Analysis of outcomes of emergency general and gastrointestinal surgery during the COVID-19 pandemic.

BACKGROUND: Few surgical studies have provided adjusted comparative postoperative outcome data among contemporary patients with and without COVID-19 infection and patients treated before the pandemic. The aim of this study was to determine the impact of performing emergency surgery in patients with concomitant COVID-19 infection. METHODS: Patients who underwent emergency general and gastrointestinal surgery from March to June 2020, and from March to June 2019 in 25 Spanish hospitals were included in a retrospective study (COVID-CIR). The main outcome was 30-day mortality. Secondary outcomes included postoperative complications and failure to rescue (mortality among patients who developed complications). Propensity score-matched comparisons were performed between patients who were positive and those who were negative for COVID-19; and between COVID-19-negative cohorts before and during the pandemic. RESULTS: Some 5307 patients were included in the study (183 COVID-19-positive and 2132 COVID-19-negative during pandemic; 2992 treated before pandemic). During the pandemic, patients with COVID-19 infection had greater 30-day mortality than those without (12.6 versus 4.6 per cent), but this difference was not statistically significant after propensity score matching (odds ratio (OR) 1.58, 95 per cent c.i. 0.88 to 2.74). Those positive for COVID-19 had more complications (41.5 versus 23.9 per cent; OR 1.61, 1.11 to 2.33) and a higher likelihood of failure to rescue (30.3 versus 19.3 per cent; OR 1.10, 0.57 to 2.12). Patients who were negative for COVID-19 during the pandemic had similar rates of 30-day mortality (4.6 versus 3.2 per cent; OR 1.35, 0.98 to 1.86) and complications (23.9 versus 25.2 per cent; OR 0.89, 0.77 to 1.02), but a greater likelihood of failure to rescue (19.3 versus 12.9 per cent; OR 1.56, 95 per cent 1.10 to 2.19) than prepandemic controls. CONCLUSION: Patients with COVID-19 infection undergoing emergency general and gastrointestinal surgery had worse postoperative outcomes than contemporary patients without COVID-19. COVID-19-negative patients operated on during the COVID-19 pandemic had a likelihood of greater failure-to-rescue than prepandemic controls.

Partial complementation between the immediate early proteins ICP4 of herpes simplex virus type 1 and IE180 of pseudorabies virus.

We previously described that the immediate early (IE) IE180 protein of PRV can down-regulate the transactivation of the ICP4 promoter of HSV-1, and that the d120 virus (an ICP4-deficient HSV-1 strain) can partially replicate its viral DNA in the presence of the IE180 protein. Herein, we demonstrate that this partial complementation of d120 by IE180 is sufficient for transcription of ß, γ1 and γ2 products such as DNA pol, VP16 and gC, respectively. However, expression levels are low for VP16 and even lower for the gC, such that IE180 is unable to fully substitute for ICP4 functionally. Viral progeny was not detected in PK15 cells expressing PRV IE180.

Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cells.

The objective of this study was to characterize Huh7 cells' baseline capacity to metabolize drugs and to investigate whether the drug metabolism was enhanced upon treatment with dimethyl sulfoxide (DMSO). The messenger RNA (mRNA) levels of major Phase I and Phase II enzymes were determined by quantitative real-time-polymerase chain reaction (RT-PCR), and activities of major drug-metabolizing enzymes were examined using probe drugs by analysing relevant metabolite production rates. The expression levels of drug-metabolizing enzymes in control Huh7 cells were generally very low, but DMSO treatment dramatically increased the mRNA levels of most drug-metabolizing enzymes as well as other liver-specific proteins. Importantly, functionality assays confirmed concomitant increases in drug-metabolizing enzyme activity. Additionally, treatment of the Huh7 cells with 3-methylcholanthrene induced cytochrome P450 (CYP) 1A1 expression. The results indicate that DMSO treatment of Huh7 cells profoundly enhances their differentiation state, thus improving the usefulness of this common cell line as an in vitro hepatocyte model.

Expression of the immediate early IE180 protein under the control of the hTERT and CEA tumor-specific promoters in recombinant pseudorabies viruses: Effects of IE180 protein on promoter activity and apoptosis induction.

Since the pseudorabies virus (PRV) genome encodes for a single immediate-early protein, IE180, we reasoned that this strong transactivating protein could represent a key regulatory switch that could be genetically manipulated in order to alter its tropism towards cancer cells. We therefore initiated studies to test whether the human telomerase reverse transcriptase (hTERT) and carcinoembryonic antigen (CEA) tumor promoters could functionally replace the IE180 promoter. We show that both promoters can functionally substitute the IE180 promoter in plasmid constructs and recombinant viruses, and observed that IE180 differentially auto-regulated each promoter tested, with PRV IE180 negatively regulating the hTERT promoter but positively hyper-activating the CEA promoter. Interestingly, we also observed that the recombinant PRV-TER and PRV-CEA viruses preferentially replicated in diverse cancer cell lines compared to control non-cancer cells, and the PRV-CEA was capable of additionally inducing a profound apoptotic phenotype which we correlated to the overexpression of IE180.

The fuss over lipo"fuss"cin: not all autofluorescence is the same.

Since the first description of cellular autofluorescence over a century ago, we have now come to appreciate that autofluorescence should not be discarded as a biological artifact but embraced as a biological phenomenon with potentially important cellular relevance. Indeed, cellular and tissue autofluorescence has been attributed to a spectrum of unrelated molecules such as porphyrins, vitamins (vitamin A, riboflavin, thiamine), structural proteins, lipofuscin and ceroid pigments. We have recently shown that freshly isolated epithelial cancer stem cells (CSCs) bear autofluorescent vesicles in the cytoplasm. Our studies definitively prove that riboflavin and not lipofuscin is the source of autofluorescence in CSCs as the inhibition of ATP and not autophagy eliminates CSC autofluorescence, that the ATP-dependent transporter ABCG2, for which riboflavin is a substrate, is overexpressed in autofluorescent CSCs and co-localizes with the membrane of intracellular autofluorescent vesicles, the ABCG2-specific inhibitor Fumitremorgin C reversibly eliminates CSC autofluorescence, riboflavin is a substrate for ABCG2, and only the addition of riboflavin to vitamin-deprived CSC cultures is capable of restoring autofluorescence. Thus, the sum of these data unequivocally supports the conclusion that the source of CSC autofluorescence is the vitamin riboflavin.

HSV-1 migration in latently infected and naive rabbits after penetrating keratoplasty.

PURPOSE: To investigate the migration of herpes simplex virus type 1 (HSV-1) between latently infected and naive corneal tissues and trigeminal ganglion (TG) in rabbits after penetrating keratoplasty (PKP) and transcorneal epinephrine iontophoresis. METHODS: Two mutants, genetically constructed from HSV-1 strain 17syn+, were used to inoculate rabbit corneas: 17deltaPst, a latency associated transcript (LAT) negative, low-reactivating virus and 17Pr, a high-reactivating, LAT-positive rescuant of 17deltaPst. Latently infected rabbits were given corneal allografts from naive rabbits, and naive rabbits received grafts from latently infected rabbits. Ninety days after PKP, groups of the transplanted rabbits were induced to reactivate by transcorneal epinephrine iontophoresis, but others were not induced. Viral shedding was monitored by tear film cultures. Rabbits were killed 5 days after iontophoresis. Transplanted grafts, recipient corneal rims, and corresponding TG were obtained. Nucleic acids were extracted and amplified for detection of HSV-1 DNA and viral gene transcription. RESULTS: In naive rabbits receiving grafts transplanted from rabbits latently infected with 17Pr (LAT+), 3 of 6 corneal rims contained HSV DNA after induction. In contrast, none of the 5 corneal rims from naive rabbits receiving grafts from rabbits latent with 17deltaPst (LAT-) contained viral DNA. Viral DNA and gene transcripts were detected in 2 of 6 TG from naive rabbits that received grafts from 17Pr (LAT+) latently infected rabbits. In recipient corneal rims and TG of latently infected rabbits receiving grafts from naive rabbits, viral DNA concentration was significantly greater with induced reactivation, compared with the results in noninduced rabbits. The amount of viral DNA in naive grafts transplanted into 17Pr (LAT+) latently infected rabbits was significantly higher with induction than without induction (P = 0.018). More viral DNA and viral gene transcripts were found in tissues from rabbits latently infected with 17Pr (LAT+) than in rabbits latently infected with 17deltaPst (LAT-). CONCLUSIONS: Corneas from latently infected rabbits contain HSV-1 DNA that can replicate after induced reactivation. Viral migration can occur in both anterograde and retrograde directions between the transplanted graft and the recipient corneal rim and TG. The LAT negative HSV-1 construct 17deltaPst has a significantly reduced ability to replicate and migrate.

Effects of dopaminergic drugs, occlusal disharmonies, and chronic stress on non-functional masticatory activity in the rat, assessed by incisal attrition.

Observational methods and the recording of nonspecific jaw movements or masticatory muscle activity have been used to evaluate oral parafunctional movements in animal models of bruxism. In this study, we have used a new approach in which the non-functional masticatory activity in the rat was assessed by the measurement of incisal attrition, with the aim of investigating the role of diverse factors involved in the etiology of bruxism. We quantified the attrition rate weekly by making superficial notches in the lower incisors and measuring the distances to the incisor edges. Repeated stimulation of the dopaminergic system with apomorphine led to an enhancement of the non-functional masticatory activity (p < 0.0001). The severity of the apomorphine-induced oral behavior was positively correlated (r(s) = 0.69, p < 0.01) with an increase in the incisal attrition rate (20.9%, p < 0.0001). Apomorphine-induced non-functional masticatory activity was strongly enhanced by the placement of an acrylic cap on both lower incisors (306%, p < 0.0001), but not by the cutting of a lower incisor. Repeated cocaine administration also increased the attrition rate (22.5%, p < 0.0001). However, neither chronic blockade of dopaminergic receptors with haloperidol, nor its withdrawal, modified attrition. In addition, since emotional disturbances are considered to be causal factors of bruxism, we tested whether experimental stress might accelerate tooth wear. Exposure to two different chronic stress regimes did not induce significant changes in incisal attrition. Moreover, exposure to chronic stress after the withdrawal of chronic haloperidol treatment did not alter attrition either. These results partially support the role of the central dopaminergic system in bruxism and suggest that stress, in general, may not be a relevant factor in tooth wear.

Occlusal disharmonies modulate central catecholaminergic activity in the rat.

Occlusal disharmonies have classically been thought to be involved in the etiopathogenesis of bruxism, as have, more recently, alterations in central neurotransmission, particularly dopaminergic neurotransmission. However, the connection between these two factors has still not been established. In this study, we assessed the effects of diverse occlusal disharmonies, maintained for either 1 day or 14 days, on neurochemical indices of dopaminergic and noradrenergic activity in the striatum, frontal cortex, and hypothalamus of the rat. The in vivo activity of tyrosine hydroxylase, determined as the accumulation of 3,4-dihydroxyphenylalanine (DOPA), 30 min after the administration of 3-hydroxybenzylhydrazine, a DOPA decarboxylase inhibitor, and dopamine and noradrenaline contents were quantified by high-performance liquid chromatography with electrochemical detection. The wearing of an acrylic cap on both lower incisors for 1 day induced a significant increase in DOPA accumulation in the regions analyzed, with parallel increases in dopamine levels in the hypothalamus and dopamine and noradrenaline in the frontal cortex. After the cap was maintained for 14 days, DOPA accumulation tended to return to control values, except in the left striatum, thereby causing an imbalance between hemispheres. In contrast, 1 or 14 days after the lower left and the upper right incisors were cut, less pronounced changes in catecholaminergic neurotransmission were found in the brain areas studied. Moreover, the cutting of one lower incisor did not modify either DOPA accumulation or dopamine and noradrenaline contents in the striatum or hypothalamus. These results provide experimental evidence of a modulation of central catecholaminergic neurotransmission by occlusal disharmonies, being dependent on the nature of the incisal alteration and on the time during which it was maintained.

Stress-associated immunomodulation and herpes simplex virus infections.

Stress has been shown to modulate an individual's immune system through the release of certain signal molecules such as catecholamines, cytokines and glucocorticoids. These signal molecules can significantly alter the host immune system and leave it susceptible to a primary or recurrent viral infection. Focusing on herpes simplex virus types-1 and -2 as examples, the authors explain how stress-associated immunomodulation can influence the recurrence of herpes simplex viral infections. Specific signal molecules such as epinephrine, interleukin-6, cyclic adenosine monophosphate, glucocorticoids and prostaglandins are upregulated during episodes of acute and chronic stress and have been implicated as effectors of herpes simplex viral reactivation and recurrent disease. The authors suggest that the release of immunomodulating signal molecules due to stress can compromise the host's cellular immune response and trigger herpes simplex viral reactivation.

[Application of extracorporeal lithotripsy in intestinal subocclusion caused by a clam shell]. / Aplicación de la litotricia extracorpórea en la suboclusión intestinal por valva de molusco.

A patient with intestinal obstruction secondary to a foreign body (clam shell) impacted in the ileocecal valve was treated by extracorporeal shock wave lithotripsy. The resolution of ileus without complications was obtained.

Implementación universal de un cribado de defectos congénitos de garantía en un área sanitaria: área hospitalaria de Valme, Sevilla, España / Implementation of a standardised and universal screening on congenital defect in a health area: Valme hospital area, Seville, Spain

Antecedentes: La posibilidad de que un recién nacido presente algún tipo de defecto congénito al nacimiento es de un 2-4 por ciento y la aplicación de métodos de cribado de cromosomopatías y de malformaciones estructurales puede reducir la prevalencia de estos defectos congénitos al nacimiento. Objetivos: Demostrar que es posible la implantación de un cribado de malformaciones congénitas de garantía (sensibilidad de diagnóstico para malformaciones estructurales mayores y para síndrome de Down del 80 por ciento) y universal (aplicado al 90 por ciento de gestantes). Proponemos que la implantación de este cribado supone una disminución de la tasa de los defectos congénitos no diagnosticados al nacimiento a menos del 0,5 por ciento de los recién nacidos. Método: Estudio prospectivo. Hemos valorado 12.478 gestantes (julio 2006-septiembre de 2009). Método de cribado de defecto congénitos: test combinado asociado a ecografía morfológica (18-22 semanas) Resultados: La prevalencia de defecto congénito fue de 2,26 por ciento [IC 95 por ciento: 1,9-2,5] (282/12478). Valoración ecográfica fue del 99,2 por ciento de las gestantes. Tasa de diagnóstico de malformaciones estructurales fue de 79,3 por ciento [IC 95 por ciento: 74,3-84,4] (196/247) y 95,6 por ciento [IC 95 por ciento: 91,8-99,3] (110/115) para las malformaciones mayores. Se ofertó un cribado de cromosomopatias al 95,1 por ciento de las gestantes con una tasa de diagnóstico del 88,5 por ciento [IC 95 por ciento: 79,9-99] (31/35). Conclusiones: Un cribado de defectos congénitos universal y de garantías logró disminuir la prevalencia de defectos congénitos al nacimiento sin diagnosticar a un 0,5 por ciento.

Background: The probability of a newborn presenting some kind of congenital defect at birth is 2-4 percent and the application of methods of screening for chromosomal and structural abnormalities can reduce the prevalence of these defects at birth. Objectives: The aim of this study is to prove that it is possible to implement a screening for congenital malformations that is standardised (diagnostic sensitivity [Sen]>80 percent for major structural deformations and Down's syndrome) and universal (90 percent of pregnant women). We also want to prove that this screening reduces the rate of undiagnosed congenital defects at birth. Methods: Prospective study. We assessed 12,478 pregnant women (July 2006- September 2009). A morphological ultrasound (18-22 weeks) and a combined test were carried out as the methods for screening for congenital defects. Results: The prevalence of congenital defects was 2.26 percent [95 percent CI: 1.9-2.5] (282/12478). The ultrasound scan was performed on 99.2 percent of the pregnant women. There was a Sen of 79.3 percent [95 percent CI: 74.3-84.4] (196/247) for structural malformation and 95.6 percent [95 percent CI: 91.8-99.3] (110/115) for major malformations). Screening for chromosomal anomalies was performed on 95.1 percent of pregnant women with a Sen of 88.5 percent [95 percent CI: 79.9-99] (31/35). Conclusions: A standardised and universal screening for congenital defects reduced the prevalence of undiagnosed congenital defects at birth to 0.5 percent.

A possible attenuation of stress-induced increases in striatal dopamine metabolism by the expression of non-functional masticatory activity in the rat.

It is thought that the expression of oral parafunctions may provide an outlet for stress or aggressiveness in man. Stress-induced increases in central noradrenergic neurotransmission are attenuated in rats which are allowed to bite during stress. Striatal dopaminergic neurotransmission is involved in the genesis of parafunctional oral movements in rodents. As tail pinch is the stressor which most clearly provokes non-functional masticatory activity (NFMA), and also increases striatal dopamine (DA) activity in rats, we investigated whether the expression of NFMA during tail pinch could modify the changes in striatal dopaminergic neurotransmission induced by this stressor. Rats were subjected to tail pinch for 5 min, and the duration of the NFMA displayed was recorded. As an index of dopaminergic activity, 3,4-dihydroxyphenylalanine (DOPA) accumulation and DA and 3,4-dihydroxyphenylacetic (DOPAC) contents in both striata were determined by high-performance liquid chromatography. Striatal DOPA accumulation was similarly increased in relation to control, both in rats which did and did not display NFMA during tail pinch. However, the increases in striatal DOPAC contents, reported 24 min after the stress session, were lower in animals which had displayed NFMA. These results provide further evidence in support of the assumption that the expression of parafunctional masticatory activity attenuates the effects of stress on central catecholaminergic neurotransmission.

Effect of famciclovir on herpes simplex virus type 1 corneal disease and establishment of latency in rabbits.

Famciclovir (FCV) is efficacious in the treatment of acute herpes zoster and recurrent genital infections but has not been used to treat ocular herpes simplex virus (HSV) infections. We evaluated the efficacy of orally administered FCV in treating HSV-1 epithelial keratitis and determined its effects on the establishment of latency and subsequent reactivation. Rabbits were inoculated with HSV-1 strain 17 syn+ and treated twice daily with increasing concentrations of FCV (60 to 500 mg/kg of body weight). This resulted in a significant, dose-dependent improvement in keratitis scores, as well as prolonged survival. Regardless of the dose of drug used, all groups exhibited the high rates of spontaneous and induced reactivation characteristic of 17syn+. The efficacy of 250 mg of FCV per kg was also compared to topical treatment with 1% trifluorothymidine (TFT). Although TFT treatment was more effective at reducing eye disease, FCV-treated rabbits had a better survival rate. Real-time quantitative PCR analysis of rabbit trigeminal ganglia (TG) demonstrated that FCV significantly reduced the HSV-1 copy number compared to that after treatment with TFT or the placebo but not in a dose-dependent manner. In summary, oral FCV treatment significantly reduces the severity of corneal lesions, reduces the number of HSV-1 genomes in the TG, improves survival, and therefore may be beneficial in reducing the morbidity of HSV keratitis in the clinic.