Relationship between cognition and age at onset of first-episode psychosis: comparative study between adolescents, young adults, and adults.

Psychotic disorders typically manifest from late adolescence to early adulthood, and an earlier onset might be associated with greater symptom severity and a worse long-term prognosis. This study aimed to compare the cognitive characteristics of patients with first-episode psychosis (FEP) by their age at onset. We included 298 patients diagnosed with FEP and classified them as having an early onset (EOS), youth onset (YOS), or adult onset (AOS) based on age limits of ≤ 18 years (N = 61), 19-24 years (N = 121), and ≥ 25 years (N = 116), respectively. Socio-demographic and clinical variables included age at baseline, gender, socio-economic status, antipsychotic medication, DSM-IV diagnoses assessed by clinical semi-structured interview, psychotic symptom severity, and age at onset. Neuropsychological assessment included six cognitive domains: premorbid intelligence, working memory, processing speed, verbal memory, sustained attention, and executive functioning. The EOS group had lower scores than the YOS or AOS groups in global cognition, executive functioning, and sustained attention. Although the scores in the YOS group were intermediate to those in the EOS and AOS groups for most cognitive factors, no statistically significant differences were detected between the YOS and AOS groups. Age at onset results in specific patterns of cognitive interference. Of note, impairment appears to be greater with EOS samples than with either YOS or AOS samples. A longitudinal study with a larger sample size is needed to confirm our findings.

Experiencia en cirugía de urgencia de Divertículo de Meckel en adultos / Experience in emergency surgery of Meckel's Diverticulum in adults

Objetivo: Describir la experiencia en cirugía de urgencia de divertículo de Meckel en pacientes mayores de 15 años en un hospital terciario de la Región Metropolitana. Materiales y Método: Estudio observacional retrospectivo y descriptivo, en el cual se analizan las intervenciones quirúrgicas de urgencia realizadas entre marzo de 2010 y marzo de 2021. Mediante búsqueda de registros de pabellón y ficha electrónica. Resultados: Dentro del período analizado se obtuvo 14 pacientes con diagnóstico posoperatorio y/o hallazgo de divertículo de Meckel. En un 78% se resecó el divertículo de Meckel, 100% de los divertículos resecados corresponden a casos complicados. Desde el año 2018, un 75% del abordaje fue mínimamente invasivo, con un 14% de conversión a cirugía abierta. El tipo de resección del divertículo fue un 77% en su base a través de sección con stappler o sutura manual, La ubicación media del divertículo de Meckel fue 77 cm. Un 14% de los pacientes requirieron reoperación por filtración anastomótica. No hubo mortalidad. Discusión: A diferencia de algunas series, en nuestro estudio existe una mayor proporción de abordaje mínimamente invasivo y mayor cantidad de resección en base del divertículo con resultados aceptables. Conclusión: El presente estudio, presenta una población de 14 pacientes con hallazgo de divertículo de Meckel complicado, a partir de los hallazgos de la cirugía en contexto de urgencias; se cumple el objetivo del estudio de caracterizar en un período de 11 años los resultados quirúrgicos de dicha serie, algo no reportado previamente en la literatura chilena.

Aim: To describe the experience in emergency surgery for Meckel's diverticulum in patients over 15 years of age in a tertiary hospital in the Metropolitan Region. Materials and Method: Retrospective and descriptive observational study, in emergency surgical interventions performed between March 2010 to March 2021 are analyzed. By searching the ward records and electronic file. Results: Within the analyzed period, 14 patients were obtained with a postoperative diagnosis and / or finding of Meckel's diverticulum. Meckel's diverticulum was resected in 78%, 100% of resected diverticula correspond to complicated cases. Since 2018, 75% of the approach was minimally invasive, with 14% conversion to open surgery. The type of resection of the diverticulum was 77% at its base through section with stappler or manual suture. The mean location of Meckel's diverticulum was 77 cm. 14% of the patients required reoperation due to anastomotic leakage. There was no reported mortality. Discussion: Unlike some series, in our study there is a higher proportion of minimally invasive approach and a greater amount of resection based on the diverticulum with acceptable results. Conclusion: These study presents a population of 14 patients with a finding of complicated Meckel's diverticulum, based on the findings of surgery in an emergency setting. the objective of the study is fulfilled to characterize in a period of 11 years the surgical results of this series, something not previously reported in the chilean literature.

Lifetime psychopathology in child and adolescent offspring of parents diagnosed with schizophrenia or bipolar disorder: a 2-year follow-up study.

Having one parent diagnosed with a severe mental disorder is considered one of the main risk factors for developing that disorder in adulthood, and it also increases the risk of a wide range of mental disorders in the offspring. The aim of this study is to compare the prevalence of several psychopathological diagnoses, the presence of prodromal symptoms, and global functioning in offspring of parents with schizophrenia or bipolar disorder and in offspring of controls at baseline and 2-year follow-up. This study included 41 offspring of parents with schizophrenia, 90 offspring of parents with bipolar disorder, and 107 offspring of controls (mean age 11.7 ± 3.2 at baseline and 13.9 ± 3.2 at follow-up). The prevalence of psychopathology and comorbidity was higher in offspring of parents with schizophrenia and offspring of parents with bipolar disorder than in offspring of controls at baseline and at 2-year follow-up. Interestingly, mood disorders were more prevalent in offspring of parents with bipolar disorder and disruptive disorders were more prevalent in offspring of parents with schizophrenia. Prodromal symptoms were more frequent in offspring of parents with schizophrenia than in offspring of controls, while the offspring of parents with bipolar disorder showed an intermediate pattern. Finally, global functioning was lower in the offspring of parents with schizophrenia than the offspring of parents with bipolar disorder and the offspring of controls. Screening patients' children is clinically relevant, since, as a group, they have an elevated risk of developing a psychiatric disorder and of experiencing their first symptoms during childhood and adolescence.

The usefulness of Olanzapine plasma concentrations in monitoring treatment efficacy and metabolic disturbances in first-episode psychosis.

INTRODUCTION: The role of Olanzapine therapeutic drug monitoring is controversial. The present study explores the associations of Olanzapine plasma concentrations with clinical response and metabolic side effects in first episode psychosis (FEP) after 2 months of treatment. METHODS: Forty-seven patients were included. Improvement in clinical symptomatology was assessed using the PANSS. Metabolic assessment included weight, blood pressure, waist circumference, blood glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. RESULTS: The Olanzapine plasma concentrations after 2 months of treatment were positively correlated with weight gain (r = 0.49, p = 0.003), and a concentration > 23.28 ng/mL was identified as a positive predictor of weight gain (≥ 7%). The Olanzapine concentration to dose (C/D) ratio was positively correlated with the percentage of improvement in the total PANSS (r = 0.46, p = 0.004), and a C/D ratio > 2.12 was identified as a positive predictor of a good response (percentage of improvement > 30%) after 2 months of treatment. We also identified several factors that could alter Olanzapine pharmacokinetics: gender (p = 0.03), diagnosis (p = 0.05), smoking habit (p = 0.05), and co-medications such as valproic acid (p = 0.05) and anxiolytics (p = 0.01). DISCUSSION: In conclusion, our results suggest that therapeutic drug monitoring of Olanzapine could be helpful to evaluate therapeutic efficacy and metabolic dysfunction in FEP patients treated with Olanzapine.

Neuropsychological development in the child and adolescent offspring of patients diagnosed with schizophrenia or bipolar disorder: A two-year follow-up comparative study.

There has been growing scientific evidence in recent years that schizophrenia and bipolar disorder share clinical, cognitive, neuroimaging and genetic characteristics. This overlap might also be present in their offspring, who have an increased risk of developing both disorders. Comparing the characteristics of these samples may have important implications for understanding etiological processes. This study aimed to assess the development of cognitive functions over two years in a sample of child and adolescent offspring of patients diagnosed with schizophrenia (SZoff) or bipolar disorder (BDoff), comparing them with a community control group (CCoff). METHODS: 90 BDoff, 41 SZoff and 107 CCoff aged between 6 and 17 years were included at baseline. At the two-year follow-up, 84.9% of the sample was re-assessed (78 BDoff, 32 SZoff and 92 CCoff). All subjects were assessed with a comprehensive neuropsychological test battery at baseline and at the two-year follow-up to evaluate: intelligence quotient, working memory, processing speed, verbal memory and learning, visual memory, executive functions and sustained attention. RESULTS: Processing speed, verbal memory and executive functions showed different developmental patterns among the SZoff, BDoff and CCoff groups. The SZoff group maintained baseline performances in the three variables over time, while the BDoff group presented improved processing speed and executive functioning and the CCoff group showed improvements in verbal memory and executive functions at follow-up. CONCLUSIONS: These findings suggest that the development of some cognitive functions might differ between child and adolescent SZoff and BDoff, indicating different trajectories during neurodevelopment.

Influence of social cognition as a mediator between cognitive reserve and psychosocial functioning in patients with first episode psychosis.

BACKGROUND: Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Therefore, the main aim of this study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years. METHODS: The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis. RESULTS: At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (-10.215 to -0.337) and (-4.731 to -0.605) respectively). CONCLUSIONS: Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.

Active tuberculosis patients have high levels of IgA anti-alpha-crystallin and isocitrate lyase proteins.

SETTING: Mexico City, Mexico. OBJECTIVE: To identify proteins synthetised by Mycobacterium tuberculosis in hypoxic culture, which resemble more closely a granuloma environment than aerobic culture, and to determine if they are recognised by antibodies from patients with active pulmonary tuberculosis (PTB). DESIGN: Soluble extracts from M. tuberculosis H37Rv cultured under aerobic or hypoxic conditions were analysed using two-dimensional polyacrylamide gel electrophoresis, and proteins over-expressed under hypoxia were identified by mass spectrometry. The presence of immunoglobulin (Ig) G, IgA and IgM antibodies against these proteins was determined in the serum of 42 patients with active PTB and 42 healthy controls. RESULTS: We selected three M. tuberculosis H37Rv proteins (alpha-crystallin protein [Acr, Rv2031c], universal stress protein Rv2623 and isocitrate lyase [ICL, RV0467]) that were over-expressed under hypoxia. Titres of anti-Acr and anti-ICL IgA antibodies were higher in patients than in healthy controls, with an area under the receiver operating characteristic curve of 0.71 for anti-ICL IgA antibodies. CONCLUSION: ICL could be used in combination with other M. tuberculosis antigens to improve the sensitivity and specificity of current serological TB diagnostic methods.

[Severe complications of orotracheal intubation in the Intensive Care Unit: An observational study and analysis of risk factors]. / Complicaciones graves en la intubación orotraqueal en cuidados intensivos: estudio observacional y análisis de factores de riesgo.

OBJECTIVE: A study is made to determine the characteristics of endotracheal intubation (ETI) procedures performed in an Intensive Care Unit, and to describe the associated severe complications and related risk factors. DESIGN: A prospective cohort study involving a 2-year period was carried out. SETTING: The combined clinical/surgical Intensive Care Unit in a secondary university hospital. PATIENTS: All ETIs carried out by intensivists were included. INTERVENTIONS: None. MAIN VARIABLES: We analyzed the data associated with the patient, the procedure and the postoperative complications after intubation. The study of risk factors was performed using multiple logistic regression analysis. RESULTS: Seventy-six percent of the ETIs were performed immediately. Most of them were carried out by Intensive Care Units residents (60%). A total of 34% of the procedures had severe complications, including respiratory (16%) or hemodynamic (5%) disorders, or both (10%). Three patients died (1%), and 2% of the subjects experienced cardiac arrest. Logistic regression analysis identified the following independent risk factors for complications: age (OR 1.1; 95% CI: 1.1-1.2), systolic blood pressure≤90mmHg (OR 3.0; 95% CI: 1.4-6.4) and SpO2≤90% (OR 4.4; 95% CI: 2.3-8.1) prior to intubation, the presence of secretions (OR 2.2; 95% CI: 1.1-4.6), and the need for more than one ETI attempt (OR 3.5; 95% CI: 1.4-8.7). CONCLUSIONS: ETI in Intensive Care Unit patients is associated with respiratory and hemodynamic complications. The independent risk factors associated with the development of complications were advanced age, hypotension and previous hypoxemia, the presence of secretions, and the need for more than one ETI attempt.

Low-dose amphotericin B and murine dialyzable spleen extracts protect against systemic candida infection in mice.

Candida albicans causes opportunistic systemic infections with high mortality (30%-50%). Despite significant nephrotoxicity, amphotericin (AmB) is still used for the treatment of this serious fungal infection. Therefore, alternative treatments are urgently needed. Dialyzable leukocyte extracts have been used successfully to treat patients with mucocutaneous candidiasis, but their effectiveness in systemic candidiasis has not been evaluated. In this study, low-dose AmB (0.1 mg/kg) plus 10 pg of murine dialyzable spleen extracts (mDSE) were tested in a systemic candidiasis mouse model. Survival, tissue fungal burden, kidney damage, kidney cytokines, and serum levels of IL-6 and hepcidin were evaluated. Our results showed that the combined treatment of low-dose AmB plus mDSE improved survival and reduced kidney fungal burden and histopathology; these effects correlated with increased kidney concentration of IFN- γ and TGF- ß 1, decreased levels of TNF- α , IL-6, and IL-10, as well as high levels of systemic IL-6 and hepcidin. Low-dose AmB and mDSE synergized to clear the infectious agent and reduced tissue damage, confirming the efficacy of a low dose of AmB, which might decrease the risk of drug toxicity. Further studies are necessary to explore these findings and its implications in future therapeutic approaches.

Assessment of real-world daily-living skills in early-onset schizophrenia trough the Life Skills Profile scale.

BACKGROUND: Adolescents with early-onset schizophrenia (EOS) have marked deficits in their functional outcome. However, few short and reliable instruments for assessing real-world functioning have been specifically validated in EOS. The Life Skills Profile (LSP) is a brief scale widely used in schizophrenia and considered one of the optimal instruments for assessing real-world daily living skills. The purpose of this study was to examine the usefulness and the feasibility of the LSP to assess daily living skills in EOS. METHODS: The sample included 53 clinically and pharmacologically stabilized adolescent patients with EOS and 53 healthy adolescents. Content review of the scale and internal consistency analysis were conducted in the EOS group. A subgroup of 30 patients was re-assessed over a 10-day interval to establish the test-retest reliability. Measures of functional outcome were used to assess convergent validity, and measures of intelligence and symptoms were used to assess divergent validity. Discriminant validity was analyzed through logistic analysis and the receiver-operating characteristic curve. RESULTS: The LSP and its subscales showed high reliability, adequate internal consistency and adequate convergent and divergent validity. The LSP was also found to be a sensitive instrument for detecting differences between patients and healthy adolescents, correctly classifying 84% of the sample. The estimated area under the curve was 0.925 (95% CI 0.875-0.976). CONCLUSIONS: The LSP showed adequate psychometric characteristics in adolescents with EOS and appeared to be a valid, reliable and time-efficient instrument for use in clinical practice and research settings to assess real-world daily-living skills in EOS.

Neuropsychological evidence for abnormal neurodevelopment associated with early-onset psychoses.

BACKGROUND: The longitudinal neuropsychological study of first-episode early-onset psychosis (EOP) patients, whose brain maturation is still in progress at the time of illness onset, provides a unique opportunity to compare their cognitive development with that of healthy subjects, in search of specific patterns resulting from the interaction between neurodevelopmental processes and the presence of psychotic disorders. Method Seventy-five first-episode EOP patients (schizophrenia n = 35; bipolar disorder n = 17; other forms of psychosis n = 23) with a mean age of 15.53 years were assessed with a neuropsychological battery that included measures of attention, working memory, memory and executive functions within 6 months following the onset of the first psychotic symptom (baseline) and 2 years later. Psychotic symptoms were assessed at both times with the Positive and Negative Symptom Scale (PANSS). Seventy-nine healthy subjects matched for age and education served as controls. RESULTS: EOP patients showed significant cognitive impairment at both baseline and the 2-year follow-up, with no significant differences between diagnostic groups at either time. Both healthy controls and EOP patients improved in all cognitive measures, except for patient working memory. Improvement in patient attention lost significance after controlling for psychotic symptom reduction. No significant time/diagnosis interaction was found among patients (p > 0.405). CONCLUSIONS: Cognitive impairment in EOP is already present at the first episode, and cognitive development seems to be arrested early in EOP patients compared to their healthy peers, at least for some cognitive functions. These and previous similar results support the neurodevelopmental hypothesis of psychosis.

Processing speed and executive functions predict real-world everyday living skills in adolescents with early-onset schizophrenia.

Cognition and clinical variables are known to be among the most predictive factors of real-world social functioning and daily living skills in adult-onset schizophrenia. Fewer studies have focused on their impact in adolescents with early-onset schizophrenia (EOS). The aim of this study is to examine the relationships and the predictive value of cognition and clinical variables on real-world daily living skills in a sample of adolescents with EOS. Cognitive, clinical and real-world everyday living skills measures were administered to 45 clinically and pharmacologically stabilized adolescent outpatients with EOS and 45 healthy control subjects matched by age and sex. Multi-variant analyses to compare cognitive and real-world functioning profiles between patients and controls and regression analysis to identify predictors of real-world functioning scores in patients were used. Adolescents with EOS showed a generalized cognitive and real-world daily living skills dysfunction. Several cognitive and clinical variables significantly correlated with real-world daily living skills functioning but only the processing speed and executive functions emerged as independent predictors of everyday living skills scores, explaining 25.1% of the variance. Slowness in processing information and executive dysfunction showed a significant impact on real-world daily living skills in EOS, independently from clinical symptoms and other cognitive variables. Nevertheless, much of the variance in the daily living skills measure remained unaccounted for, suggesting that other factors were involved as well in this young population.

Longitudinal study of neurological soft signs in first-episode early-onset psychosis.

BACKGROUND: In recent decades, the assessment of neurological soft signs (NSS) in patients with psychosis has become a subject of special interest. The study of the progression of NSS during adolescence will provide valuable information about the role of NSS as endophenotypes or biomarkers and about brain development at a stage in which brain maturation has not yet been completed. METHODS: Neurological soft signs were assessed in a sample of 110 first episodes of early-onset psychosis (EOP) and 98 healthy children and adolescents at two different times in a 2-year follow-up period. RESULTS: Patients with EOP showed more NSS than controls both at baseline (p < .001) and the 2-year follow-up (p < .001). No differences were found in the number of signs among the different diagnostic subgroups (schizophrenia, bipolar disorder, and other psychoses). When we examined the changes in NSS over the follow-up, the reduction of NSS in the patients was greater than the controls for 'Motor coordination' (p = .032), 'Others' (p < .001), and 'Total score' (p < .001) of the NES. CONCLUSION: Despite the greater reduction of NSS in patients than in controls along the follow-up, patients still have more neurological signs than healthy controls; therefore, these signs may be considered a trait marker. NSS do not seem to be specific to schizophrenia as they are present in different EOPs.

Ovariectomy, a model of menopause in rodents, causes a premature aging of the nervous and immune systems.

Ovariectomy in rodents is a good model for mimicking human ovarian hormone loss. This work studies the consequences of ovariectomy on the nervous and immune systems in the context of biological aging. Ovariectomy accelerates the process of aging by impairing the sensorimotor abilities (with loss of muscular vigor and impaired equilibrium and traction capacities) and the exploratory capacities (with reduction of vertical exploratory activity). It also leads to a premature immunosenescence with regard to chemotaxis index, lymphoproliferative response and natural killer activity, parameters investigated in the spleen and axillary nodes. Therefore, ovariectomy deteriorates homeostasis and may be a model of premature aging.

Improvement of leucocyte functions in ovariectomised aged rats after treatment with growth hormone, melatonin, oestrogens or phyto-oestrogens.

Ageing is accompanied by an impairment of the physiological activity of the nervous, endocrine and immune system, as well as in neuroendocrine-immune communication. However, age-related changes in this communication axis have been scarcely studied. In mammals, the process of ageing is associated with an important decline in the secretion of several hormones, such as growth hormone (GH), melatonin (MEL) and oestrogens (Os). Ovariectomy, a model of menopause in rats, has been found to lead to premature immunosenescence. In the present study, the effect of ovariectomy and the role of replacement therapies with GH, MEL, O and natural phyto-oestrogens (POs) have been assessed on several functions in leucocytes from the spleen and the axillary nodes of intact and ovariectomised rats. Chemotaxis, lymphoproliferative response to the mitogen concanavalin A (Con A), the release of interleukin-2 (IL-2) and the natural killer (NK) cell activity have been investigated. Age-controlled rats were used to compare immune functions in hormone treated aged rats with those in younger untreated animals. In all experimental groups, the immune impairment caused by ageing and ovariectomy was partially or completely reversed by hormone treatments. Since the immune system is a marker of health and a predictor of longevity, the results suggest that treatment with hormones could slow down the effects of the ageing process.