Silicene growth mechanisms on Au(111) and Au(110) substrates.

Despite the remarkable theoretical applications of silicene, its synthesis remains a complex task, with epitaxial growth being one of the main routes involving depositing evaporated Si atoms onto a suitable substrate. Additionally, the requirement for a substrate to maintain the silicene stability poses several difficulties in accurately determining the growth mechanisms and the resulting structures, leading to conflicting results in the literature. In this study, large-scale molecular dynamics simulations are performed to uncover the growth mechanisms and characteristics of epitaxially grown silicene sheets on Au(111) and Au(110) substrates, considering different temperatures and Si deposition rates. The growth process has been found to initiate with the nucleation of several independent islands homogeneously distributed on the substrate surface, which gradually merge to form a complete silicene sheet. The results consistently demonstrate the presence of a buckled silicene structure, although this characteristic is notably reduced when using an Au(111) substrate. Furthermore, the analysis also focuses on the quality and growth mode of the silicene sheets, considering the influence of temperature and deposition rate. The findings reveal a prevalence of the Frank-van der Merwe growth mode, along with diverse forms of defects throughout the sheets.

Anaerobic bacteraemia: A score predicting mortality.

The objectives of this study were to report those variables which are readily identifiable at the bedside and that are able to predict mortality in patients with bacteraemia caused by anaerobes. Patients with clinically significant anaerobic bacteraemias detected between January 2016 and December 2019 in a tertiary hospital in Granada (Spain) were retrospectively included. Species identification was performed by MALDI-TOF MS and/or molecular methods. Finally, 136 cases of anaerobic bacteraemia were included, being the most frequent anaerobes Bacteroides (45.5%; n = 62), Clostridium (24.2%, n = 33), and Gram-positive anaerobic cocci (16.1%, n = 22). Crude mortality was 25.7%, corresponding to 35 patients who died, with 82.8% of deaths directly attributable to bacteraemia. A multivariable logistic regression model with non-parametric bootstrap estimation identified three variables that were independently and significantly associated with an increased risk of death: 1) hospitalization in the intensive care unit; 2) septic shock; and 3) presence of any kind of cancer. These variables were as recorded at the time that the first positive blood culture was obtained. An index score, obtained from these variables, was calculated and divided patients into two groups with increasing likelihood of mortality resulting from anaerobic bacteraemia. The sensitivity and specificity of a prediction of death based on this model were 65.2% and 97%, respectively.

Leishmaniasis due to Leishmania infantum: Integration of human, animal and environmental data through a One Health approach.

The aim of this study was to explore Leishmania infantum epidemiology through a One Health approach that promotes a better estimation of leishmaniasis burden and a deeper understanding of the spatial distribution of the key actors of the parasite life cycle (vectors, reservoirs and humans). We conducted a 14-year mixed retrospective and prospective study of leishmaniasis cases in an endemic area in southern Spain (Granada province), to estimate the human incidence and its association with the vector presence, cryptic leishmaniasis rates and canine leishmaniasis prevalence. We found an annual linear increase in the incidence that cannot be fully explained by active case surveillance and the improvement of PCR diagnostic techniques. 49.4% of cases were not reported to the surveillance system. Approximately half of the human cases correspond to the visceral form that occurred more frequently in men; cutaneous, mucosal and cryptic forms were also detected. Leishmaniasis is no longer a disease of young children, accounting for a quarter of immunocompetent patients and most infected people remained asymptomatic. Human and canine leishmaniasis, cryptic or symptomatic, are present in the whole province, where there is a medium/high risk of the presence of Phlebotomus perniciosus, the main vector. We found association between the incidence of human leishmaniasis and the presence of the vector, but not with the prevalence of canine leishmaniasis and cryptic human leishmaniasis. A potential hot spot was also found, where high leishmaniasis incidence may be associated to the involvement of host species other than dogs.

Antimicrobial susceptibility and clinical findings of significant anaerobic bacteria in southern Spain.

The objectives of this study were to report on the antimicrobial susceptibility of 276 clinically significant anaerobic bacteria belonging to the major genera isolated between May 2017 and November 2018 in a tertiary hospital in Granada (Spain) and to describe key clinical features of the patients. Species identification was performed by MALDI-TOF MS. Antimicrobial susceptibility tests were performed against penicillin, amoxicillin-clavulanic, imipenem, meropenem, moxifloxacin, clindamycin, metronidazole, vancomycin, and piperacillin-tazobactam using the gradient diffusion technique and EUCAST breakpoints (except for moxifloxacin). The most frequent anaerobes were Bacteroides (29.7%; n = 82), Clostridioides difficile (15.9%, n = 44), Prevotella (10.8%, n = 30), and Propionibacterium (10.7%, n = 25). Metronidazole was not universally active against all genera tested, and some isolates showed resistance to this drug. Almost all tested anaerobes were susceptible to carbapenems and amoxicillin-clavulanate except for Clostridioides difficile (resistance rate of 94%) and Bacteroides (19%), respectively. High overall resistance rates to clindamycin were observed, especially for genera Finegoldia (54%), Bacteroides (49%), and Prevotella (40%). Resistance rates to carbapenems and amoxicillin-clavulanate were very low for the majority of tested genera but were high for Clostridioides difficile and Bacteroides spp., respectively. Resistance to clindamycin was very high, especially for Bacteroides, Finegoldia magna, Prevotella and Peptoniphilus. Routine antimicrobial susceptibility testing for anaerobes contributes information on the global situation and allows empirical therapies to be selected in accordance with local data on resistant strains.

Asymptomatic Leishmania infection in blood donors from the Southern of Spain.

OBJECTIVES: To investigate the proportion of asymptomatic infection among blood donors in a region endemic for Leishmania; and to ascertain epidemiological and genetic factors associated with this condition. METHODS: We studied 1260 blood donors in the Province of Granada in the Southern Spain. After obtaining informed consent in each participant, a poll about habits, housing and contact with animals were carried out. Blood samples were obtained for determining antileishmanial antibodies and a PCR assay. HLA typing was performed in a randomly sample among the donors with positive serology. RESULTS: We have found that L. infantum antibodies were present in 7.9% of blood donors and DNA in blood was detected in 2.5% of donors. There was no concordance between both determinations, except in one patient. Taking into consideration both techniques, 129 participants were considered to have asymptomatic Leishmania infection. No participant in this study developed clinical leishmaniasis during a follow-up period of 2 years. HLA were typed in 51 donors. Asymptomatic Leishmania infection might be associated with certain HLA antigens. A multivariate analysis was done with the variables obtained through the participants' interview. The contact with livestock (goats, pigs, and sheep), but not dogs, either at home or in the environment, was significantly and independently associated with asymptomatic leishmania infection. CONCLUSIONS: Asymptomatic leishmanial infection among blood donors is frequent in the Granada Province, south of Spain. The presence of livestock in this region is related to this infection, perhaps influencing vector density of this disease. Some HLA genes might be associated with asymptomatic leishmanial state.

Nocardia paucivorans brain abscess. Clinical and microbiological characteristics.

Nocardia paucivorans brain abscesses are unusual in humans. Sixteen cases of this infection have been reported in the world medical literature. There is precise clinical information available from nine patients. All of these patients recovered or were cured from their brain disease with long-term antimicrobial treatment. Surgical drainage was performed in four patients.

Executive summary of the diagnosis and treatment of urinary tract infection: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC) / Resumen ejecutivo del diagnóstico y tratamiento de las infecciones del tracto urinario. Guía de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC)

Most urinary tract infections (UTI) are uncomplicated infections occurring in young women. An extensive evaluation is not required in the majority of cases, and they can be safely managed as outpatients with oral antibiotics. Escherichia coli is by far the most common uropathogen, accounting for >80% of all cases. Other major clinical problems associated with UTI include asymptomatic bacteriuria, and patients with complicated UTI. Complicated UTIs are a heterogeneous group associated with conditions that increase the risk of acquiring infection or treatment failure. Distinguishing between complicated and uncomplicated UTI is important, as it influences the initial evaluation, choice, and duration of antimicrobial therapy. Diagnosis is especially challenging in the elderly and in patients with in-dwelling catheters. The increasing prevalence of resistant uropathogens, including extended-spectrum β-lactamases and carbapenemase-producing Enterobacteriaceae, and other multidrug-resistant Gram-negative organisms further compromises treatment of both complicated and uncomplicated UTIs. The aim of these Clinical Guidelines is to provide a set of recommendations for improving the diagnosis and treatment of UTI

La mayoría de infecciones del tracto urinario (ITU) son infecciones no complicadas que se presentan en mujeres jóvenes. En la mayoría de los casos no se requieren pruebas diagnósticas complementarias y se pueden tratar ambulatoriamente de forma segura con antibióticos por vía oral. Escherichia coli es el uropatógeno más frecuente causando más del 80% de estas infecciones. La bacteriuria asintomática (BA) y las ITUs complicadas son otras formas de presentación de la ITU. Las ITU complicadas son un grupo heterogéneo de condiciones que incrementan el riesgo de adquisición de la infección o de fracaso del tratamiento. La distinción entre ITU complicada y no complicada es fundamental para decidir la evaluación inicial del paciente, la elección del antimicrobiano y la duración del mismo. El diagnóstico es especialmente difícil en ancianos y en pacientes con sondaje permanente. El incremento de cepas resistentes a los antibióticos, especialmente Enterobacterías productoras de beta-lactamasas de espectro extendido y de carbapenemasas y de otros Gram negativos multirresistentes, dificultan la elección del tratamiento de las ITU complicadas y no complicadas. El objetivo de esta guía clínica es proporcionar recomendaciones basadas en la evidencia para mejorar el diagnóstico y tratamiento de las ITU

Executive summary of the diagnosis and treatment of urinary tract infection: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC).

Most urinary tract infections (UTI) are uncomplicated infections occurring in young women. An extensive evaluation is not required in the majority of cases, and they can be safely managed as outpatients with oral antibiotics. Escherichia coli is by far the most common uropathogen, accounting for >80% of all cases. Other major clinical problems associated with UTI include asymptomatic bacteriuria, and patients with complicated UTI. Complicated UTIs are a heterogeneous group associated with conditions that increase the risk of acquiring infection or treatment failure. Distinguishing between complicated and uncomplicated UTI is important, as it influences the initial evaluation, choice, and duration of antimicrobial therapy. Diagnosis is especially challenging in the elderly and in patients with in-dwelling catheters. The increasing prevalence of resistant uropathogens, including extended-spectrum ß-lactamases and carbapenemase-producing Enterobacteriaceae, and other multidrug-resistant Gram-negative organisms further compromises treatment of both complicated and uncomplicated UTIs. The aim of these Clinical Guidelines is to provide a set of recommendations for improving the diagnosis and treatment of UTI.

Pulsed radiofrequency modulates pain regulatory gene expression along the nociceptive pathway.

BACKGROUND: Pulsed radiofrequency (PRF) therapy is a clinical treatment utilizing electromagnetic energy aimed to relieve neuropathic pain. This is the first study examining the modulated expression of pain regulatory genes following the induction of the spared nerve injury (SNI) pain model and subsequently treated with PRF therapy. OBJECTIVES: The present study investigated the behavioral efficacy of PRF therapy in rats exhibiting sciatic nerve injury and examined gene expression changes in the sciatic nerve, ipsilateral L5 dorsal root ganglia (DRG), and spinal cord. STUDY DESIGN: A randomized, experimental trial. SETTING: Department of Biological Sciences, Illinois State University and Department of Psychology, Illinois Wesleyan University. METHODS: An SNI model was used in male Sprague-Dawley rats (weight 260-310 g). A sham surgery was also performed as a control group. After 3 days development of the SNI model, an RF electrode was applied to the sciatic nerve proximal to the site of injury and stimulated for 3 minutes. The response to mechanical stimuli was assessed throughout the duration of the study. Furthermore, changes in gene expression along the nociceptive tract (sciatic nerve, DRG, and spinal cord) were assessed 24 hours post-PRF therapy. RESULTS: It was observed that the mechanical allodynia, induced by SNI model, was reversed to control values within 24 hours post-PRF therapy. Additionally, modulated expression of pain regulatory genes was observed after induction of the SNI model. Following PRF therapy, expression of many of these genes returned to control values (sham) in each of the tissues tested. Increased proinflammatory gene expression, such as TNF-α and IL-6, observed in the sciatic nerve (site of injury) in the SNI group was returned to baseline values following PRF therapy. Up-regulation of GABAB-R1, Na/K ATPase, and 5-HT3r as well as down regulation of TNF-α and IL-6 were also observed in the DRG in the SNI-PRF group relative to the SNI group. Up-regulation of Na/K ATPase and c-Fos was found in the spinal cord following PRF treatment relative to the SNI group. LIMITATIONS: Immediate changes in gene expression were observed at 24 hours to better determine the mechanism with no long-term data at this time. Protein expression was not assessed in addition to gene expression changes. CONCLUSION: These results indicate that the electromagnetic energy applied via PRF therapy influences the reversal of behavioral and molecular effects of hypersensitivity developed from a peripheral nerve injury.

Percutaneous sacroplasty and sacroiliac joint cementation under fluoroscopic guidance for lower back pain related to sacral metastatic tumors with sacroiliac joint invasion.

Cancer patients with bone metastases are at risk of a variety of skeletal events, including vertebral compression and pathologic fractures. Approximately 30% to 40% of patients with advanced lung cancer will develop bone metastases in the course of their disease, resulting in a significant negative impact on both morbidity and survival. Skeletal complications of bone metastases include pain, pathologic fractures, spinal cord compression, and hypercalcemia. The spine is the most frequent site of skeletal metastases. We present a 48-year-old female with intractable and incapacitating low back pain because of metastatic bone tumor in the left lateral side of S1 and S2 with left sacroiliac invasion. Imaging identified a metastatic invasion of the sacrum. Percutaneous sacroplasty, a safe and effective procedure for sacral-insufficient fractures, was performed under fluoroscopy guidance. However, the expected pain relief was not achieved. At 1 month, the patient remained invalided by severe back pain, which was localized to the left sacroiliac joint. In a second procedure, the sacroiliac joint was cemented. Pain relief was complete, immediate, and sustained until the patient's death related to the underlying oncologic disease. No complications were observed. Few reports exist about the treatment of sacral metastatic tumors with percutaneous sacroplasty. Further, no previous reports about sacroiliac joint cementation for joint stabilization have been found. In the present case, sacroiliac joint cementation successfully resolved residual pain that remained despite percutaneous sacroplasty treatment of the pathologic sacral fracture.

Mediterranean spotted fever with encephalitis.

Rickettsia conorii infection is endemic in the Mediterranean basin, where it is known as Mediterranean spotted fever, also known as Boutonneuse fever and Marseilles fever. We report the case of a 66-year-old diabetic man who presented a severe form of the disease, complicated by acute renal failure, thrombocytopenia and encephalitis. Diagnosis was confirmed by indirect immunofluorescence assay. Despite appropriate treatment, severe neurological sequelae have remained. Medical literature on encephalitis caused by R. conorii is also reviewed.

[Distribution of anesthesia practice, types of anesthesia, and human resources in Catalonia, Spain, in 2003]. / Distribución de la actividad, tipos de anestesia y recursos humanos en Cataluña en 2003.

BACKGROUND AND OBJECTIVE: The aim of this arm of the ANESCAT 2003 study was to describe the temporal distribution and types of anesthesia used in Catalonia, Spain, in 2003, along with the associated human resources used. PATIENTS AND METHOD: Data were used from a survey of 23,136 anesthetic procedures collected on 14 randomly selected days in 2003 and an individual questionnaire was completed by 765 anesthesiologists working in Catalonia. RESULTS: Anesthesia practice was divided into that associated with surgery (78.4%), obstetrics (11.3%), and other nonsurgical procedures (10.4%). Of all anesthetic procedures performed, 84.3% took place in operating theaters and 7.0% in obstetric areas. Emergency procedures accounted for 20.3% of the total. Most procedures (71.2%) were undertaken within 08:00 and 16:00 h, and the lowest number of procedures performed on workdays took place on Fridays. The median duration of anesthesia was 60 minutes. The most common technique was regional anesthesia (41.4%), with spinal block being the most widely used. There were an estimated 12.5 anesthesiologists per 100,000 inhabitants, with a median (10th-90th percentile) age of 45 (34-57) years; women made up 47.2% of that group. The mean number of standard working hours was 46 hours per week and 65% of anesthesiologists also undertook on duty shifts. Anesthesiologists spent 77% of their time performing anesthesia and the remainder in postoperative recovery and critical care units and pain clinics. CONCLUSIONS: Emergency anesthesia represents 20% of the total workload and obstetrics and nonsurgical procedures another 20%. The use of regional anesthesia was very widespread. The population density of anesthesiologists is comparable to that of other European countries, but with a higher proportion of women.

Distribución de la actividad, tipos de anestesia y recursos humanos en Cataluña en 2003 / Distribution of anesthesia practice, types of anesthesia, and human resources in Catalonia, Spain, in 2003

Fundamento y objetivo: Describir la distribución temporal y los tipos de anestesia administrada en Cataluña en el año 2003, así como los recursos humanos para su realización. Pacientes y método: Para ello se utilizaron datos del estudio epidemiológico ANESCAT sobre 23.136 anestesias recogidas en 14 días aleatorios del año 2003 y de un cuestionario individual contestado por 765 anestesiólogos que trabajaban en Cataluña (España). Resultado: La actividad anestésica se repartió en un 78,4% para procedimientos quirúrgicos, en un 11,3% para obstetricia y en un 10,4% para técnicas y exploraciones. El 84,3% de todas las anestesias se realizó en quirófano y el 7,0%, en las salas de partos. El 20,3% de toda la actividad fue urgente. El 71,2% de la actividad se realizó de las 8 a las 16 h y entre los días laborables fue menor los viernes. La duración mediana de la anestesia fue de 60 min. El tipo de anestesia más frecuente fue la regional (41,4%), y el bloqueo subaracnoideo fue el más utilizado. La densidad de anestesiólogos se estimó en 12,5 por 100.000 habitantes, con edad mediana (percentiles 10-90) de 45 (34-57) años; el 47,2% eran mujeres. El promedio de horas de trabajo en horario regular fue de 46 h semanales y además el 65% hacía guardias. El 77% del tiempo global de los anestesiólogos estuvo dedicado a la anestesia y el resto, a reanimación y dolor. Conclusiones: La actividad anestésica urgente supone el 20% de toda la actividad y también el 20% de toda ésta se realiza para procedimientos no quirúrgicos. El uso de anestesia regional es muy elevado. La densidad de anestesiólogos es comparable con la del entorno europeo, con un porcentaje mayor de mujeres

Background and objective: The aim of this arm of the ANESCAT 2003 study was to describe the temporal distribution and types of anesthesia used in Catalonia, Spain, in 2003, along with the associated human resources used. Patients and method: Data were used from a survey of 23,136 anesthetic procedures collected on 14 randomly selected days in 2003 and an individual questionnaire was completed by 765 anesthesiologists working in Catalonia. Results: Anesthesia practice was divided into that associated with surgery (78.4%), obstetrics (11.3%), and other nonsurgical procedures (10.4%). Of all anesthetic procedures performed, 84.3% took place in operating theaters and 7.0% in obstetric areas. Emergency procedures accounted for 20.3% of the total. Most procedures (71.2%) were undertaken within 08:00 and 16:00 h, and the lowest number of procedures performed on workdays took place on Fridays. The median duration of anesthesia was 60 minutes. The most common technique was regional anesthesia (41.4%), with spinal block being the most widely used. There were an estimated 12.5 anesthesiologists per 100,000 inhabitants, with a median (10th-90th percentile) age of 45 (34-57) years; women made up 47.2% of that group. The mean number of standard working hours was 46 hours per week and 65% of anesthesiologists also undertook on duty shifts. Anesthesiologists spent 77% of their time performing anesthesia and the remainder in postoperative recovery and critical care units and pain clinics. Conclusions: Emergency anesthesia represents 20% of the total workload and obstetrics and nonsurgical procedures another 20%. The use of regional anesthesia was very widespread. The population density of anesthesiologists is comparable to that of other European countries, but with a higher proportion of women

[Primary aldosteronism: analysis of a series of 54 patients]. / Hiperaldosteronismo primario: análisis de una serie de 54 pacientes.

BACKGROUND AND OBJECTIVE: The prevalence of primary aldosteronism (PA) has experienced an important increase, and many authors consider this condition as the main cause of secondary hypertension (HT). PATIENTS AND METHOD: Retrospective study of a series of 54 patients having PA who were studied in our Unit between 1999 and 2003. RESULTS: The prevalence of PA was 5.1%. Out of 54 PA cases, 13 corresponded to aldosterone-producing adenomas (APA), 30 to bilateral adrenal hyperplasia (BAH), one was one case of nodular bilateral hyperplasia and another case was a nodular unilateral hyperplasia. In 9 cases, an etiologic diagnosis could not be done. APA were more frequent in women and BAH in men; with regard to sex, no significant differences were found. The blood pressure (BP) was significantly higher in patients with APA compared with BAH patients. In patients with APA, kalemia was significantly lower than in BAH patients. Adrenal CT scan identified 90% of APA, while scintigraphy detected 100% of BAH. Spironolactone therapy significantly decreased the BP in APA and BAH patients, although this fall was higher in patients with APA. CONCLUSIONS: The prevalence of PA was 5.1%. Although the tests used for the screening and diagnosis of PA are controversial, a PA ought to be investigated in all patients with refractory HT, independently of the existence of hypokalemia. Spironolactone is an effective therapy for BAH and it is an adequate option for APA treatment when an adrenalectomy is not viable.

Hiperaldosteronismo primario: análisis de una serie de 54 pacientes / Primary aldosteronism: analysis of a series of 54 patients

FUNDAMENTO Y OBJETIVO: La prevalencia del hiperaldosteronismo primario (HAP) ha aumentado notablemente en los últimos años y algunos autores lo consideran la principal causa de hipertensión arterial secundaria. PACIENTES Y MÉTODO: Estudio retrospectivo de 54 pacientes con HAP estudiados en nuestra unidad entre 1999 y 2003.RESULTADOS: La prevalencia de HAP fue del 5,1%. Hubo 13 casos de adenoma productores dealdosterona (APA), 30 casos de hiperplasia bilateral suprarrenal (HBS), un caso de hiperplasianodular bilateral y otro caso de hiperplasia nodular unilateral. En 9 casos no se llegó a ningún diagnóstico etiológico. Los APA se diagnosticaron más en mujeres y las HBS más en varones; no hubo diferencias en cuanto al sexo. La presión arterial en los casos de APA fue significativamente superior a la encontrada en los pacientes con HBS. La potasemia en los casos de APA fue significativamente menor que en las HBS. La tomografía computarizada identificó el 90%de los APA y la gammagrafía el 100% de las HBS. El tratamiento con espironolactona redujo la presión arterial significativamente en todos los grupos, pero de manera más acusada en los APA. CONCLUSIONES: La prevalencia de HAP en nuestra serie fue del 5,1%. Aunque existe controversia respecto a los métodos de cribado y diagnósticos, el HAP debe investigarse en pacientes con hipertensión arterial resistente, con o sin hipopotasemia mantenida. La espironolactona fue eficaz para el tratamiento de la HBS y es un tratamiento alternativo adecuado para los APA cuando éstos no pueden intervenirse quirúrgicamente

BACKGROUND AND OBJECTIVE: The prevalence of primary aldosteronism (PA) has experienced an important increase, and many authors consider this condition as the main cause of secondary hypertension(HT).PATIENTS AND METHOD: Retrospective study of a series of 54 patients having PA who were studied in our Unit between 1999 and 2003.RESULTS: The prevalence of PA was 5.1%. Out of 54 PA cases, 13 corresponded to aldosterone producing adenomas (APA), 30 to bilateral adrenal hyperplasia (BAH), one was one case of nodular bilateral hyperplasia and another case was a nodular unilateral hyperplasia. In 9 cases, an etiologic diagnosis could not be done. APA were more frequent in women and BAH in men; with regard to sex, no significant differences were found. The blood pressure (BP) was significantly higher in patients with APA compared with BAH patients. In patients with APA, kalemiawas significantly lower than in BAH patients. Adrenal CT scan identified 90% of APA, whiles cintigraphy detected 100% of BAH. Spironolactone therapy significantly decreased the BP inAPA and BAH patients, although this fall was higher in patients with APA.CONCLUSIONS: The prevalence of PA was 5.1%. Although the tests used for the screening and diagnosis of PA are controversial, a PA ought to be investigated in all patients with refractoryHT, independently of the existence of hypokalemia. Spironolactone is an effective therapy for BAH and it is an adequate option for APA treatment when an adrenalectomy is not viable

[Immunological, virological and clinical response in patients infected with HIV after highly active antiviral therapy with nelfinavir: prospective cohort study]. / Respuesta inmunológica, virológica y clínica en pacientes infectados por el VIH tras terapia antirretroviral de gran eficacia con nelfinavir: estudio sobre una cohorte prospectiva.

INTRODUCTION: To assess the long-term effectiveness, safety and response-related factors in a cohort of HIV-infected persons receiving antiretroviral therapy containing nelfinavir. Design and setting. Prospective, non-randomized multicenter study. METHOD: A total of 792 patients were included: 254 (32.1%) treatment-naive patients and 538 (67.9%) patients previously treated with protease inhibitors who were switched to a nelfinavir-containing regimen due to virological failure or intolerance. Factors related to virological response and to treatment failure were assessed by standard survival techniques and Cox proportional risk models. RESULTS: Nelfinavir was well tolerated; treatment had to be interrupted in only 57 patients (7.1%) because of toxicity. During a median follow-up of 12 months, 31 patients (3.9%) experienced a new AIDS-defining event or death, and 463 (58.4%) showed immunological response. Overall, 52% patients achieved plasma HIV-1 RNA levels below 500 copies/mL (57% of naive and 49% of previously treated patients), but a high rate of virological rebound (24% and 49%, respectively) was observed. Low baseline viral load and few prior treatments were factors related to virological response. Naive treatment status and a high increase in CD4 cell count were predictive of longer viral response. CONCLUSIONS: Highly active antiretroviral therapy with a nelfinavir-containing regimen was associated with favorable virological response in nearly half of previously treated patients, and most experienced clinical and immunological benefits. Nevertheless, the limited duration of virological response indicates the need for new alternative drugs.

Respuesta inmunológica, virológica y clínica en pacientes infectados por el VIH tras terapia antirretroviral de gran eficacia con nelfinavir: estudio sobre una cohorte prospectiva / Immunological, virological and clinical response in patients infected with HIV after highly active antiviral therapy with nelfinavir: prospective cohort study

INTRODUCCIÓN. Evaluar la eficacia, tolerancia y factores asociados a la respuesta a largo plazo en una cohorte de pacientes infectados por el virus de la inmunodeficiencia humana (VIH) con un tratamiento que incluya nelfinavir. DISEÑO. Estudio prospectivo y multicéntrico, no aleatorizado. MÉTODO. Se incluyeron un total de 792 pacientes: 254 (32,1 por ciento) sin ningún tratamiento previo y 538 (67,9 por ciento) previamente tratados con inhibidores de la proteasa (IP) que cambiaron a un régimen con nelfinavir. El análisis se realizó mediante el método de curvas actuariales de Kaplan-Meier y modelos de riesgo proporcional de Cox. RESULTADOS. Nelfinavir fue bien tolerado y tan sólo 57 pacientes (7,1 por ciento) interrumpieron el tratamiento debido a efectos secundarios. Tras un año de seguimiento medio, 31 pacientes (3,9 por ciento) tuvieron un nuevo episodio definitorio de sida o muerte y se observó respuesta inmunológica en 463 (58,4 por ciento). Globalmente, el 52 por ciento de los pacientes alcanzó una carga viral indetectable (57 por ciento de vírgenes y 49 por ciento de pretratados), pero un alto porcentaje de ellos (24 y 49 por ciento, respectivamente) experimentó un rebrote tras una favorable respuesta inicial. Los factores relacionados con la respuesta virológica fueron una baja carga viral al inicio y un menor número de tratamientos previos. Los pacientes sin tratamiento previo y con una respuesta inmunológica mayor tuvieron una respuesta viral más duradera. CONCLUSIONES. El tratamiento antirretroviral con nelfinavir consigue una respuesta viral favorable en casi la mitad de los pacientes pretratados y la mayoría experimentan un beneficio clínico e inmunológico. Sin embargo, la limitada durabilidad de la respuesta virológica pone de manifiesto la necesidad de nuevos fármacos alternativos (AU)

Localized mucosal leishmaniasis due to Leishmania (Leishmania) infantum: clinical and microbiologic findings in 31 patients.

The clinical and microbiologic characteristics of 31 patients with mucosal leishmaniasis due to Leishmania (Leishmania) infantum are described. Twenty-eight (90%) patients were male. Mean age at presentation was 48 +/- 14 years. Thirteen (42%) patients had no underlying disease, while 18 (58%) patients had several other medical conditions. Fifteen (48%) patients were immunocompromised, 7 patients were infected with human immunodeficiency virus (HIV), and 3 were graft recipients. The primary location of lesions was the larynx in 11 (35%) patients, oral mucosa in 10 (32%) patients, and the nose in 5 (16%) patients. Mucosal lesions were painless in all patients but 2 and consisted of whitish, red, or violaceous nodular swelling or tumorlike masses. Ulceration was reported in 6 patients. Pathologically, the lesions showed a chronic inflammatory infiltrate. Granuloma may be seen. The localization of the lesions determined the symptomatology of the disease. Symptoms included hoarseness, difficulty swallowing, and nasal obstruction. The disease presentation was usually protracted, with a mean time from the onset of symptoms to diagnosis of 13 months (range, 3 wk-4.5 yr), and the clinical diagnosis was usually mistaken for neoplasia of the upper aerodigestive tract. No laboratory abnormalities were found in these patients due to the localized disease, apart from those attributed to underlying diseases. Parasites were easily identified in smears or sections by Giemsa stain or hematoxylin-eosin stain. Leishmania was grown in culture in 12 (60%) patients; culture was negative in 8 (40%) patients. Leishmania (Leishmania) infantum was identified in only 9 instances. The following zymodemes were reported: MON-1 (2 patients), MON-24 (2 patients), MON-27 (1 patient), and MON-34 (1 patient). Serologic test results were known in 25 patients. Serology was usually positive at low titer; 6 (24%) patients had negative serologic test results. Twenty patients were treated with antimonial compounds for between 3 and 36 days. Three patients were given drugs other than antimonial drugs. Five patients were treated only locally, by surgery (3 patients) or topical medical therapy. One patient received no therapy, and treatment was not reported in 2 cases. Patients were cured in 25 (89%) cases, and sequelae were uncommon (14%). Relapse was detected in 2 individuals and 1 patient developed visceral leishmaniasis after treatment. Two HIV-coinfected patients died of causes unrelated to leishmaniasis. The results of the present report stress the clinical importance of searching for the presence of Leishmania in patients with suspected neoplasia of the upper respiratory tract if they have visited or resided in zones endemic for Leishmania (Leishmania) infantum. The treatment of choice for these patients is not established yet, but most patients respond to antimonial compounds given for 28 days or less.