155.

The 16 kDa di-heme cytochrome c from the bacterium Shewanella baltica OS155 (Sb-DHC) was cloned and expressed in E. coli and investigated through UV-Vis, MCD and 1H NMR spectroscopies and protein voltammetry. The model structure was obtained by means of comparative modeling using the X-ray structure of Rhodobacter sphaeroides di-heme cytochrome c (DHC) (with a 37% pairwise sequence identity) as a template. Sb-DHC folds into two distinct domains, each containing one heme center with a bis-His axial ligation. Both secondary and tertiary structures of the N-terminal domain resemble those of class I cytochrome c, displaying three \uf061-helices and a compact overall folding. The C-terminal domain is less helical, as the corresponding domain of R. sphaeroides DHC. The two heme groups are bridged by Tyr26 in correspondence of the shortest edge-to-edge distance, a feature which would facilitate fast internal electron transfer. The electronic properties of the two prosthetic centers are equivalent and sensitive to two acid-base equilibria with pKa values of approximately 2.4 and 5, likely corresponding to protonation and detachment of the axial His ligands from the heme iron and ionization of the heme propionate-7, respectively. Reduction potentials of -0.144 and -0.257 V (vs SHE), were determined for the C- and N-terminal heme group, respectively. An approach based on the extended Debye-H\ufcckel equation was applied for the first time to a two-centered metalloprotein and found to reproduce successfully the ionic strength dependence of E\ub0\u2019

A Nonclassical Stereoselective Semi-Synthesis of Drospirenone via Cross-Metathesis Reaction

A new synthetic approach for the construction of the spirolactone moiety of the progestin drospirenone is presented. Highly efficient cross-metathesis reaction catalyzed by Grubbs-Hoveyda second generation catalyst (6 mol%) is employed as the key step for the introduction of the ester moiety in the position C-17. The no need for protecting groups and the absence of harmful heavy metal-based oxidants constitute a valuable synthetic alternative to the existent approaches

Glucocorticoid-Induced Leucine Zipper-Mediated TLR2 Downregulation Accounts for Reduced Neutrophil Activity Following Acute DEX Treatment

Glucocorticoids are the most powerful anti-inflammatory and immunosuppressive pharmacological drugs available, despite their adverse effects. Glucocorticoid-induced leucine zipper (GILZ) is a glucocorticoid-induced gene that shares several anti-inflammatory properties with glucocorticoids. Although immunosuppressive effects of glucocorticoids on neutrophils remain poorly understood, we previously demonstrated that GILZ suppresses neutrophil activation under glucocorticoid treatment. Here, we sought to explore the regulation of Toll-like receptor 2 (TLR2) by the synthetic glucocorticoid dexamethasone (DEX) on neutrophils and the associated GILZ involvement. Peripheral blood neutrophils were isolated from wild type and GILZ-knock-out (KO) mice. TLR2 was found to be downregulated by the in vivo administration of glucocorticoids in wild type but not in GILZ-KO neutrophils, suggesting the involvement of GILZ in TLR2 downregulation. Accordingly, the TLR2-associated anti-fungal activity of neutrophils was reduced by DEX treatment in wild type but not GILZ-KO neutrophils. Furthermore, GILZ did not interact with NF-κB but was found to bind with STAT5, a pivotal factor in the regulation of TLR2 expression. A similar modulation of TLR2 expression, impaired phagocytosis, and killing activity was observed in circulating human neutrophils treated in vitro with DEX. These results demonstrate that glucocorticoids reduce the ability of neutrophils to respond to infections by downregulating TLR2 via GILZ, thereby reducing critical functions

Urine neutrophil gelatinase-associated lipocalin to diagnose and characterize acute kidney injury in dogs

Background Urine neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of acute kidney injury (AKI) in dogs. Objectives To evaluate the utility of urinary NGAL for characterizing AKI according to volume responsiveness, presence of inflammation and sepsis, and prognosis. Animals Dogs with AKI (n = 76) and healthy controls (n = 10). Methods Prospective study. Clinical and clinicopathologic data including absolute urine NGAL concentration (uNGAL) and NGAL normalized to urine creatinine concentration (uNGALC) were measured upon admission. Dogs were graded according to International Renal Interest Society (IRIS) AKI guidelines and compared based on AKI features: volume-responsive (VR-) AKI vs. intrinsic (I-) AKI based on IRIS criteria; VR-AKI and I-AKI based on urine chemistry; inflammatory versus noninflammatory; septic versus nonseptic; and survivors versus nonsurvivors. Nonparametric statistics were calculated, and significance set at P &lt; .05. Results Urinary NGAL was significantly higher in dogs with AKI compared to controls, regardless of AKI grade. Urinary NGAL did not differ between dogs with VR-AKI and I-AKI based on IRIS criteria, whereas higher uNGALC was recorded in dogs with I-AKI based on urine chemistry. Urinary NGAL was significantly higher in dogs with inflammatory AKI, whereas no difference with respect to sepsis or outcome was identified. Conclusions and Clinical Importance Urinary NGAL is a sensitive marker for AKI in dogs, but its specificity is affected by systemic inflammation. Increased urinary NGAL in both I-AKI and VR-AKI also suggests the presence of tubular damage in transient AKI. Combining urine chemistry data with IRIS criteria could facilitate AKI characterization in dogs

FEATURE IN YOUNG PATIENTS SURGICALLY TREATED FOR ACUTE DIVERTICULITIS

Introduzione There is lack of consensus whether to consider acute diverticulitis in younger patients a more aggressive disease than in other. While some authors considered diverticulitis in younger worst than in older patients, others suggested similar outcomes. In this study we evaluate differences between patients \uf0a3 45 years old and > 45 who underwent surgery for acute diverticulitis. Pazienti e metodi From September 2011 to May 2015 119 patients underwent emergency surgical intervention for acute diverticulitis in our unit. Pre-, intra- and postoperative findings were collected in a prospective database. 12 patients (Group A, 10,1%) were \uf0a3 45 years old. We compared clinical and pathological data between Group A patients and the remaining 145 (Group B 89.9) to find out any difference for characteristics of patients, clinical presentation, operative and short-term results. Uni- and multivaiate analysis were performed with SPSS v. 13.0 and satistical significance considered with p value < 0.05. Risultati Slight difference between Group A and Group B was found about presence of males (75.0% vs 43.9%; p=0.065). Significant differences were found for patients with one ore more comorbidities (16.7% vs 86.9%; p<0.001) and in particular for cardiovascular diseases (0% vs 67.3; p<0.001). Also ASA score was lower in younger patients with ASA 1-2 in 91.7% of patients versus 29.0% in group B patients (p<0.001). Localization of disease differed between two group with prevalence of right colonic side in 41.7% of Group A patients rspect to 10.3% of older patients (p=0.010). Group A patients treated in emergency were at first admission in 91.7% of cases respect to 83.2% of group B but this difference was not found to be statistically significant (p=0.688). In group A, laparoscopy was performed in 50% of patients while in group B only in 20.6% of cases (p=0.033) with no difference in conversion rate. The majority of Group A patients did not required an ostomy after surgical exploration respect to Group B patients (33.3% vs 74.8% p=0.006). No significant difference was found for the incidence of purulent or fecal generalized peritonitis (33.3% vs 57.9%; p=0.131). For postoperative results, morbidity rate according Clavien-Dindo classification was lower in Group A patients (8.3% vs 57.9%; p=0.001) and also the incidence of medical complications favoured younger patients (8.3% vs 44.9%; p=0.015). On the other hand the two groups did not differ for postoperative mortality (8.3% vs 17.8% p=0.688). Mean length of postoperative stay was shorter in Group A patients respect to Group B (6.3\uf0b12.0 vs 15.3\uf0b114.6; p=0.002). Multivariate analysis between Group A and B showed only a higher incidence of ostomy after surgery in group B (HR 4.0; 95%CI0.85-19.0) that did not reached statistical significance (p=0.08). Conclusioni Acute diverticulitis in young patients shows some peculiar issues, in particular for the localization of the disease, but does not seem to be more aggressive than in older people. For these reasons surgical intervention should be taken into account not considering age but the actual clinical, laboratoristic and instrumental findings

Association between echocardiographic indexes and urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in dogs with myxomatous mitral valve disease

Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of tubular damage, and its elevation has been described in human and canine cardiorenal syndrome. The aim was to evaluate the association between echocardiographic indexes and urine NGAL (uNGAL) and uNGAL normalized to urine creatinine (uNGALC) in dogs with MMVD. This is a multicentric prospective cross-sectional study. A total of 77 dogs with MMVD at different ACVIM stages were included. All dogs underwent echocardiography, serum chemistry, and urinalysis. Echocardiographic data analyzed were shortening fraction (SF), left ventricular diastolic (LVIDDn) and systolic (LVIDSn) diameters normalized for body weight, left atrium to aortic root ratio (LA/Ao), maximal (LAVMax) and minimal (LAVMin) left atrial volumes, LA stroke volume (LASV), early diastolic mitral peak velocity (EVmax), EVmax to tissue Doppler E' wave (E/E'), aortic (VTIAo) and mitralic (VTIMit) velocity time integrals and their ratio (VTIMit/VTIAo), and tricuspid regurgitation velocity (TRVmax). In the univariate analysis LASV, TRVmax, LAVMax, LVIDDn, and VTIMit/VTIAo were independent predictors of increased uNGAL and uNGALC; however, only LASV [(OR: 1.96, 95% CI: 1.16 to 3.31) P = 0.01 for NGAL, and (OR: 2.79, 95% CI: 1.50 to 5.17) P &lt; 0.001 for NGALC] and TRVmax [(OR: 1.73, 95% CI: 1.20–2.51) P = 0.002 for NGAL, and (OR: 1.50, 95% CI: 10.07–2.10) P = 0.015 for NGALC] remained statistically significant in the multivariable analysis. Based on our results, LASV and TRVmax are associated with increased uNGAL and uNGALC. These parameters might detect dogs with MMVD at higher risk of developing kidney damage