[Implementation of a Plan of Patient Safety in Service of Pediatric Surgery. First results]. / Implementación de un Plan de Seguridad del Paciente en un Servicio de Cirugía Pediátrica. Primeros resultados.

OBJECTIVES: In 2014 our department starts to apply the PatientSafety Strategic in Pediatric Surgery. Our aim is to describe the results obtained. METHODS: For the measurement of adverse events (AE) we used a modification of the Global Trigger Tool of the Institute for Healthcare Improvement. Population analysed: patients undergoing surgery with hospitalization. On a monthly basis, audits of the medical records of 12 patients discharged in the prior week of the assessment were performed. The evaluation team was composed by experienced pediatric surgeon, two staff nurses, and a doctor and nurse from the Quality Department. RESULTS: 95 clinical records and a total of 406 days of hospital stay were reviewed. 31 patients (32.6%) experienced one or more AE. Total AE: 43. The AE/1000 patients/day ratio: 105.9. The most common AE were: vomiting, itching and pain. 28 EA were considerd mild and 3 moderate in severity, according to the classification of the National Coordinating Council for Medication Error Reporting and Prevention. No EA were considered serious or critical. CONCLUSIONS: The analysis of prevalence through regular assessments of medical records is an easy method to obtain information about the frequency of occurrence, exact understanding of the AE types and the implementation of corrective measures. The main limitation of this method is that it can miss some of the serious EA and miss the records and analysis of sentinel events that may occur in the period between assessments.

OBJETIVOS: Durante el año 2014 se aplica el Plan de Seguridad del Paciente en un Servicio de Cirugía Pediátrica, elaborado previamente por nuestro Servicio. Se describen los resultados. MATERIAL Y METODOS: El método empleado para la medición de eventos adversos (EAs) es una modificación del Global Trigger Tool del Institute for Health care Improvement. Población analizada: pacientes intervenidos quirúrgicamente con hospitalización. Con una periodicidad mensual, se realizaron 12 auditorias de las historias clínicas correspondientes a los pacientes dados de alta en la semana anterior al día de la evaluación. El equipo evaluador estaba compuesto por: un cirujano pediátrico experto, dos enfermeras de planta más un médico y una enfermera del Servicio de Calidad. RESULTADOS: Se revisaron 95 historias y 406 días de estancia. 31 pacientes (32,6%) sufrieron uno o más eventos adversos. Total EAs: 43. Número EAs/1.000 pacientes/día: 105,9. Los 3 EA más frecuentes fueron: vómitos, prurito y dolor. 28 EAs fueron de gravedad leve y 3 moderada, según la clasificación del National Coordinating Council for Medication Error Reporting and Prevention. Ningún EA fue grave o crítico. CONCLUSIONES: La determinación de la prevalencia mediante evaluaciones regulares de historias clínicas es un método que permite obtener información de forma fácil sobre la frecuencia de aparición, el conocimiento exacto de los tipos de EAs y la aplicación de medidas correctoras. Este método tiene como limitación principal la posible falta de recogida EAs graves así como registro y análisis de eventos centinelas que pueden ocurrir en el periodo entre evaluaciones.

Taste and olfactory status in a gourmand with a right amygdala lesion.

In a patient with a lesion of the right amygdala and temporal pole who had the characteristics of the gourmand syndrome, sensory and hedonic testing was performed to examine the processing of taste, olfactory, and some emotional stimuli. The gourmand syndrome describes a preoccupation with food and a preference for fine eating and is associated with right anterior lesions. It was found that the taste thresholds for sweet, salt, bitter, and sour were normal; that the patient did not dislike the taste of salt (NaCl) at low and moderate concentrations as much as age-matched controls; that this also occurred for monosodium glutamate (MSG); that there were some olfactory differences from normal controls; and that there was a marked reduction in the ability to detect face expressions of disgust.

[Teaching basic life support to the general population. Alumni intervention analysis]. / Enseñando soporte vital básico a la población general. Análisis de las intervenciones de los alumnos.

OBJECTIVES: The aim of this study was to investigate the rate at which the alumni of basic life support courses witnessed and intervened in out-of-hospital emergency situations, and to identify the variables characterizing those alumni associated with a greater number of witnessing events and interventions. An analysis of the efficiency of the courses was also carried out. DESIGN: A descriptive, cross-sectional study was made. SETTING: A district in the province of Almería (Spain). PATIENTS: Alumni of a mass basic life support training program targeted to the general population «Plan Salvavidas¼ conducted between 2003-2009. INTERVENTIONS: In 2010 the alumni were administered a telephone survey asking whether they had witnessed an emergency situation since attending the program, with the collection of information related to this emergency situation. MAIN VARIABLES OF INTEREST: Rate of out-of-hospital emergencies witnessed by the alumni. Rate of intervention of the alumni in emergency situations. Variables characterizing alumni with a greater likelihood of witnessing an emergency situation. RESULTS: A total of 3,864 trained alumni were contacted by telephone. Of 1,098 respondents, 63.9% were women, and the mean age was 26.61±10.6 years. Of these alumni, 11.75% had witnessed emergency situations, an average of three years after completing the course. Of these emergencies, 23.3% were identified as cardiac arrest. The alumni intervened in 98% of the possible cases. In 63% of the cases, there was no connection between the alumni and the victim. The majority of the emergency situations occurred in the street and in public spaces. A greater likelihood of witnessing an emergency situation was associated with being a healthcare worker and with being over 18 years of age. CONCLUSIONS: The rate of out-of-hospital emergencies witnessed by these alumni after the course was 11.75%. The level of intervention among the alumni was high. The most efficient target population consisted of healthcare workers.

[Design of a plan for patient safety in pediatric surgery service]. / Elaboración de un plan de seguridad del paciente en un Servicio de Cirugía Pediátrica.

INTRODUCTION: Patient safety is a key priority in quality management for healthcare services providers. Every patient is entitled to receive safe and effective healthcare. AIMS: The aim of this study was to design a patient safety plan for a Paediatric Surgery Department. METHODS: We carried out a literature review and we established a work group that included healthcare professionals from the Paediatric Surgery Department and the Quality and Medical Records Department. The group identified potential adverse events, failures and causes and established a rating using Failure Mode Effects Analysis. Potential risks were mapped out and a plan was designed establishing actions to reduce risks. We designated leaders to ensure the effective implementation of the plan. RESULTS: A total of 58 adverse events were identified in the Paediatric Surgery Department. We detected 128 failures that were produced by 211 different causes. The group developed a proposal with 424 specific measures to carry out preventive and/or remedial actions that were then narrowed down to 322. The group designed a plan to apply the programme, which is currently being implemented. CONCLUSIONS: The methodology used enabled obtaining key information for improvement of patient safety and developing preventive and/or remedial actions. These measures are applicable in practice, as they were designed using proposals and agreements with professionals that take active part in the care of children with surgical conditions.

Steroid 5α-reductase in adult rat brain after neonatal dihydrotestosterone administration.

Testosterone (T) is known to play an important masculinizing role in the developing brain of rat, including the regulation of 5α-reductase (5α-R) isozymes. However, the effects of dihydrotesterone (DHT), a more potent androgen than T, have not been elucidated. In this study, DHT was administered from day 5 through day 20 of postnatal life (period of postnatal sexual differentiation of the central nervous system) at doses of: 12 mg/kg/d on days 5, 6, 7, 8, 19, and 20; 15 mg/kg/d on days 9, 10, 11, 12, 16, 17, and 18; and 18 mg/kg/d on days 13, 14, and 15. In adulthood, quantitative RT-PCR was used to measure mRNA levels of 5α-R1 and 5α-R2 isozymes in the prefrontal cortex (PFC) of male and female rats with varied androgenic status. Under our study conditions, neonatal DHT administration influenced on adult PFC 5α-R isozymes levels and their regulation pattern by androgens, and this pattern was the inverse of that reported in adult neonatally T-treated rats.

COVID-19 pandemic on coronary artery and cerebrovascular diseases in Southern Spain: interrupted time series analysis.

OBJECTIVE: Healthcare systems have been put under intense pressure by the COVID-19 pandemic, although some studies have shown a decline in hospital admissions for cardiovascular and cerebrovascular diseases during the first and second wave of the pandemic. In addition, studies analyzing gender and procedural differences are scarce. The present study aimed to determine the impact of the pandemic on hospital admissions for acute myocardial infarction (AMI) and cerebrovascular disease (CVD) in Andalusia (Spain) and analyzed differences by gender and by percutaneous coronary interventions performed. PATIENTS AND METHODS: An interrupted time series analysis of AMI and CVD hospital admissions in Andalusia (Spain) was carried out to measure the impact of the COVID-19 outbreak. AMI and CVD cases admitted daily in public hospitals of Andalusia between January 2018 and December 2020 were included. RESULTS: During the pandemic, significant reductions in AMI [-19%; 95% confidence interval (CI): (-29%, -9%), p<0.001] and CVD [-17%; 95% CI: (-26%, -9%); p<0.01] in daily hospital admissions were observed. Differences were also produced according to the diagnosis (ST-Elevation Myocardial Infarction, Non-ST-Elevation Myocardial Infarction, other AMI and stroke), with a greater reduction in females for AMI and in males for CVD. Although there were more percutaneous coronary interventions during the pandemic, no significant reductions were observed. CONCLUSIONS: A decline in AMI and CVD daily hospital admissions during the first and second wave of COVID-19 pandemic was noted. Gender differences were observed, but no clear impact was observed in percutaneous interventions.

Poly(ADP-ribose) polymerase expression in kidney transplantation: from alfa (alpha) to Omega (Omega).

INTRODUCTION: Overactivation of the enzyme poly(ADP-ribose) polymerase (PARP-1) can be induced by ischemia-reperfusion and involved in the renal injury subsequent to kidney transplant. The poly(ADP-ribosy)lation mechanism alters free radical-induced DNA damage, which is repair by PARP-1 polymer. However, PARP-1 overexpression induces cellular necrosis. Our aim was to study the immunohistochemical PARP-1 expression in kidney transplant biopsies associated with various events. MATERIALS AND METHODS: We studied the nuclear expression of PARP-1 in kidney tubule cells by immunohistochemistry using the monoclonal antibody PAR01 in donor biopsies without acute tubular necrosis (ATN) (n = 60; controls), allografts that suffer ATN (n = 90) or an episode of acute humoral rejection (n = 12) or acute tubulointerstitial rejection (n = 25), or chronic allograft nephropathy (n = 25). Furthermore, we also studied protocol biopsies with subclinical rejection (n = 60). Renal lesions in transplant biopsies were graded blindly using 1997 Banff criteria without any clinical information. RESULTS: Biopsies without morphological features of ATN, namely acute tubulointerstitial rejection, borderline or subclinical rejection, showed lesser PARP-1 expression compared with biopsies with ATN or with ischemic mechanism of acute humoral rejection or chronic allograft nephropathys. We observed an inverse relation between PARP-1 expression and renal function (P < .001). Overall, renal biopsies showing ATN revealed greater expression of PARP-1 (r = 0.785, Pearson test). A significant relationship with PARP-1 expression was demonstrated with renal function (effective diuresis, serum creatinine levels) and pretransplant cold ischemia time (P < .001). CONCLUSION: Kidney transplant events including ischemia were associated with the highest PARP-1 expression and worse allograft renal function.

Primary Sjögren's syndrome: Extraglandular manifestations and hydroxychloroquine therapy.

The use of hydroxychloroquine (HCQ) in Primary Sjögren's Syndrome (pSS) has been assessed in different studies over the last years, with conflicting results regarding its efficacy in sicca syndrome and extraglandular manifestations (EGM). The goal of this study was to compare the incidence rate of EGM in pSS patients with and without HCQ therapy.We performed a multicenter retrospective study, including patients with pSS (European classification criteria) with at least 1 year of follow-up. Subjects with concomitant fibromyalgia, autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis were excluded. Demographics and pSS characteristics were recorded. The EGM were defined by EULAR-SS disease activity index (ESSDAI). Patients were divided into two groups according to their use or not of HCQ therapy. We evaluated the use of HCQ and its relationship to EGM. HCQ therapy was defined as the continuous use of the drug for at least 3 months. A descriptive analysis of demographics and pSS characteristics was performed. We compared the incidence of EGM between groups defined by HCQ therapy using chi2 test or Fisher's exact test. A total of 221 patients were included (97.3% women), mean age, 55.7 years (SD 14). Mean age at diagnosis, 48.8 years (SD 15); median disease duration, 60 months (IQR 35-84). One hundred and seventy patients (77%) received HCQ. About half of the patients had at least one EGM during the course of the disease, 20% of them developed an EGM before the onset of the sicca syndrome and 26% simultaneously with dryness symptom. Overall, EGM were less frequent in those on HCQ therapy (36.5% vs 63.5%, p < 0.001). Considering each EGM individually, the following manifestations were more frequent in the non-treated group: arthritis (p < 0.001), fatigue (p < 0.001), purpura (p = 0.01), Raynaud phenomenon (p = 0.003), and hypergammaglobulinemia (p = 0.006). Immunosuppressive treatment was indicated on 28 patients (12.7%), 13 of which were receiving also HCQ. The first reason for those treatments was the presence of arthritis in 12/28 patients (42.8%), and the drug used in all the cases was methotrexate. Only three patients required immunosuppressive therapy with cyclophosphamide, due to the presence of glomerulonephritis, vasculitis, and interstitial lung disease. None of the patients received biologic therapy. The lower incidence of EGM was observed in patients on HCQ therapy supports its efficacy in pSS. However, further large scale prospective studies are needed to confirm these findings.

Effects of testosterone on brain mRNA levels of steroid 5alpha-reductase isozymes in early postnatal life of rat.

The enzyme 5alpha-reductase (5alpha-R) (EC 1.3.99.5) exists as two isoforms, 5alpha-R type 1 (5alpha-R1) and 5alpha-R type 2 (5alpha-R2), and both are present in the brain. 5alpha-R1 has been proposed as a constitutive enzyme that essentially plays a catabolic and neuron protective role whereas 5alpha-R2 has been associated with sexually dimorphic functions of the male. In this work, we studied the effects of testosterone (T), the masculinizing hormone of the central nervous system (CNS), on mRNA levels of both 5alpha-R isoforms in the prefrontal cortex of male and female rats during the postnatal sexual differentiation of the CNS in the rat, using one-step quantitative RT-PCR coupled with laser-induced fluorescence capillary electrophoresis (LIF-CE). We found an increase in 5alpha-R2 mRNA levels in both male and female rats after T treatment, while 5alpha-R1 mRNA levels were decreased in the same experimental conditions. Our results clearly indicated that T regulates the expression of both 5alpha-R1 and 5alpha-R2 genes in an opposite manner and independently of the sex. This could point to a crucial role of T in the sexual dimorphism for both 5alpha-R isozymes in the neonatal brain. These results open up a new research line that could improve understanding of the role of 5alpha-R isozymes in the physiology of the CNS.

Role of poly-(ADP-ribose) polymerase in transplant acute tubular necrosis and its relationship with delayed renal function.

The enzyme poly(ADP-ribose) polymerase (PARP-1) participates in the repair of DNA damaged by genotoxic agents such as oxygen-derived free radicals. If the allograft suffers pretransplant cold ischemia and subsequent ischemia-reperfusion injury (IR), overactivation of PARP-1 can be induced, which may lead to an increase in acute tubular necrosis (ATN) and a delay in total recovery of renal function (RRF) of the transplanted organ. We studied the nuclear expression of PARP-1 in tubular cells by immunohistochemistry with the monoclonal antibody PAR01 in 104 kidney transplant biopsies from allografts with ATN. In 50% of biopsies with ATN, >50% of tubular nuclei were PARP-1+; only 9.6% of biopsies were negative. The increase in the immunohistochemical expression of PARP-1 showed a statistically significant relationship with the duration of cold ischemia, with serum creatinine levels, and with the time required to achieve effective diuresis (P < .0001, Spearman test). Cold ischemia of >24 hours and serum creatinine levels >1.7 mg/dL showed a statistically significant relationship with the highest PARP-1 expression levels (2.83 +/- 0.4 vs 1.36 +/- 0.8, P < .0001, Mann-Whitney U test). We conclude that PARP-1 plays an important role in ATN and RRF and is related to the extent and severity of ATN and to the renal allograft function.

Role of poly (ADP-ribose) polymerase in kidney transplant and its relationship with delayed renal function: multivariate analysis.

UNLABELLED: Kidney allografts undergo pretransplant cold ischemia and consequent ischemia-reperfusion injury (IR). Poly (ADP-Ribose) polymerase (PARP-1) overactivation leads to massive NAD+ consumption and ATP depletion with induction of cellular necrosis under ischemic conditions, which may lead to an increase in acute tubular necrosis (ATN) and a delay in total recovery of renal function (RFR) of the transplanted organ. MATERIALS AND METHODS: Nuclear PARP-1 immunohistochemical expression (clone: PARP01) was studied in 155 paraffin-embedded renal biopsies from suboptimal donors and 95 kidney allograft biopsies with histopathological diagnosis of ATN. RESULTS: In 50% of ATN biopsies, more than 50% of tubular nuclei were immunostained for PARP-1. PARP-1 expression was higher in ATN biopsies than in those from suboptimal donors (2.40 +/- 0.74 vs 0.92 +/- 1.13, P = 0.0001 Mann-Whitney). PARP-1 showed a statistically significant relationship with the time required to achieve effective diuresis (Rho:0.779), with serum creatinine, and with duration of cold ischemia (Rho:0.803). These relationships were stronger in the biopsies with ATN. In conclusion, multivariate analysis demonstrated that PARP-1 expression and cold ischemia duration in kidney biopsies with ATN predicted the short-term delay in total recovery of renal function and serum creatinine in the first month.

Interactions between radiotherapy and endocrine therapy in breast cancer.

Whenever radiation therapy is given with curative intent there is the risk of serious damage to normal tissue. This risk increases with the dose of radiation, as does the probability of local tumour control. In the attempt to cure, the doses reach a level that inevitably causes some undesirable adverse effects, ranging from undetectable, or minimal, to unacceptably severe. Over the last few years, a number of reports have suggested that the prediction of normal tissue response after radiotherapy may be achieved by assays on samples withdrawn from the patients prior to treatment, although recent reports have described mixed results. The ability to predict tumour response to anti-hormones in patients with breast cancer has important implications with regard to treatment. Recent discoveries promise to provide individualized treatment options. However, there are no data to support that, used jointly, the combination of radiotherapy and hormone therapy may achieve an enhancement of breast cancer tumour response. Nowadays, development in cancer therapy is increasingly arising out of studies in basic science; its implementation in the hands of clinicians is improving the management of patients with cancer. In addition, as the biological aspects of irradiation and hormonal therapy offer an explanation, at least in part, for the outcome observed in patients with breast cancer after therapy, we have focused this review on trying to analyse the most relevant experimental research about the relative roles of radiotherapy and hormonal therapy, the corresponding side-effects and, taking into account recent advances, future areas of research that we consider of major importance in the field.

Altered drug membrane permeability in a multidrug-resistant Leishmania tropica line.

We selected a Leishmania tropica cell line resistant to daunomycin (DNM) that presents a multidrug-resistant (MDR) phenotype characterized by overexpression of a P-glycoprotein of 150 kDa. The resistant line overexpressed an MDR-like gene, called ltrmdr1, located in an extrachromosomal circular DNA. DNM uptake experiments using laser flow cytometry showed a significant reduction in drug accumulation in the resistant parasites. The initial stages of the interaction of DNM with membranes from wild-type and DNM-resistant parasites were defined by a rapid kinetic stopped-flow procedure which can be described by two kinetic components. On the basis of a previous similar kinetic study with tumor cells, we ascribed the fast component to rapid interaction of DNM with membrane surface components and the slow component to passive diffusion of the drug across the membranes. The results reported here indicate that entrance of DNM into wild-type parasites was facilitated in respect to the resistant ones. We propose that resistance to DNM in L. tropica is a multifactorial event involving at least two complementary mechanisms. an altered drug membrane permeability and the overexpression of a protein related to P-glycoprotein that regulates drug efflux.

Report of a case: acromesomelic dysplasia: radiologic, clinical, and pathological study.

We report a 51-year-old woman with acromesomelic dysplasia. Pathologic studies on adult bone are reported. Hydrocephalus and mild oligophrenia are additional findings.

Antiproliferative effect of topic hyaluronic acid gel. Study in gingival biopsies of patients with periodontal disease.

Hyaluronic acid (HA) is the most abundant glycosaminoglycan of high molecular weight in the extracellular matrix of soft periodontal tissues. Our group recently demonstrated an HA-induced reduction in lymphoplasmocyte inflammatory infiltrate in periodontal disease. The objective of this study was to determine the effect of an HA gel of high molecular weight on cell proliferation, inflammation, and different periodontal lesion parameters. A double-blind clinical trial was conducted on the effect of an HA gel on cell proliferation in gingival biopsies from 28 patients with periodontal disease. A split-mouth design was used, randomly applying the gel to one quadrant and a placebo to the contralateral one. A gingival biopsy was taken for histopathological and immunohistochemical study, in order to determine the expression of cell proliferation antigen Ki-67 and to evaluate the inflammatory infiltrate. HA gel treatment induced a significant reduction in the proliferation index of the gingival epithelium, with 276 (range 234-317) Ki-67-positive cells per mm2 in treated samples versus 514 (range 158-876) per mm2 in controls (Mann-Whitney U test, p<0.003). In 13 patients, the number of Ki-67-positive fibroblastic cells was reduced by the treatment, whereas in 6 patients no differences were found (global difference, p=0.12). In 10 patients, Ki-67-positive cells were decreased in chronic inflammatory infiltrate present in the lamina propria, whereas in 6 patients no differences were found (global difference, p=0.054). We conclude that high molecular-weight HA gel reduces cell proliferation in epithelial cells such as fibroblasts and lymphocytes, abates the inflammatory process, and improves the periodontal lesion in patients with chronic periodontitis.

Intraepithelial and lamina propria leucocyte subsets in inflammatory bowel disease: an immunohistochemical study of colon and rectal biopsy specimens.

AIMS: To gain new insights into the pathogenesis and differential diagnosis of ulcerative colitis and colonic Crohn's disease. METHODS: Immunohistochemistry for different leucocyte subsets was performed in biopsy specimens of the sigmoid colon and rectum from 55 patients with inflammatory bowel disease and 11 healthy controls. RESULTS: Colonic biopsy specimens from patients with active ulcerative colitis had significantly higher numbers of CD45+ and CD3+ leucocytes compared with those from patients with inactive disease, and higher numbers of total leucocytes and macrophages than those from patients with Crohn's disease. Rectal biopsy specimens from patients with Crohn's disease had greater numbers of intraepithelial leucocytes (CD45, CD3 and CD8 cells) than specimens from patients with active or inactive ulcerative colitis, or from healthy controls. CONCLUSIONS: Because of the phenotypic differences in the inflammatory infiltrate in the mucosa from the sigmoid colon and the rectum, the segment of the intestine to be biopsied should be specified. Assessment of the leucocytic component of the intraepithelial infiltrate in rectal biopsy specimens was more useful than examination of colonic biopsy specimens in the differential diagnosis of ulcerative colitis and Crohn's disease.