Nasal airflow simulations suggest convergent adaptation in Neanderthals and modern humans.

Both modern humans (MHs) and Neanderthals successfully settled across western Eurasian cold-climate landscapes. Among the many adaptations considered as essential to survival in such landscapes, changes in the nasal morphology and/or function aimed to humidify and warm the air before it reaches the lungs are of key importance. Unfortunately, the lack of soft-tissue evidence in the fossil record turns difficult any comparative study of respiratory performance. Here, we reconstruct the internal nasal cavity of a Neanderthal plus two representatives of climatically divergent MH populations (southwestern Europeans and northeastern Asians). The reconstruction includes mucosa distribution enabling a realistic simulation of the breathing cycle in different climatic conditions via computational fluid dynamics. Striking across-specimens differences in fluid residence times affecting humidification and warming performance at the anterior tract were found under cold/dry climate simulations. Specifically, the Asian model achieves a rapid air conditioning, followed by the Neanderthals, whereas the European model attains a proper conditioning only around the medium-posterior tract. In addition, quantitative-genetic evolutionary analyses of nasal morphology provided signals of stabilizing selection for MH populations, with the removal of Arctic populations turning covariation patterns compatible with evolution by genetic drift. Both results indicate that, departing from important craniofacial differences existing among Neanderthals and MHs, an advantageous species-specific respiratory performance in cold climates may have occurred in both species. Fluid dynamics and evolutionary biology independently provided evidence of nasal evolution, suggesting that adaptive explanations regarding complex functional phenotypes require interdisciplinary approaches aimed to quantify both performance and evolutionary signals on covariation patterns.

Serum and gene expression levels of CT-1, IL-6, and TNF-α after a lifestyle intervention in obese children.

BACKGROUND: Inflammation related molecules such as tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and cardiotrophin-1 (CT-1) are highly expressed in obese individuals and could partly explain some comorbidities associated to obesity. In obese children, lifestyle interventions are able to lower inflammation and reduce cardiovascular risk factors associated with obesity. The aim of the present work was to study changes in inflammation-related molecules serum and peripheral blood mononuclear cells (PBMC) transcript levels after a 10-week lifestyle intervention in obese children and asses their potential association with glucose metabolism. METHODS: Twenty-three obese children (mean age 11.5 years; 48% males) underwent a 10-week lifestyle not controlled intervention trial. Anthropometric and biochemical measurements were analyzed. Transcript analysis for CT-1, IL-6, and TNF-α in PBMC were performed by RT-PCR. Serum cytokine levels were also measured at baseline and after 10-weeks. RESULTS: Participants achieved a significant reduction in body adiposity (0.34 decrease in body mass index-standard deviation), total cholesterol, and glucose levels after 10-weeks. A Significant decrease in serum TNF-α and C reactive protein (CRP) were observed. CT-1 transcript levels were significantly reduced (P = .005) after lifestyle intervention, and these changes were significantly correlated with changes in serum CT-1 levels (r = 0.451; P = .031). In multiple regression analysis baseline CT-1 transcript levels were positively associated with final insulin (R2 = 0.506; P = .035) and HOMA-IR values (R2 = 0.473; P = .034). CONCLUSIONS: We reported that serum CRP, TNF-α, as well as PBMC CT-1 transcript levels were reduced after lifestyle intervention in obese children. More studies are needed to clarify the role of inflammation-related molecules in glucose metabolism.

Adherence to the Mediterranean dietary pattern and BMI change among US adolescents.

BACKGROUND: Among adults, the Mediterranean dietary pattern (MDP) is inversely related to body mass index (BMI). Data are lacking on adherence to the MDP among youth in the United States and whether the MDP is related to weight change in that group. OBJECTIVE: To assess whether adherence to the MDP was associated with BMI change among adolescents. To examine temporality, we studied the association between baseline and 2-3-year changes in adherence to the MDP with concurrent changes in BMI, as well as subsequent changes in BMI over a 7-year period. METHODS: We prospectively followed 6002 females and 4916 males in the Growing Up Today Study II, aged 8-15 years in 2004, living across United States. Data were collected by questionnaire in 2004, 2006, 2008 and 2011. Dietary intake was assessed by the Youth/Adolescent Questionnaire. The KidMed Index was derived to measure the adherence to the MDP. We used generalized estimating equations with repeated measures within subjects to assess the association between MDP and BMI change. RESULTS: A two-point increment in the KidMed Index was independently associated with a lower gain in BMI (-0.04 kg m(-2); P=0.001). A greater increase in adherence to the KidMed Index was independently related to a lower gain in BMI in both the concurrent (P-for-trend<0.001) and the subsequent period (P-for-trend=0.002). CONCLUSIONS: Adherence to MDP was inversely associated with change in BMI among adolescents. Two-year improvement in adherence to MDP was independently associated with less steep gain in the BMI in both the concurrent and the subsequent period.

Whooping cough in a renal transplant recipient.

Whooping cough is a respiratory infection with a severity that varies with age, immune status, and probably with other factors such as the degree of exposure and the virulence of the organism. The most frequent microorganism responsible for whooping cough is Bordetella pertussis. We present the case of a 62-year-old renal transplant recipient presenting with typical and severe manifestations of whooping cough caused by B. pertussis.

Association between individual and combined SNPs in genes related to innate immunity and incidence of CMV infection in seropositive kidney transplant recipients.

In this study, we assessed the association between single-nucleotide polymorphisms (SNPs) in seven candidate genes involved in orchestrating the immune response against cytomegalovirus (CMV) and the 12-month incidence of CMV infection in 315 CMV-seropositive kidney transplant (KT) recipients. Patients were managed either by antiviral prophylaxis or preemptive therapy. CMV infection occurred in 140 patients (44.4%), including 13 episodes of disease. After adjusting for various clinical covariates, patients harboring T-allele genotypes of interleukin-28B (IL28B) (rs12979860) SNP had lower incidence of CMV infection (adjusted hazard ratio [aHR]: 0.66; 95% confidence interval [CI]: 0.46-0.96; p-value = 0.029). In the analysis restricted to patients not receiving prophylaxis, carriers of the TT genotype of toll-like receptor 9 (TLR9) (rs5743836) SNP had lower incidence of infection (aHR: 0.61; 95% CI: 0.38-0.96; p-value = 0.035), whereas the GG genotype of dendritic cell-specific ICAM 3-grabbing nonintegrin (DC-SIGN) (rs735240) SNP exerted the opposite effect (aHR: 1.86; 95% CI: 1.18-2.94; p-value = 0.008). An independent association was found between the number of unfavorable SNP genotypes carried by the patient and the incidence of CMV infection. In conclusion, specific SNPs in IL28B, TLR9 and DC-SIGN genes may play a role in modulating the susceptibility to CMV infection in CMV-seropositive KT recipients.

Ocular impairment as the first and only manifestation of Bardet-Biedl syndrome: A case report.

Bardet-Biedl syndrome is a ciliopathy mainly associated with retinal dystrophy, renal dysfunction, post-axial polydactyly, obesity, cognitive deficit and hypogonadism. The symptoms associated with retinal dystrophy do not usually appear until the first decade of life, so the diagnosis is usually delayed. Ocular involvement may be the initial form of manifestation of this syndrome, it may even be the only one, so it should be taken into account in the differential diagnosis of amblyopia in a child who does not improve despite correct compliance with treatment. A case of low visual acuity in a pediatric patient is presented as an initial manifestation that leads to the diagnosis of Bardet-Biedl Syndrome, and which is also the only symptom that the patient presents to date, despite being a multisystem disease.

Prospective evaluation of the emetogenic profile and analgesic efficacy of intravenous ibuprofen and metamizole in the immediate postoperative period of pediatric acute appendicitis. / Evaluación prospectiva del perfil emético y la eficacia analgésica del ibuprofeno y el metamizol intravenosos en el postoperatorio inmediato de la apendicitis aguda pediátrica.

BACKGROUND: Literature comparing different alternatives for pain control in the immediate postoperative period of pediatric acute appendicitis (PAA) is scarce. MATERIALS AND METHODS: We prospectively compared the analgesic and emetogenic profile of intravenous ibuprofen and metamizole in the immediate postoperative period of PAA. For this purpose, we used a sample of patients operated on in 2021 in our center. Participants were recruited on arrival at the Emergency Department and histopathological confirmation of the diagnosis was obtained in all of them. Pain was evaluated every 8 hours after the surgery with validated visual analog scales ranging from 0 to 10 points. Repeated measures ANOVA was used to compare the evolution of pain in the 48 hours after surgery between the two groups. RESULTS: The sample included 95 patients (65% males) with a mean age of 9.7 years (sd: 3.14). 41 patients were treated with Ibuprofen (group 1) and 54 with metamizole (group 2). No significant differences were found in the level of pain either in the comparisons of point measurements or in its evolution in the 48 hours after surgery (p= 0.58). After adjusting for the received fluid therapy, children in the metamizole group had significantly more emetic episodes and needed significantly more doses of ondansetron. CONCLUSIONS: In our cohort, ibuprofen had a similar analgesic efficacy and a better emetogenic profile than metamizole in the immediate postoperative period of PAA. Future prospective, adequately controlled studies with larger sample sizes are needed to validate these findings.

INTRODUCCION: En la literatura existen pocas referencias que comparen las distintas alternativas disponibles para controlar el dolor en el postoperatorio inmediato de la apendicitis aguda pediátrica (AAP). MATERIAL Y METODOS: Comparación prospectiva del perfil analgésico y emético del ibuprofeno y el metamizol intravenosos en el postoperatorio inmediato de la AAP, para lo cual se recurre a una muestra de pacientes operados en 2021 en nuestro centro. Los participantes fueron reclutados a su llegada a Urgencias, obteniéndose confirmación histopatológica del diagnóstico en todos ellos. La evaluación del dolor se llevó a cabo cada 8 horas tras la cirugía mediante escalas analógicas visuales validadas, con valoraciones entre los 0 y los 10 puntos. Se realizó un ANOVA de las medidas repetidas entre los dos grupos para comparar la evolución del dolor en las 48 horas posteriores a la cirugía. RESULTADOS: La muestra estaba compuesta por un total de 95 pacientes (65% de ellos varones) con una edad media de 9,7 años (DT: 3,14). 41 pacientes fueron tratados con ibuprofeno (grupo 1) y 54 con metamizol (grupo 2). No se hallaron diferencias significativas en lo que respecta al dolor, ni en las comparaciones de las mediciones puntuales, ni en su evolución en las 48 horas posteriores a la cirugía (p= 0,58). Una vez realizado el ajuste correspondiente a la terapia de fluidos recibida, los niños del grupo metamizol tuvieron significativamente más episodios eméticos y necesitaron significativamente más dosis de ondansetrón. CONCLUSIONES: En nuestra cohorte, el ibuprofeno tuvo una eficacia analgésica similar y un mejor perfil emético que el metamizol en el postoperatorio inmediato de la AAP. Se hacen necesarios nuevos estudios prospectivos, adecuadamente controlados y con mayor tamaño muestral que validen estos hallazgos.

Approaches to the epidemiology of NOHL in the region of Madrid: Survey of neuro-ophthalmologists.

OBJECTIVE: To estimate the epidemiology of Leber's optic neuropathy (NOHL) in the Region of Madrid. MATERIAL AND METHODS: The neuro-ophthalmologists who work at public hospitals of the CAM were interviewed by telephone. They were asked about the number of patients with NOHL that they had diagnosed during the time that they had been responsible for the neuro-ophthalmology department of that public hospital. The time worked and the population attended by the hospital were used to calculate the number of inhabitant-years in follow-up by each center during the corresponding period. The basic information of each case (date of birth, mutation, date of visual loss) was registered to avoid duplications. RESULTS: Our work estimates a global incidence of 2.34 cases for 10,000,000 inhabitants-year and a prevalence estimated from incidence of one case for each 106.682 inhabitants. This prevalence was very similar in all the studied areas and considerably lower than that reported by other studies. CONCLUSION: This work constitutes the first approach to the epidemiology of this disease in Spain. The prevalence of LHON in the region of Madrid, is probably lower than that reported in the literature in other regions. The prevalence and the incidence were homogeneously low in the 26 studied areas.

The development and validation of a new simulator for endourology.

INTRODUCTION: Simulation in medicine has developed a lot in the last few decades. There is a broad range of simulators available, above all for training in surgical procedures. Endourology can benefit much from simulation because the minimally-invasive procedures of endourology frequently have long learning curves, which can be reduced by training with simulators. MATERIALS AND METHODS: A low-fidelity simulator was designed for practicing endourology techniques that use cystoscopy. The process of validation involved 5 experts and 19 non-experts. Experts comprised medical professionals working in a department of urology who had performed at least 100 flexible cystoscopy procedures. Non-experts were residents in internal medicine without experience in any type of endoscopy. Information about face and content validity was collected by means of Likert scales from 1 to 5. To evaluate construct validity, we measured the time to complete two tasks, for which the procedure was evaluated by means of the OSATS global evaluation scale. RESULTS: New simulator was successfully built according to its design. For all evaluated aspects of construct validity, there was a significant difference (p<0.05) between the group of experts and the group of non-experts. Content validity was scored 4.66 (standard deviation ±0.56) by the experts and 4.41 (±0.71) by the non-experts. In the face validity questionnaire, the average score was 4.14 (±0.94), the question receiving the highest score: 4.6 (±0.84) concerned immersion in the procedure. CONCLUSION: The simulator presented is valid both for training up new urologists in endourology technique and for experts seeking to perfect their skills.

Usefulness of transoesophageal echocardiography before circumferential pulmonary vein ablation in patients with atrial fibrillation: is it really mandatory?

AIMS: Transoesophageal echocardiography (TEE) is recommended prior to circumferential pulmonary vein ablation (CPVA) in patients with atrial fibrillation (AF) to identify left atrial (LA) or left atrial appendage (LAA) wall thrombi. It is not clear whether all patients undergoing CPVA should receive pre-procedural TEE. We wanted to assess the incidence of LA thrombus in these patients and to identify factors associated with its presence. METHODS AND RESULTS: Consecutive patients referred for CPVA from 2004 to 2009 underwent TEE within 48 h prior to the procedure. Of 408 patients included in the study, 6 patients (1.47%) had LA thrombi, persistent AF, and LA dilation. Compared with patients without thrombus, these six patients had larger LA diameter (P = 0.0001) and more frequently were women (P = 0.002), had persistent AF (P = 0.04), and had underlying structural cardiac disease (P = 0.014). The likelihood of presenting LA thrombus increased with the number of these four risk factors present (P < 0.001). None of the patients with paroxysmal AF and without LA dilation had LA thrombus. A cut-off value of 48.5 mm LA diameter yielded 83% sensitivity, 92% specificity, and a 10.1 likelihood ratio to predict LA thrombus appearance. CONCLUSION: The incidence of LA thrombus prior to CPVA is low. Persistent AF, female sex, structural cardiopathy, and LA dilation were associated with the presence of LA thrombus. Our data suggest that the use of TEE prior to CPVA to detect LA thrombi might not be needed in patients with paroxysmal AF and no LA dilation or structural cardiopathy.

Mammalian target of rapamycin signal inhibitors could play a role in the treatment of BK polyomavirus nephritis in renal allograft recipients.

UNLABELLED: BK virus (BKV) nephropathy is a common viral infection in renal transplant patients, with a prevalence of 1-9% at approximately 12 months after surgery. While it is widely agreed that reduction of immunosuppression should be the first intervention after diagnosis of BKV infection, there is no consensus on whether calcineurin inhibitors or antiproliferative drugs should be reduced first. Furthermore, target levels of immunosuppressive drugs are poorly defined, as are criteria for replacing one immunosuppressive agent with another. RESULTS: We report our series of 15 renal transplant patients who underwent surgery between September 2004 and March 2010 and who developed BKV infection. The first 8 patients were treated with reduction of immunosuppression; 7 of these patients received cidofovir and 6 received intravenous immunoglobulin. The remaining 7 renal transplant recipients received mammalian target of rapamycin inhibitors (imTOR). In this group, we observed faster and more efficacious BKV clearance in plasma and urine and a steady improvement in allograft function, with no episodes of acute allograft rejection during follow-up. The polymerase chain reaction assay for BKV in urine became positive in 2 patients in whom imTOR were stopped due to severe side effects. CONCLUSIONS: The use of imTOR should be considered a first step in the treatment of renal transplant recipients with BKV infection. In our experience, this change in treatment was safe and resulted in viral clearance.

Pragmatic, open-label, single-center, randomized, phase II clinical trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus in patients with severe pneumonia secondary to COVID-19: The TACROVID trial protocol.

INTRODUCTION: Some COVID-19 patients evolve to severe lung injury and systemic hyperinflammatory syndrome triggered by both the coronavirus infection and the subsequent host-immune response. Accordingly, the use of immunomodulatory agents has been suggested but still remains controversial. Our working hypothesis is that methylprednisolone pulses and tacrolimus may be an effective and safety drug combination for treating severe COVID-19 patients. METHODS: and analysis: TACROVID is a randomized, open-label, single-center, phase II trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) versus SoC alone, in patients at advanced stage of COVID-19 disease with lung injury and systemic hyperinflammatory response. Patients are randomly assigned (1:1) to one of two arms (42 patients in each group). The primary aim is to assess the time to clinical stability after initiating randomization. Clinical stability is defined as body temperature ≤37.5 °C, and PaO2/FiO2 > 400 and/or SatO2/FiO2 > 300, and respiratory rate ≤24 rpm; for 48 consecutive hours. DISCUSSION: Methylprednisolone and tacrolimus might be beneficial to treat those COVID-19 patients progressing into severe pulmonary failure and systemic hyperinflammatory syndrome. The rationale for its use is the fast effect of methylprednisolone pulses and the ability of tacrolimus to inhibit both the CoV-2 replication and the secondary cytokine storm. Interestingly, both drugs are low-cost and can be manufactured on a large scale; thus, if effective and safe, a large number of patients could be treated in developed and developing countries. TRIAL REGISTRATION NUMBER: NCT04341038 / EudraCT: 2020-001445-39.

Neurologic Involvement in COVID-19: Cause or Coincidence? A Neuroimaging Perspective.

The rapid spread of the coronavirus disease 2019 (COVID-19) pandemic has shaken hospitals worldwide. Some authors suggest that neurologic involvement could further complicate the disease. This descriptive study is a cross-sectional review of 103 patients diagnosed with COVID-19 who underwent neuroimaging (of a total of 2249 patients with COVID-19 in our center). Analyzed variables were neurologic symptoms and acute imaging findings. The most frequent symptoms that motivated neuroimaging examinations were mild nonfocal neurologic symptoms, code stroke (refers to patients presenting with signs and symptoms of stroke whose hyperacute assessment and care is prioritized), focal neurologic symptoms, postsedation encephalopathy, and seizures. No cases of encephalitis or direct central nervous system involvement were detected. Thirteen patients presented with acute ischemic events, and 7, with hemorrhagic events; however, most reported multiple vascular risk factors. Despite the large cohort of patients with COVID-19, we found a large number of symptomatic patients with negative neuroimaging findings, and no conclusions can be drawn concerning concrete associations between neuroimaging and COVID-19.

Evaluación prospectiva del perfil emético y la eficacia analgésica del ibuprofeno y el metamizol intravenososen el postoperatorio inmediato de la apendicitis agudapediátrica / Prospective evaluation of the emetogenic profile and analgesic efficacy of intravenous ibuprofen and metamizole in the immediate postoperative period of pediatric acute appendicitis

Introducción: En la literatura existen pocas referencias que comparen las distintas alternativas disponibles para controlar el dolor enel postoperatorio inmediato de la apendicitis aguda pediátrica (AAP).Material y métodos: Comparación prospectiva del perfil anal-gésico y emético del ibuprofeno y el metamizol intravenosos en elpostoperatorio inmediato de la AAP, para lo cual se recurre a unamuestra de pacientes operados en 2021 en nuestro centro. Los participantes fueron reclutados a su llegada a Urgencias, obteniéndoseconfirmación histopatológica del diagnóstico en todos ellos. La evaluación del dolor se llevó a cabo cada 8 horas tras la cirugía medianteescalas analógicas visuales validadas, con valoraciones entre los 0 ylos 10 puntos. Se realizó un ANOVA de las medidas repetidas entrelos dos grupos para comparar la evolución del dolor en las 48 horasposteriores a la cirugía.Resultados: La muestra estaba compuesta por un total de 95 pacientes (65% de ellos varones) con una edad media de 9,7 años (DT:3,14). 41 pacientes fueron tratados con ibuprofeno (grupo 1) y 54 conmetamizol (grupo 2). No se hallaron diferencias significativas en lo querespecta al dolor, ni en las comparaciones de las mediciones puntuales,ni en su evolución en las 48 horas posteriores a la cirugía (p= 0,58). Unavez realizado el ajuste correspondiente a la terapia de fluidos recibida,los niños del grupo metamizol tuvieron significativamente más episodioseméticos y necesitaron significativamente más dosis de ondansetrón.Conclusiones: En nuestra cohorte, el ibuprofeno tuvo una eficaciaanalgésica similar y un mejor perfil emético que el metamizol en elpostoperatorio inmediato de la AAP. Se hacen necesarios nuevos estudiosprospectivos, adecuadamente controlados y con mayor tamaño muestralque validen estos hallazgos.(AU)

Background: Literature comparing different alternatives for paincontrol in the immediate postoperative period of pediatric acute appendicitis (PAA) is scarce.Materials and methods: We prospectively compared the analgesicand emetogenic profile of intravenous ibuprofen and metamizole in theimmediate postoperative period of PAA. For this purpose, we used asample of patients operated on in 2021 in our center. Participants wererecruited on arrival at the Emergency Department and histopathologi-cal confirmation of the diagnosis was obtained in all of them. Pain wasevaluated every 8 hours after the surgery with validated visual analogscales ranging from 0 to 10 points. Repeated measures ANOVA wasused to compare the evolution of pain in the 48 hours after surgerybetween the two groups. Results: The sample included 95 patients (65% males) with a meanage of 9.7 years (sd: 3.14). 41 patients were treated with Ibuprofen(group 1) and 54 with metamizole (group 2). No significant differ-ences were found in the level of pain either in the comparisons of pointmeasurements or in its evolution in the 48 hours after surgery (p= 0.58).After adjusting for the received fluid therapy, children in the metamizolegroup had significantly more emetic episodes and needed significantlymore doses of ondansetron. Conclusions: In our cohort, ibuprofen had a similar analgesic ef-ficacy and a better emetogenic profile than metamizole in the immediatepostoperative period of PAA. Future prospective, adequately controlledstudies with larger sample sizes are needed to validate these findings.(AU)

Inter-individual differences in novelty-seeking behavior in rats predict differential responses to desipramine in the forced swim test.

RATIONALE: Antidepressant medications are effective only in a subpopulation of patients with depression, and some patients respond to certain drugs, but not others. The biological bases for these clinical observations remain unexplained. OBJECTIVE: To investigate individual differences in response to antidepressants, we have examined the effects of the norepinephrine reuptake inhibitor desipramine (DMI) and the selective serotonin reutake inhibitor fluoxetine (FLU) in the forced swim test (FST) in rats that differ in their emotional behavior. METHODS: As response to novelty correlates with numerous other measures of emotionality and substance abuse, we contrasted animals that are high responders (HR) in a novel environment with animals that are low responders (LR) and asked whether the two groups exhibit differential responses to DMI (10mg/kg) and FLU (20mg/kg). RESULTS: At the behavioral level, DMI caused a significant decrease in immobility in LR animals only, while FLU caused a significant reduction in immobility in both groups. Moreover, at the neural level, DMI treatment led to a decrease in FST-induced c-fos messenger RNA levels in medial prefrontal cortex (PFC) and paraventricular nucleus of the hypothalamus (PVN) in LR but not HR animals. CONCLUSIONS: Taken together, our results suggest that the HR-LR model is a useful tool to investigate individual differences in responses to norepinephrine reuptake inhibitors (NRIs) and that a differential activation of PFC and/or PVN could underlie some of the inter-individual differences in the efficacy of NRIs.

[Irbesartan in hypertensive non-diabetic advanced chronic kidney disease. Comparative study with ACEI]. / Irbesartan y enfermedad renal crónica avanzada de causa no diabética. Estudio comparativo con IECAS.

UNLABELLED: Angiotensin-converting enzyme inhibitors (ACEI) have proved an antihypertensive and renoprotective effect with reduction of proteinuria in diabetic and non diabetic nephropathy, but not exempt of side effects in advanced chronic kidney disease (ACKD) patients. Angiotensin receptor blockers (ARB) have emerged as antiproteinuric, renoprotective and cardioprotective therapy. Only a few reports have been published studying ARB effects on non-diabetic ACKD patients. Our aim is to study Irbesartan (ARB) on non-diabetic ACKD patients and compare its effects with ACEI. PATIENTS AND METHODS: Forty three non-diabetic patients at ACKD stage IV NKF-DOQI (CrCl <30 ml/min) were enrolled in a prospective study. Group I: 21 received Irbesartan monodose 150-300 mg/day (63+/-17 y/o, 12 F, 9 M,ClCr 22.1+/-8 ml/m.), Group II: 22 received ACEI (65+/-13 y/o, 8 F, 14 M, CrCl 22.3+/-7 ml/m). Parameters studied: blood pressure (BP), pulse pressure (PP), renal function (CrCl), proteinuria (in patients with proteinuria >or= 0.5 g/d), serum K+ and serum uric acid, at month 0, 3, 6, 9 and 12. RESULTS: At 12 months, BP was controlled in 57% of Group I vs 39% of Group II. Mean systolic BP was decreased from 154/85 to 138/77 in G I, and from 146/85 to 133/77 in GII, with a decrease in 10.7% of mean BP in GI and 8.5% in GII (NS). Irbesartan reduced PP in 7.2% vs 8.3% with ACEI (NS). CrCl reduction with Irbesartan was 0.23 vs 0.21 ml/min/month with ACEI (NS). The antiproteinuric effect was higher with Irbesartan (from 2.1 to 1.3 g/day) vs. ACEI (from 1.35 to 1.33 gr /day), being statistically significant the reduction percentage between the two groups (p >or= 0.041). Serum K+ level do not change in Irbesartan group and increased 10% in ACEI group (p<0.001). Uric acid was decreased by Irbesartan in 17% and increased in 4% by ACEI (p<0.001). CONCLUSIONS: Irbesartan in non-diabetics patients with advanced chronic renal disease, compared with ACEI showed similar blood pressure control and similar effect on chronic kidney disease progression, with higher antiproteinuric effect. On the other side, Irbesartan showed a reduction of serum uric acid, and did not increase serum K+ levels.

Study of anemia after late introduction of everolimus in the immunosuppressive treatment of renal transplant patients.

INTRODUCTION: mTOR inhibitors (imTOR) are immunosuppressive drugs that have a concentration-related effects on hematopoiesis, potentially resulting in anemia. The reason is uncertain, but a pathogenic link between sirolimus-induced anemia and the appearance of an inflammatory state was recently suggested. Because inflammation-related anemia is characterized by a functional iron deficiency, we studied whether everolimus influenced iron homeostasis. METHODS: We studied iron homeostasis in 43 patients after late introduction of everolimus into the immunosuppressive treatment. Thirty-seven patients (86%) were receiving mycophenolate. Hemoglobin concentration, red blood cell count, mean corpuscular volume, serum iron, ferritin, C-reactive protein levels, and transferrin saturation were evaluated 3 months before and 1, 3, and 6 months after the switch. RESULTS: The percentage of anemic patients preconversion was 18.6% and it was 34.9% at 3 months and 18.6% at 6 months. We did not observe a significant reduction in hemoglobin, but there was increased red blood cell count after everolimus introduction, with a significant reduction in mean corpuscular volume. Serum iron and transferrin saturation levels were also markedly reduced after the switch, while ferritin serum concentrations remained stable. An improvement in renal function was observed. CONCLUSIONS: The anemia caused by everolimus--microcytosis, low serum iron, despite high ferritinemia, and elevated C-reactive protein levels--was consistent with the anemia of a chronic inflammatory state. This alteration occurred within the first months postconversion and disappeared at 6 months. The combination of mycophenolate and everolimus seemed to be useful without significant secondary effects.

Preemptive kidney transplant from deceased donors: an advantage in relation to reduced waiting list.

BACKGROUND: Preemptive living donor kidney transplantation is associated with better allograft and recipient survival. However, it remains unclear whether preemptive transplantation from deceased donors is beneficial too. An increased number of deceased donors has reduced the waiting list in our hospital in the last years allowing preemptive deceased donor kidney transplantation (PDDKT). AIM: We compared our experience with preemptive transplantation with patients who underwent dialysis before transplantation. PATIENTS AND METHODS: Thirty-three PDDKT, including 77.5% male patients of overall mean age of 48 +/- 14 years, were performed in our hospital between January 1999 and December 2004 (8% of transplantations). We compared the outcomes of these patients with those of renal transplants in subjects who had undergone dialysis. The donors for both groups had similar characteristic; they were paired donor kidneys in most cases. RESULTS: The types of donors in both groups were: non-heart-beating (49%), heart-beating deceased (27%) or en bloc pediatric (24%). The serum creatinine of the recipients was 6.9 +/- 1.8 mg/dL prior to transplantation, and the creatinine clearance was 14.6 +/- 3.6 mL/min (estimated by the Cockroft-Gault formula). The Charlson comorbidity index adapted for patients with advanced chronic kidney disease (ACKD) was 0.8 +/- 0.2 in the preemptive group versus 1.7 +/- 0.4 in the dialysis group (P < .05). Delayed graft function rates were 0% versus 25% in preemptive vs dialysis groups, respectively. No differences in 1-month or 1-year renal function as determined by serum creatinine were observed between the groups. We did not observe differences in the incidence of acute rejection or 1- and 2-year graft and patient survivals. CONCLUSION: PDDKT is the treatment of choice for ACKD. It is associated with less delayed graft function and similar 2-year graft and patient survivals than kidney transplantation after dialysis. The Charlson index reflected less comorbidity among patients with PDDKT, a finding that must influence long-term outcomes.

Better mycophenolic acid 12-hour trough level after enteric-coated mycophenolate sodium in patients with gastrointestinal intolerance to mycophenolate mofetil.

INTRODUCTION: Enteric-coated mycophenolate sodium (EC-MPS) is the enteric-coated salt form of mycophenolic acid (MPA), the active component of the prodrug mycophenolate mofetil. EC-MPS was developed to reduce the upper-gastrointestinal (GI) effects of mycophenolate mofetil. There are no studies available comparing trough plasma levels in patients with GI intolerance to MMF when they are converted to EC-MPS. AIM: To compare the GI tolerance and the MPA levels in patients previously treated with MMF in whom this drug was replaced by EC-MPS. MATERIALS AND METHODS: A prospective study was conducted in 133 renal transplant patients after conversion from MMF to EC-MPS (median time posttransplant 42 months, range 1 to 240 months). The causes for EC-MPS switching were GI intolerance to MMF (51.9%; group A), low trough plasma levels with MMF (29.3%; group B), and others (18.8%; group C). These patients were converted to equipotent doses of EC-MPS. RESULTS: The trough plasma MPA levels increased from 1.5 +/- 1.1 microg/mL at baseline to 2.5 +/- 2.0 microg/mL at 1 month postconversion despite the equipotent EC-MPS doses not being increased. These higher plasma levels were maintained throughout the study. In group A, this increase was from 1.8 +/- 1.0 to 2.7 +/- 2.1 microg/mL (P = .01) and in group B from 0.8 +/- 0.4 to 2.4 +/- 1.4 microg/mL (P < .001). The doses and levels of calcineurin inhibitor decreased from baseline. Creatinine clearance improved from 56.5 +/- 24.7 mg/dL at baseline to 61.9 +/- 28.6 at 6 months postconversion (P = .02). There was a statistically significant increase in hemoglobin levels. In group A, the GI tolerance improved in 78% of the patients. CONCLUSIONS: At equipotent doses, patients converted to EC-MPS have higher and more adequate levels of MPA. At 6 months postconversion, we observed an improvement of the renal function, probably due to a reduction of calcineurin inhibitor drugs. However, the possibility that a better immunosuppressive efficacy as demonstrated by more suitable trough plasma levels may have been a contributing factor cannot be discarded.