Aponeurotic-Cutaneous Tract Exeresis in Patients With Persistent Lymphorrhea After Kidney Transplantation: A Valid Approach in a Day Surgery Setting.

BACKGROUND: Lymphatic disorders (LDs) are the most common minor complications after kidney transplantation (KT), with an incidence rate between 0.6% and 33.9%, which appears to be related to both surgical and medical factors. LDs mostly resolve spontaneously, but occasionally a surgical approach may be required. MATERIALS AND METHODS: We report our experience with 7 KT recipients who developed persistent lymphorrhea (>150 mL/24 h) between October 2017 and March 2019. All cases were treated as outpatients with parietal fistulectomy (PF). The fibrotic aponeurotic-cutaneous tract was thoroughly excised, and the residual aponeurotic defect was closed by watertight suturing. Serial abdominal ultrasounds (US) were carried out after the procedure. RESULTS: A small perirenal graft lymphocele of <2 cm was detected by US in all patients after 48 to 72 hours, without any evidence of either vascular or ureteral compression. During the subsequent scheduled US follow-up, lymphoceles did not increase in size, and additional interventions were not needed. Neither superficial nor deep surgical-site infections were recorded in such patients. CONCLUSIONS: PF was found to be a safe and effective minimally invasive approach for persistent lymphorrhea after KT. It could be easily performed with local anesthesia in a day surgery setting and did not require patient hospitalization.

Open and minimally invasive pancreatic neoplasms enucleation: a systematic review.

BACKGROUND: Pancreatic enucleation (pEN) as parenchyma-sparing procedure for small pancreatic neoplasms is quickly becoming the most common surgical option in such setting. Nowadays, pEN is frequently carried out through a minimally invasive approach either laparoscopic or robotic. Its impact on overall perioperative complications and pancreatic fistula (POPF) is still under evaluation. The scope of our systematic review is to assess pEN's perioperative outcomes and to evaluate the effect of the minimally invasive techniques over POPF and other surgical complications. METHODS: We performed a systematic literature search (time-frame January 1999-September 2018), considering exclusively those studies which included at least 5 cases of either open or minimally invasive pEN. Data regarding postoperative outcome and POPF were extracted and analyzed. We defined postoperative morbidities by the Clavien-Dindo classification while POPF according to the International Study Group of Pancreatic Fistula (ISGPF) definition. RESULTS: Sixty-three studies met the criteria selected, accounting for a study population of 2485 patients. 27.7% had a minimally invasive pEN. The overall postoperative morbidity rate was 46.1% with 11.9% rated as severe (Clavien-Dindo ≥ 3). Mortality rate was 0.69%. The minimally invasive approach to pEN led to a statistically significant reduction of both the overall POPF rate (28.7% vs. 45.9%, p < 0.001), and clinically significant B-C POPF (p < 0.027). The postoperative overall morbidity rate was clearly in favor of the minimally invasive approach (27.6% vs. 55.2%, p < 0.001). CONCLUSIONS: Our review confirms that pEN is a safe and feasible technique for the treatment of small benign or low-grade pancreatic neoplasms and it can be implemented with an acceptable morbidity rate along with low mortality. The minimally invasive approach is gaining widespread acceptance due to its supposed non-inferiority compared with the traditional open approach. In our review, it showed to be even better in terms of POPF incidence rate and short-term postoperative outcome. Still, such data need to be corroborated by randomized clinical trials.

Implementing a Ureteric Magnetic Stent in the Kidney Transplant Setting: Report of 100 Consecutive Cases.

BACKGROUND: Kidney transplantation (KT) is the treatment of choice for end-stage kidney disease. The double-J-stent has been used to prevent urological complications (UCs), but it requires cystoscopy extraction. The novel magnetic black star (MBS) stent provided with a customized retrieval device (9 or 15 Fr) has been developed to spare cystoscopy. Scope of the paper is to analyze MBS in 100 consecutive KTs. METHODS: We report a retrospective analysis of 100 consecutive KT performed between April 2015 and September 2018 using MBS (4.8 Fr, 15 cm) to protect Lich-Gregoir ureteroneocystotomy. MBS was removed 4 weeks after KT by either the 9 Fr (61 cases) or the 15 Fr (39 cases) retrieval device. RESULTS: Intraoperative MBS insertion was straightforward in all cases, and its extraction was carried out in the outpatient setting in 93 patients. Extraction time was <30 seconds in 45 out of 61 patients (73.8%) and in 38 out of 39 patients (97.4%) using the 9 Fr and the 15 Fr retrieval device, respectively. In 15 patients, MBS removal took between 30 seconds and 3 minutes. Only 2 cases required extraction by cystoscopy. We observed 2 UC (ureteric leak and stenosis), 8 urinary tract infections, and 9 stent-related symptoms. 7 patients experienced distressing pain according to Visual Analog Scale for Pain. CONCLUSIONS: In our cohort, MBS appeared to be safe and cost-effective. We advocate its routine implementation in KT because of an easy and comfortable extraction in the outpatient setting even by nondedicated staff, without detrimental impact on UC and urinary tract infection rates.

Treatment of postoperative accessory bile duct injury by fibrin glue and balloon tamponade: a case report.

Laparoscopic cholecystectomy has become the gold standard for the treatment of symptomatic cholelithiasis. Iatrogenic bile duct injuries are still a diagnostic and therapeutic problem and their incidence increased with the introduction of laparoscopic technique. This case report documents a patient with a biliary fistula from an accessory bile duct - Lushka's duct - after routine laparoscopic cholecystectomy, unresponsive to relaparoscopy, ERCP with papillosphincterotomy, biliary stent and nosobiliary tube placement and finally treated with injection of fibrin glue and balloon tamponade through the external drain. Iatrogenic bile duct injuries remain a challenging problem, in particular when they do not communicate with central biliary tree. The detection of this fistulas is more difficult and their management should be multidisciplinary. This case presentation is to emphasize importance of correct diagnostic evaluation and timely and adequate non-surgical methods of treatment of biliary fistulas. (www.actabiomedica.it).

Rapid Biolayer Interferometry Measurements of Urinary CXCL9 to Detect Cellular Infiltrates Noninvasively After Kidney Transplantation.

INTRODUCTION: Measuring the chemokine CXCL9 in urine by enzyme-linked immunosorbent assay (ELISA) can diagnose acute cellular rejection (ACR) noninvasively after kidney transplantation, but the required 12- to 24-hour turnaround time is not ideal for rapid, clinical decision-making. METHODS: We developed a biolayer interferometry (BLI)-based assay to rapidly measure urinary CXCL9 in <1 hour. We validated this new assay versus standard ELISA in 86 urine samples from kidney transplantation recipients with various diagnoses. We then used BLI to analyze samples from 56 kidney transplantation recipients, including 46 subjects who experienced an acute rise in serum creatinine associated with biopsy-proven ACR (n = 22), subclinical rejection (n = 15), or no infiltrates (n = 9), and 10 stable kidney transplantation recipients with surveillance biopsies. To assess its usefulness in detecting adequacy of therapy we serially measured serum creatinine and urinary CXCL9 in 6 subjects after treatment for ACR, and correlated the results with histological diagnoses on follow-up biopsies. RESULTS: BLI accurately and reproducibly detected urinary CXCL9 in <1 hour. BLI-based results showed that urinary CXCL9 was >200 pg/ml in subjects with ACR and ≤100 pg/ml in subjects with stable kidney function without cellular infiltrates. In samples obtained after treatment for ACR, BLI CXCL9 measurements detected biopsy-proven intragraft infiltrates despite treatment-induced reduction in serum creatinine. DISCUSSION: Together, our proof-of-principle results demonstrate that BLI-based urinary CXCL9 detection has potential as a point-of-care noninvasive biomarker to diagnose and guide therapy for ACR in kidney transplantation recipients.

Once-daily prolonged-release tacrolimus formulations for kidney transplantation: what the nephrologist needs to know.

Tacrolimus has long been the cornerstone of the immunosuppressive standard-of-care in kidney transplantation. Until recently, only an immediate-release formulation of tacrolimus was available in the clinic for twice-daily administration, a schedule that is known to hamper prescription adherence and contributes to the already significant tacrolimus interactions with other drugs and meals. In order to improve patient compliance, two once-daily prolonged-release formulations of tacrolimus have recently been developed and approved. Here we will analyze the main characteristics of these two prolonged-release formulations with the aim to provide practical clinical information for a fully aware drug prescription. Finally, the theoretical advantages of the prolonged-release formulations in terms of prescription adherence, blood level steadiness and drug efficacy and tolerability will be critically reviewed, in order to define the profile of renal recipients who may benefit most from the switch to once-daily tacrolimus.

[Metabolic acidosis]. / Acidosi metabolica.

Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

Survival in cats with primary and secondary cardiomyopathies.

OBJECTIVES: Feline cardiomyopathies (CMs) represent a heterogeneous group of myocardial diseases. The most common CM is hypertrophic cardiomyopathy (HCM), followed by restrictive cardiomyopathy (RCM). Studies comparing survival and outcome for different types of CM are scant. Furthermore, little is known about the cardiovascular consequences of systemic diseases on survival. The aim of this retrospective study was to compare survival and prognostic factors in cats affected by HCM, RCM or secondary CM referred to our institution over a 10 year period. METHODS: The study included 94 cats with complete case records and echocardiographic examination. Fifty cats presented HCM, 14 RCM and 30 secondary CM. RESULTS: A statistically significant difference in survival time was identified for cats with HCM (median survival time of 865 days), RCM (273 days) and secondary CM (<50% cardiac death rate). In the overall population and in the primary CM group (HCM + RCM), risk factors in the multivariate analysis, regardless of the CM considered, were the presence of clinical signs, an increased left atrial to aortic root (LA/Ao) ratio and a hypercoagulable state. CONCLUSIONS AND RELEVANCE: Primary CMs in cats share some common features (ie, LA dimension and hypercoagulable state) linked to feline cardiovascular physiology, which influence survival greatly in end-stage CM. The presence of clinical signs has to be regarded as a marker of disease severity, regardless of the underlying CM. Secondary CMs are more benign conditions, but if the primary disease is not properly managed, the prognosis might also be poor in this group of patients.

[Living donor kidney transplantation: new modalities and future directions]. / Il Trapianto da vivente: nuove modalità e future direzioni.

Due to the scarce supply of deceased donor kidneys, living donor kidney transplantation is becoming an increasingly important resource of organs for patients with end-stage renal disease. Laparoscopic nephrectomy, now the most common form of surgical procedure, produces better cosmetic results, less pain, and shorter hospital stay compared to open surgery. Therefore it represents an incentive to improve rates of living kidney donation. Since surgery is scheduled in advance, living donor kidney transplantation offers an unique opportunity to overcome immunological barriers, such as ABO-incompatibility and HLA-incompatibility. Unfortunately, unlike ABO-incompatibility, HLA-incompatibility (i.e. kidney transplantation in a recipient with positive complement-dependent cytotoxic or flow-cytometric crossmatch against the donor) it still leaves many unresolved issues nowadays, concerning the long-term efficacy, safety, and costs of the current treatment protocols. Kidney paired donation represents the ideal solution to immunological barriers, since it avoids the costs and side effects associated with ABO- and HLA-incompatible kidney transplantation. Living donor kidney transplantation also represents the ideal condition for developing tolerance-induction protocols. Indeed, a dramatic progress in this line of research has recently been made with the publication of the results of an apparently safe and efficacious protocol inducing durable high-level hematopoietic chimerism in recipients of living donor kidney transplantation.

Prealbumin improves death risk prediction of BNP-added Seattle Heart Failure Model: results from a pilot study in elderly chronic heart failure patients.

BACKGROUND: An accurate prognosis prediction represents a key element in chronic heart failure (CHF) management. Seattle Heart Failure Model (SHFM) prognostic power, a validated risk score for predicting mortality in CHF, is improved by adding B-type natriuretic peptide (BNP). We evaluated in a prospective study the incremental value of several biomarkers, linked to different biological domains, on death risk prediction of BNP-added SHFM. METHODS: Troponin I (cTnI), norepinephrine, plasma renin activity, aldosterone, high sensitivity-C reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 2 soluble receptor, leptin, prealbumin, free malondialdehyde, and 15-F2t-isoprostane were measured in plasma from 142 consecutive ambulatory, non-diabetic stable CHF (mean NYHA-class 2.6) patients (mean age 75±8years). Calibration, discrimination, and risk reclassification of BNP-added SHFM were evaluated after individual biomarker addition. RESULTS: Individual addition of biomarkers to BNP-added SHFM did not improve death prediction, except for prealbumin (HR 0.49 CI: (0.31-0.76) p=0.002) and cTnI (HR 2.03 CI: (1.20-3.45) p=0.009). In fact, with respect to BNP-added SHFM (Harrell's C-statistic 0.702), prealbumin emerged as a stronger predictor of death showing the highest improvement in model discrimination (+0.021, p=0.033) and only a trend was observed for cTn I (+0.023, p=0.063). These biomarkers showed also the best reclassification statistic (Integrated Discrimination Improvement-IDI) at 1-year (IDI: cTnI, p=0.002; prealbumin, p=0.020), 2-years (IDI: cTnI, p=0.018; prealbumin: p=0.006) and 3-years of follow-up (IDI: cTnI p=0.024; prealbumin: p=0.012). CONCLUSIONS: Individual addition of prealbumin allows a more accurate prediction of mortality of BNP enriched SHFM in ambulatory elderly CHF suggesting its potential use in identifying those at high-risk that need nutritional surveillance.

[Ultrafiltration in heart failure]. / Ultrafiltrazione nello scompenso cardiaco.

In patients with heart failure fluid overload is clinically evident as systemic and/or pulmonary congestion, and represents a key issue in the therapeutic approach to the syndrome. Ultrafiltration, obtained by dedicated machines or standard dialysis machines (isolated ultrafiltration), or by the use of the peritoneal membrane (peritoneal ultrafiltration), has been recently proposed for fluid overload correction. This review is aimed at illustrating the operative background, safety, efficacy and cost issues of the different ultrafiltration modalities in heart failure. We retrieved all full-text non-duplicated articles documenting clinical studies on ultrafiltration in heart failure and describing patient characteristics, ultrafiltration procedures, renal outcome and adverse effects, by searching MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials up to December 31, 2011, with the terms ''heart failure'' and ''ultrafiltration OR hemofiltration'' and ''heart failure'' and "peritoneal dialysis". Isolated ultrafiltration can be considered potentially safe for the heart and the kidney in heart failure, and is efficacious for fluid overload removal. However, the available evidence does not support its widespread use as a substitute for conventional diuretic therapy. Isolated ultrafiltration should be employed neither as a quicker way to achieve mechanical diuresis nor as a remedy for an apparently inadequate response to conventional diuretic therapy. Peritoneal ultrafiltration is a promising ultrafiltration procedure that can be safely and successfully performed in heart failure; however, also in this case larger-scale randomized controlled trials are needed. The available evidence supports the concept of reserving ultrafiltration modalities for selected patients with advanced heart failure and true diuretic resistance, as part of a more integrated strategy aimed at fluid overload control.

Nutritional assessment and delivery in renal replacement therapy patients.

The present review is aimed at illustrating and discussing literature data and recent guidelines concerning artificial nutrition in patients with acute kidney injury (AKI) on renal replacement therapy (RRT). Protein-energy wasting often complicates the clinical course of AKI in critically ill patients, increasing their morbidity and mortality risk. The most severe forms of the syndrome - those observed in ICU patients - are characterized by hypercatabolism with relevant lean body mass loss. In this clinical condition, artificial nutrition (enteral and/or parenteral nutrition) is considered an integral part of the complex therapeutic approach. Even though many issues concerning nutrition in AKI are common to other critically ill patients, the presence of AKI with the ensuing impairment of the kidney homeostatic function introduces specific problems and can make more difficult to give the patient an adequate nutrient provision. Thus, peculiarities of the syndrome - and of RRT itself - must be taken into account in nutritional planning for these patients. Recent guidelines have suggested that the enteral route should be the preferred one, even though parenteral nutrition is often required to target nutritional needs (25-30 kcal/kg body weight/day, and 1.5 + 0.2 g/kg/day to compensate for amino acid losses during RRT). Special attention should be paid to the impact of different forms of RRT on the possible loss of both macro- and micronutrients and vitamins, as well as to the risk of metabolic complications. Finally, close integration between nutritional support and RRT is required, aiming at carefully tailoring both therapies on patient's changing needs.

Ultrafiltration in heart failure.

Fluid overload is a key pathophysiologic mechanism underlying both the acute decompensation episodes of heart failure and the progression of the syndrome. Moreover, it represents the most important factor responsible for the high readmission rates observed in these patients and is often associated with renal function worsening, which by itself increases mortality risk. In this clinical context, ultrafiltration (UF) has been proposed as an alternative to diuretics to obtain a quicker relief of pulmonary/systemic congestion. This review illustrates technical issues, mechanisms, efficacy, safety, costs, and indications of UF in heart failure. The available evidence does not support the widespread use of UF as a substitute for diuretic therapy. Owing to its operative characteristics, UF cannot be expected to directly influence serum electrolyte levels, azotemia, and acid-base balance, or to remove high-molecular-weight substances (eg, cytokines) in clinically relevant amounts. Ultrafiltration should be used neither as a quicker way to achieve a sort of mechanical diuresis nor as a remedy for an inadequately prescribed and administered diuretic therapy. Instead, it should be reserved to selected patients with advanced heart failure and true diuretic resistance, as part of a more complex strategy aiming at an adequate control of fluid retention.

Nutritional assessment and support in acute kidney injury.

PURPOSE OF REVIEW: Acute kidney injury (AKI) in the ICU is associated with an increased risk of protein-energy wasting (PEW), a major negative prognostic factor. This review illustrates recently published data and guidelines concerning nutritional problems in AKI, pointing out complexities and peculiarities of the syndrome. RECENT FINDINGS: The main goals of nutritional support in AKI on renal replacement therapy (RRT) are to ensure the provision of adequate amounts of nutrients, to prevent PEW, to promote tissue reparation, to support the immune system, and possibly to reduce mortality. The enteral route should be preferred, even though parenteral nutrition is often required to target nutritional needs. Special attention should be paid both to the impact of RRT on macronutrient and micronutrient losses, and to the risk of complications. In fact, due to both the acute loss of the kidneys' homeostatic function, and the frequent need of RRT, patients with AKI are especially prone to hypoglycemia and hyperglycemia, hypertriglyceridemia, fluid balance alterations, electrolyte and acid-base derangements. SUMMARY: This review highlights the most recent concepts and recommendations for nutritional support in AKI, stressing the need for a close integration between adequate nutrition and RRT in this clinical condition, with the aim of carefully tailoring both therapies on patients' changing needs. Recent findings about the renoprotective role of some nutrients (glutamine, omega-3 fatty acids) are also discussed.

Characterization of myocardial hypertrophy in prehypertensive spontaneously hypertensive rats: interaction between adrenergic and nitrosative pathways.

OBJECTIVE AND METHODS: Left ventricular hypertrophy in human and experimental hypertension is not always associated with pressure overload but seems to precede an increase in blood pressure. In this study, performed in male 5-week-old prehypertensive spontaneously hypertensive rats (SHR; n = 65) and age-matched Wistar-Kyoto rats (n = 56), the relationship between myocardial structure and activation of the adrenergic and nitric oxide systems was evaluated. RESULTS: Body weight, blood pressure and heart rate were similar in both groups. A higher left ventricle/body weight ratio was found in SHR, as a result of greater mononuclear (+47%) and binuclear (+43%) myocyte volumes, without changes in interstitial collagen. Both adrenergic and nitric oxide pathways were activated in SHR, as expressed by higher myocardial norepinephrine content, tyrosine hydroxylase activity, myocardial nitric oxide synthase 3 expression and protein nitration, indicating greater peroxynitrite (ONOO) generation from nitric oxide and superoxide. No difference was measured in nitric oxide synthase 1 expression, whereas nitric oxide synthase 2 was undetectable. A positive correlation between myocardial tyrosine hydroxylase activity and protein nitration was observed in SHR (r = 0.328; P < 0.01). Early treatment with a superoxide dismutase mimetic, 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl, from the third to the fifth week of age, reduced ONOO generation, protein nitration and sympathetic activation in SHR without changes in myocardial structure. CONCLUSION: In prehypertensive SHR, left ventricular hypertrophy is associated with adrenergic and nitrosative imbalance. Early superoxide dismutase mimetic treatment in SHR effectively reduces higher myocardial ONOO generation, sympathetic activation, and heart rate without affecting the development of myocardial hypertrophy.