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.

Atypical indications for transanal endoscopic microsurgery to avoid major surgery.

BACKGROUND: Transanal endoscopic microsurgery (TEM) was originally designed for the removal of rectal tumors, principally incipient adenomas, and adenocarcinomas up to 20 cm from the anal verge. However, with the evolution of the technique and the increase in surgeons' experience, new indications have emerged and TEM may now be used in place of other surgical procedures which are associated with higher morbidity. The aim of our study was to evaluate our group's use of TEM or transanal endoscopic operations (TEO) for conditions other than rectal tumors. METHODS: An observational study of TEM (using Wolf equipment) or TEO (using Storz equipment) for indications other than excision of rectal tumors was conducted from June 2004 to July 2012. RESULTS: Four hundred twenty-four procedures were performed using TEM/TEO: removal of adenocarcinomas in 148 (34.9 %) patients, adenomas in 236 (55.7 %), post-polypectomy excision in 12 (2.8 %), removal of neuroendocrine tumors in 8 (1.9 %), and atypical indications in 20 (4.7 %). Atypical indications were pelvic abscess (3), benign rectal stenoses (2), rectourethral fistula after prostatectomy (3), gastrointestinal stromal tumor (3), endorectal condylomata acuminata (1), rectal prolapse (2), extraction of impacted fecaloma in the rectosigmoid junction (1), repair of traumatic and iatrogenic perforation of the rectum (2), and presacral tumor (3). CONCLUSIONS: The use of TEM/TEO in atypical indications may benefit patients by avoiding surgical procedures associated with greater morbidity.

Aplicación de la revisión terciaria en el manejo inicial del paciente politraumatizado / Tertiary survey in the management of patients with multiple injuries

Objetivo: La revisión terciaria puede disminuir la incidencia de lesiones inadvertidas y de lesiones inadvertidas clínicamente relevantes y puede reducir la morbi-mortalidad de los pacientes politraumatizados. Método: Estudio prospectivo que incluye pacientes politraumatizados mayores de 16años ingresados en una área de pacientes críticos, excluidos los que murieron en las primeras 24 h. Comparación de un grupo a quien se aplicó la revisión terciaria, con un grupo control a quién no se aplicó. Hemos registrado la incidencia de lesiones inadvertidas y de lesiones inadvertidas clínicamente relevantes. Hemos analizado los principales errores asociados a la aparición de lesiones inadvertidas y los factores de riesgo inevitables. Se estudió la mortalidad de ambos grupos y sus complicaciones. Resultados: Se ha protocolizado la revisión terciaria en 119 pacientes frente a 117 en los que no se realizó. Con la aplicación de la revisión terciaria, la incidencia de lesiones inadvertidas se ha reducido de un 40,2% a un 15,1%, y la incidencia de lesiones inadvertidas clínicamente relevantes de un 17,1% a un 3,4%. La mortalidad ha disminuido de un 10,2% a un 4,2%, y desaparecieron las muertes causadas por fracaso multiorgánico. Ha disminuido el error radiológico han desaparecido los errores de comunicación y quirúrgicos. Los principales factores asociados a la detección de lesiones inadvertidas y de lesiones inadvertidas clínicamente relevantes son la presión arterial, el número de lesiones y, como factor más relevante, la aplicación de la revisión terciaria. Conclusiones: La aplicación de la revisión terciaría debería ser obligada en el manejo inicial de los pacientes politraumatizados (AU)

Background: Implementing tertiary trauma surveys can reduce the incidence of clinically significant missed injury, thereby reducing morbidity and mortality in patients with multiple injuries. Methods: Prospective study of patients admitted to the critical care unit with multiple injuries. The patients were over the age of 16 years and survived at least 24 hours. Patients undergoing tertiary examination were compared to a historical control group that did not undergo additional assessment. We recorded missed injuries and clinically significant missed injuries in both groups. Also analyzed were the main errors associated with the appearance of missed injuries, avoidable risk factors, mortality, and complications in both groups. Results: A total of 119 patients underwent tertiary examination and their data were compared to those of 117 in the historical control group. The incidence of missed injuries was lower in the test period (15.13%) than the control period(40.17%). The incidence of clinically significant missed injuries was also lower in the test period (3.36% vs 17.09 in the control period). Mortality fell to 4.25% with tertiary examination (vs 10.25% in the control period), and mortality due to multiorgan failure was 0% in the test period. Radiologic errors were fewer with implementation of tertiary trauma surveys and communication and surgical errors disappeared. The main risk factors for detecting clinically significant missed injuries were to blood pressure, the number of injuries and, particularly, the inclusion of a tertiary examination or not. Conclusion: Tertiary trauma surveys should be considered an obligatory component of the initial management of patients with multiple injuries (AU)

Surgical excision of retrorectal tumour using transanal endoscopic microsurgery.

Abstract Surgical excision is the best therapeutic option for tumours in the retrorectal space. Classically, surgery in this area required an abdominal or posterior approach, or a combination of the two methods. We report the use of transanal endoscopic microsurgery for the treatment of retrorectal tumours as an alternative to classical procedures.

Effect of dietary coenzyme Q and fatty acids on the antioxidant status of rat tissues.

Wistar rats were fed with different diets with or without supplement coenzyme Q(10) (CoQ(10)) and with oil of different sources (sunflower or virgin olive oil) for six or twelve months. Ubiquinone contents (CoQ(9) and CoQ(10)) were quantified in homogenates of livers and brains from rats fed with the four diets. In the brain, younger rats showed a 3-fold higher amount of ubiquinone than older ones for all diets. In the liver, however, CoQ(10) supplementation increased the amount of CoQ(9) and CoQ(10) in both total homogenates and plasma membranes. Rats fed with sunflower oil as fat source showed higher amounts of ubiquinone content than those fed with olive oil, in total liver homogenates, but the total ubiquinone content in plasma membranes was similar with both fat sources. Older rats showed a higher amount of ubiquinone after diets supplemented with CoQ(10). Two ubiquinone-dependent antioxidant enzyme activities were measured. NADH-ferricyanide reductase activity in hepatocyte plasma membranes was unaltered by ubiquinone accumulation, but this activity increased slightly with age. Both cytosolic and membrane-bound dicumarol-sensitive NAD(P)H:(quinone acceptor) oxidoreductase (DT-diaphorase, EC 1.6.99.2) activities were decreased by diets supplemented with CoQ(10). Animals fed with olive oil presented lower DT-diaphorase activity than those fed with sunflower oil, suggesting that the CoQ(10) antioxidant protection is strengthened by olive oil as fat source.

Inhibition of neutral Mg2+-dependent sphingomyelinase by ubiquinol-mediated plasma membrane electron transport.

Sphingomyelin is an abundant constituent of the plasma membranes of mammalian cells. Ceramide, its primary catabolic intermediate, has emerged as an important lipid signaling molecule. Previous work carried out by our group has documented that plasma membrane Mg(2+)-dependent neutral sphingomyelinase can be effectively inhibited by exogenous ubiquinol. In this work, we have tested whether or not plasma-membrane-associated electron transport can also achieve this inhibition through endogenous ubiquinol. Our results have shown that Mg(2+)-dependent neutral sphingomyelinase in isolated plasma membranes was inhibited by NAD(P)H under conditions where ubiquinone is reduced to ubiquinol. This inhibition was potentiated in the presence of an extra amount of NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2). Depletion of plasma membranes from lipophilic antioxidants by solvent extraction abolished the inhibition by reduced pyridine nucleotides without affecting the sensitivity of the neutral sphingomyelinase to exogenous ubiquinol. Reconstitution of plasma membranes with ubiquinone restored the ability of NAD(P)H to inhibit the enzyme. Our results support that the reduction of endogenous ubiquinone to ubiquinol by NAD(P)H-driven electron transport may regulate the activity of the plasma membrane neutral sphingomyelinase.

Expression of NAD(P)H:quinone oxidoreductase 1 in HeLa cells: role of hydrogen peroxide and growth phase.

The aim of this work was to study the role of H(2)O(2) in the regulation of NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase, EC ) with relation to cell density of HeLa cells cultures and the function played by NQO1 in these cells. Levels of NQO1 activity were much higher (40-fold) in confluent HeLa cells than in sparse cells, the former cells being much more resistant to H(2)O(2). Addition of sublethal concentrations of H(2)O(2) (up to 24 microm) produced a significant increase of NQO1 (up to 16-fold at 12 microm) in sparse cells but had no effect in confluent cells. When cells reached confluency in the presence of pyruvate, a H(2)O(2) scavenger, NQO1 activity was decreased compared with cultures grown to confluency without pyruvate. Inhibition of quinone reductases by dicumarol substantially decreased viability of confluent cells in serum-free medium. This is the first demonstration that regulation of NQO1 expression by H(2)O(2) is dependent on the cell density in HeLa cells and that endogenous generation of H(2)O(2) participates in the increase of NQO1 activity as cell density is higher. This enzyme is required to promote survival of confluent cells.

Coenzyme Q protects cells against serum withdrawal-induced apoptosis by inhibition of ceramide release and caspase-3 activation.

Coenzyme Q10 (CoQ10) is a component of the antioxidant machinery that protects cell membranes from oxidative damage and decreases apoptosis in leukemic cells cultured in serum-depleted media. Serum deprivation induced apoptosis in CEM-C7H2 (CEM) and to a lesser extent in CEM-9F3, a subline overexpressing Bcl-2. Addition of CoQ10 to serum-free media decreased apoptosis in both cell lines. Serum withdrawal induced an early increase of neutral-sphingomyelinase activity, release of ceramide, and activation of caspase-3 in both cell lines, but this effect was more pronounced in CEM cells. CoQ10 prevented activation of this cascade of events. Lipids extracted from serum-depleted cultures activated caspase-3 independently of the presence of mitochondria in cell-free in vitro assays. Activation of caspase-3 by lipid extracts or ceramide was prevented by okadaic acid, indicating the implication of a phosphatase in this process. Our results support the hypothesis that plasma membrane CoQ10 regulate the initiation phase of serum withdrawal-induced apoptosis by preventing oxidative damage and thus avoiding activation of downstream effectors as neutral-sphingomyelinase and subsequent ceramide release and caspase activation pathways.

Interactions between ascorbyl free radical and coenzyme Q at the plasma membrane.

A role for coenzyme Q in the stabilization of extracellular ascorbate by intact cells has been recently recognized. The aim of this work was to study the interactions between reduced ubiquinone in the plasma membrane and the ascorbyl free radical, as an approach to understand ubiquinone-mediated ascorbate stabilization at the cell surface. K-562 cells stabilized ascorbate and decreased the steady-state levels of the semiascorbyl radical. The ability of cells to reduce ascorbyl free radical was inhibited by the quinone analogs capsaicin and chloroquine and stimulated by supplementing cells with coenzyme Q10. Purified plasma membranes also reduced ascorbyl free radical in the presence of NADH. Free-radical reduction was not observed in quinone-depleted plasma membranes, but restored after its reconstitution with coenzyme Q10. Addition of reduced coenzyme Q10 to depleted membranes allowed them to reduce the signal of the ascorbyl free radical without NADH incubation and the addition of an extra amount of purified plasma membrane quinone reductase further stimulated this activity. Reduction was abolished by treatment with the reductase inhibitor p-hydroximercuribenzoate and by blocking surface glycoconjugates with the lectin wheat germ agglutinin, which supports the participation of transmembrane electron flow. The activity showed saturation kinetics by NADH and coenzyme Q, but not by the ascorbyl free radical in the range of concentrations used. Our results support that reduction of ascorbyl free radicals at the cell surface involves coenzyme Q reduction by NADH and the membrane-mediated reduction of ascorbyl free radical.

Role of plasma membrane coenzyme Q on the regulation of apoptosis.

Serum withdrawal is a model to study the mechanisms involved in the induction of apoptosis caused by mild oxidative stress. Apoptosis induced by growth factors removal was prevented by the external addition of antioxidants such as ascorbate, alpha-tocopherol and coenzyme Q (CoQ). CoQ is a lipophilic antioxidant which prevents oxidative stress and participates in the regeneration of alpha-tocopherol and ascorbate in the plasma membrane. We have found an inverse relationship between CoQ content in plasma membrane and lipid peroxidation rates in leukaemic cells. CoQ10 addition to serum-free culture media prevented both lipid peroxidation and cell death. Also, CoQ10 addition decreased ceramide release after serum withdrawal by inhibition of magnesium-dependent plasma membrane neutral-sphingomyelinase. Moreover, CoQ10 addition partially blocked activation of CPP32/caspase-3. These results suggest CoQ of the plasma membrane as a regulator of initiation phase of oxidative stress-mediated serum withdrawal-induced apoptosis.

Selective induction of apoptosis by capsaicin in transformed cells: the role of reactive oxygen species and calcium.

Capsaicin is a vanilloid quinone analog that inhibits the plasma membrane electron transport (PMOR) system and induces apoptosis in transformed cells. Using a cytofluorimetric approach we have determined that capsaicin induces a rapid increase of reactive oxygen species (ROS) followed by a subsequent disruption of the transmembrane mitochondrial potential (DeltaPsim) and DNA nuclear loss in transformed cell lines and in mitogen activated human T cells. This apoptotic pathway is biochemically different from the typical one induced by either ceramide or edelfosine where, in our system, the DeltaPsim dissipation precedes the generation of reactive oxygen species. Neither production of ROS nor apoptosis was found in capsaicin-treated resting T cells where the activity of the PMOR system is minimal when compared with mitogen activated or transformed T cells. Capsaicin also induces Ca2+ mobilization in activated but not in resting T cells. However, preincubation of cells with BAPTA-AM, which chelate cytosolic free calcium, did not prevent ROS generation or apoptosis induced by capsaicin, suggesting that ROS generation in capsaicin treated cells is not a consequence of calcium signaling and that the apoptotic pathway may be separated from the one that mobilizes calcium. Moreover, we present data for the implication of a possible vanilloid receptor in calcium mobilization, but not in ROS generation. These results provide evidence that the PMOR system may be an interesting target to design antitumoral and anti-inflammatory drugs.

Role of ascorbate in the activation of NF-kappaB by tumour necrosis factor-alpha in T-cells.

The first product of ascorbate oxidation, the ascorbate free radical (AFR), acts in biological systems mainly as an oxidant, and through its role in the plasma membrane redox system exerts different effects on the cell. We have investigated the role of ascorbate, AFR and dehydroascorbate (DHA) in the activation of the NF-kappaB transcription factor in Jurkat T-cells stimulated by tumour necrosis factor-alpha (TNF-alpha). Here we show, by electrophoretic mobility shift assays, that ascorbate increases the binding of NF-kappaB to DNA in TNF-alpha-stimulated Jurkat cells. The ability of ascorbate to enhance cytoplasmic inhibitory IkBalpha protein degradation correlates completely with its capacity to induce NF-kappaB binding to DNA and to potentiate NF-kappaB-mediated transactivation of the HIV-1 long terminal repeat promoter in TNF-alpha-stimulated Jurkat cells but not in cells stimulated with PMA plus ionomycin. AFR behaves like ascorbate, while DHA and ascorbate phosphate do not affect TNF-alpha-mediated NF-kappaB activation. These results provide new evidence for a possible relationship between the activation of the electron-transport system at the plasma membrane by ascorbate or its free radical and redox-dependent gene transcription in T-cells.

Ascorbate and alpha-tocopherol prevent apoptosis induced by serum removal independent of Bcl-2.

Cells require serum to maintain growth in vitro. Serum provides growth and survival factors and its removal causes an oxidative stress that induces peroxidations in membrane lipids and development of programmed cell death (apoptosis) in some cells. Cells containing Bcl-2 are partially protected against both lipid peroxidation and apoptosis and some cell lines, such as Daudi, which lack this protein, are very sensitive to serum removal. Thus, cells are grown for 48 h in the absence of fetal calf serum and apoptotic cells are scored. HL-60 cells containing a moderate amount of Bcl-2 show 30% apoptosis, while 55% cells are apoptotic of the Bcl-2-negative Daudi cell population. Apoptosis is reduced to 15% in the transiently transfected Daudi/Bcl-2 cells. Ascorbate (Asc) and alpha-tocopherol (alphaTOH) can prevent lipid peroxidation and apoptosis caused by serum withdrawal, when added to culture media, even in the absence of Bcl-2. Also, these two antioxidants increase survival of cells grown in the absence of serum independent of their Bcl-2 content. Immunostaining and quantification of Bcl-2 show that HL-60 cell line is a heterogeneous population relative to the expression of Bcl-2. When these cells are grown in the presence of serum, cells lacking Bcl-2 survive, but no Bcl-2-negative cells survive without serum. Part of this population of Bcl-2-negative cells is rescued by Asc and alphaTOH. Antioxidants effective at the plasma membrane such as Asc and alphaTOH can protect cells from oxidative damage and prevent apoptosis independent of Bcl-2 content.

Antioxidant ascorbate is stabilized by NADH-coenzyme Q10 reductase in the plasma membrane.

Plasma membranes isolated from K562 cells contain an NADH-ascorbate free radical reductase activity and intact cells show the capacity to reduce the rate of chemical oxidation of ascorbate leading to its stabilization at the extracellular space. Both activities are stimulated by CoQ10 and inhibited by capsaicin and dicumarol. A 34-kDa protein (p34) isolated from pig liver plasma membrane, displaying NADH-CoQ10 reductase activity and its internal sequence being identical to cytochrome b5 reductase, increases the NADH-ascorbate free radical reductase activity of K562 cells plasma membranes. Also, the incorporation of this protein into K562 cells by p34-reconstituted liposomes also increased the stabilization of ascorbate by these cells. TPA-induced differentiation of K562 cells increases ascorbate stabilization by whole cells and both NADH-ascorbate free radical reductase and CoQ10 content in isolated plasma membranes. We show here the role of CoQ10 and its NADH-dependent reductase in both plasma membrane NADH-ascorbate free radical reductase and ascorbate stabilization by K562 cells. These data support the idea that besides intracellular cytochrome b5-dependent ascorbate regeneration, the extracellular stabilization of ascorbate is mediated by CoQ10 and its NADH-dependent reductase.

Plasma membrane ubiquinone controls ceramide production and prevents cell death induced by serum withdrawal.

Serum provides cultured cells with survival factors required to maintain growth. Its withdrawal induces the development of programmed cell death. HL-60 cells were sensitive to serum removal, and an increase of lipid peroxidation and apoptosis was observed. Long-term treatment with ethidium bromide induced the mitochondria-deficient rho(o)HL-60 cell line. These cells were surprisingly more resistant to serum removal, displaying fewer apoptotic cells and lower lipid peroxidation. HL-60 cells contained less ubiquinone at the plasma membrane than rho(o)HL-60 cells. Both cell types increased plasma membrane ubiquinone in response to serum removal, although this increase was much higher in rho(o) cells. Addition of ubiquinone to both cell cultures in the absence of serum improved cell survival with decreasing lipid peroxidation and apoptosis. Ceramide was accumulated after serum removal in HL-60 but not in rho(o)HL-60 cells, and exogenous ubiquinone reduced this accumulation. These results demonstrate a relationship between ubiquinone levels in the plasma membrane and the induction of serum withdrawal-induced apoptosis, and ceramide accumulation. Thus, ubiquinone, which is a central component of the plasma membrane electron transport system, can represent a first level of protection against oxidative damage caused by serum withdrawal.

Ascorbate stabilization is stimulated in rho(0)HL-60 cells by CoQ10 increase at the plasma membrane.

Long-term treatment with ethidium bromide of HL-60 cells induced a mitochondria-deficient rho degree cell line, where mitochondrial DNA can not be identified by PCR and cytochrome c oxidase activity was 80% decreased. These cells showed a progressive increase of ascorbate stabilization which was 52% higher in the established rho degree HL-60 cells. Both CoQ10 and NADH-ascorbate free radical reductase of the plasma membrane were increased in rho(0)HL-60 cells compared to parental cells, while NADH-cytochrome c reductase was unchanged. CoQ10 is a component of the ascorbate stabilization activity in the plasma membrane that would provide both a mechanism to deplete the excess of NADH produced in rho(0)HL-60 cells and for resistance to oxidative stress.

Role of cytochrome b5 reductase on the antioxidant function of coenzyme Q in the plasma membrane.

Cytochrome b5 reductase purified from liver plasma membrane reduces coenzyme Q (CoQ) in reconstituted liposomes in the absence of cytochrome b5. Both CoQ and its reductase are responsible for the reduction of the ascorbate free radical at the cell surface. Thus, NADH-CoQ reductase represents a partial reaction of NADH-AFR reductase in the plasma membrane. Cytochrome b5 reductase maintains CoQ and ascorbate in their reduced state to support antioxidations. Reduced CoQ prevents lipid peroxidation in liposomes and plasma membranes. Also, oxidized CoQ can prevent lipid peroxidations in the presence of cytochrome b5 reductase and NADH. Addition of CoQ to intact cells prevents serum withdrawal-induced lipid peroxidation and apoptosis. The prevention of apoptosis by CoQ is independent of the bcl-2 protein content in the cell. Antioxidants that act at the plasma membrane as CoQ and ascorbate would represent a first barrier to protect lipids from oxidative stress and subsequent apoptosis. Cytochrome b5 reductase is then an enzyme leading this function at the plasma membrane. These data support the idea that when the plasma membrane barrier fails, bcl-2 protein would be required to prevent cell death.

[Laryngopyocele: apropos a case with onset as acute respiratory insufficiency]. / Laringopiocele: a proposito de un caso que debuto con insuficiencia respiratoria aguda.

Report of an unwonted case of laryngopyocele because of its presentation. The patient came into Hospital suffering from acute laryngeal dyspnea, which made us to carry out an urgent tracheotomy. Afterwards a direct laryngoscopy discovered a large tumor, covered by a mucosa of normal appearance, blocking the laryngeal inlet. The laryngopyocele was confirmed by thyrotomy after the previous direct laryngoscopy awaken the suspicious either a malignant grown or a cancer with a laryngocele association.