Serum Caspase-1 as an Independent Prognostic Factor in Traumatic Brain Injured Patients.

BACKGROUND: The objectives of this study were to assess the association between serum caspase 1 levels and known clinical and radiological prognostic factors and determine whether caspase 1was a more powerful predictor of outcome after traumatic brain injury (TBI) than clinical indices alone, to determine the association between the serum levels of caspase 1 and the 6-month outcome, and to evaluate if there is any association between caspase 1 with clinical and radiological variables. METHODS: This prospective and observational study was conducted in a university hospital and included patients with TBI who required hospital admission. Serum samples were collected at hospital admission and 24 h after TBI. Caspase 1 levels were determined by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were obtained to test the potential of caspase 1 to predict mortality (Glasgow Outcome Scale Extended score of 1) and unfavorable outcome (Glasgow Outcome Scale Extended scores of 1-4). Multivariate logistic regression was used to assess the effect of serum caspase 1 levels, adjusted by known clinical and radiological prognostic indices, on the outcome. RESULTS: One hundred thirty-two patients and 33 healthy controls were included. We obtained 6-month outcome in 118 patients. On admission, the mean serum levels of caspase 1 were higher in patients with TBI compared with controls (157.9 vs. 108.5 pg/mL; p < 0.05) but not at 24 h after TBI. Serum caspase 1 levels on admission were higher in patients with unfavorable outcomes (189.5 vs. 144.1 pg/mL; p = 0.009). Similarly, serum caspase 1 levels on admission were higher in patients who died vs. patients who survived (213.6 vs. 146.8 pg/mL; p = 0.03). A logistic regression model showed that the serum caspase 1 level on admission was an independent predictor of 6-month unfavorable outcomes (odds ratio 1.05; 95% confidence interval 1-1.11; p = 0.05). Caspase 1 levels were higher in patients with severe TBI compared with those with moderate TBI, those with mild TBI, and healthy controls (p < 0.001). We did not find any correlation between caspase 1 and the radiological variables studied. CONCLUSIONS: In this cohort of patients with TBI, we show that serum caspase 1 protein levels on admission are an independent prognostic factor after TBI. Serum caspase 1 levels on admission are higher in patients who will present unfavorable outcomes 6 months after TBI. Caspase 1 levels on admission are associated with the injury severity determined by the Glasgow Coma Scale.

Risk and protective factors for anxiety and obsessive-compulsive disorders: an umbrella review of systematic reviews and meta-analyses.

BACKGROUND: A multitude of risk/protective factors for anxiety and obsessive-compulsive disorders have been proposed. We conducted an umbrella review to summarize the evidence of the associations between risk/protective factors and each of the following disorders: specific phobia, social anxiety disorder, generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder, and to assess the strength of this evidence whilst controlling for several biases. METHODS: Publication databases were searched for systematic reviews and meta-analyses examining associations between potential risk/protective factors and each of the disorders investigated. The evidence of the association between each factor and disorder was graded into convincing, highly suggestive, suggestive, weak, or non-significant according to a standardized classification based on: number of cases (>1000), random-effects p-values, 95% prediction intervals, confidence interval of the largest study, heterogeneity between studies, study effects, and excess of significance. RESULTS: Nineteen systematic reviews and meta-analyses were included, corresponding to 216 individual studies covering 427 potential risk/protective factors. Only one factor association (early physical trauma as a risk factor for social anxiety disorder, OR 2.59, 95% CI 2.17-3.1) met all the criteria for convincing evidence. When excluding the requirement for more than 1000 cases, five factor associations met the other criteria for convincing evidence and 22 met the remaining criteria for highly suggestive evidence. CONCLUSIONS: Although the amount and quality of the evidence for most risk/protective factors for anxiety and obsessive-compulsive disorders is limited, a number of factors significantly increase the risk for these disorders, may have potential prognostic ability and inform prevention.

Analysis of KCNH2 and CACNA1C schizophrenia risk genes on EEG functional network modulation during an auditory odd-ball task.

A deficit in task-related functional connectivity modulation from electroencephalogram (EEG) has been described in schizophrenia. The use of measures of neuronal connectivity as an intermediate phenotype may allow identifying genetic factors involved in these deficits, and therefore, establishing underlying pathophysiological mechanisms. Genes involved in neuronal excitability and previously associated with the risk for schizophrenia may be adequate candidates in relation to functional connectivity alterations in schizophrenia. The objective was to study the association of two genes of voltage-gated ion channels (CACNA1C and KCNH2) with the functional modulation of the cortical networks measured with EEG and graph-theory parameter during a cognitive task, both in individuals with schizophrenia and healthy controls. Both CACNA1C (rs1006737) and KCNH2 (rs3800779) were genotyped in 101 controls and 50 schizophrenia patients. Small-world index (SW) was calculated from EEG recorded during an odd-ball task in two different temporal windows (pre-stimulus and response). Modulation was defined as the difference in SW between both windows. Genetic, group and their interaction effects on SW in the pre-stimulus window and in modulation were evaluated using ANOVA. The CACNA1C genotype was not associated with SW properties. KCNH2 was significantly associated with SW modulation. Healthy subjects showed a positive SW modulation irrespective of the KCNH2 genotype, whereas within patients allele-related differences were observed. Patients carrying the KCNH2 risk allele (A) presented a negative SW modulation and non-carriers showed SW modulation similar to the healthy subjects. Our data suggest that KCNH2 genotype contributes to the efficient modulation of brain electrophysiological activity during a cognitive task in schizophrenia patients.

An Idic(7)(q11.2) Resulting in Two Copies of 7p and Deletion 7q: A Rare Cytogenetic Event in a Case of Acute Myeloid Leukemia.

OBJECTIVES: A 67-year-old male patient was diagnosed with acute myeloid leukemia (AML) in April 2018. Chromosome analysis showed an abnormal male karyotype with an isodicentric chromosome 7q resulting in deletion 7q and two copies of 7p and a derivative chromosome 18 in 13 of the 20 metaphase cells examined. This karyotype was described as 46,XY,idic(7)(q11.2),der(18)t(1;18)(q23;q21.1)[13]/46,XY[7]. Additionally, subsequent sequencing analysis displayed FLT3-ITD and RUNX1 mutations (data not shown). The bone marrow showed an overwhelming number of blast cells, with co-expression of CD34, CD117, TdT, MPO, CD7, CD13, CD33, CD38, CD19, and HLA-DR. Molecular cytogenetic studies showed a deletion of one RELN/TES (7q22/7q31) signal in 80.5% of nuclei and a gain of a BCR/ABL1 (22q11.2/9q34) signal in 3.5% of interphase nuclei examined. These findings were described as nuc ish(RELN,TES)x1[161/200],(ABL1x2,BCRx3)[7/200], (EVI1,TAS2R1,EGR1,DEK,MYC,NUP214,KMT2A,DLEU1,DLEU2,Clone 163C9,PML,CBFB,RARA,PTPRT,MYBL2,RUNX1)x2[200]. The patient relapsed with AML in September 2019 and underwent treatment. However, all AML treatment options were exhausted by March 2020. An isodicentric chromosome 7 leading to two copies of the short arm of chromosome 7 (7p) and deletion 7q is a rare event in AML and is rarely described in the literature. The key element here is that this specific rearrangement leads to deletion 7q which is a well-known abnormality in AML that places the patient in the Poor/Adverse risk category.

Students and teachers' satisfaction and perspectives on high-fidelity simulation for learning fundamental nursing procedures: A mixed-method study.

BACKGROUND: High-fidelity clinical simulation enables skills to be acquired safely and securely by bridging the gap between theory and clinical practice. This method has traditionally been used to address complex clinical scenarios. Students often report high levels of satisfaction and self-confidence, as this method allows them to put techniques and procedures into practice in a safe environment. Most studies assess simulation solely from the students' perspective, disregarding the opinions of teaching staff. OBJECTIVES: To assess the implementation of high-fidelity simulation as a teaching tool for fundamental nursing procedures from the perspectives of students and teachers. DESIGN: A two-phase mixed-methods study. SETTING: A simulation centre environment at the University of the Balearic Islands (Spain) during the 2018 academic year. PARTICIPANTS: Second-year nursing students and staff teaching practical classes on basic patient assessment and monitoring of vital signs. METHODS: Satisfaction with clinical experience simulation scale, including an open-ended question for students, was used. A focus group session was also held with teachers. RESULTS: A total of 91 students completed the scale, yielding an overall satisfaction score of 9.3 out of 10. The practical dimension attained the highest scores. Motivation to attend class was the lowest-rated aspect of this dimension, although students' expectations and satisfaction increased during the class. In the open-ended question and the debriefing session, students described the simulation as a playful learning method allowing them to put their theoretical knowledge into practice and helping them to manage their fears before coming into contact with real care settings. In the focus group session, teachers analysed their own experiences and described how they perceived students' satisfaction and practical skills. CONCLUSIONS: High-fidelity simulation produces good academic outcomes and is highly satisfying for students and teachers.

FISH is Still an Excellent Tool to Monitor High-Grade Lymphomas.

OBJECTIVES: A 61-year-old male patient whose core needle biopsies of tissue involved a malignant lymphoid infiltrate composed of intermediate to large cells positive for CD20, PAX5, CD10, BCL6, BCL2, and cMYC, and negative for MUM1. Mitotic activity was brisk with a correspondingly high index of proliferation by Ki67 (~95%) and the patient was diagnosed with a diffuse large B-cell lymphoma, germinal center phenotype. DNA FISH analysis was performed on the paraffin embedded tissue from the right external iliac lymph node using the LSI BCL6 (3q27) and MYC (8q24) dual color break apart probes from Cytocell and the LSI BCL2 (18q21) dual color break apart probe from Abbott. We found rearrangements of BCL6 in 95% of the cells examined, MYC rearrangements in 77% of the cells and BCL2 rearrangements in 95% of the nuclei. These findings allowed us to classify this case as a triple-hit lymphoma now called "high-grade B-cell lymphomas" with MYC, BCL2, and/or BCL6 rearrangements.

Interobserver agreement for post mortem renal histopathology and diagnosis of acute tubular necrosis in critically ill patients.

BACKGROUND: The renal histopathology of critically ill patients dying with acute kidney injury (AKI) in intensive care units of high income countries remains uncertain. METHODS: Retrospective observational assessment of interobserver agreement in the reporting of renal post mortem histopathology, and the ability of pathologists blinded to the clinical context to independently identify the presence of pre-mortem AKI from digital images of histological sections from 34 critically ill patients dying in teaching hospitals in Australia and Canada. RESULTS: We identified a heterogeneous cohort with a median age of 65 years (interquartile range [IQR], 56.5-77), APACHE II score of 27 (IQR, 19-33), and sepsis as the most common admission diagnosis (12/34; 35%). The most common proximate causes of death were cardiovascular (19/34; 56%) and respiratory (7/34; 21%) failure. AKI was common, with 23 patients (68%) developing RIFLE-F AKI, and 21 patients (62%) receiving renal replacement therapy. Structured reporting for tubular inflammation showed excellent agreement (kappa = 1), but no other subdomain demonstrated better than moderate agreement (kappa < 0.6). Only fair agreement (55.9% of cases; kappa = 0.23) was demonstrated on the diagnosis of moderate to severe acute tubular necrosis (ATN). Pathologist A predicted RIFLE-I or worse AKI with the diagnosis of ATN, with an overall accuracy of 61.8%; pathologist B predicted AKI with an accuracy of 35.3%. CONCLUSIONS: Post mortem assessment of the renal histopathology in critically ill patients is neither robust nor reproducible; independent pathologists agree poorly on the diagnosis of ATN, and their structural assessment appears dissociated from ante-mortem renal function.

Pericentric inversion (12)(p12q13-14) as the sole chromosomal abnormality in a leiomyoma of the vulva.

We present a case of a leiomyoma of the vulva with karyotype 46,XX,inv(12)(p12q13-14). It is noteworthy that the breakpoint at 12q13 approximately q14 is flanked by the HMGA2 gene. Although the gene remained intact, the presence of HMGA2 protein in the neoplastic cells indicates that it became activated by the rearrangement. It is curious that activation of the HMGA2 gene, while not restricted to smooth muscle tumors, was so far found only in genital leiomyomata (uterus, vulva, vagina) and not in any smooth muscle tumors arising in extragenital locations.