Neuropsychiatric and Laboratory Outcomes of Hepatitis C Treatment in an Early-Treated HIV Cohort in Thailand.

Background: Hepatitis C virus (HCV) coinfection may further compromise immunological and cognitive function in people with HIV (PWH). This study compared laboratory and neuropsychiatric measures across the periods of HCV seroconversion and direct-acting antiviral (DAA) therapy with sustained virologic response (SVR) among PWH who initiated antiretroviral therapy (ART) during acute HIV infection (AHI) and acquired HCV after 24 weeks of ART. Methods: Participants from the RV254 AHI cohort underwent paired laboratory and neuropsychiatric assessments during regular follow-up. The former included measurements of CD4 + and CD8 + T-cell counts, HIV RNA, liver enzymes, and lipid profiles. The latter included the Patient Health Questionnaire-9 (PHQ-9), Distress Thermometer (DT), and a 4-test cognitive battery that evaluated psychomotor speed, executive function, fine motor speed and dexterity. The raw scores in the battery were standardized and averaged to create an overall performance (NPZ-4) score. Parameters of HCV-coinfected participants were compared across HCV seroconversion and DAA treatment groups. Results: Between 2009 and 2022, 79 of 703 RV254 participants acquired HCV after ≥ 24 weeks of ART; 53 received DAA, and 50 (94%) achieved SVR. All participants were Thai males (median age: 30 years); 34 (68%) denied past intravenous drug use, and 41 (82%) had a history of other sexually transmitted infections during follow-up. Following SVR, aspartate transferase (AST) and alanine transaminase (ALT) decreased (p < 0.001), while total cholesterol, low-density lipoprotein, and triglycerides increased (p < 0.01). The median CD4+/CD8 + ratio increased from 0.91 to 0.97 (p = 0.012). NPZ-4 improved from 0.75 to 0.91 (p = 0.004). The median DT score increased from 1.7 to 2.7 (p = 0.045), but the PHQ-9 score remained unchanged. Conclusion: HCV coinfection is common in this group of high-risk PWH, highlighting the need for regular screening, early diagnosis, and treatment. There was a modest improvement in the CD4+/CD8 + T-cell ratio and cognitive performance after DAA therapy in patients who achieved SVR. Future studies should examine potential neuropsychiatric impacts during early HCV infection as well as the longer-term neuropsychiatric outcomes after DAA treatment with SVR.

Update on Central Nervous System Effects of the Intersection of HIV-1 and SARS-CoV-2.

PURPOSE OF REVIEW: Research has shown myriad neurologic and mental health manifestations during the acute and subsequent stages of COVID-19 in people with HIV (PWH). This review summarizes the updates on central nervous system (CNS) outcomes following SARS-CoV-2 infection in PWH and highlight the existing knowledge gaps in this area. RECENT FINDINGS: Studies leveraging electronic record systems have highlighted the excess risk of developing acute and lingering neurological complications of COVID-19 in PWH compared to people without HIV (PWoH). However, there is a notable scarcity of neuroimaging as well as blood and cerebrospinal fluid (CSF) marker studies that can confirm the potential synergy between these two infections, particularly in PWH receiving suppressive antiretroviral therapy. Considering the unclear potential interaction between SARS-CoV-2 and HIV, clinicians should remain vigilant regarding new-onset or worsening neurological symptoms in PWH following COVID-19, as they could be linked to either infection.

Current status and challenges in the care of patients with bacterial meningitis in the Philippines: A scoping review.

OBJECTIVE: Bacterial meningitis is associated with high morbidity and mortality if not treated early. Due to the high disease burden, there are barriers in the provision of healthcare services for these patients, especially in low- to middle-income countries, such as the Philippines. We aimed to give an overview of healthcare services delivery and identify gaps in the provision of care for patients with bacterial meningitis in the Philippines. METHOD: We conducted a scoping review on the available literature on the epidemiology, research, health services delivery, diagnostics and management of Filipino patients with bacterial meningitis. A qualitative summary of the results was conducted to provide an overview of the findings. RESULTS: There is a paucity of epidemiological data and research on bacterial meningitis. Healthcare expenditure remains out-of-pocket, with limited coverage from the national health insurance programme. There is an inadequate number of neurologists as well as inequities in the distribution of manpower and facilities due to the devolution of the healthcare system. Diagnosis remains a challenge due to the inaccessibility of tests for CSF analysis. Costs of antibiotics, adjunctive treatment, neurosurgical interventions and rehabilitation are also prohibitive. Outbreaks can be prevented by strengthening existing surveillance systems and improving vaccination coverage against the most common causative organisms. CONCLUSION: Enormous challenges still exist with regards to health services delivery in patients with bacterial meningitis in the Philippines in terms of epidemiologic data and research, access to healthcare facilities and diagnostic tools, healthcare costs, surveillance systems and immunisation against causative pathogens.

Treatment of stuporous catatonia with repetitive transcranial magnetic stimulation (rTMS) therapy in a Filipino adult patient: A case report.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive treatment option for psychiatric conditions, including catatonia. Our patient is a 30-year-old Filipino female admitted due to mutism, motor, and behavioral changes. Laboratory tests, cranial magnetic resonance imaging, electroencephalogram and cerebrospinal fluid analysis were unremarkable. The patient was diagnosed with stuporous catatonia and was given psychiatric medications, without significant improvement. The patient underwent 10 sessions of rTMS and showed marked improvement of symptoms. This highlights rTMS as a treatment option for catatonic patients that do not respond to pharmacotherapy or in situations where ECT is contraindicated or not available.

Diagnostic accuracy of the FilmArray™ Meningitis/Encephalitis panel in adult patients with suspected bacterial Meningitis in a tertiary care hospital in the Philippines

Objective@#Bacterial meningitis is associated with significant morbidity and mortality if not diagnosed and treated early. Isolation of the causative agent from cerebrospinal fluid culture is the gold standard for the diagnosis of this condition; however, it takes several days for results to be available. The FilmArray™ Meningitis/Encephalitis (ME) panel is a nucleic acid-based test that allows simultaneous detection of 14 bacterial, viral, and fungal pathogens in the cerebrospinal fluid with a rapid turnaround time. Our aim was to evaluate the diagnostic performance of the ME panel in detecting bacterial pathogens in the cerebrospinal fluid of adult patients with suspected bacterial meningitis in a tertiary hospital in the Philippines. @*Methods@#We performed a retrospective review of hospital records of adult patients with suspected bacterial meningitis who were admitted at our institution and underwent diagnostic testing with the FilmArray™ ME panel from January 1, 2018 to July 31, 2019. Overall percent agreement, sensitivity, and specificity for individual bacterial pathogens included in the panel were determined. @*Results@#A total of 88 cerebrospinal fluid samples were included in the analysis of diagnostic accuracy. The ME panel demonstrated 93.2% overall agreement, 50% sensitivity for E. coli, and 99–100% specificity in comparison with CSF culture in detecting bacterial pathogens that are included in the ME panel. @*Conclusion@#The results show that the FilmArray™ ME panel has high diagnostic accuracy and can be utilized in the rapid diagnosis and targeted treatment of patients with suspected bacterial meningitis.

Human Herpes Virus 6 Encephalitis Presenting as Fatal Refractory Status Epilepticus: a Case Report and Systematic Review.

PURPOSE: Encephalitis secondary to human herpesvirus 6 (HHV-6) infection is frequently encountered in immunocompromised patients; in contrast, HHV-6 encephalitis in immunocompetent patients is rare. There are only 3 reports of status epilepticus due to HHV-6 encephalitis in immunocompetent adults. In the present study, a case of refractory status epilepticus secondary to HHV-6 encephalitis was reported in an immunocompetent female. CASE REPORT: We report a case of a previously healthy 46-year-old female who presented with a one-week history of back pain, fever and generalized tonic-clonic seizures that progressed to status epilepticus. The video electroencephalography showed epileptiform discharges on both frontotemporal regions. Neuroimaging showed hyperintensities on the bilateral insula and temporal lobes. The cerebrospinal fluid showed elevated pressure and was positive for HHV-6. She was given ganciclovir and a total of eleven antiepileptic drugs. Despite these medications, she developed refractory status epilepticus and eventually succumbed due to multiple medical complications. CONCLUSION: This case highlights HHV-6 encephalitis as an important diagnostic consideration in patients presenting with refractory status epilepticus, regardless of immune status.

Favipiravir strikes the SARS-CoV-2 at its Achilles heel, the RNA polymerase.

The ongoing Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emphasized the urgent need for antiviral therapeutics. The viral RNA-dependent-RNA-polymerase (RdRp) is a promising target with polymerase inhibitors successfully used for the treatment of several viral diseases. Here we show that Favipiravir exerts an antiviral effect as a nucleotide analogue through a combination of chain termination, slowed RNA synthesis and lethal mutagenesis. The SARS-CoV RdRp complex is at least 10-fold more active than any other viral RdRp known. It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19.

Tratamiento endobronquial de neumotórax persistente en síndrome de dificultad respiratoria aguda / Endobronchial treatment of persistent pneumothorax in acute respiratory distress syndrome

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La monitorización convencional no es suficiente para valorar el esfuerzo respiratorio durante la ventilación asistida / Conventional monitoring is not sufficient to assess respiratory effort during assisted ventilation

Objetivo: Analizar la relación y concordancia entre el esfuerzo respiratorio calculado con las señales del respirador (Pmus) y el medido con presión esofágica (Pes), en ventilación mecánica con diferentes niveles de asistencia respiratoria. Diseño: Estudio prospectivo de una cohorte. Ámbito: Unidad de cuidados intensivos polivalente en 2 hospitales terciarios. Pacientes: Pacientes en fase de retirada de la ventilación mecánica. Intervenciones: La presión en la vía aérea, esofágica y flujo respiratorio se registraron en CPAP, ventilación asistida controlada por volumen (ACV) y presión soporte (PS) con asistencia respiratoria completa (ACV1, PS1) y parcial (ACV5, PS5). Variables medidas en Pes y Pmus: amplitud respiratoria (Δ: cmH2O) y el producto presión tiempo por minuto (PTPm: cmH2O·s/m). Resultados: En 10 pacientes se estudiaron 41 registros. La asistencia en CPAP fue de 5cmH2O, PS1 15±5 y PS59±4cmH2O. En ACV1 el flujo inspiratorio fue 1±0,2l/s, reducido a 0,49±0,1l/s para ACV5. El esfuerzo respiratorio disminuyó con el aumento de la asistencia respiratoria: ΔPes (CPAP, ACV5, ACV1, PS5, PS1): 11±3, 6±3, 5±3, 9±6, 7±7 y en ΔPmus 16±5, 10±6, 5±3, 10±6, 5±4cmH2O (p<0,001). PTPm Pes: 213±87, 96±91, 23±24, 206±121, 108±100 (p=0,001) y en Pmus: 293±117, 156±84, 24±32, 233±121, 79±90cmH2O·s/m (p<0,001). Las medidas en Pes y Pmus mostraron una correlación Δ:0,72 y PTPm: 0,87. El análisis de Bland-Altman demostró que la diferencia ΔPes-Pmus puede ser de 16cmH2O y el PTPm de 264 y el error sistemático en Δ: −0,98±4,4 y PTPm −23,69±66,3cmH2O·s/m. Conclusiones: Los parámetros calculados de esfuerzo respiratorio y los medidos directamente presentan diferencias que no son aceptables en la práctica clínica

Objective: Study the relationship and concordance between calculated respiratory effort using the signals of the ventilator (Pmus) and that measured in esophageal pressure (Pes) on mechanical ventilation with different levels of respiratory assistance. Design: Prospective cohort study. Ambit: Intensive Care Unit of 2 universitary hospitals. Patients Patients on weaning time. Procedure: Airway, esophageal and respiratory flow were recorded on CPAP, assist volume control (ACV) and pressure support (PS), with complete (ACV1,PS1) and partial assistance (ACV5,PS5). Measurement: respiratory variations of Pes and Pmus (Δ: cmH2O) and pressure time product (PTPm: cmH2O·s/m). Results: Fourty one records were studied, the assistance was in CPAP of 5cmH2O, PS1 of 15±5 reduced to 9±4cmH2O. In ACV1 the inspiratory flow was 1±0.2l/s, reduced to 0.49±0.1l/s for ACV5. The increase in respiratory assistance decreases respiratory effort, measured in Delta Pes (CPAP, ACV5, ACV1, PS5, PS1): 11±3, 6±3, 5±3, 9±6, 7±7 and in Pmus 16±5, 10±6, 5±3, 10±6, 5±4cmH2O (P<.001). The PTP per minute measured in Pes: 213±87, 96±91, 23±24, 206±121, 108±100 (P=.001) and in Pmus: 293±117, 156±84, 24±32, 233±121, 79±90 (P<.001). The measurements in Pes and Pmus showed the following correlation, in Delta: 0.72 and PTPm, 0.87. The Bland-Altman analysis indicates that the difference between Delta Pes-Pmus can be 16 and the PTPm of 264 and the systematic error in Delta: −0.98±4.4 and PTPm −23.69±66.3cmH2O·s/m. Conclusions: Calculated and measured parameters of respiratory effort showed unacceptable differences in clinical practice

Conventional monitoring is not sufficient to assess respiratory effort during assisted ventilation. / La monitorización convencional no es suficiente para valorar el esfuerzo respiratorio durante la ventilación asistida.

OBJECTIVE: Study the relationship and concordance between calculated respiratory effort using the signals of the ventilator (Pmus) and that measured in esophageal pressure (Pes) on mechanical ventilation with different levels of respiratory assistance. DESIGN: Prospective cohort study. AMBIT: Intensive Care Unit of 2 universitary hospitals. Patients Patients on weaning time. PROCEDURE: Airway, esophageal and respiratory flow were recorded on CPAP, assist volume control (ACV) and pressure support (PS), with complete (ACV1,PS1) and partial assistance (ACV5,PS5). MEASUREMENT: respiratory variations of Pes and Pmus (Δ: cmH2O) and pressure time product (PTPm: cmH2O·s/m). RESULTS: Fourty one records were studied, the assistance was in CPAP of 5cmH2O, PS1 of 15±5 reduced to 9±4cmH2O. In ACV1 the inspiratory flow was 1±0.2l/s, reduced to 0.49±0.1l/s for ACV5. The increase in respiratory assistance decreases respiratory effort, measured in Delta Pes (CPAP, ACV5, ACV1, PS5, PS1): 11±3, 6±3, 5±3, 9±6, 7±7 and in Pmus 16±5, 10±6, 5±3, 10±6, 5±4cmH2O (P<.001). The PTP per minute measured in Pes: 213±87, 96±91, 23±24, 206±121, 108±100 (P=.001) and in Pmus: 293±117, 156±84, 24±32, 233±121, 79±90 (P<.001). The measurements in Pes and Pmus showed the following correlation, in Delta: 0.72 and PTPm, 0.87. The Bland-Altman analysis indicates that the difference between Delta Pes-Pmus can be 16 and the PTPm of 264 and the systematic error in Delta: -0.98±4.4 and PTPm -23.69±66.3cmH2O·s/m. CONCLUSIONS: Calculated and measured parameters of respiratory effort showed unacceptable differences in clinical practice.

Identificación del trigger inverso en UCI / Trigger reverse identification in critical care setting

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Presión intraabdominal y torácica en pacientes críticos con sospecha de hipertensión intraabdominal / Intraabdominal and thoracic pressure in critically ill patients with suspected

ObjetivoAnalizar la correlación entre la presión intraabdominal e intratorácica en pacientes con sospecha de hipertensión intraabdominal (HIA).DiseñoEstudio prospectivo observacional de una cohorte.ÁmbitoUnidad de medicina intensiva polivalente de un hospital universitario.PacientesSe incluyó a 27 pacientes medicoquirúrgicos dependientes de ventilación mecánica controlada por fallo respiratorio agudo y con factores de riesgo de hipertensión intraabdominal.Principales variablesMedimos las presiones intraabdominal (PIA), esofágica (Peso) y de la vía aérea en condiciones estáticas (est) y dinámicas (din). Calculamos la distensibilidad del sistema respiratorio (Csr), pulmón (Cp) y pared torácica (Cpt).ResultadosEn 10 pacientes la PIAest fue mayor de 12mmHg (HIA, PIAest, 14±2 [12-21] mmHg) y en el resto fue normal (n=17; PIAest, 8±2 [3-11] mmHg). La Pesoest fue 11±5 (2-27) y Pesodin, 7±4 (2-24) cmH2O. Considerando la presencia o no de HIA, Pesoest fue 9±4 vs. 7±3cmH2O (p=0,2) y Pesodin, 6±2 vs. 4±3cmH2O (p=0,3), respectivamente. La correlación de Pesoest y din con PIAest fue 0,5 (p=0,003) y 0,4 (p=0,03), respectivamente. Los componentes de la distensibilidad del sistema respiratorio estaban disminuidos (Csr, 31±8; Cp, 52±22; Cpt, 105±50ml/cmH2O), Cpt fue significativamente más baja en los pacientes con HIA (81±31 vs. 118±55ml/cmH2O; p=0,02). El coeficiente de correlación entre la PIAest y Cpt fue –0,7 (p<0,001) y de –0,5 (p=0,002) con Csr.ConclusionesLa pared torácica es más rígida en pacientes con hipertensión abdominal. En presencia de factores de riesgo de HIA las presiones en estos compartimentos son muy variables (AU)

Objective: To study the correlation between intraabdominal and intrathoracic pressure inpatients with suspected intraabdominal hypertension.Design: A prospective, observational cohort study.Setting: Polyvalent intensive care unit of a University hospital.Patients: Twenty-seven medical-surgical patient dependent upon controlled mechanical ventilationdue to acute respiratory failure and with several risk factors for intraabdominalhypertension (IAH).Main variables: Intraabdominal (IAP), esophageal (Peso) and airways pressure were measuredunder static (st) and dynamic (dyn) conditions. Respiratory system (Crs), lung (Cl) and chestwall compliance (Ccw)were calculated.Results: In 10 patients IAP > 12mmHg (IAH, IAPst, 14±2 [12-21] mmHg), while in the rest thepressure proved normal (n = 17; IAPst, 8±2 [3-11] mmHg). Peso st was 11±5 (2-27) and Pesodyn 7±4 (2-24) cmH2O. Depending on the presence or absence of IAH, Peso st was 9±4 vs7±3 cmH2O (p = 0.2) and Peso dyn 6±2 vs 4±3 cmH2O (p = 0.3), respectively. The correlationbetween Peso st and dyn with IAPst was 0.5 (p = 0.003) and 0.4 (p = 0.03), respectively. Thecompliance components were decreased (Crs, 31±8; Cl, 52±22 and Ccw, 105±50 ml/cmH2O);Ccw was significantly lower in patients with IAH (81±31 vs 118±55 ml/cmH2O; p = 0.02). Thecorrelation coefficient between IAPst and Ccw was —0.7 (p < 0.001), and —0.5 (p = 0.002) withrespect to Crs.Conclusions: A stiffer chest wall was observed in patients with IAH. In patients with risk factorsfor IAH, pressures in these compartments were highly variable (AU)

[Intraabdominal and thoracic pressure in critically ill patients with suspected intraabdominal hypertension]. / Presión intraabdominal y torácica en pacientes críticos con sospecha de hipertensión intraabdominal.

OBJECTIVE: To study the correlation between intraabdominal and intrathoracic pressure in patients with suspected intraabdominal hypertension. DESIGN: A prospective, observational cohort study. SETTING: Polyvalent intensive care unit of a University hospital. PATIENTS: Twenty-seven medical-surgical patient dependent upon controlled mechanical ventilation due to acute respiratory failure and with several risk factors for intraabdominal hypertension (IAH). MAIN VARIABLES: Intraabdominal (IAP), esophageal (Peso) and airways pressure were measured under static (st) and dynamic (dyn) conditions. Respiratory system (Crs), lung (Cl) and chest wall compliance (Ccw)were calculated. RESULTS: In 10 patients IAP > 12 mmHg (IAH, IAPst, 14 ± 2 [12-21] mmHg), while in the rest the pressure proved normal (n = 17; IAPst, 8 ± 2 [3-11] mmHg). Peso st was 11 ± 5 (2-27) and Peso dyn 7 ± 4 (2-24) cmH2O. Depending on the presence or absence of IAH, Peso st was 9 ± 4 vs 7 ± 3 cmH2O (p = 0.2) and Peso dyn 6 ± 2 vs 4 ± 3 cmH2O (p = 0.3), respectively. The correlation between Peso st and dyn with IAPst was 0.5 (p= 0.003) and 0.4 (p = 0.03), respectively. The compliance components were decreased (Crs, 31 ± 8; Cl, 52 ± 22 and Ccw, 105 ± 50 ml/cmH2O); Ccw was significantly lower in patients with IAH (81 ± 31 vs 118 ± 55 ml/cmH2O; p = 0.02). The correlation coefficient between IAPst and Ccw was -0.7 (p < 0.001), and -0.5 (p = 0.002) with respect to Crs. CONCLUSIONS: A stiffer chest wall was observed in patients with IAH. In patients with risk factors for IAH, pressures in these compartments were highly variable.

Optimización de la dosis de meropenem en infecciones graves. Resultados de un estudio multicéntrico observacional / Obtain best usage of meropenem dose in severe infections. Results of an observational multicenter study

Objetivo. Describir la efectividad y tolerabilidad delajuste de dosis de meropenem en el tratamiento empíricode infecciones nosocomiales en pacientes críticos ingresadosen Servicios de Medicina Intensiva (SMI).Método. Estudio prospectivo, observacional y multicéntricode pacientes ingresados en 17 SMI con infecciones nosocomialesy tratamiento inicial con meropenem a dosis de1 g cada 8 h. Se ajustó la dosis inicial a 0,5 g cada 8 h cuandocumplían las siguientes condiciones: a) evolución clínicafavorable y b) un aislamiento microbiológico sensible a meropenemo ausencia de microorganismos en los cultivos realizados.Resultados. Se incluyeron 92 pacientes en los que seajustó la dosis de meropenem a 0,5 g cada 8 h. La infeccióntratada más frecuentemente fue la neumonía relacionadacon ventilación mecánica, seguido de las bacteriemias. Losestudios microbiológicos fueron positivos en 53 pacientesen los que predominaron bacterias grampositivas (53,7 %),en especial Staphylococcus aureus sensible a la meticilina,seguido de bacterias gramnegativas (42,7%).En 18 casos los pacientes no fueron evaluables al finaldel tratamiento. De los 74 casos evaluables, 67 (90,5%) presentaronuna evolución favorable (curación: 54 pacientes;mejoría: 13). En 50 de los 53 casos evaluables por Microbiologíase logró la erradicación o supuesta erradicación de losmicroorganismos iniciales y en 3 persistió el patógeno inicial:Acinetobacter baumannii (2 casos) y Pseudomonasaeruginosa (1 caso). Se detectó la aparición de nuevos microorganismosdurante el tratamiento en tres ocasiones: A. baumannii(2 casos) y 1 de S. aureus resistente a la meticilina.Aparecieron efectos adversos en 3 pacientes (4%), ninguno valorado como grave, que no precisaron la retirada del tratamiento.Fallecieron 25 (27,2%) pacientes, 3 de ellos en relacióncon la infección (AU)

Objective. To describe the effectiveness and tolerabilityof the dose adjustment of meropenem in empiricaltreatment of nosocomial infections in critically-ill patientsadmitted to intensive care medicine services.Methods. Prospective, observational and multicenterstudy in patients admitted to 17 intensive care medicineservices with nosocomial infection, who were initiallytreated with meropenem, 1 g every 8 h, were eligible.The initial dose was adjusted to 0.5 g every 8 h if therewere: a) a favorable clinical course, and b) microbiologicalisolation of meropenem-susceptible pathogens or absenceof pathogens in cultures.Results. Ninety-two patients in whom meropenemdoses were adjusted to 0.5 g every 8 h were included.Ventilator-associated pneumonia followed by bacteremiawas the most frequently treated infections. Microbiologicalstudies were positive in 53 patients, with apredominance of gram-positive bacteria (53.7%), especiallymethicillin-susceptible Staphylococcus aureus,followed by gram-negative bacteria (42.7 %). A total of18 patients were not evaluable at the end of treatmentSixty-seven (90.5 %) of the 74 evaluable patients had afavorable clinical course (54 patients cured and 13 improved).In 50 out of 53 microbiologically evaluable cases,eradication or apparent eradication of initial microorganismswas achieved. In 3 cases, the initial pathogenpersisted: Acinetobacter baumannii (2 cases) and Pseudomonasaeruginosa (1 case). On three occasions, new pathogensdeveloped during treatment: A. baumannii (2cases) and methicillin-resistant S. aureus (1 case). Adverseevents occurred in 3 patients (4%), none of whichwas considered severe, and withdrawal of meropenemwas not necessary. A total of 25 (27.2 %) patients died,three of them in relation to the infectious process(AU)

SPINE bioinformatics and data-management aspects of high-throughput structural biology.

SPINE (Structural Proteomics In Europe) was established in 2002 as an integrated research project to develop new methods and technologies for high-throughput structural biology. Development areas were broken down into workpackages and this article gives an overview of ongoing activity in the bioinformatics workpackage. Developments cover target selection, target registration, wet and dry laboratory data management and structure annotation as they pertain to high-throughput studies. Some individual projects and developments are discussed in detail, while those that are covered elsewhere in this issue are treated more briefly. In particular, this overview focuses on the infrastructure of the software that allows the experimentalist to move projects through different areas that are crucial to high-throughput studies, leading to the collation of large data sets which are managed and eventually archived and/or deposited.

Cambios en la auto-PEEP durante la ventilación mecánica relacionados con la frecuencia respiratoria según el análisis de la constante de tiempo / Changes in auto-peep during mechanical ventilation associated with respiratory steady according to time-constant analysis

Objetivo. El análisis de la constante de tiempo espiratorio (tau) indica el tiempo necesario para que el sistema respiratorio alcance un estado estable. Estudiamos, durante la ventilación mecánica controlada, si el ajuste de la frecuencia respiratoria, según el valor de tau, puede reducir o eliminar la auto-PEEP (presión positiva telespiratoria). Diseño. Estudio clínico prospectivo de una cohorte de pacientes en ventilación mecánica. Ámbito. Unidad de medicina intensiva de un hospital universitario. Pacientes y método. Estudiamos a 17 pacientes con lesión pulmonar aguda (n = 10) o con insuficiencia respiratoria crónica agudizada (n = 7). En ventilación mecánica controlada, medimos la mecánica respiratoria, la auto-PEEP estática y el valor de tau en la fase espiratoria de la curva de volumen (V[t] = V0 e -[t/RC] + b). Conociendo el valor de tau, cambiamos la frecuencia respiratoria manteniendo el volumen por minuto constante (TE = tau × 4, I:E = 0,5) y analizamos el cambio en la auto-PEEP y mecánica respiratoria. Resultados. El valor de la constante b fue 0,02 (0,04) l y se correlacionó con el valor de tau (r = 0,8). En los pacientes con insuficiencia respiratoria crónica agudizada, el valor de tau fue de 1,04 (0,44) s, y la frecuencia respiratoria fue disminuida de 13,49 (2,87) a 11,72 (3,07) respiraciones/min (p = 0,06), sin un descenso significativo en la auto-PEEP (5,29 [5,11] a 4,87 [5,21] cmH2O). En los pacientes con lesión pulmonar aguda, tau fue de 0,53 (0,16) s y la frecuencia respiratoria fue aumentada desde 15,22 (2,74) a 20,62 (7,26) respiraciones/min (p = 0,05), sin modificar significativamente la auto-PEEP (2,80 [2,03] a 2,40 [1,67] cmH2O). Conclusiones. El análisis de la constante de tiempo no permitió disminuir la auto-PEEP en los pacientes con insuficiencia respiratoria crónica agudizada (FRCA). En el grupo con lesión pulmonar aguda fue posible utilizar frecuencias respiratorias elevadas sin aumentar la auto-PEEP (AU)

Results of respiratory mechanics analysis in the critically ill depend on the method employed.

OBJECTIVE: To compare the measurements of total resistance and dynamic elastance determined by different techniques of respiratory mechanics analysis based on the time or frequency domains. DESIGN: Prospective study. SETTING: A 12-bed medical and surgical intensive care unit in a 700-bed university hospital. PATIENTS: Eighteen sedoparalyzed patients who needed controlled mechanical ventilation for acute or chronic acute respiratory failure. MEASUREMENTS: The total resistance and dynamic elastance in the time domain were determined by the occlusion technique and by multiple linear regression. The Fourier analysis was used to study the impedance of the respiratory system for elastance and resistance values in the frequency domain. RESULTS: The ANOVA analysis of the elastance variable showed no statistical differences (Ef: 41.4+/-19.0 cmH(2)O/l, Emlr: 40.8+/-17.2 cmH(2)O/l Edyn,occ: 39.5+/-14.0 cmH(2)O/l; ns) and the correlation was very good (r=0.8-0.9). The total resistances were less with multiple linear regression (13.5+/-9.3 cmH(2)O/l per s, p<0.05) than Rmax (17.0+/-11.9 cmH(2)O/l per s) or Rf (17.6+/-10.2 cmH(2)O/l per s). There were no differences between Rmax and Rf (p=0.7) and the correlation between resistances was 0.7-0.9. The agreement analysis for variables without statistical differences showed the following limits: Edyn,occ-f: -17 to 13 cmH(2)O/l; Edyn,occ-mlr: -12 to 9 cmH(2)O/l; Emlr-f: -6 to 8 cmH(2)O/l; Rmax-f: -18 to 19 cmH(2)O/l per s. This last range was related to the autoPEEP level (r=0.9). CONCLUSION: The wide agreement limits show that respiratory mechanics analysis is very dependent on the measurement technique used, particularly for resistance, perhaps due to the higher dependence on frequency.

Histochemical method for characterization of enzyme crystals: application to crystals of Torpedo californica acetylcholinesterase.

Histochemical methods are employed to detect and localize a wide range of enzymes. Even though protein crystallographers do not commonly use this technique, the extensively used colorimetric reaction of Karnovsky was successfully adapted for easy and quick identification of acetylcholinesterase crystals. The method relies on the reduction of ferricyanide to ferrocyanide by thiocholine, released from acetylthiocholine by enzymatic hydrolysis, followed by formation of a cupric ferrocyanide precipitate, and allows rapid differentiation between salt and enzyme crystals and between native and inhibited crystals of the enzyme.