The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study.

INTRODUCTION: Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction. METHODS: Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days. RESULTS: In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC. DISCUSSION: These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality.

Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: recurrent disease.

This manuscript reports the consensus statements regarding recurrent ovarian cancer (ROC), reached at the fifth Ovarian Cancer Consensus Conference (OCCC), which was held in Tokyo, Japan, in November 2015. Three important questions were identified: (i) What are the subgroups for clinical trials in ROC? The historical definition of using platinum-free interval (PFI) to categorise patients as having platinum-sensitive/resistant disease was replaced by therapy-free interval (TFI). TFI can be broken down into TFIp (PFI), TFInp (non-PFI) and TFIb (biological agent-free interval). Additional criteria to consider include histology, BRCA mutation status, number/type of previous therapies, outcome of prior surgery and patient reported symptoms. (ii) What are the control arms for clinical trials in ROC? When platinum is considered the best option, the control arm should be a platinum-based therapy with or without an anti-angiogenic agent or a poly (ADP-ribose) polymerase (PARP) inhibitor. If platinum is not considered the best option, the control arm could include a non-platinum drug, either as single agent or in combination. (iii) What are the endpoints for clinical trials in ROC? Overall survival (OS) is the preferred endpoint for patient cohorts with an expected median OS < or = 12 months. Progression-free survival (PFS) is an alternative, and it is the preferred endpoint when the expected median OS is > 12 months. However, PFS alone should not be the only endpoint and must be supported by additional endpoints including pre-defined patient reported outcomes (PROs), time to second subsequent therapy (TSST), or time until definitive deterioration of quality of life (TUDD).

Therapy with ombitasvir/paritaprevir/ritonavir plus dasabuvir is effective and safe for the treatment of genotypes 1 and 4 hepatitis C virus (HCV) infection in patients with severe renal impairment: A multicentre experience.

Limited data are available on direct-acting antivirals for treating hepatitis C virus (HCV) infection in patients with severe renal impairment. The aim of this study was to evaluate the effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) in patients with stage 4 or 5 chronic kidney disease (CKD) and HCV genotype 1 or 4 infection in real clinical practice, and to investigate pharmacological interactions. This retrospective study included patients treated with OBV/PTV/r+DSV±RBV or OBV/PTV/r+RBV with CKD stage 4 (eGFR: 15-29 mL/min/1.73m2 ) or 5 (eGFR<15 mL/min/1.73m2 or requiring dialysis) and HCV infection by genotypes 1 and 4 between April 2015 and October 2015 in nine Spanish centres. Sustained virological response at 12 weeks (SVR12) was assessed, and clinical and laboratory data, fibrosis stage, adverse events and pharmacological interactions were reported. Forty-six patients were included: 10 (21.7%) had CKD stage 4 and 36 (78.2%) CKD stage 5. Seventeen (36.9%) had cirrhosis. SVR12 rate in the intention-to-treat population was 95.7%. Twenty-one (45.6%) received RBV, which was discontinued in two (9.5%) patients. Anaemia (haemoglobin <10 g/dl) occurred in 12 patients (57.1%) with RBV vs 10 (40.0%) without RBV (P=.246). Renal function remained stable during antiviral therapy. Nine patients (19.5%) experienced serious adverse events unrelated to antiviral therapy. Concomitant medication was discontinued or modified in 41.3% of patients. In conclusion, the effectiveness of OBV/PTV/r±DSV±RBV in patients with CKD 4-5 was similar to that observed in those with normal renal function and was not associated with severe adverse events.

Effectiveness and safety of sofosbuvir-based regimens plus an NS5A inhibitor for patients with HCV genotype 3 infection and cirrhosis. Results of a multicenter real-life cohort.

Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014-October 2015). In total, 208 patients were included: 98 (47%) treatment-experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events.

Effectiveness and safety of ombitasvir, paritaprevir, ritonavir ± dasabuvir ± ribavirin: An early access programme for Spanish patients with genotype 1/4 chronic hepatitis C virus infection.

Over the last 5 years, therapies for hepatitis C virus (HCV) infection have improved significantly, achieving sustained virologic response (SVR) rates of up to 100% in clinical trials in patients with HCV genotype 1. We investigated the effectiveness and safety of ombitasvir/paritaprevir/ritonavir±dasabuvir in an early access programme. This was a retrospective, multicentre, national study that included 291 treatment-naïve and treatment-experienced patients with genotype 1 or 4 HCV infection. Most patients (65.3%) were male, and the mean age was 57.5 years. The mean baseline viral load was 6.1 log, 69.8% had HCV 1b genotype, 72.9% had cirrhosis and 34.7% were treatment-naïve. SVR at 12 weeks posttreatment was 96.2%. Four patients had virological failure (1.4%), one leading to discontinuation. There were no statistical differences in virological response according to genotype or liver fibrosis. Thirty patients experienced serious adverse events (SAEs) (10.3%), leading to discontinuation in six cases. Hepatic decompensation was observed in five patients. Four patients died during treatment or follow-up, three of them directly related to liver failure. Multivariate analyses showed a decreased probability of achieving SVR associated with baseline albumin, bilirubin and Child-Pugh score B, and a greater probability of developing SAEs related to age and albumin. This combined therapy was highly effective in clinical practice with an acceptable safety profile and low rates of treatment discontinuation.

Use of transient elastography (FibroScan®) for the noninvasive assessment of portal hypertension in HIV/HCV-coinfected patients.

The hepatic venous pressure gradient (HVPG) is the gold standard for assessing portal pressure and correlates with the occurrence of portal hypertension (PH)-related complications. Transient elastography (TE) is a new, highly accurate noninvasive technique, which enables us to evaluate hepatic fibrosis to detect advanced fibrosis and cirrhosis. We performed a hepatic haemodynamic study and TE in 38 HIV/HCV-coinfected patients. The association between HVPG and liver stiffness was assessed by linear regression. The diagnostic value of TE was assessed by receiver operating characteristic (ROC) curves. We considered clinically significant PH as an HVPG ≥ 10 mmHg and severe PH as an HVPG ≥ 12 mmHg. A total of 38 HIV/HCV-coinfected patients were included. Twenty-eight patients (73.7%) had clinically significant PH (HVPG ≥ 10 mmHg), and 23 (60.5%) of these had severe PH (HVPG ≥ 12 mmHg). We found a statistically significant association between liver stiffness (kPa) and HVPG (r(2) = 0.46, P < 0.001, straight line equation HVPG=7.4 + 0.204*TE). The areas under the ROC curves were 0.80 [95% confidence interval (CI), 0.64-0.97] and 0.80 (95% CI, 0.66-0.94) for the prediction of HVPG ≥ 10 and ≥ 12 mmHg, respectively. Our data suggest that TE can predict the presence of clinically significant and severe PH in HIV/HCV-coinfected patients.

Effects of ultraviolet-filters on Daphnia magna development and endocrine-related gene expression.

Ultraviolet (UV) filters are emerging contaminants of concern that are widely spread throughout the aquatic environment. Many organic UV filters are endocrine disrupting compounds (EDCs) in vertebrates. However, few studies have assessed their effects on invertebrates. Molting, or the shedding of the exoskeleton, may be affected by exposure to these compounds in Arthropods (the largest phylum of invertebrates). Molting is necessary for growth and development and is regulated by an arthropod specific endocrine system, the ecdysteroid pathway. Alterations of this process by EDCs can result in improper development, reduced growth, and even death. We investigated the sublethal effects of chronic exposure to three organic UV filters (4-methylbenzylidene camphor (4MBC), octylmethoxycinnamate (OMC), and benzophenone-3 (BP3) in a crustacean, Daphnia magna, with particular emphasis on molting and development. We demonstrate that 4MBC, OMC, and BP3 affect development and long-term health in neonates of exposed parents at concentrations of 130 µg/L, 75 µg/L, and 166 µg/L, respectively. Additionally, the expression of endocrine-related genes (including ultraspiracle protein, usp) are significantly altered by 4MBC and BP3 exposure, which may relate to their developmental toxicity.

Brain metastases treated with radiosurgery or hypofractionated stereotactic radiotherapy: outcomes and predictors of survival.

INTRODUCTION: To assess treatment outcome and prognostic factors associated with prolonged survival in patients with brain metastases (BM) treated with stereotactic radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (HFSRT). METHODS/PATIENTS: This study retrospectively reviewed 200 patients with 324 BM treated with one fraction (15-21 Gy) or 5-10 fractions (25-40 Gy) between January 2010 and August 2016. 26.5% of patients received whole brain radiotherapy (WBRT) and 25% initial surgery. Demographics, prognostic scales, systemic and local controls, patterns of relapse and rescue, toxicity, and cause of death were analyzed. A stratified analysis by primary tumor was done. RESULTS: Median overall survival (OS) was 8 months from SRS/HFSRT. Breast cancer patients had a median OS of 17 months, followed by renal (11 months), lung (8 months), colorectal (5 months), and melanoma (4 months). The univariate analysis showed improved OS in females (p 0.004), RPA I-II (p < 0.001) initial surgery (p < 0.001), absence of extracranial disease (p 0.023), and good disease control (p 0.002). There were no differences in OS or local control between SRS and HFSRT or in patients receiving WBRT. Among 44% of brain recurrences, 11% were in field. 174 patients died, 10% from confirmed intracranial progression. CONCLUSIONS: SRS and HSFRT are equally effective and safe for the treatment of BM, with no exceptions among different primary tumors. Disease control, surgery, age, and prognostic scales correlated with OS. However, the lack of survival benefit regarding WBRT might become logical evidence for its omission in a subset of patients.

Serum levels of fibrosis biomarkers measured early after liver transplantation are associated with severe hepatitis C virus recurrence.

This prospective study analyzed the relationship between several biological markers related to liver fibrosis at 3 months and 1 year post liver transplantation in 37 patients (19 with hepatitis C virus [HCV], 18 with alcoholic liver disease). Severe HCV recurrence (HCV-SR) was defined as fibrosis stage > or =F1 (METAVIR score) at 1 year and/or a value of hepatic venous pressure gradient > or=6 mmHg. We found HCV-SR patients had higher values of monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and hyaluronic acid (HA) than non-severe HCV recurrence patients (P<0.05). Moreover, receiver operating characteristic curve analysis showed that interferon-inducible protein 10 (IP-10) (area under the curve [AUC]: 0.74; confidence interval [CI] 95%: 0.49-0.91; P=0.043), MCP-1 (AUC: 0.78; CI 95%: 0.54-0.94; P=0.007), sVCAM-1 (AUC: 0.89; CI 95%: 0.67-0.98; P=0.005), and HA (AUC: 0.80; CI 95%: 0.55-0.94; P=0.035) have good predictive capacity for identifying severe HCV infection. The evaluation of these biomarkers may be useful in the early identification of patients in whom a more aggressive therapeutic approach could be necessary.

High rate of infection and immune disorders in patients with hepatitis C virus after liver transplantation.

The aim of this prospective study was to analyze the incidence of serious infections and changes in immunological markers after liver transplantation (LT) in a cohort of patients with hepatitis C virus (HCV). This study included 34 patients who had LT, 20 patients with HCV etiology (HCV group), and 14 patients with alcoholic etiology (non-HCV group). Patients with HCV were more likely to have severe infections (80%) in comparison with patients in the non-HCV group (42%) (P=0.05). The HCV group had a 3-fold greater likelihood of early severe bacterial infections than the non-HCV group. At 1 week post LT, the HCV group showed higher values of CD19+ B cells/microL than the non-HCV group (P<0.05). At weeks 4 and 12 post LT, the HCV group had lower values of CD19+ B cells/microL (P<0.05). Our data suggest that HCV recurrence after LT was associated with a high incidence of early severe infections and immunological alterations, which may be related to this increased risk.

BK virus in liver transplant recipients: a prospective study.

BACKGROUND: BK virus (BKV) is a polyomavirus that is associated with nephropathy and graft loss among kidney transplant recipients. The role of BK virus in nonrenal solid organ transplant recipients has not been clearly established; only anecdotal case reports have been published. METHODS: From August 2005 to September 2007, all liver transplant (OLT) recipients who gave their consent were enrolled in this prospective longitudinal study. BK viral load was measured using real-time quantitative polymerase chain reaction assays of urine and plasma, using samples collected at week 1 and months 1, 3, 6, 9, 12, 15, 18, 21, and 24 posttransplantation. We also collected demographic and clinical data, including serum creatinine and immunosuppressive therapy. RESULTS: The mean age of the 62 patients was 51.4 years including 14 (22.5%) women. Hepatitis C infection was present in 24 patients (38.7%). BK viruria was detected in 14.5% of 290 samples, corresponding to 13 patients (21%). BK viremia was detected in 5.1% of 317 samples, corresponding to 11 patients (18%). Almost all cases of BK viremia (91%) occurred in the first 3 months after OLT. BKV viremia was more common among patients experiencing a rejection episode (10.6 vs 40%, P = .01). We did not observe a relationship between single episodes of BKV replication and renal function: median plasma creatinine 1.1 mg/dL in patients without versus 1.2 mg/dL with BKV viremia. The three patients with persistent viremia displayed renal insufficiency; one of them died due to multiorgan failure of unknown origin. CONCLUSIONS: BKV is frequently detected in OLT recipients (viruria 21% and viremia 18%) early after transplantation. It is more common among patients with rejection episodes. Persistent BKV viremia may be related to renal dysfunction in OLT patients.

Sengstaken Tube Removal under Direct Hemodynamic Monitoring after Post Transplantation Venous Occlusion.

The surgical procedure for orthotopic liver transplantation (OLT) is well standardized, and most groups use the retrohepatic caval preservation or piggyback technique to improve hemodynamic tolerance. However, when a discrepancy between the site in the right upper quadrant of the liver recipient and a small graft is present, this technique can provoke a rotation on the axis of the vena cava and cause an occlusion of the suprahepatic vein drainage. This problem can be detected intraoperatively, and several methods have been described to resolve it by placing different devices to correct the position. Early withdrawal may cause the development of clinical hepatic congestion with ascites unresponsive to medical treatment. We present three cases of OLT who developed obstruction of the venous drainage solved intraoperatively with the placement of a Sengstaken-Blakemore tube. As a novelty, prior to the withdrawal of the device, a transjugular hemodynamic study was performed to ensure the correct position of the liver with adequate venous drainage.

Humoral and cellular immune monitoring might be useful to identify liver transplant recipients at risk for development of infection.

Orthotopic liver transplantation (OLT) is a successful therapy for patients with end-stage liver disease, and infection remains a significant cause of morbidity and mortality for patients undergoing this procedure. To assess humoral and cellular immunity markers as potential risk factors for development of infection, 46 consecutive liver transplant recipients (hepatitis C virus cirrhosis [n=17], alcoholic liver disease [n=15], hepatocellular carcinoma [n=9], autoimmune hepatitis [n=2], and other [n=3]) performed at a single center were prospectively studied. Maintenance therapy included tacrolimus (n=37) or cyclosporine (n=9) and prednisone. During follow-up, 27 patients had at least 1 episode of infection (58.7%). Pre-OLT immunoglobulin G (IgG) hypergammaglobulinemia (relative risk [RR] 2.78; 95% confidence interval [CI], 1.17-6.60, P=0.02), pre-OLT IgA hypergammaglobulinemia (RR 2.77, CI=1.24-6.19, P=0.012), and pre-OLT C3 hypocomplementemia (RR 3.02, CI=1.21-7.55, P=0.018) were associated with an increased risk for development of infection. Monitoring of Ig and complement levels might help to identify the risk of developing infection in OLT.

[Supplemental oxygen for the prevention of postoperative nausea and vomiting: a meta-analysis of randomized clinical trials]. / Oxígeno suplementario para la prevención de la náusea y el vómito postoperatorios: Meta-análisis de experimentos clínicos aleatorizados.

OBJECTIVE: Despite the development of antiemetic drugs, the incidence of postoperative nausea and vomiting remains between 20% and 30%. This meta-analysis examines the hypothesis that perioperative administration of supplemental oxygen reduces the incidence of these complications. METHODS: We performed a systematic search of the literature through MEDLINE, EMBASE, the Cochrane Library, reference lists, and a manual search, with no language restrictions, up to September 2007 to identify randomized clinical trials evaluating the effect o f supplemental oxygen on postoperative nausea and vomiting. The data were extracted and analyzed using the RevMan program, version 4.2.9 (Cochrane Collaboration, Oxford, UK). RESULTS: The study included 9 randomized clinical trials with a total of 1661 enrolled patients (824 assigned to the group with a higher oxygen concentration and 837 assigned to the group with a lower oxygen concentration). Perioperative supplemental oxygen has no effect on the incidence of nausea (relative risk [RR], 0.94; 95% confidence interval [CI], 0.82 to 1.08), postoperative nausea and/or vomiting (RR, 0.93; 95% CI, 0.74 to 1.17), or the need for rescue antiemetic drugs (RR, 0.90; 95% CI, 0.70 to 1.15). The incidence of vomiting, however, is reduced (RR, 0.77; 95% CI, 0.62 to 0.97). Significant differences were not found in the incidence of atelectasis (RR, 1.23; 95% CI, 0.50 to 3.00) or postoperative PaCO2 (weighted mean difference, -4.0; 95% CI, -12.3 to 4.3). CONCLUSIONS: Supplemental oxygen reduces the incidence of postoperative vomiting. Administration of supplemental oxygen could be an effective method of reducing postoperative vomiting but does not replace current indications for pharmacologic prophylaxis.

[Construction and validation of a model to predict intraoperative hypothermia]. / Construcción y validación de un modelo predictivo de hipotermia intraoperatoria.

OBJECTIVES: Perioperative hypothermia is linked to adverse effects that increase morbidity and mortality. The objectives of this study were to identify the risk factors for intraoperative hypothermia and construct an instrument for identifying patients at high risk. MATERIALS AND METHODS: We studied patients of all ages who had undergone surgery. Patients were assigned to a design group or a validation group by means of a list of randomly generated numbers. Intraoperative hypothermia was defined by an tympanic temperature of 35.9 degrees C or less. A bivariate analysis of the design group identified the predictive factors and a multivariate analysis (logistic regression with backward elimination of nonsignificant variables) provided a predictive model. Risk scores were obtained for each variable by converting them to a 4-degree risk scale (abbreviated model). Predictive power was determined by calculating the area under the receiver-operator characteristic curve (AUC). RESULTS: We enrolled 264 consecutive patients; 200 were assigned to the design group and 64 to the validation group. In the design group, the AUC was 0.85 for the complete model and 0.83 for the abbreviated model. In the validation group, the AUC was 0.85 for the complete model and 0.82 for the abbreviated model. The P value was <.01 for all curves. CONCLUSION: Age, weight, approximate duration of surgery, and body and ambient temperature during induction were the included factors that predicted intraoperative hypothermia in a heterogeneous sample of surgical patients.

Prognostic value of hepatic venous pressure gradient for in-hospital mortality of patients with severe acute alcoholic hepatitis.

BACKGROUND: Hepatic venous pressure gradient (HVPG) has prognostic value in complications and survival of patients with liver cirrhosis. However, the relationship between HVPG and the outcome of acute alcoholic hepatitis (AAH), as well as the specific features of portal hypertension syndrome in this setting, have not been defined. AIMS: To evaluate the prognostic value of HVPG and to analyse the degree of portal hypertension and hyperdynamic circulation in patients with severe AAH. METHODS: Early measurements of HVPG were performed in 60 patients with severe AAH, and compared with the haemodynamic findings of 37 and 29 liver transplantation candidates with alcoholic or viral end-stage cirrhosis respectively. RESULTS: Twenty-three patients (38%) died during hospitalization. Portal hypertension and hyperdynamic circulation were more severe in AAH patients. HVPG was greater in non-survivors [26.9 (7.4) vs. 19.4 (5.2) mmHg, P < 0.001]. Only 4/31 (13%) patients with HVPG 22 (P < 0.001). Encephalopathy (OR 9.4; CI 1.4-64.8), Model for End-Stage Liver Disease (MELD) score > 25 (OR 7.4; CI 1.4-39.9) and HVPG > 22 mmHg (OR 6.7; CI 1.1-39.9) were independently associated to in-hospital mortality. CONCLUSIONS: Early measurement of HVPG provides important prognostic information on the short-term outcome of patients with severe AAH. In addition, MELD score also seems to be a strong prognostic factor in these patients.

Treatment guidelines in ovarian cancer.

National and international specialists have met with the aim of writing down the guidelines for the treatment of epithelial ovarian cancer (in the Spanish Castilian language). These guidelines are based on the International Consensus that was published in English in the Annals of Oncology in 2005. This condition is the leading cause of death from gynaecological cancer in western countries. Its low rate of survival, barely 30% at 5 years, is above all due to late diagnosis and inappropriate surgery, so emphasis is put on these aspects. After describing the methodology for early detection and a scheme of surgical diagnostic procedures in view of the staging of an ovarian mass, the following therapeutic strategies will be recommended: cytoreductive surgery together with platinum chemotherapy under normal conditions, and also in the case of relapse. Likewise, very recent models of treatment focused on molecular targets are presented, and a broad section on methodology of clinical assays. As for this, co-operation among groups is crucial in order to make the conclusions of these studies valid for the development of new therapies.

The binding of near-ultraviolet light-induced tryptophan photoproduct(s) to DNA.

To test one possible mode of toxicity of L-tryptophan photoproduct(s) to bacterial cells, we have examined the binding of near-ultraviolet light-treated tryptophan to purified Escherichia coli DNA in vitro. The results show that co-irradiated (or pre-irradiated) [3H]tryptophan binds to purified DNA as assayed by trichloroacetic acid co-precipitation of DNA and 3H counts on cellulose filters. This was supported by co-sedimentation of DNA and 3H photoproduct(s) on CsCl gradients. Hot trichloroacetic acid extraction or enzymatic digestion of DNA prevents filter binding. The binding is most efficient when tryptophan and DNA are co-irradiated. Under these conditions, binding is more efficient with denatured rather than native DNA. From kinetic studies, the binding is DNA-dependent at constant doses of near-ultraviolet light. At a dose of 2.16 - 10(6) ergs - mm-2 we estimate that 100-150 L-[3H]tryptophan equivalents are bound per E. coli genome equivalent. The binding does not occur with another aromatic amino acid such as tyrosine.

Secretory carcinoma of the breast containing the ETV6-NTRK3 fusion gene in a male: case report and review of the literature.

BACKGROUND: Secretory carcinoma (SC) of the breast is a rare and indolent tumor. Although originally described in children, it is now known to occur in adults of both sexes. Recently, the tumor was associated with the ETV6-NTRK3 gene translocation. CASE PRESENTATION: A 52-year-old male was diagnosed with secretory breast carcinoma and underwent a modified radical mastectomy. At 18 months the tumor recurred at the chest wall and the patient developed lung metastases. He was treated concurrently with radiation and chemotherapy without response. His tumor showed the ETV6-NTRK3 translocation as demonstrated by fluorescent in situ hybridization (FISH). CONCLUSION: SC is a rare slow-growing tumor best treated surgically. There are insufficient data to support the use of adjuvant radiation or chemotherapy. Its association with the ETV6-NTRK3 fusion gene gives some clues for the better understanding of this neoplasm and eventually, the development of specific therapies.