Inhibition of endogenous nitric oxide activity impairs the colonic sparing effect of rofecoxib, the cyclooxygenase-2 inhibitor and resveratrol, the preferential cyclooxygenase-1 inhibitor in the course of experimental colitis. Role of oxidative stress biomarkers and proinflammatory cytokines.

The gut mucosal barrier plays a key role in the physiology of gastrointestinal (GI) tract, preventing under homeostatic conditions, the epithelial cells of the gastric mucosa from hydrochloric acid and intestinal mucosa from alkaline secretion, food toxins and pathogenic microbiota. Previous studies have documented that blockade of both isoforms of cyclooxygenase (COX): constitutive (COX-1) and inducible (COX-2), as well NO synthase in the stomach exacerbated the gastric damage induced by various ulcerogens, however, such as effects of non-selective and selective inhibition of COX-1, COX-2 and NOS enzymes on colonic damage have been little studied. The supplementation of NO by intragastric (i.g.) treatment with NO-releasing compound NO-aspirin (NO-ASA) or substrate for NO synthase L-arginine ameliorated the damage of upper GI-tract, but whether similar effect can be observed in colonic mucosa associated with the experimental colitis, and if above mentioned compounds can be effective in aggravation or protection of experimental colitis remains less recognized. In this study rats with experimental colitis induced by intrarectal administration of 2,4,6-trinitrobenzosulphonic acid (TNBS) were daily treated for 7 days with: 1) vehicle (i.g.), 2) ASA 40 mg/kg (i.g.), 3) rofecoxib 10 mg/kg (i.g.), 4) resveratrol 10 mg/kg (i.g.), 5) NO-ASA 40 mg/kg (i.g.), 6) L-arginine 200 mg/kg (i.g.) with or without of L-NNA 20 mg/kg (i.p.). The macroscopic and microscopic area of colonic damage was determined planimetrically, the colonic blood flow (CBF) was assessed by Laser flowmetry, and the oxidative stress biomarkers malondialdehyde and 4-hydroxynonenal (MDA+4-HNE), the antioxidative factors superoxide dismutase (SOD) and glutathione (GSH), as well as proinflammatory cytokines in the colonic mucosa (tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1ß)) were measured. We have documented that administration of TNBS produced gross and microscopic colonic damage and significantly decreased CBF (p<0.05). Treatment with ASA significantly increased the area of colonic damage (p<0.05), an effect accompanied by a significant decrease in the CBF, the significant increment of MDA+4-HNE, and the attenuation of the antioxidative properties in colonic mucosa, documented by a significant decrease of SOD activity and GSH concentration, and elevation of the colonic tissue levels of TNF-α and IL-1ß comparing to control Veh-treated TNBS rats. Administration of rofecoxib or resveratrol also significantly increased the colonic damage and significantly decreased the CBF, causing an increase in MDA+4-HNE and mucosal content of TNF-α and IL-1α and a significant decrease of the SOD activity and GSH content (p<0.05), however, these changes were significantly less pronounced as compared with ASA. On the contrary, the treatment with NO-ASA, or L-arginine, significantly diminished the area of colonic lesions, the MDA+4-HNE concentration, attenuated the TNF-α and IL-1ß levels, while increasing the CBF, SOD activity and GSH content (p<0.05). The concomitant treatment of L-NNA with rofecoxib or resveratrol reversed an increase in area of colonic damage and accompanying changes in CBF, colonic mucosa TNF-α and IL-1ß levels, the MDA+4-HNE concentration, and SOD activity and GSH content comparing to those observed in TNBS rats treated with these COX-inhibitors alone (p<0.05). In contrast, co-treatment with L-NNA and NO-ASA or L-arginine failed to significantly affect the decrease of colonic lesions accompanied by the rise in CBF, the attenuation of MDA+4-HNE concentration, TNF-α and IL-1ß levels, SOD activity and GSH content exerted by NO-ASA- or L-arginine treatment of the respective control TNBS-rats without L-NNA administration. These observations suggest that 1) the increase of NO availability either from NO-releasing donors such as NO-ASA or NO precursors such as L-arginine, can inhibit the inflammatory and microvasculature alterations, as well as increase in lipid peroxidation due to the enhanced efficacy of these compounds to increase the antioxidative properties of colonic mucosa, 2) unlike ASA which exacerbated the severity of colitis, the treatment with rofecoxib, the specific 'safer' COX-2 inhibitor or resveratrol, the polyphenolic compound known to act as the dual COX-1 and COX-2 inhibitor, can attenuate the colonic damage during course of TNBS colitis possibly via anti-inflammatory and antioxidative properties, and 3) the blockade of endogenous NO activity by L-NNA which also exacerbated the severity of mucosal damage in colitis, can abolish the sparing effect of rofecoxib and resveratrol indicating the NO bioavailability plays an important role in enhanced efficacy of both specific and dual COX inhibitors to ameliorate the experimental colitis.

Healing effect of warfarin in the course of cerulein-induced acute pancreatitis in rats.

Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations and unexpected deaths. The development of AP leads to damage of the pancreatic microcirculation with a cascade of subsequent events resulting, among others, in coagulopathy. Previous research showed that anticoagulants can be important therapeutic agents. Heparin and acenocoumarol can alleviate the course of AP, as well as accelerate healing and post-inflammatory regeneration of the pancreas. The aim of this study was to determine whether warfarin, a drug with more stable effects than acenocoumarol, affects the healing and regeneration of the pancreas in the cerulein-induced AP. AP was evoked in Wistar male rats by intraperitoneal administration of cerulein. The first dose of warfarin (45, 90 or 180 µg/kg) was administered 24 hours after the first dose of cerulein and the doses of warfarin were repeated once a day in subsequent 10 days. The severity of AP was assessed immediately after the last dose of cerulein, as well as at days 1, 2, 3, 5, and 10 after AP induction. Treatment with warfarin dose-dependently increased international normalized ratio (INR) and attenuated the severity of pancreatitis in histological examination and accelerated pancreatic recovery. These effects were accompanied with a faster reduction in the AP-evoked increase in serum activity of amylase and lipase, the serum concentration of pro-inflammatory interleukin-1ß, and the plasma level of D-Dimer. In addition, treatment with warfarin decreased pancreatic weight (an index of pancreatic edema) and improved pancreatic blood flow in rats with AP. The therapeutic effect was particularly pronounced after the administration of warfarin at a dose of 90 µg/kg. We conclude that treatment with warfarin accelerated regeneration of the pancreas and recovery in the course of cerulein-induced mild-edematous acute pancreatitis.

Administration of warfarin accelerates the recovery in ischemia/reperfusion-induced acute pancreatitis.

Acute pancreatitis is associated with activation of coagulation and there is a close relationship between coagulation and the severity of this disease. Administration of anticoagulants such as heparin or acenocoumarol has shown to reduce the severity of acute pancreatitis and accelerate the recovery. The aim of the current study was to determine the impact of warfarin administration on the course of ischemia/reperfusion-induced acute pancreatitis. Acute pancreatitis was induced in rats by pancreatic ischemia followed by reperfusion. Vehicle (1 ml/dose) or warfarin (45, 90 or 180 µg/kg/dose in 1 ml of vehicle) were administered intragastrically once a day. The first dose of warfarin was given 24 h after the start of pancreatic reperfusion. The severity of acute pancreatitis was assessed 2, 5, 9 and 14 days after the beginning of pancreatic reperfusion. Treatment with warfarin reduces pancreatic damage and accelerates recovery in histological examination and this effect is accompanied by a faster reduction in serum activity of pancreatic digestive enzymes, lipase and amylase. In addition, warfarin led to an earlier decrease in serum concentration of pro-inflammatory interleukin-1ß and plasma level of D-dimer. These effects were associated with an improvement of pancreatic blood flow. We conclude that warfarin exhibits a therapeutic effect in acute pancreatitis evoked by pancreatic ischemia followed by reperfusion.

Successful Pediatric Kidney Transplantation Into an Adult Recipient: A Case Report.

BACKGROUND: The constant shortage of kidney donors prompts exploration into new strategies of transplantation. One of these strategies is the use of pediatric donors aged up to 5 years whose kidneys can be transplanted into adult recipients, mainly en bloc. This involves retrieving kidneys en bloc with aorta and inferior vena cava and anastomosing them to the recipient's external iliac vessels. CASE PRESENTATION: In our hospital, kidneys from a 3-year-old child were transplanted to a 30-year-old man. The recipient with end-stage renal failure, due to glomerular nephritis, was dialyzed for 12 years and had 1 failed transplantation with consequent graftectomy. In 2009, kidneys were transplanted to the external iliac artery and vein with reconstruction of the renal vessels. Shortly after transplantation the patient had normal renal measures. Three months later a critical stenosis of 1 renal artery was detected. Angioplasty was performed but technical reasons did not allow for effective dilatation of the vessel. Further, 6 months after kidney transplantation (KTx) nephrotic proteinuria appeared and features of membranous nephropathy were detected in a renal biopsy. The proteinuria subsided after administration of ramipril and losartan. Doppler ultrasound revealed that 1 artery remained 90% stenotic with a peak systolic velocity of 377 cm/sec. Despite reported complications, renal function appeared normal over 7 years of observation. CONCLUSIONS: A transplantation of 2 pediatric kidneys into an adult recipient has very high efficacy. The survival of both graft and recipient is similar to the results obtained after living donor kidney transplantation.

Endoscopic Islet Autotransplantation Into Gastric Submucosa-1000-Day Follow-up of Patients.

BACKGROUND: Total pancreatectomy and autologous transplantation of pancreatic islets is a treatment option for patients with severe pain due to chronic pancreatitis. In the standard procedure, pancreatic islets are isolated and subsequently administered into the portal vein. In the case of patients with a history of thrombosis or at risk of thrombosis, this route of administration is not viable. Animal studies conducted in our department led to the development of a technique of endoscopic islets transplantation into the gastric submucosa. In 2013 and 2014, the first human autologous transplant procedures were performed. The objective of this study was to present the results of a 3-year follow-up of these patients. METHODS: Two pancreatectomies were performed in our department, the first in 2013 and another in 2014, along with subsequent autologous transplantation of pancreatic islets into the gastric submucosa. RESULTS: Both patients had been diagnosed previously with diabetes, and both had endogenous islet activity detected. Peptide C concentration after pancreatectomy and before pancreatic cell transplantation was 0.1 ng/mL. After the transplantation, peptide C concentrations for the 2 patients were 0.8 and 0.5 ng/mL on day 7, 1.2 and 0.6 ng/mL on day 30, 1.3 and 0.8 ng/mL on day 180, 1.1 and 0.7 ng/mL on day 360, and 3.0 and 0.6 ng/mL at 3 years, respectively, after transplantation. The pain symptoms resolved in both cases. CONCLUSION: Pancreatic islets may survive in the gastric wall. Endoscopic submucosal transplantation may present an alternative for the management of patients who cannot undergo a classic transplantation procedure.

Analysis of Distribution of Expanded- and Standard-Criteria Donors and Complications Among Polish Recipients by Kidney Donor Risk Index Value.

INTRODUCTION: The approach toward transplanting kidneys from expanded-criteria donors (ECDs) in Poland is largely site-dependent. The Kidney Donor Risk Index (KDRI) allows for obtaining a more precise characteristic of ECDs and further stratification into "better" and "worse" quality grafts. METHODS: Comparison of the incidence of delayed graft function (DGF) and biopsy-proven acute rejection (BPAR), median of hospitalization time and median of estimated glomerular filtration rate (eGFR) at 1 year after transplantation among kidney graft recipients (n = 468), divided by donor status (ECD/standard-criteria donor [SCD]) and KDRI value (I: 0.67-1.2, II: 1.21-1.6, III: 1.61-2.0, IV: 2.01-3.48). RESULTS: ECD kidneys have been transplanted to 32.47% of recipients. There were no ECD recipients in KDRI compartment I, 16.55% in compartment II, 79.22% in compartment III, and 100% in IV. In KDRI compartment II, DGF was diagnosed in 34.9% of SCDs and 56% of ECDs (P = .003), BPAR occurred in 7.8% of SCDs and 16% of ECDs (P = .073), median hospital stay was 12 days for SCDs and ECDs (P = 1), and eGFR was 50.7 mL/min for SCDs and 49.4 mL/min for ECDs (P = .734). In KDRI compartment III, DGF was diagnosed in 43.8% of SCDs and 49.2% of ECDs (P = .139), BPAR occurred in 6.3% of SCDs and 31.7% of ECDs (P = .001), median hospital stay was 10 days for SCDs and 12 days for ECDs (P = .634), and eGFR was 49.5 mL/min for SCDs and 45.2 mL/min for ECDs (P = .382). Among ECD recipients, DGF was diagnosed in 56.0%, 49.2%, and 47.7% of patients for KDRI compartments II, III, and IV respectively (P = .776); BPAR occurred in 16% (compartment II), 31.7% (compartment III), and 23.1% (compartment IV) (P = .273); the median hospital stay was 12 days (compartment II), 12 days (compartment III), and 12.5 days (compartment IV) (P = 1); and eGFR was 49.5 mL/min (compartment II), 45.4 mL/min (compartment III), and 36.1 mL/min (compartment IV) (P = .002). CONCLUSION: Assessment using both the ECD and KDRI systems allows for a more precise evaluation of prognosis and predicting complications among recipients.

Islets Allotransplantation Into Gastric Submucosa in a Patient with Portal Hypertension: 4-year Follow-up.

BACKGROUND: Islets transplantation is an established treatment method for patients suffering from brittle diabetes with hypoglycemia unawareness. The standard implantation technique is through the portal vein into the liver. In case of liver diseases or portal hypertension, finding an extra-hepatic site is recommended. There have been attempts to perform islets transplantations into muscles and into the gastric submucosa. OBJECTIVE: The aim of this study is to show a 4-year follow-up of allotransplantation into gastric submucosa in a case of portal hypertension observed during the procedure of islets infusion. PATIENTS AND METHODS: A 36-year-old woman with complicated diabetes for over 30 years was selected to receive simultaneous islets and kidney transplantation. The patient underwent an unsuccessful simultaneous pancreas and kidney transplantation 2 years earlier in another transplantation center. The patient's daily insulin requirement was 60 IU, which corresponded to 1.15 IU/kg of body weight. The HbA1c level was 7.4%. C-peptide levels, both fasting and stimulated, were 0.01 ng/mL. On December 7, 2013, the patient received transplanted kidney and islets procured from the same donor. Only 124,000 islets equivalents (IEQ) were isolated (2400 IEQ/kg body weight). Islets were suspended in 300 mL of Ringer's solution along with albumin, antibiotics, and heparin. After infusing 100 mL of the islets suspension into the portal vein, pressure in portal vein increased from 5 mm Hg to 23 mm Hg. Despite stopping the infusion, pressure did not drop after 30 minutes. The decision was made to transplant the reminder of the islets (200 mL) into the gastric wall. RESULTS: No complications were observed after the procedure. Serum creatinine level was 1.6 mg/dL on day 10 and 1.5 mg/dL 4 years after the transplantation. Fasting C-peptide levels were 1.7, 0.65, 0.55, 0.69, 0.68, and 0.2 ng/mL at 1, 3, 6, 12, 18, and 36 months after the transplantation, respectively. HbA1c levels were 5.2, 6.4, 4.7, 5.2, and 5.9% at 3, 6, 12, 18, and 36 months, respectively. The patient's insulin requirement dropped to 15 U/day immediately after transplantation and equaled 20 and 27 U/day at 18 and 48 months after the simultaneous islet and kidney transplantation, respectively. CONCLUSION: Allotransplantation of islets into the gastric wall may be a safe alternative in cases of contraindications for transplantation into the portal vein.

Effect of Selective Antibiotic Pressure on the MLS-B Phenotype in Methicillin-Resistant Staphylococcus aureus Strains Originating From Patients From Transplantation Wards: 24 Years of Observations.

INTRODUCTION: Staphylococcus aureus infection, and health care-associated-methicillin resistant S aureus (HA-MRSA) in particular, is a serious risk for patients treated with organ transplantation. The frequent combined resistance of these bacteria to macrolides, lincosamides, and streptogramin-B (MLS-B) limits the use of these drugs in therapy. AIM: Evaluation of the mechanism of MLS-B resistance among HA-MRSA strains derived from patients treated in surgical-transplantation wards, over a 24-year period, and assessment of correlation of clindamycin use and resistance phenotype. MATERIALS AND METHODS: One hundred and twelve HA-MRSA strains from patients in surgical-transplantation wards (clinical hospital, Warsaw), hospitalized in the period from 1991 to 2014. Methicillin-resistance was determined using phenotypic and genetic methods by detecting the mecA gene. Erythromycin/clindamycin resistance was determined by E-test, the iMLS-B (inductive) and cMLS-B (constitutive) phenotypes by the D-test method. The number of defined daily doses (DDD), statistically per 1000 person-days, was calculated in accordance with the WHO guidelines. RESULTS: Resistance to erythromycin/clindamycin in MRSA strains increased from 1991 to 2004-2007 from 64.7/11.8% to 100/76.9%, respectively. The frequency of the cMLS-B phenotype in the years 1991/2010-2011/2012 was 5.9%/76.9%/69.7%, respectively, and correlated with the increased use of clindamycin in the examined wards. In 2012, the percentage of MLS-B-sensitive isolates increased from 3.9 to 21.7%, while constitutive resistance decreased to 69.7%, which correlated with a decrease in the use of clindamycin. CONCLUSIONS: The proportion of cMLS-B to iMLS-B phenotypes in HA-MRSA is related to the amount of clindamycin used in hospital wards. Limiting the selection pressure of antibiotics can lead to complete loss of resistance or return to the inductive mechanism of its regulation.

Role of sensory afferent nerves, lipid peroxidation and antioxidative enzymes in the carbon monoxide-induced gastroprotection against stress ulcerogenesis.

Carbon monoxide (CO) is a physiological gaseous mediator recently implicated in the mechanism of gastric mucosal defense due to its vasodilatory and antioxidative properties. Small quantities of endogenous CO are produced during heme degradation by heme oxygenase (HO-1), however, the involvement of the capsaicin-sensitive afferent neurons releasing calcitonin gene related peptide (CGRP) and anti-oxidative factors and mechanisms in the CO-induced gastroprotection against stress ulcerogenesis has been little studied. We investigated the possible role of CO released from the CO donor, tricarbonyldichlororuthenium (II) dimer (CORM-2) in the protection against water immersion and restraint stress (WRS)-induced lesions in rats with intact sensory nerves and those with capsaicin denervation and the accompanying changes in malondialdehyde (MDA) content considered as an index of lipid peroxidation, the activity of GSH and SOD-2 and gastric mucosal expression of antioxidative enzymes glutathione peroxidase (GPx) and SOD-2. Wistar rats with intact sensory nerves or those with capsaicin administered in total dose of 125 mg/kg s.c. within 3 days (capsaicin denervation) were pretreated either with 1) vehicle (saline) or 2) CORM-2 (0.1 - 0 mg/kg i.g.) with or without exogenous CGRP (10 µg/kg i.p.) and 30 min later exposed to 3.5 h of WRS. At the termination of WRS, the number of gastric lesions was counted and gastric blood flow (GBF) was assessed by H2-gas clearance technique. The mucosal content of MDA and reduced glutathione (GSH) and the activity of SOD-2 were determined and the expression of GPx-1 and SOD-2 mRNA in the gastric mucosa was analyzed by real-time PCR. The exposure of rats to 3.5 h of WRS resulted in numerous hemorrhagic gastric lesions and significantly decreased the GBF, raised MDA content and significantly decreased the mucosal SOD and GSH contents compared with intact gastric mucosa and these changes were exacerbated in rats with capsaicin denervation. Pretreatment with CORM-2 (1 mg/kg i.g.) which in our previous studies significantly reduced the ethanol and aspirin-induced gastric damage, significantly decreased the number of WRS-induced gastric lesions while raising the GBF and significantly increasing the activity of SOD and GSH (P < 0.05). The pretreatment with CORM-2 significantly decreased MDA content as compared with vehicle-pretreated rats exposed to WRS (P < 0.05). The reduction of WRS damage and the accompanying increase in the GBF as well as the significant decrease in MDA content and the increase in GSH content and SOD activity induced by CORM-2 (1 µg/kg i.g.) were all significantly altered in rats with capsaicin denervation (P < 0.05). The concurrent treatment of CORM-2 with exogenous CGRP in rats with or without sensory nerves tended to decrease the number of WRS lesions as compared with CORM-2 alone pretreated animals and significantly increased the GBF over the values measured in gastric mucosa of CORM-2 alone pretreated rats with or without capsaicin denervation. Such combined administration of CORM-2 and CGRP in rats with capsaicin denervation significantly inhibited an increase in MDA and 4-HNE content and evoked a significant increase in the GSH concentration (P < 0.05) remaining without significant effect on the increase in SOD activity observed with CORM-2 alone. The gastric mucosal expression of SOD-2- and GPx-1 mRNA was significantly increased as compared with those in intact gastric mucosa (P < 0.05). The pretreatment with CORM-2 applied with or without CGRP failed to significantly alter the mRNA expression for SOD-2 and GPx in the gastric mucosa of rats exposed to WRS. Both, the expression of SOD-2- and GPx-1 mRNA was significantly increased in capsaicin denervated rats exposed to WRS rats (P < 0.05) and this effect was abolished by the pretreatment with CORM-2. The expression of SOD-2 tended to decrease, though insignificantly, in rats pretreated with the combination of CORM-2 and CGRP as compared with that detected in CORM-2 alone in rats with capsaicin denervation. In contrast, the mRNA expression of GPx-1 was significantly decreased in gastric mucosa of capsaicin-denervated rats treated with the combination of CORM-2 and CGRP as compared with CORM-2 alone pretreated animals. We conclude that 1) CORM-2 releasing CO exerts gastroprotective activity against stress ulcerogenesis and this effect depends upon an increase in the gastric microcirculation and the vasodilatory activity of this gaseous mediator, and 2) the sensory nerve endings releasing CGRP can contribute, at least in part, to the CO-induced gastric hyperemia, the attenuation of gastric mucosal lipid peroxidation and prevention of oxidative stress as indicated by the CORM-2-induced normalization of the antioxidative enzyme expression enhanced in gastric mucosa of capsaicin-denervated rats.

SIRT1 and SIRT7 expression in adipose tissues of obese and normal-weight individuals is regulated by microRNAs but not by methylation status.

BACKGROUND/OBJECTIVE: Given their importance in the regulation of metabolism, sirtuins (SIRTs) constitute promising subjects of research on the pathogenesis of obesity and the metabolic syndrome. The aim of this study was to assess whether obesity in humans is associated with changes in the expression of SIRT genes in adipose tissue and whether epigenetic mechanisms, DNA methylation and microRNA (miRNA) interference, mediate in this phenomenon. SUBJECTS/METHODS: The expression of SIRTs and of SIRT1 and SIRT7 mRNA-interacting miRNAs was evaluated by real-time PCR in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of 58 obese (body mass index (BMI) >40 kg m-2) and 31 normal-weight (BMI 20-24.9 kg m-2) individuals. The methylation status of SIRTs was studied by the methylation-sensitive digestion/real-time PCR method. RESULTS: SIRT1 mRNA levels were lower in adipose tissues of obese patients than of normal-weight controls (VAT: P=0.0002, SAT: P=0.008). In contrast, expression of SIRT7 was higher in adipose tissues of obese patients than in the control group (VAT: P=0.001, SAT: P=0.008). The mean methylation of the SIRT1 and SIRT7 CpG islands was similar in tissues with high and low expression of these genes, and there was no correlation between the level of expression and the level of methylation. On the other hand, expression of SIRT1 in VAT of obese subjects correlated negatively with the expression of miR-22-3p (P<0.0001, rs=-0.514), miR-34a-5p (P=0.01, rs=-0.326) and miR-181a-3p (P<0.0001, rs=-0.536). In turn, expression of SIRT7 in VAT of slim individuals correlated negatively with the expression of miR-125a-5p (P=0.003, rs=-0.562) and miR-125b-5p (P=0.018, rs=-0.460). CONCLUSIONS: We observed obesity-associated downregulation of SIRT1 and upregulation of SIRT7 mRNA levels that were not associated with the methylation status of their promoters. We found a negative correlation between mRNA levels of SIRT1 in VAT of obese individuals and SIRT7 in VAT of the normal-weight subjects and expression of the relevant miRNAs.

Assessment of Donation Potential After Circulatory Death as the First Step in Implementing and Running a Hospital Program of Organ Procurement.

BACKGROUND: In Poland the potential for organ donation from donation after circulatory death (DCD) donors is not known. This assessment will allow the hospital to create a quality organ harvesting system from this group of donors. AIMS: The aim of this study was to assess the DCD potential based on retrospective analysis of hospital deaths at Hospital Infant Jesus in Warsaw. METHODS: Documentation of 718 deceased patients from 2010 to 2014 was analyzed. This population could be classified as potential DCD donors in IIb category. The deceased's characteristics were analyzed while undergoing the qualification process for DCD. The analysis was to confirm the presence or absence of factors disqualifying kidneys from donation and transplantation. Data from particular departments and from the entire hospital were analyzed. RESULTS: The total number of deaths was 718. Excluding factors from the DCD donation process were found in 664 cases (92%), mainly age >60 and concomitant diseases. The rest of the patients (n = 54.8%) did not have factors that would exclude DCD donation. Group characteristics are given in detail. SUMMARY: The attempt to measure donation potential was done at the Hospital of the Infant Jesus in Warsaw, a large, multispecialty hospital with intensive organ donation and transplantation programs. Results show a potential for DCD donation (54 potential donations over the last 4years), which allows us to create a quality system and algorithms for organ donation after circulation death.

Drug Susceptibility Assessment in Stenotrophomonas Maltophilia Strains Isolated From the Blood of Organ Transplantation Recipients in a Warsaw Teaching Hospital During 2011 to 2014.

BACKGROUND: Blood infections with multidrug-resistant Gram-negative carbapenem-resistant bacilli are particularly dangerous and challenging to treat in organ transplant recipients. Resistance to carbapenems may be acquired, for example, in Enterobacteriaceae, Pseudomonas, or Acinetobacter spp. or innate, for example, in Stenotrophomonas maltophilia. The purpose of this study was to analyze blood infections caused by S maltophilia in organ transplant recipients and to compare drug susceptibility of these bacteria and the same species isolated from the blood of other inpatients. METHODS: A total of 26 S maltophilia strains isolated from blood samples of 26 patients (including 14 liver or kidney transplant recipients) hospitalized during 2011 to 2014 were evaluated in this study. Antibiotic susceptibility was determined via E-test and disk diffusion methods. RESULTS: Stenotrophomonas maltophilia strains isolated from blood exhibited sensitivity to trimethoprim/sulfamethoxazole (100%), levofloxacin (96.2%), ciprofloxacin (92.3%), ticarcillin/clavulanic acid (80.8%), and ceftazidime (53.9%). CONCLUSIONS: Because appropriate antibiotic therapy in the case of S maltophilia differs from the standard empirical therapy administered in the case of most other Gram-negative bacilli, early identification of this pathogen is of particular significance. The use of antibiotics to which this pathogen is sensitive eliminates the infection and helps avoid graft loss.

Clinical and Microbiological Evaluation of Removable Prosthetic Restorations in Patients Treated With an Organ Transplant.

BACKGROUND: Removable dentures improve function and aesthetics of masticatory organ. Their proper scheme of use and hygiene procedures have an impact on biofilm formation. Microorganisms in biofilm are often resistant to many antibiotics and may pose a potential threat to patients treated with organ transplant. The study provided for evaluation of dental prostheses hygiene standards with reference to staphylococcal microflora in kidney transplant recipients. METHODS: The study involved 62 patients with removable prostheses. Thirty-seven subjects of this group had renal replacement therapy. The other 25 were volunteers with normal renal function. Medical and dental history was collected. Denture hygiene was assessed and swab sampling for microbiological testing were performed on the impression surface of the denture plate. RESULTS: Denture hygiene standards and proper scheme of their use were significantly better in patients of the control group. In both groups, significantly with longer denture use, patient care to provide proper hygiene standards declines. Staphylococcal strains were found in 92% patients of the study group and 84% of the control group, 43% of which were multi-drug resistant strains. No relation was found between patients overall health conditions as well as denture use methods and composition of staphylococcal denture plaque. CONCLUSIONS: Overall health conditions and denture use methods might not have an influence on staphylococcal denture plaque composition. However, the studies conducted did not answer the question of whether the above factors cause quantitative differences. Multidrug-resistant staphylococcal strains inhabiting denture surface may pose a threat to the health of kidney transplant recipients.

Epidemiological and Drug-Resistance Types of Methicillin-Resistant Staphylococcus Aureus Strains Isolated From Surgical and Transplantation Ward Patients During 2010 to 2011.

BACKGROUND: The increasing prevalence of multi-drug-resistant methicillin-resistant Staphylococcus aureus (MRSA) is a substantial problem in hospitals worldwide, especially in wards with immunocompromised patients undergoing organ transplant. Epidemiological characteristics and antibiotic susceptibility profiles of hospital-acquired (HA) MRSA strains isolated from surgical/transplantation ward patients were studied. METHODS: We analyzed 26 HA-MRSA strains isolated from 22 patients hospitalized at 3 different surgical and transplantation wards at a Warsaw clinical hospital during 2010 to 2011. Eleven patients were MRSA-asymptomatic carriers. Strain relatedness was evaluated through the use of multi-locus sequence typing (MLST), multi-locus variable-number tandem repeat analysis (MLVA), and random amplified polymorphic DNA/arbitrarily primed PCR (RAPD) methods. Antibiotic susceptibility was assessed the use of routine diagnostic methods. RESULTS: The evaluated strains belonged to 4 clonal complexes (CCs) and 4 sequence types (STs): CC30/ST36 (65.4%), CC8/ST8 (15.4%), CC5/ST1827 (11.5%), and CC1/ST1 (7.7%). Six MLVA types and 6 RAPD types were isolated. A ciprofloxacin-, erythromycin-, and clindamycin-resistant CC30/ST36 clone (MLVA type 1, RAPD type 1A) was isolated in all wards. The isolated HA-MRSA strains were most often resistant to ciprofloxacin (100%), erythromycin (96.2%), clindamycin (84.6%), and gentamycin (30.8%). CONCLUSIONS: A ciprofloxacin-, erythromycin-, and clindamycin-resistant HA-MRSA ST36 CC30 clone, which prevailed on transplantation wards in the years 2010 to 2011, is probably one of the international epidemic clones named UK EMRSA-16 or USA200.

Pathologies in Living Kidney Donors Diagnosed in the Long-Term Care System.

Kidney donation should not lead to deterioration of the donor's health condition, both during the perisurgical period and in the long term. Safety of a living kidney donor becomes a prerequisite for his/her qualification. Detailed diagnostic procedures are performed to exclude any abnormalities of his/her health condition. Additionally, a long-term post-donation follow-up system for kidney donors has been set up in Poland besides the restrictive qualification system. Transplantation centers are obligated to provide a diagnostic procedures for living organ donors as a part of the monitoring of their health condition and to ensure them a medical follow-up for 10 years after the donation. A total of 141 cases of unilateral nephroureterectomy performed in 2003-2014 to obtain a kidney for transplantation were considered. Medical files of post-donation diagnostic or therapeutic methods and their outcomes were retrospectively analyzed. The aim of the study was to assess the efficacy of monitoring of donors' health condition within the framework of the long-term follow-up system for kidney donors in the aspect of detection of the donation-independent abnormalities.

Human Pooled Immunoglobulin as Treatment of Active Antibody-Mediated Rejection of Transplanted Kidney.

BACKGROUND: Antibody-mediated rejection (ABMR) has emerged as the leading cause of renal graft loss. The optimal treatment protocol in ABMR remains unknown. This study aimed to assess the efficacy of intravenous immunoglobulin (IVIG) for treatment of ABMR in renal recipients. METHODS: Thirty-nine ABO-compatible cross-match-negative renal recipients with biopsy-proven ABMR composed the study group. Pulses of methylprednisolone (MP) and appropriate enhancement of net state of immunosuppression were applied in all individuals; 17/39 recipients were administered IVIG (IVIG group); the remaining 22/39 patients, identified to be nonadherent or unsatisfactorily immunosuppressed, were kept on the initial treatment (MP group). Serum creatinine concentration was obtained at each of 10 intended visits, and glomerular filtration rate (GFR) was estimated with the use of the standard Modification of Diet in Renal Disease (MDRD) formula. Generalized linear mixed model was used for statistical analysis. RESULTS: Renal function (modeled as linear slope of MDRD-based GFR change over time, separately for the pre- and post-intervention periods) improved significantly in IVIG-treated recipients. Pre-intervention slopes were -0.72 and -0.46 mL/min/mo for IVIG and MP groups, respectively (P = NS), whereas post-intervention the slopes changed to -0.03 and -0.47 mL/min/mo (IVIG and MP, respectively; P < .005). Within-group changes of slopes at the time of intervention were 0.69 and -0.01 mL/min/mo in IVIG (P < .01) and MP (P = NS) groups, respectively. The relative slope change (pre- to post-intervention) was 0.7 mL/min/mo in favor of the IVIG group (P < .033). None of the classic immunologic or nonimmunologic graft function predictors influenced GFR during 12 months of follow-up. CONCLUSIONS: IVIG improved graft function in renal recipients diagnosed with ABMR.

Renal Transplantation Using Kidneys Procured From Elderly Donors Older Than 70 Years.

AIM: A major problem for the transplant society is a shortage of organs for transplantation compared with the number of patients on the waiting list. This study aimed to assess the results of the transplantation of kidneys procured from older donors. PATIENTS AND METHODS: A total of 27 kidneys procured from donors age 70 years or older were transplanted between January 1, 2010, and April 25, 2015. These represented only 4.1% of the 657 kidneys transplanted from deceased donors during this period at the same center. RESULTS: Delayed graft function (DGF) in the recipients of kidneys procured from donors age 70 or older occurred in 46.1% of patients, whereas the recipients of kidneys from younger donors showed DGF at a frequency of 32.7% (P = NS). The annual and 3-year survival rates of kidneys in the study group were 85% and 80%, respectively, and in the control group were 92.5% and 88.6%, respectively (P = NS). According to the Polish National Organ Procurement Organization (Poltransplant), the annual survival rate of a transplanted kidney in Poland stands at 89%, whereas the 3-year survival rate is 82%. We detected no significant posttransplantation differences in the serum creatinine concentration and in the estimated glomerular filtration rate between the study and control groups. The donor age and donor creatinine were the variables independently associated with DGF. CONCLUSIONS: The results of transplantation of kidneys from elderly donors were comparable to those of transplantation from younger donors. Kidneys harvested from elderly donors should be used for a transplant after a preliminary assessment.

Living-Donor Versus Deceased-Donor Kidney Transplantation: Comparison of Psychosocial Consequences for Recipients.

INTRODUCTION: Health benefits of a living-donor kidney transplantation are numerous and well known. There is, however, a dearth of knowledge on postoperative quality of life among the living-donor (LD) compared to deceased-donor (DD) transplant recipients. MATERIALS AND METHODS: The study involved 89 patients after renal transplantation: 48 from LDs and 41 from DDs. Interview data indirectly indicated the patients' health, whereas physiological parameters directly pinpointed the patients' health and the graft function. All study participants completed questionnaires to measure quality of life and the specificity of emotional and cognitive functioning. RESULTS: LD kidney recipients were younger than DD recipients (40 years vs. 49 years). LD and DD transplantation patients were similar in health status assessed by indirect methods (data from an interview) and direct methods (laboratory tests results). They, however, differed in their psychosocial functioning. LD patients had a greater sense of happiness (P < .01) and of self-efficacy (P = .07). Moreover, these patients were more actively involved in their social lives (P < .02) and were more satisfied with their social relationships (P = .07). LD recipients also had a higher quality of life in terms of mental functioning (P < .01) and satisfaction with their environments (P < .01). Additionally, there were significant correlations between quality of life and the quality of cognitive and emotional functioning in the group of LD recipients. The perceived impact of health on physical and professional activity and daily routines was similar in LD and DD groups. CONCLUSIONS: LD post-transplantation patients may derive greater psychosocial benefits from this form of treatment. This effect is not dependent on somatic parameters (comparable data from an interview and laboratory tests results). This study suggests that patients should be assisted by a multidisciplinary healthcare team, and receive continuous support from relatives during the post-transplantation adaptation process. This facilitates the patients' postoperative quality of life.

Tacrolimus Metabolite M-III May Have Nephrotoxic and Myelotoxic Effects and Increase the Incidence of Infections in Kidney Transplant Recipients.

BACKGROUND: Tacrolimus (Tac) is one of the most commonly used immunosuppressive drugs after solid organ transplantation. Eight Tac metabolites have been described, but their clinical importance remains unclear. The aim of this study was quantification of the 2 major Tac metabolites, 13-O-demethyl (M-I) and 15-O-demethyl (M-III), in kidney transplant recipients and to link them with parameters of kidney and liver function, peripheral blood cell counts, and infection incidence. METHODS: In 81 kidney transplant recipients, concentrations of Tac, M-I, and M-III were measured with the use of liquid chromatography combined with tandem mass spectrometry (LC-MS-MS). RESULTS: There was a negative correlation between M-III levels and estimated glomerular filtration rate (eGFR; r = -0.244; P < .05). Also, a negative correlation between M-III concentrations and red blood cell count (RBC) was found (r = -0.349; P < .05). Neither concentrations of Tac nor of M-I correlated with eGFR or RBC. M-I, M-III, and Tac were not related to alanine aminotransferase activity. Significantly higher Tac and M-III concentrations in the group with all types of infections in comparison with the group without infections were observed (6.95 ± 2.09 ng/mL vs 5.73 ± 2.43 ng/mL [P = .03] and 0.27 ± 0.17 ng/mL vs 0.20 ± 0.11 ng/mL [P = .04], respectively). CONCLUSIONS: The results suggest that higher concentrations of M-III may have a nephrotoxic or myelotoxic effect and result in higher incidence of infections. Further studies are needed to confirm if monitoring of M-III could minimalize adverse effects such as nephrotoxicity or infections.

Cardiovascular Risk Evaluated With the Use of Heartscore in Kidney Transplant Recipients-Three Years of Follow-up.

BACKGROUND: Cardiovascular (CV) complications are the major cause of death in kidney transplant (KT) patients. METHODS: During a 3-year follow-up, 112 KT recipients, from living (LD KTRs; n = 54), and deceased (DD KTRs; n = 58) donors, were assessed for 10-year risk of fatal CV events with the use of the Heartscore tool (www.heartscore.org). In post-KT months 6, 12, and 36, current and optimum (target) CV risks (CVRs) were estimated. RESULTS: Current risk was lower in the LD KTRs and remained stable. In DD KTRs, the risk was at the highest level in months 6 and 12 of follow-up and decreased in month 36. Change in CVR, ie, the difference between the current and target risk, was the highest in DD KTRs in month 36 of follow-up (P = .014). In the increased-CVR group, recipients were older (P < .01), primarily male (P = .08), and more frequently smokers (P < .01) and had a higher systolic blood pressure (P < .05) despite taking more hypotensive medicines (P < .01), and had higher total cholesterol (P < .01) and low-density lipoprotein (P < .01) levels. In this group, body mass index (BMI) was higher (P < .01) and metabolic syndrome was diagnosed significantly more often (P < .01). The high-risk group (estimated CVR, ≥5) was different also in longer durations of pre-transplantation dialysis (P < .05) and higher rates of CV episodes before transplantation (P < .05). In logistic regression, higher BMI and lower estimated glomerular filtration rate (eGFR) were the parameters strongly correlated with higher CVR. CONCLUSIONS: Mean CVR applicable to all kidney transplant recipients was stable throughout the follow-up. Changes in the risk affected mainly DD KTRs. In months 6 and 12, CVR was the highest in this group and was substantially reduced in the 3rd year of follow-up, probably owing to medical interventions. In the high-CVR group, impaired function of the transplanted kidney was recorded. CVR scores in patients with renal conditions and after kidney transplantation should additionally account for eGFR.