Outcomes of an enhanced recovery after radical cystectomy program in a prospective multicenter study: compliance and key components for success.

OBJECTIVE: To investigate the effect of an Enhanced Recovery After Surgery (ERAS) program on complications and length of stay (LOS) after radical cystectomy (RC) and to assess if the number and type of components of ERAS play a key role on the decrease of surgical morbidity. MATERIALS AND METHODS: We analyzed the data of 277 patients prospectively recruited in 11 hospitals undergoing RC initially managed according to local practice (Group I) and later within an ERAS program (Group II). Two main outcomes were defined: 90-day complications rate and LOS. As secondary variables we studied 90-day mortality, 30-day readmission and transfusion rate. RESULTS: Patients in Group II had a higher use of ERAS measures (98.6%) than those in Group I (78.2%) (p < 0.05). Patients in Groups I and II experienced similar complications (70.5% vs. 66%, p = 0.42). LOS was not different between Groups I and II (12.5 and 14 days, respectively, p = 0.59). The risk of having any complication decreases for patients having more than 15 ERAS measures adopted [RR = 0.815; 95% confidence interval (CI) 0.667-0.996; p = 0.045]. Avoidance of transfusion and nasogastric tube, prevention of ileus, early ambulation and a fast uptake of a regular diet are independently associated with the absence of complications. CONCLUSIONS: Complications and LOS after RC were not modified by the introduction of an ERAS program. We hypothesize that at least 15 measures should be applied to maximize the benefit of ERAS.

Antitumoral gene-based strategy involving nitric oxide synthase type III overexpression in hepatocellular carcinoma.

Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO) synthase type III (NOS-3) overexpression induces cell death in hepatoblastoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. The first-generation adenoviruses were designed to overexpress NOS-3 or green fluorescent protein, and luciferase complementary DNA under the regulation of murine alpha-fetoprotein (AFP) and Rous Sarcoma Virus (RSV) promoters, respectively. Both adenovirus and Hepa 1-6 cells were used for in vitro and in vivo experiments. Adenoviruses were administered through the tail vein 2 weeks after orthotopic tumor cell implantation. AFP-NOS-3/RSV-luciferase increased oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8, -9 and -3 activities in cultured Hepa 1-6 cells. The increased expression of CD95/CD95L and caspase-8 activity was abolished by Nω-nitro-l-arginine methyl ester hydrochloride, p53 and CD95 small interfering RNA. AFP-NOS-3/RSV-luciferase adenovirus increased cell death markers, and reduced cell proliferation of established tumors in fibrotic livers. The increase of oxidative/nitrosative stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L expression and cell death in hepatocellular carcinoma cells. The effectiveness of the gene therapy has been demonstrated in vitro and in vivo.

CD34+ circulating progenitor cells after different training programs.

Circulating progenitor cells (CPC) are bone marrow-derived cells that are mobilized into the circulation. While exercise is a powerful mediator of hematopoiesis, CPC levels increase, and reports of their activation after different types of exercise are contradictory. Moreover, few studies have compared the possible effects of different training programs on CPC concentrations. 43 physically active healthy male subjects (age 22±2.4 years) were assigned to 4 different training groups: aerobic, resistance, mixed and control. Except for the control group, all participants trained for 6 weeks. Peripheral blood samples were collected through an antecubital vein, and CPC CD34(+) was analyzed on different days: pre-training, post-training, and 3 weeks after finishing the training period. While no significant differences in CPC were observed either within or between the different training groups, there was a tendency towards higher values post-training and large intra- and intergroup dispersion. We detected an inverse linear relationship between pre-training values and % of CPC changes post-training (p<0.001). In the CPC values 3 weeks after training this inverse relationship was maintained, though to a lower extent (p<0.001). No changes in CPC CD34(+) were detected after 6 weeks of different training groups, or after 3 weeks of follow-up.

[Enuresis: Perception and attitude in population of our country]. / Enuresis: percepción y actitud en la población de nuestro país.

OBJECTIVE: To know the perception and attitude towards enuresis from families and caregivers with the aim of establishing a rational therapeutic plan. MATERIAL AND METHODS: A 25-question survey was performed among parents over 18years old with at least a child between 5 and 13years old, maintaining national representativeness in terms of residence, social class and age of the children. Data collection was performed in April 2021. RESULTS: Data from 501 out of 626 sent surveys was obtained, mostly from middle-class families from Andalusia, Catalonia and the Community of Madrid. From all the participants, 47.9% knew about the existence of enuresis, although only 23.8% knew which was the medical term. Only 16.6% and 9.6% remembered that the pediatrician or the nurse, respectively, had referred to the condition at any time. Among the respondents with some knowledge about enuresis, their main information source were close cases (36.6%), media outlets (31.1%) and the pediatrician (27.8%). Parents would be very (35.3%) or somewhat (43.1%) worried in the event of an enuresis case. However, the level of knowledge was higher, and the level of concern was lower among parents with a child with enuresis in comparison to those without a case in their family. CONCLUSION: Improving parent knowledge about enuresis and changing their perception towards this condition might be of importance to improve their attention and anticipate its resolution.

Radiofrequency-assisted transection of the pancreas versus stapler in distal pancreatectomy: study protocol for a multicentric randomised clinical trial (TRANSPAIRE).

INTRODUCTION: To date, no pancreatic stump closure technique has been shown to be superior to any other in distal pancreatectomy. Although several studies have shown a trend towards better results in transection using a radiofrequency device (radiofrequency-assisted transection (RFT)), no randomised trial for this purpose has been performed to date. Therefore, we designed a randomised clinical trial, with the hypothesis that this technique used in distal pancreatectomies is superior in reducing clinically relevant postoperative pancreatic fistula (CR-POPF) than mechanical closures. METHODS AND ANALYSIS: TRANSPAIRE is a multicentre randomised controlled trial conducted in seven Spanish pancreatic centres that includes 112 patients undergoing elective distal pancreatectomy for any indication who will be randomly assigned to RFT or classic stapler transections (control group) in a ratio of 1:1. The primary outcome is the CR-POPF percentage. Sample size is calculated with the following assumptions: 5% one-sided significance level (α), 80% power (1-ß), expected POPF in control group of 32%, expected POPF in RFT group of 10% and a clinically relevant difference of 22%. Secondary outcomes include postoperative results, complications, radiological evaluation of the pancreatic stump, metabolomic profile of postoperative peritoneal fluid, survival and quality of life. Follow-ups will be carried out in the external consultation at 1, 6 and 12 months postoperatively. ETHICS AND DISSEMINATION: TRANSPAIRE has been approved by the CEIM-PSMAR Ethics Committee. This project is being carried out in accordance with national and international guidelines, the basic principles of protection of human rights and dignity established in the Declaration of Helsinki (64th General Assembly, Fortaleza, Brazil, October 2013), and in accordance with regulations in studies with biological samples, Law 14/2007 on Biomedical Research will be followed. We have defined a dissemination strategy, whose main objective is the participation of stakeholders and the transfer of knowledge to support the exploitation of activities. REGISTRATION DETAILS: ClinicalTrials.gov Registry (NCT04402346).

Hormonal response of nestlings to predator calls.

Chicks of altricial birds may perceive predation risk by acoustic cues produced by predators. This capacity involves changes to a less conspicuous behavior to avoid being detected and predated. However, little is known about the physiological mechanisms underlying this capacity. Potential mechanisms may involve corticosterone and testosterone, two hormones related to begging, an acoustic signal, which could be used by predators to locate and predate the nest. However, given the species-specificity of this relationship, it is difficult to make particular predictions. We manipulated perceived risk of nest predation in the common blackbird (Turdus merula) and analyzed nestlings' plasma levels of these hormones to look for nest predation risk effects. Our experimental manipulation showed hormonal changes in response to nest predation risk. Chicks under a high risk of nest predation reduced their corticosterone plasma levels but increased their testosterone levels in comparison with nestlings exposed to a low nest predation risk. We explain our results as mechanisms to reduce begging activity and discuss them within the framework of hormonal modifications in developing animals. These findings highlight the importance of studying nest predation from the unusually considered chick perspective and underlined the benefits from including physiological variables in the study of predator-prey interactions.

Effects of climate variation on bird escape distances modulate community responses to global change.

Climate and land use are rapidly changing environmental conditions. Behavioral responses to such global perturbations can be used to incorporate interspecific interactions into predictive models of population responses to global change. Flight initiation distance (FID) reflects antipredator behaviour defined as the distance at which an individual takes flight when approached by a human, under standardized conditions. This behavioural trait results from a balance between disturbance, predation risk, food availability and physiological needs, and it is related to geographical range and population trends in European birds. Using 32,145 records of flight initiation distances for 229 bird species during 2006-2019 in 24 European localities, we show that FIDs decreased with increasing temperature and precipitation, as expected if foraging success decreased under warm and humid conditions. Trends were further altered by latitude, urbanisation and body mass, as expected if climate effects on FIDs were mediated by food abundance and need, differing according to position in food webs, supporting foraging models. This provides evidence for a role of behavioural responses within food webs on how bird populations and communities are affected by global change.

Prevalence of hepatitis A and B markers and vaccine indication in cirrhotic patients evaluated for liver transplantation in Spain.

Vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is generally recommended for patients with chronic liver disease and those evaluated for liver transplantation in the absence of immunity. HAV and HBV infections after liver transplantation are frequent and associated with a worse prognosis. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV and HBV is substantial, and that new vaccination strategies are needed. The aim of this study was to determine the level of immunity from hepatitis A and B infections and the need for HBV and HAV vaccination among cirrhotic patients evaluated for liver transplantation. We studied HBV and HAV serological markers (HbsAg, anti-HBc, anti-HBs, IgG anti-HAV) in 451 cirrhotic patients evaluated for liver transplantation to investigate the association with gender, age, and etiology of cirrhosis. Negative HBV markers were observed in 57% of patients with 43% displaying one positive HBV marker: HBsAg (+), 9.5%; anti-HBc (+)/anti-HBs (-), 11.5%; anti-HBc (-)/anti-HBs(+), 4.2%; anti-HBc(+)/anti-HBs(+), 17.7%. HBV vaccine indication established in 68.5% of patients was greater among women and hepatitis C virus-negative patients. No differences were observed in age or cause of cirrhosis. HAV vaccination indicated in 6.7% of patients (IgG anti-HVA-negative) was greater among patients with negative HBV markers (9.3% vs 3.3%, P = .018) and younger patients (25.3% of patients

Evaluation of two commercial enzyme immunoassays for the detection of norovirus in faecal samples from hospitalised children with sporadic acute gastroenteritis.

Two commercially available enzyme immunoassays (EIAs), IDEIA and Ridascreen, for norovirus antigen detection were evaluated with 117 faecal samples from hospitalised children with acute gastroenteritis. Eighteen of 39 samples positive by RT-PCR were characterised by sequence analysis, and 17 of these were related to norovirus genogroup II. When compared with RT-PCR, the sensitivity and specificity values were 76.9% and 85.9%, respectively, for the IDEIA assay, and 59.0% and 73.1%, respectively, for the Ridascreen assay. The sensitivity and specificity of both EIA tests require improvement, but they could both eventually be of use in the diagnosis of norovirus diarrhoea in clinical laboratories.

[Role of malnutrition in intestinal anastomosis collagenization: an analysis of procollagen (PINP) and carboxyterminal telopeptide (ICTP) by radioimmunoassay]. / Efectos de la desnutrición sobre la colagenización de anastomosisintestinales: análisis de procolágeno y telopéptido carboxiterminalmediante radioinmunoanálisis.

INTRODUCTION: some clinical, anatomo-pathological, and technical factors influence the correct healing of intestinal suture following an intestinal resection. One of the most influential factors is patient nutritional status. OBJECTIVES: to evaluate the influence of malnutrition on the viability of primary intestinal anastomosis by the analysis of collagen I deposition. METHODS: 40 Wistar rats, radioimmunoassay material. We used 2 groups of rats, 20 animals in each group: a control group (A) and a "malnutrition" group (B). RESULTS: there was a decrease in PINP (procollagen) deposition in the colon of group B rats as compared to the colon of group A (0.3620 and 0.4340 mg/g respectively) (p = 0.032). There is an increase in ICTP (carboxyterminal telopeptide) in the colon of group B (0.9545 as against 0.8460 mg/g in group A) (p = 0.875). In anastomoses of group B there was a decrease in PINP synthesis as compared to group A (0.376 and 0.468 mg/g respectively, p = 0.002). As regards ICTP, there was an increase in group B (p = 0.330). In relation to the control group no differences were observed in ICTP increases in group B (p = 1). CONCLUSIONS: colonic anastomosis increases the levels of PINP and ICTP in healed tissue (p = 0.000); malnutrition reduces collagenization in anastomoses (p = 0.000).

A novel semi-robotized device for high-precision 18F-FDG-guided breast cancer biopsy.

PURPOSE: To assess the 3D geometric sampling accuracy of a new PET-guided system for breast cancer biopsy (BCB) from areas within the tumour with high 18F-FDG uptake. MATERIALS AND METHODS: In the context of the European Union project MammoCare, a prototype semi-robotic stereotactic prototype BCB-device was incorporated into a dedicated high resolution PET-detector for breast imaging. The system consists of 2 stacked rings, each containing 12 plane detectors, forming a dodecagon with a 186mm aperture for 3D reconstruction (1mm3 voxel). A vacuum-assisted biopsy needle attached to a robot-controlled arm was used. To test the accuracy of needle placement, the needle tip was labelled with 18F-FDG and positioned at 78 target coordinates distributed over a 35mm×24mm×28mm volume within the PET-detector field-of-view. At each position images were acquired from which the needle positioning accuracy was calculated. Additionally, phantom-based biopsy proofs, as well as MammoCare images of 5 breast cancer patients, were evaluated for the 3D automated locating of 18F-FDG uptake areas within the tumour. RESULTS: Needle positioning tests revealed an average accuracy of 0.5mm (range 0-1mm), 0.6mm (range 0-2mm), and 0.4mm (range 0-2mm) for the x/y/z-axes, respectively. Furthermore, the MammoCare system was able to visualize and locate small (<10mm) regions with high 18F-FDG uptake within the tumour suitable for PET-guided biopsy after being located by the 3D automated application. CONCLUSIONS: Accuracy testing demonstrated high-precision of this semi-automatic 3D PET-guided system for breast cancer core needle biopsy. Its clinical feasibility evaluation in breast cancer patients scheduled for neo-adjuvant chemotherapy will follow.

Morbidity and mortality in liver retransplantation.

INTRODUCTION: The incidence of orthotopic liver retransplantation (re-OLT) ranges from 6% to 11%. The most frequent causes of early re-OLT are allograft failure, uncontrolled acute rejection, and vascular complications. MATERIALS AND METHODS: A retrospective study of 512 orthotopic liver transplants (OLTs) in 482 patients over 15 years. RESULTS: The incidence of re-OLT was 6.6%, with a higher percentage of men requiring re-OLT than first-time OLT (75.0% vs 63.0%, P < .05). The reasons for re-OLT were thrombosis 21.7%, aneurysm 6.5%, stenosis 3.2%, primary nonfunction (PNF) 21.7%, and chronic rejection or recurrence of the initial disease 40.4%. Complications included PNF (22.0%), acute renal failure (65.6%), postoperative infection (87.5%), and adult respiratory distress syndrome (9.4%; P < .05). No differences were seen in the incidence of septicemia or postoperative hemorrhage. The average survival was much lower in re-OLT (21.8 days) compared with OLT (194.5 days; P < .05). The mortality rates in re-OLT were 100% for primary biliary cirrhosis, 85.7% for HCV, 50% for alcoholic cirrhosis, and 20% for HBV. A direct association between the Model for End-stage Liver Disease (MELD) score and the number of complications was present. DISCUSSION: There was a greater requirement for re-OLT in men and those patients transplanted due to hepatitis B virus cirrhosis and fulminant hepatitis (P < .05). The re-OLT patients had no greater incidence of sepsis compared with the OLT patients, although they did have a greater incidence of primary graft dysfunction, acute renal failure, adult respiratory distress syndrome, and postoperative infection (P < .05). The MELD was a good parameter for predicting graft evolution. Re-OLT in patients with primary biliary cirrhosis and hepatitis C virus was associated with a high degree of mortality.

Survey of hemostasis management and transfusion in liver transplantation.

OBJECTIVE: To determine the management of haemostasis and transfusion practice in the field of liver transplantation in Spain. METHODS: A questionnaire was developed for physicians in anaesthesiology of all centres performing liver transplantation in Spain. The information required made reference to the 12 months prior to its distribution, from January 1 to December 31, 2011. RESULTS: Data were collected from 24 centres in which liver transplantation is performed in Spain. Only 46% reported that they had protocols or practice guidelines for the management of haemostasis, and 83% of hospitals responded that they knew the percentage of transfused patients, but only 57% knew the mean transfusion. Regarding the degree of satisfaction with the management of haemostasis/coagulation, 50% said they were not satisfied. Thromboelastometry was used as an additional method of preoperative monitoring in only 8% of the centres and intra-operatively in one-third. Less than half (46%) of the centres performed preoperative correction of coagulation deficits based on conventional tests. The mean number of packed red cells used was ≤4 in 57% of centres. Consumption of fresh frozen plasma was highly variable, while 100% of centres consumed less than 4 pools of platelets per patient. CONCLUSIONS: There is a wide variability in the management of haemostasis and transfusion practice among Spanish centres. There are no guidelines or they are not widely used. The mean use of transfused blood products remain high. There was a decrease in centres using new methods of monitoring.

Comorbidity indices in hematopoietic stem cell transplantation: a new report card.

Comorbid conditions have not been studied systematically for impact upon patient outcome in the setting of hematopoietic stem cell transplantation (HSCT). Patients formerly excluded from myeloablative transplant due to comorbid illnesses now receive reduced-intensity conditioning regimens; hence, the incidence of comorbid conditions in HSCT recipients is expected to increase. Comorbid grading systems developed without regard for oncology patients have been applied in retrospective fashion to HSCT patients. Two commonly used scales (Charlson Comorbidity Index and the Adult Comorbidity Inventory-27) fail to include critical information: tumor and histologic type/stage, extent of prior treatment, donor stem cell source and cell type and preparative regimen. Further, data are reported in retrospective rather than prospective fashion. Despite limitations, however, such grading systems exhibit ease and utility for evaluation and may have predictive value for patient outcome. Modifying such approaches to include additional factors and appropriate weighting of components may enable an improved comparison of techniques and study results. These scoring systems may elucidate predictors of outcome and disease natural history and enhance statistical efficiency methods of HSCT. Refined scoring could be used effectively to assign patients to differing transplant conditioning regimens, that is, myeloablative vs reduced intensity. Prospective validation of such grading systems is encouraged.

Mycotic pseudoaneurysms after liver transplantation.

The most frequent etiology of visceral artery aneurysms is arteriosclerosis, but vascular manipulation during hepatic transplantation may also cause a mycotic pseudoaneurysm. Treatment with embolization, stents or percutaneous thrombin injection have been recommended but surgical revascularization is indicated when interventional techniques fail. A 43-year-old man with hepatitis C virus cirrhosis who underwent orthotopic liver transplantation from a cadaveric donor was treated with cyclosporine, mycophenolate, and steroids and was discharged from hospital at 35 days. Two months later he was readmitted with a febrile syndrome. Abdominal computed tomography showed necrosis of hepatic segments IV, V, and VI. Magnetic resonance imaging and angiography revealed partial thrombosis of the hepatic artery and stenosis of the portal anastomosis secondary to an aneurysm of the hepatic artery. A few hours after the radiological diagnosis, the patient suffered a bout of upper gastrointestinal bleeding and shock. Emergency surgery revealed a mycotic pseudoaneurysm of the common hepatic artery, which had ruptured into the bile tract with hemobilia. The liver graft was removed because of severe necrosis of the right liver. The patient died awaiting a new liver transplantation.

Fascicular ligation in the prevention and treatment of painful terminal neuroma: an experimental study in the rat.

The role of microfascicular double ligation and interligature coagulation in the prevention of painful neuroma was studied in an experimental model of section of the sciatic nerve in the rat. The experimental parameters used were the onset of autotomy and the weekly autotomy score. The autotomy of the denervated limb is a behavioral pattern that occurs in the experimental animal after the severing of peripheral nerves and has been related to anomalous electrical activity originating from the neuroma. Microfascicular ligation was performed immediately after section of the sciatic nerve or 10 days later. The results were compared to those of control groups treated with simple nerve section or simple neuroma resection 10 days after nerve section. The results show that immediate or delayed microfascicular ligation has no effect on pain as measured by the development of autotomy.

Intraventricular flow patterns and stasis in the LVAD-assisted heart.

Left ventricular assist device (LVAD) support disrupts the natural blood flow path through the heart, introducing flow patterns associated with thrombosis, especially in the presence of medical devices. The aim of this study was to quantitatively evaluate the flow patterns in the left ventricle (LV) of the LVAD-assisted heart, with a focus on alterations in vortex development and stasis. Particle image velocimetry of a LVAD-supported LV model was performed in a mock circulatory loop. In the Pre-LVAD flow condition, a vortex ring initiating from the LV base migrated toward the apex during diastole and remained in the LV by the end of ejection. During LVAD support, vortex formation was relatively unchanged although vortex circulation and kinetic energy increased with LVAD speed, particularly in systole. However, as pulsatility decreased and aortic valve opening ceased, a region of fluid stasis formed near the left ventricular outflow tract. These findings suggest that LVAD support does not substantially alter vortex dynamics unless cardiac function is minimal. The altered blood flow introduced by the LVAD results in stasis adjacent to the LV outflow tract, which increases the risk of thrombus formation in the heart.

Is "intra-operating room" thromboelastometry useful in liver transplantation? A case-control study in 303 patients.

Coagulation monitoring during liver transplantation (LT) is, even today, fundamental to reduce blood loss during surgery. Thromboelastometry (TEM) is a proven technique for controlling the various parameters that influence coagulation. However, there are no studies linking "intra-operating room" TEM (orTEM) with LT outcomes. We describe a case-control study in 303 liver graft recipients analyzing variables associated with operative complications and long-term LT outcomes. The results showed that orTEM reduced the use of blood products in patients with Model for End-Stage Liver Disease scores of ≥ 21, retransplantation, and high surgical difficulty and important intraoperative bleeding. In addition, results in survival and postoperative complications were better when orTEM was used. In conclusion, we confirm that use of orTEM is associated with less use of blood products and a lower rate of complications after LT.