Arginine vasopressin deficiency and conivaptan (a V1a-V2 receptor antagonist) treatment reverses liver damage and fibrosis in rats with chronic portocaval anastomosis.

Arginine vasopressin (AVP) is a naturally occurring hormone synthesized in the hypothalamus. AVP demonstrates pro-fibrotic effects as it stimulates hepatic stellate cells to secrete transforming growth factor-ß (TGF-ß) and collagen. Previous work in liver cirrhotic (CCL4 -induced) hamsters demonstrated that AVP deficiency induced by neurointermediate pituitary lobectomy (NIL) can restore liver function. Therefore, we hypothesized that liver fibrosis would decrease in portocaval anastomosis (PCA) rats, which model chronic liver diseases, when they are treated with the V1a-V2 AVP receptor antagonist conivaptan (CV). In this study, changes in liver histology and gene expression were analysed in five experimental groups: control, PCA, NIL, PCA + NIL and PCA + CV, with NIL surgery or CV treatment administered 8 weeks after PCA surgery. Body weight gain was assessed on a weekly basis, and serum liver function, liver weight and liver glycogen content were assessed following euthanasia. Most PCA-induced phenotypes were reverted to normal levels following AVP-modelled deficiency, though hypoglycemia and ammonium levels remained elevated in the PCA + CV group. Liver histopathological findings showed a significant reversal in collagen content, less fibrosis in the triad and liver septa and increased regenerative nodules. Molecular analyses showed that the expression of fibrogenic genes (TGF-ß and collagen type I) decreased in the PCA + CV group. Our findings strongly suggest that chronic NIL or CV treatment can induce a favourable microenvironment to decrease liver fibrosis and support CV as an alternative treatment for liver fibrosis.

Treatment with low-intensity transcranial magnetic stimulation in women with fibromyalgia improves diagnostic variables up to 6 months after treatment completion.

OBJECTIVES: Fibromyalgia (FM) is a disease treated with various therapeutic approaches that have limited success. Pulsed electromagnetic field therapy has been proposed as a possible solution to reduce several symptoms. This study aims to analyse the therapeutic effects of transcranial low-intensity magnetic stimulation (LIMS) in women diagnosed with FM at 2, 12 and 24 weeks from the last LIMS administration treatment session. METHODS: 560 women (53.7 ± 11.3 years) diagnosed with FM according to the ACR 2016 criteria were randomly allocated in two groups: 280 received standard pharmacological treatment and 280 received the same treatment plus eight sessions of LIMS, 20 minutes long, once a week. The variables analysed were the widespread pain index (WPI), symptoms severity score (SS score) and the Spanish-validated version of the FM impact questionnaire (S-FIQ). The evaluations were performed at the beginning of LIMS treatment and at 2, 12 and 24 weeks after the end of the last LIMS treatment session. RESULTS: From the second week after the last LIMS session, there was significant improvement (p <0.001) in the variables WPI, SS score and S-FIQ. This improvement was maintained throughout the 24 weeks of monitoring after the last intervention. The age of the patients and the severity of the symptoms at the time of diagnosis did not affect the improvement observed in the three variables studied. CONCLUSIONS: Treatment with LIMS for eight weeks resulted in significant improvement in FM diagnostic variables, which was maintained up to 24 weeks after the last treatment session. This therapy could be recommended as a part of a multimodal approach for FM treatment.

Impact of biliary drainage prior to pancreatectomy.

BACKGROUND: There is still a lack of clarity about the benefits of preoperative biliary drainage (PBD), which was introduced to improve the perioperative outcome in patients with obstructive jaundice caused by a periampullary tumour. The aim of this study was to determine whether operative and postoperative complications increase in patients undergoing PBD during pancreatoduodenectomy (PD). MATERIAL AND METHODS: Retrospective examination was made of patients who underwent PBD for a periampullary tumour in our hospital between 2006 and 2014. From these, the patients were identified who had PBD with endoscopic retrograde cholangiopancreatography and these patients were further separated into two groups, as one group of patients with plastic stents and the other group of patients with metallic stents. Patients with pancreas head cancer were also separated into two groups as those who were and were not applied with PBD. The preoperative, intraoperative and postoperative characteristics of the patients were evaluated. RESULTS: A total of 123 patients were retrospectively reviewed. Biliary stent placement with PBD was applied to 48 patients, of whom 31 had metallic stents and 17 had plastic stents. In general, there was no difference between the PBD and the non-PBD groups in respect of the preoperative, operative and postoperative results. When patients with tumour of the pancreas head only were examined, the rate of wound infection was higher in the PBD group and there was no difference in the other parameters. Moreover, there was no difference between the patients with metallic stents and those with plastic stents in respect of outcomes. CONCLUSIONS: With the exception of wound site infection, although no difference was observed between the PBD and the non-PBD groups based on intraoperative and postoperative complications, because of the distinctive inherent complications of PBD it is essential to manage such patients properly and to carefully select the patients for the PBD procedure.

Improvement of digestive symptoms in fibromyalgia patients following a diet modification according to histamine release test - an observational study.

Introduction: There is growing interest in the relationship between fibromyalgia and processes related to food, such as food intolerances. In fact, different associations have been described between the control of dietary habits and the improvement of the different symptoms of fibromyalgia. Material and methods: We collected the results of applying a specific test of histamine release related to the diet of patients with fibromyalgia, and evaluated the changes in terms of the symptoms usually described by the patients. A total of 84 patients who met the established criteria were recruited; 40 of them underwent the exclusion diet for a period of 6 months, while the remaining ones continued with their usual dietary habits. All patients were instructed not to modify any other parameter during the study, such as medication, exercise, or other complementary treatments. The parameters studied were as follows: the Fibromyalgia Impact Questionnaire (FIQ), the Gastrointestinal Symptoms Rating Scale (GSRS), the pain Visual Analogue Scale (VAS), as well as the patients' body weight was controlled. Results: There was a significant improvement (p < 0.05) in the group of patients who underwent the exclusion diet in assesment by GSRS and in total in total body weight. There were no differences compared to the rest of the patients in terms of VAS and FIQ. Conclusions: Diet modification in patients with fibromyalgia by specific histamine relase test improves certain clinical parameters related to the symptoms of the digestive sphere, compared to the control group. Our work opens a possible way of non-pharmacological treatment to improve some symptoms of this very prevalent disease.

Dysphagia secondary to autoimmune necrotizing anti-HGMCR myopathy.

We present the case of an 87-year-old female who presented with upper dysphagia to solids, weight loss of 5 kg and weakness in the upper limbs of a seven months duration. Gastroscopy showed a hiatal hernia and an esophagogram showed gastroesophageal reflux and contrast aspiration into the trachea. Esophageal manometry was not possible due to intolerance. Analytics showed elevated CPK (3,386 UI/l; 34-145) and positivity to anti-HMGCR antibodies. An electromyogram was performed, with more intense myopathy data in the proximal regions of the upper limbs and signs of myositis. A muscle biopsy was performed (deltoids and biceps) that showed signs of necrotizing myopathy. Treatment with oral steroids and methotrexate was started with a good subsequent evolution.

[Prescription appropriateness in elderly patients with polypharmacy in primary care: Cluster-randomized controlled trial PHARM-PC]. / Adecuación de la prescripción en pacientes mayores polimedicados en atención primaria. Ensayo clínico controlado aleatorizado por grupos PHARM-PC.

OBJECTIVES: To assess the effectiveness of a pharmacist-led systematic review of medications on: potentially inappropriate medications (PIM), health outcomes and costs. DESIGN: Prospective, open, controlled and cluster-randomized clinical trial. SETTING: Six primary care clinics from Balearic Islands. PARTICIPANTS: Forty-two clusters (21 per group), and 549 patients aged ≥65 years and ≥5 chronic medications were included; of which 277 were allocated to Intervention Group (IG) and 272 to Control Group (CG). Patients were excluded if they were: institutionalized, temporarily displaced, routinely monitored under private healthcare, or home care. INTERVENTION: PIM detection by the pharmacist using a combination of explicit and implicit methods; and communication of the most appropriate therapeutic strategies to the physician. MEASUREMENTS: Proportion of patients with PIM and mean number of PIM/patient (main outcomes); and morbidity, mortality, and costs (secondary outcomes) were assessed. STATISTICAL PLAN: Following an intention-to-treat approach, quantitative and qualitative outcomes variables were compared by T-Student and Chi-square tests, respectively. Results were providing as difference in proportions for qualitative outcomes and difference in means for quantitative outcomes with respective 95% confidence intervals (95% CI). RESULTS: After intervention, proportion of patients with PIM decreased by 13.7% (95% CI: 9.3; 18.2) more in IG than CG. Mean number of PIM/patient and mean cost of PIM/patient decreased by 0.43 (95% CI: 0.32; 0.54) and 72.11€ (95% CI: 26.15; 118.06) more in IG than CG, respectively. However, no statistically significant differences were observed in morbidity, mortality or costs of healthcare resources. CONCLUSIONS: PIM detection and recommendations provided by pharmacist could contribute to reduce significantly PIM and drug expenditure; but without reaching statistically significant differences in morbidity, mortality, and healthcare resources costs.

Effectiveness and safety of direct-acting antivirals in hepatitis C infected patients with mental disorders: Results in real clinical practice.

The aim of this study is to analyze the effectiveness and safety of direct-acting antivirals (DAAs) in psychiatric patients with chronic hepatitis C (CHC). Secondary objectives included adherence and drug-drug interaction (DDIs) evaluations. Prospective observational comparative study carried out during 3 years. Psychiatric patients were included and mental illness classified by a psychiatric team based on clinical records. Main effectiveness and safety variables were sustained virologic response (SVR) at posttreatment week 12 (SVR12) and rate of on-treatment serious drug-related adverse events (AEs), respectively. A total of 242 psychiatric and 900 nonpsychiatric patients were included. SVR12 by intention-to-treat (ITT) analysis of psychiatric vs nonpsychiatric patients was 92.6% (95% confidence interval [CI], 89.1-96.1) vs 96.2% (95% CI, 94.9-97.5) (P = .02). SVR12 by modified-ITT analysis was 97.8% (95% CI, 95.0-99.3) vs 98.4% (95% CI, 97.5-99.3) (P = .74). 92.2% of psychiatric patients with mental disorders secondary to multiple drug use (MDSDU) and 93.0% of psychiatric patients without MDSDU vs 96.2% of nonpsychiatric patients reached SVR12 (P = .05 and P = .20, respectively). The percentage of adherent patients to DAAs did not show differences between cohorts (P = .08). 30.2% of psychiatric patients and 27.6% of nonpsychiatric patients presented clinically relevant DDIs (P = .47). 1.7% vs 0.8% of psychiatric vs nonpsychiatric patients developed serious AEs (P = .39); no serious psychiatric AEs were present. DAAs have shown a slightly lower effectiveness in psychiatric patients with CHC, as a result of loss of follow up, which justifies the need for integrated and multidisciplinary health care teams. DAAs safety, adherence, and DDIs, however, are similar to that of nonpsychiatric patients.

Experimental keratitis in rats caused by Acanthamoeba griffini: A kinetic histopathological study.

The aim of this study was to evaluate the inflammation process that resulted from the inoculation of Wistar Rats with Acanthamoeba griffini, a virulent T3 Acanthamoeba genotype that produces keratitis. Haematoxylin and eosin, periodic acid stain, immunohistochemistry and morphometry were used to analyse tissues from rats of an Acanthamoeba keratitis (AK) model. Two weeks after inoculating the rats with A griffini trophozoites, the thickness of the stroma had diminished, followed by an increase in thickness at 4 weeks. At the latter time, an abundance of inflammatory infiltrate cells was observed, some found to express IL-1ß, IL-10 and/or caspase 3. Intercellular adhesion molecule-1 was expressed in corneal blood vessels amid the abundant vascularization characteristic of the development of AK. Through an immunohistochemical technique, trophozoites were detected at 2 and 4 weeks post-inoculation. By 8 weeks, there were a low number of trophozoites and cysts and the corneas of infected rats were similar in thickness to those of the controls. Thus, the rats were capable of healing experimental AK in the present rat model. Diverse immunological mechanisms regulated the inflammatory process in acute AK induced by A griffini in a murine model.

Case report: multiple and atypical amoebic cerebral abscesses resistant to treatment.

BACKGROUND: The parasite Entamoeba histolytica is the causal agent of amoebiasis, a worldwide emerging disease. Amebic brain abscess is a form of invasive amebiasis that is both rare and frequently lethal. This condition always begins with the infection of the colon by E. histolytica trophozoites, which subsequently travel through the bloodstream to extraintestinal tissues. CASE PRESENTATION: We report a case of a 71-year-old female who reported an altered state of consciousness, disorientation, sleepiness and memory loss. She had no history of hepatic or intestinal amoebiasis. A preliminary diagnosis of colloidal vesicular phase neurocysticercosis was made based on nuclear magnetic resonance imaging (NMRI). A postsurgery immunofluorescence study was positive for the 140 kDa fibronectin receptor of E. histolytica, although a serum analysis by ELISA was negative for IgG antibodies against this parasite. A specific E. histolytica 128 bp rRNA gene was identified by PCR in biopsy tissue. The final diagnosis was cerebral amoebiasis. The patient underwent neurosurgery to eliminate amoebic abscesses and was then given a regimen of metronidazole, ceftriaxone and dexamethasone for 4 weeks after the neurosurgery. However, a rapid decline in her condition led to death. CONCLUSIONS: The present case of an individual with a rare form of cerebral amoebiasis highlights the importance of performing immunofluorescence, NMRI and PCR if a patient has brain abscess and a poorly defined diagnosis. Moreover, the administration of corticosteroids to such patients can often lead to a rapid decline in their condition.

Role of Bedside Multimodality Monitoring in the Detection of Cerebral Vasospasm Following Subarachnoid Hemorrhage.

BACKGROUND: Detection of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) in patients with a poor clinical exam is challenging. Brain tissue oxygen tension monitoring (PbtO2) and cerebral microdialysis (CMD) can detect ischemia and metabolic derangements. Our aim was to evaluate efficacy of these modalities in real-time detection of DCI. METHODS: All patients with aSAH who underwent with multimodality monitoring (MMM) with PbtO2 and/or CMD between the years of 2013 and 2015 at our institution were retrospectively studied. Mean PbTO2, lactate to pyruvate ratio (LPR), and glucose over the 24-h period prior to each angiogram for evaluation and treatment of vasospasm were correlated to the extent of vasospasm observed in the hemisphere with the monitors. The average measurements were also compared in the setting of presence and absence of angiographically significant vasospasm. RESULTS: A total of ten patients with aSAH who underwent MMM were identified. PbtO2 decline correlates with severity of proximal vasospasm (r = -0.66). PbtO2 was significantly lower in the setting of vasospasm (17.6 vs. 25.8, p = 0.003), but LPR (34.5 vs. 26.8, p = 0.1) and glucose (0.8 vs. 1.1, p = 0.6) were not significantly different. CONCLUSION: Proximal vasospasm after aSAH is associated with MMM indicator of tissue ischemia and/or metabolic derangement. PbtO2 and CMD help in real-time detection and management of DCI.

Early seizures and temporal lobe trauma predict post-traumatic epilepsy: A longitudinal study.

OBJECTIVE: Injury severity after traumatic brain injury (TBI) is a well-established risk factor for the development of post-traumatic epilepsy (PTE). However, whether lesion location influences the susceptibility of seizures and development of PTE longitudinally has yet to be defined. We hypothesized that lesion location, specifically in the temporal lobe, would be associated with an increased incidence of both early seizures and PTE. As secondary analysis measures, we assessed the degree of brain atrophy and functional recovery, and performed a between-group analysis, comparing patients who developed PTE with those who did not develop PTE. METHODS: We assessed early seizure incidence (n = 90) and longitudinal development of PTE (n = 46) in a prospective convenience sample of patients with moderate-severe TBI. Acutely, patients were monitored with prospective cEEG and a high-resolution Magnetic Resonance Imaging (MRI) scan for lesion location classification. Chronically, patients underwent a high-resolution MRI, clinical assessment, and were longitudinally monitored for development of epilepsy for a minimum of 2 years post-injury. RESULTS: Early seizures, occurring within the first week post-injury, occurred in 26.7% of the patients (n = 90). Within the cohort of subjects who had evidence of early seizures (n = 24), 75% had a hemorrhagic temporal lobe injury on admission. For longitudinal analyses (n = 46), 45.7% of patients developed PTE within a minimum of 2 years post-injury. Within the cohort of subjects who developed PTE (n = 21), 85.7% had a hemorrhagic temporal lobe injury on admission and 38.1% had early (convulsive or non-convulsive) seizures on cEEG monitoring during their acute ICU stay. In a between-group analysis, patients with PTE (n = 21) were more likely than patients who did not develop PTE (n = 25) to have a hemorrhagic temporal lobe injury (p < 0.001), worse functional recovery (p = 0.003), and greater temporal lobe atrophy (p = 0.029). CONCLUSION: Our results indicate that in a cohort of patients with a moderate-severe TBI, 1) lesion location specificity (e.g. the temporal lobe) is related to both a high incidence of early seizures and longitudinal development of PTE, 2) early seizures, whether convulsive or non-convulsive in nature, are associated with an increased risk for PTE development, and 3) patients who develop PTE have greater chronic temporal lobe atrophy and worse functional outcomes, compared to those who do not develop PTE, despite matched injury severity characteristics. This study provides the foundation for a future prospective study focused on elucidating the mechanisms and risk factors for epileptogenesis.

The epilepsy bioinformatics study for anti-epileptogenic therapy (EpiBioS4Rx) clinical biomarker: Study design and protocol.

The Epilepsy Bioinformatics Study for Anti-epileptogenic Therapy (EpiBioS4Rx) is a longitudinal prospective observational study funded by the National Institute of Health (NIH) to discover and validate observational biomarkers of epileptogenesis after traumatic brain injury (TBI). A multidisciplinary approach has been incorporated to investigate acute electrical, neuroanatomical, and blood biomarkers after TBI that may predict the development of post-traumatic epilepsy (PTE). We plan to enroll 300 moderate-severe TBI patients with a frontal and/or temporal lobe hemorrhagic contusion. Acute evaluation with blood, imaging and electroencephalographic monitoring will be performed and then patients will be tracked for 2 years to determine the incidence of PTE. Validation of selected biomarkers that are discovered in planned animal models will be a principal feature of this work. Specific hypotheses regarding the discovery of biomarkers have been set forth in this study. An international cohort of 13 centers spanning 2 continents will be developed to facilitate this study, and for future interventional studies.

[Microbiological analysis of the maternal genital tract and umbilical cord blood and its association with neonatal damage]. / Análisis microbiológico del tracto genital materno y de la sangre del cordón umbilical en relación con el daño neonatal.

The etiology leading to neonatal damage is multifactorial, being genital infections one of the causes. The objective of the study was to identify microorganisms of the maternal genital tract that are associated with neonatal damage, in order to prevent future perinatal complications. Seven hundred and eleven pregnant patients attended their prenatal control during the period January 2010-July 2013. Ureaplasma urealyticum and Mycoplasma hominis presence was investigated in umbilical cord blood by metabolic substrates (Micofast-Biomerieux) and that of T.vaginalis, by PCR using specific primers. The microbiological study of the vaginal contents of 288 pregnant patients at weeks 35 to 37 was performed by conventional methods, adding the modified thioglycolate culture for T.vaginalis. GroupB streptococcus (GBS) was investigated in anorectal and vaginal introitus swabs, using selective broth enrichment and subsequent isolation in chromogenic medium. The χ2 Yates test and Fisher's test were used for independent samples. A p value <0.05 was considered statistically significant. The pathogens significantly related to neonatal damage were M.hominis (p=0.03), T.vaginalis (p=0.03), and BV (p=0.02). Main complications were preterm birth, premature rupture of membranes (PRM), low weight and Apgar score ≤7. U.urealyticum (p=0.35), Candidaspp. (p=0.94) and GBS (p=0.18) were not related to neonatal damage. Since different microorganisms of the maternal genital tract were related to neonatal damage, it is very important to perform the microbiological study of vaginal contents during pregnancy to prevent possible maternal and perinatal complications.

Staphylococcus aureus bloodstream infections in Latin America: results of a multinational prospective cohort study.

BACKGROUND: Substantial heterogeneity in the epidemiology and management of Staphylococcus aureus bacteraemia (SAB) occurs in Latin America. We conducted a prospective cohort study in 24 hospitals from nine Latin American countries. OBJECTIVES: To assess the clinical impact of SAB in Latin America. PATIENTS AND METHODS: We evaluated differences in the 30 day attributable mortality among patients with SAB due to MRSA compared with MSSA involving 84 days of follow-up. Adjusted relative risks were calculated using a generalized linear model. RESULTS: A total of 1030 patients were included. MRSA accounted for 44.7% of cases with a heterogeneous geographical distribution. MRSA infection was associated with higher 30 day attributable mortality [25% (78 of 312) versus 13.2% (48 of 363), adjusted RR: 1.94, 95% CI: 1.38-2.73, P < 0.001] compared with MSSA in the multivariable analysis based on investigators' assessment, but not in a per-protocol analysis [13% (35 of 270) versus 8.1% (28 of 347), adjusted RR: 1.10, 95% CI: 0.75-1.60, P = 0.616] or in a sensitivity analysis using 30 day all-cause mortality [36% (132 of 367) versus 27.8% (123 of 442), adjusted RR: 1.09, 95% CI: 0.96-1.23, P = 0.179]. MRSA infection was not associated with increased length of hospital stay. Only 49% of MSSA bloodstream infections (BSI) received treatment with ß-lactams, but appropriate definitive treatment was not associated with lower mortality (adjusted RR: 0.93, 95% CI: 0.70-1.23, P = 0.602). CONCLUSIONS: MRSA-BSIs in Latin America are not associated with higher 30 day mortality or longer length of stay compared with MSSA. Management of MSSA-BSIs was not optimal, but appropriate definitive therapy did not appear to influence mortality.

A Prospective Cohort Multicenter Study of Molecular Epidemiology and Phylogenomics of Staphylococcus aureus Bacteremia in Nine Latin American Countries.

Staphylococcus aureus is an important pathogen causing a spectrum of diseases ranging from mild skin and soft tissue infections to life-threatening conditions. Bloodstream infections are particularly important, and the treatment approach is complicated by the presence of methicillin-resistant S. aureus (MRSA) isolates. The emergence of new genetic lineages of MRSA has occurred in Latin America (LA) with the rise and dissemination of the community-associated USA300 Latin American variant (USA300-LV). Here, we prospectively characterized bloodstream MRSA recovered from selected hospitals in 9 Latin American countries. All isolates were typed by pulsed-field gel electrophoresis (PFGE) and subjected to antibiotic susceptibility testing. Whole-genome sequencing was performed on 96 MRSA representatives. MRSA represented 45% of all (1,185 S. aureus) isolates. The majority of MRSA isolates belonged to clonal cluster (CC) 5. In Colombia and Ecuador, most isolates (≥72%) belonged to the USA300-LV lineage (CC8). Phylogenetic reconstructions indicated that MRSA isolates from participating hospitals belonged to three major clades. Clade A grouped isolates with sequence type 5 (ST5), ST105, and ST1011 (mostly staphylococcal chromosomal cassette mec [SCCmec] I and II). Clade B included ST8, ST88, ST97, and ST72 strains (SCCmec IV, subtypes a, b, and c/E), and clade C grouped mostly Argentinian MRSA belonging to ST30. In summary, CC5 MRSA was prevalent in bloodstream infections in LA with the exception of Colombia and Ecuador, where USA300-LV is now the dominant lineage. Clonal replacement appears to be a common phenomenon, and continuous surveillance is crucial to identify changes in the molecular epidemiology of MRSA.

Metabolic crisis occurs with seizures and periodic discharges after brain trauma.

OBJECTIVE: Traumatic brain injury (TBI) results in persistent disruption of brain metabolism that has yet to be mechanistically defined. Early post-traumatic seizures are one potential mechanism for metabolic crisis and hence could be a therapeutic target. We hypothesized that seizures and pseudoperiodic discharges (PDs) may be mechanistically linked to metabolic crisis as measured by cerebral microdialysis. METHODS: A prospective multicenter study of surface and intracortical depth electroencephalography (EEG) was performed in conjunction with cerebral microdialysis in a cohort of severe TBI patients with time-locked analysis of the neurochemical response to seizures and pseudoperiodic discharges. RESULTS: Seizures or PDs occurred in 61% of 34 subjects, with 42.9% of these seizures noted only on intracortical depth EEG and in some cases lasting for many hours. Metabolic crisis as measured by elevated cerebral microdialysis lactate/pyruvate ratio occurred during seizures or PDs but not during electrically nonepileptic epochs. INTERPRETATION: In TBI patients, seizures and periodic discharges are one mechanism for metabolic crisis, and hence represent a therapeutic target for future study.

Carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter baumannii in the nosocomial setting in Latin America.

Increasing prevalence of carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii strains in the nosocomial setting in Latin America represents an emerging challenge to public health, as the range of therapeutic agents active against these pathogens becomes increasingly constrained. We review published reports from 2002 to 2013, compiling data from throughout the region on prevalence, mechanisms of resistance and molecular epidemiology of carbapenem-resistant strains of P. aeruginosa and A. baumannii. We find rates of carbapenem resistance up to 66% for P. aeruginosa and as high as 90% for A. baumannii isolates across the different countries of Latin America, with the resistance rate of A. baumannii isolates greater than 50% in many countries. An outbreak of the SPM-1 carbapenemase is a chief cause of resistance in P. aeruginosa strains in Brazil. Elsewhere in Latin America, members of the VIM family are the most important carbapenemases among P. aeruginosa strains. Carbapenem resistance in A. baumannii in Latin America is predominantly due to the oxacillinases OXA-23, OXA-58 and (in Brazil) OXA-143. Susceptibility of P. aeruginosa and A. baumannii to colistin remains high, however, development of resistance has already been detected in some countries. Better epidemiological data are needed to design effective infection control interventions.

Altered Underlying Renal Tubular Function in Patients With Chronic Hepatitis B Receiving Nucleos(t)ide Analogs in a Real-World Setting: The MENTE Study.

BACKGROUND: Cases of renal tubular dysfunction have been reported in patients with hepatitis B and in patients with human immunodeficiency virus who are undergoing tenofovir treatment. However, little is known about the impact on tubular function in patients with chronic hepatitis B (CHB) under long-term use of entecavir (ETV) and tenofovir disoproxil fumarate (TDF). We evaluated markers of renal tubular function and bone turnover in patients with CHB treated with ETV or TDF. PATIENTS AND METHODS: A multicenter, cross-sectional study was performed on markers of renal tubular function and bone turnover in hepatitis B virus-monoinfected patients on long-term treatment with Entecavir or Tenofovir (the MENTE study). The analyzed parameters were: retinol-binding protein/creatinine, neutrophil gelatinase-associated lipocalin/creatinine, excretion of phosphates, uric acid excretion, glomerular filtrate, protein/creatinine, albumin/creatinine, serum creatinine, phosphate, CTX, P1NP, vitamin D, and parathormone. RESULTS: A total of 280 patients (ETV: 89, TDF: 69, control: 122) were included in this study. The TDF group was associated with altered levels of retinol-binding protein (RBP)/creatinine (TDF 25% vs. 7% ETV and control; P<0.001). Protein/creatinine, uric acid excretion, P1NP1, and parathormone were higher in the TDF group. The proportion of patients with serum phosphate <2.5 mg/dL was higher in both the ETV and the TDF groups compared with the control. The multivariate analysis showed that the use of TDF was independently associated with a higher risk of altered excretion of RBP/creatinine (4.4; interquartile range: 1.4 to 14; P=0.013). CONCLUSIONS: We found an independent association between TDF use and altered RBP excretion. This finding indicates subclinical tubular damage. Because tubular dysfunction can precede the decline of renal function, close monitoring of RBP levels in patients with CHB on nucleos(t)ide analog treatment must be performed for early detection of TDF-related renal toxicity. In this study, these differences in tubular function were not associated with concomitant changes in markers of bone turnover.

Modulation of innate immune response by the vagus nerve in experimental hepatic amebiasis in rats.

The parasympathetic nervous system has a crucial role in immunomodulation of the vagus nerve, its structure provides a pathogen detection system, and a negative feedback to the immune system after the pathogenic agent has been eliminated. Amebiasis is a disease caused by the protozoan parasite Entamoeba histolytica, considered the third leading cause of death in the world. The rats are used as a natural resistance model to amoebic liver infection. The aim of this study is to analyze the interaction of Entamoeba histolytica with neutrophils, macrophages, and NK cells in livers of intact and vagotomized rats. Six groups were studied (n = 4): Intact (I), Intact + amoeba (IA), Sham (S), Sham + amoeba (SA), Vagotomized (V) and Vagotomized + amoeba (VA). Animals were sacrificed at 8 h post-inoculation of E. histolytica. Then, livers were obtained and fixed in 4% paraformaldehyde. Tissue liver slides were stained with H-E, PAS and Masson. The best development time for E. histolytica infection was at 8 h. Amoeba was identified with a monoclonal anti-220 kDa E. histolytica lectin. Neutrophils (N) were identified with rabbit anti-human neutrophil myeloperoxidase, macrophages (Mɸ) with anti-CD68 antibody and NK cells (NK) with anti-NK. Stomachs weight and liver glycogen were higher in V. Collagen increased in VA, whereas vascular and neutrophilic areas were decreased. There were fewer N, Mɸ, NK around the amoeba in the following order IA > SA > VA (p < 0.05 between IA and VA). In conclusion, these results suggest that the absence of parasympathetic innervation affects the participation of neutrophils, macrophages and NK cells in the innate immune response, apparently by parasympathetic inhibition on the cellular functions and probably for participation in sympathetic activity.