Incorporating PHI in decision making: external validation of the Rotterdam risk calculators for detection of prostate cancer.

PURPOSE: External validation of existing risk calculators (RC) to assess the individualized risk of detecting prostate cancer (PCa) in prostate biopsies is needed to determine their clinical usefulness. The objective was to externally validate the Rotterdam Prostate Cancer RCs 3 and 4 (RPCRC-3/4) and that incorporating PHI (RPCRC-PHI) in a contemporary Spanish cohort. METHODS: Multicenter prospective study that included patients suspicious of harboring PCa. Men who attended the urology consultation were tested for PHI before prostate biopsy. To evaluate the performance of the prediction models: discrimination (receiver operating characteristic (ROC) curves), calibration and net benefit [decision curve analysis (DCA)] were calculated. These analyses were carried out for detection of any PCa and clinically significant (cs)PCa, defined as ISUP grade ≥ 2. RESULTS: Among the 559 men included, 337 (60.28%) and 194 (34.7%) were diagnosed of PCa and csPCa, respectively. RPCRC-PHI had the best discrimination ability for detection of PCa and csPCa with AUCs of 0.85 (95%CI 0.82-0.88) and 0.82 (95%CI 0.78-0.85), respectively. Calibration plots showed that RPCRC-3/4 underestimates the risk of detecting PCa showing the need for recalibration. In DCA, RPCRC-PHI shows the highest net benefit compared to biopsy all men. CONCLUSIONS: The RPCRC-PHI performed properly in a contemporary clinical setting, especially for prediction of csPCa.

Hypopituitarism and pregnancy: clinical characteristics, management and pregnancy outcome.

PURPOSE: To describe the clinical characteristics, management and pregnancy outcome of women with prepregnancy hypopituitarism (HYPO) that received care at our center. METHODS: Retrospective study describing 12 pregnancies in women with prepregnancy HYPO (two or more pituitary hormonal deficiencies under replacement treatment) that received care during pregnancy at Hospital Santa Creu i Sant Pau. Clinical characteristics, management and pregnancy outcome were systematically collected. RESULTS: Average patients' age was 35 years and HYPO duration at the beginning of pregnancy was 19 years. The most frequent cause of HYPO was surgical treatment of a sellar mass (8 pregnancies). Eight pregnancies were in primigravid women and 10 required assisted reproductive techniques. The hormonal deficits before pregnancy were as follows: GH in 12 women, TSH in 10, gonadotropin in 9, ACTH in 5 and ADH in 2. All deficits were under hormonal substitution except for GH deficit in 4 pregnancies. During pregnancy, 4 new deficits were diagnosed. The dosage of replacement treatment for TSH, ACTH and ADH deficits was increased and GH was stopped. Average gestational age at birth was 40 weeks, gestational weight gain was excessive in 9 women, 8 patients required induction/elective delivery and cesarean section was performed in 6. Average birthweight was 3227 g. No major complications were observed. Five women were breastfeeding at discharge. CONCLUSIONS: In this group of women with long-standing HYPO, with careful clinical management (including treatment of new-onset hormonal deficits) pregnancy outcome was satisfactory but with a high rate of excessive gestational weight gain and cesarean section.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Infection on Pregnancy Outcomes: A Population-based Study.

BACKGROUND: We performed a population-based study to describe the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on pregnancy outcomes. METHODS: This prospective, population-based study included pregnant women who consecutively presented at first/second trimester visits or at delivery at 3 hospitals in Barcelona, Spain. SARS-CoV-2 antibodies (immunoglobulin [Ig] G and IgM/IgA) were measured in all participants, and nasopharyngeal real-time polymerase chain reaction (RT-PCR) was performed at delivery. The primary outcome was a composite of pregnancy complications in SARS-CoV-2-positive vs negative women that included miscarriage, preeclampsia, preterm delivery, perinatal death, small-for-gestational-age newborn, or neonatal admission. Secondary outcomes were components of the primary outcome plus abnormal fetal growth, malformation, or intrapartum fetal distress. Outcomes were also compared between positive symptomatic and positive asymptomatic SARS-CoV-2 women. RESULTS: Of 2225 pregnant women, 317 (14.2%) were positive for SARS-CoV-2 antibodies (n = 314, 99.1%) and/or RT-PCR (n = 36, 11.4%). Among positive women, 217 (68.5%) were asymptomatic, 93 (29.3%) had mild coronavirus disease 2019 (COVID-19), and 7 (2.2%) had pneumonia, of whom 3 required intensive care unit admission. In women with and without SARS-CoV-2 infection, the primary outcome occurred in 43 (13.6%) and 268 (14%), respectively (risk difference, -0.4%; 95% confidence interval, -4.1% to 4.1). Compared with noninfected women, those with symptomatic COVID-19 had increased rates of preterm delivery (7.2% vs 16.9%, P = .003) and intrapartum fetal distress (9.1% vs 19.2%, P = .004), while asymptomatic women had rates that were similar to those of noninfected cases. Among 143 fetuses from infected mothers, none had anti-SARS-CoV-2 IgM/IgA in cord blood. CONCLUSIONS: The overall rate of pregnancy complications in women with SARS-CoV-2 infection was similar to that of noninfected women. However, symptomatic COVID-19 was associated with modest increases in preterm delivery and intrapartum fetal distress.

Can Cognitive-Behavioral Therapy Be Optimized With Parent Psychoeducation? A Randomized Effectiveness Trial of Adolescents With Major Depression in Puerto Rico.

This is a longitudinal randomized control trial on the impact of adding a parent psychoeducation intervention (TEPSI) as part of cognitive-behavioral therapy (CBT) for adolescents with Major Depressive Disorder (MDD) in a Puerto Rican sample. We tested the efficacy of adding 8 group sessions of TEPSI to 12 sessions of individual CBT on reducing depressive symptoms, MDD diagnosis, and improving family functioning. Participants (n = 121) were randomized to individual CBT with or without TEPSI. No main group effects were found for most patient domains including depression symptoms, as well as presence of adolescent's MDD diagnosis at posttreatment. Results did show a main effect of CBT over time for depression symptoms, suicide ideation, family criticism, and the presence of MDD diagnosis decreasing from pre- to postintervention. A year post treatment, almost 70% of adolescents in both conditions (CBT and CBT + TEPSI) remained in remission. A main effect was obtained for treatment in the adolescent's perception of familism and family emotional involvement. The primary hypothesis that family psychoeducation would optimize CBT for depression in adolescents was not supported. Both conditions yielded similar clinical end points. The culturally adapted CBT was found effective with Latino/a adolescents showing clinically significant improvements from pretreatment to posttreatment and remained stable at a 1-year follow-up. Regarding family outcomes, adolescents in CBT + TEPSI remained stable from pretreatment to posttreatment on family emotional involvement, while adolescents in CBT-alone showed an increase. The implication of these findings is discussed.

Este es un ensayo clínico longitudinal aleatorizado y controlado sobre el efecto de agregar una intervención psicoeducativa para los padres (TEPSI, en inglés) como parte de la terapia cognitivo-conductual (TCC) para adolescentes con trastorno depresivo mayor (TDM) en una muestra puertorriqueña. Evaluamos la eficacia de agregar 8 sesiones grupales de TEPSI a 12 sesiones de TCC individual en la reducción de síntomas depresivos, en el diagnóstico de TDM y en la mejora del funcionamiento familiar. Los participantes (n = 121) fueron distribuidos al azar a la TCC individual con o sin TEPSI. No se encontraron efectos grupales principales en la mayoría de las áreas de los pacientes, como en los síntomas de depresión ni en la presencia de un diagnóstico de TDM en los adolescentes después del tratamiento. Los resultados sí demostraron un efecto principal de la TCC con el tiempo para los síntomas de depresión, las ideas suicidas, la crítica familiar y la presencia de un diagnóstico de TDM que disminuye desde antes hasta después de la intervención. Un año después del final del tratamiento, casi el 70 % de los adolescentes en ambas condiciones (TCC y TCC + TEPSI) se mantuvo en remisión. Se obtuvo un efecto principal del tratamiento en la percepción de los adolescentes del familismo y la implicación emocional familiar. No se respaldó la hipótesis principal de que la psicoeducación familiar optimizaría la TCC para la depresión en los adolescentes. Ambas condiciones dieron variables clínicas similares. Se descubrió que la TCC culturalmente adaptada fue eficaz con los adolescentes latinos, ya que demostró mejoras clínicas considerables desde antes del tratamiento hasta después del tratamiento y permaneció estable un año después al momento del seguimiento. Con respecto a los resultados familiares, los adolescentes de la TCC + TEPSI se mantuvieron estables desde antes del tratamiento hasta después del tratamiento en la implicación emocional familiar, mientras que los adolescentes de la TCC sola demostraron un aumento. Se debaten las implicancias de estos resultados.

Lack of transferability between different immunoassays and LC-MS/MS for total 25-hydroxyvitamin D measurement and disagreement defining deficiency.

BACKGROUND: Over the last few years, it has become much more common to measure concentrations of vitamin D, as its deficiency has been associated with an increasing number of health problems. Recently, a number of new immunoassays for measurement of total 25-hydroxyvitamin D (25OH-D) concentration have been released but their results may not be transferable. METHODS: Our main objective was to compare results from the Cobas(®) e411 (Roche Diagnostics), Advia Centaur(®) (Siemens), Architect (Abbott), IDS-iSYS (Vitro S.A.), and Liaison(®) (Diasorin) immunoassay systems with each other and with liquid chromatography-tandem mass spectrometry (LC-MS/MS). We obtained 184 routine serum samples, covering the whole measuring range, for these methods. RESULTS: Kappa values above 0.8 were considered to indicate excellent agreement. With a cut-off of 50 nmol/L Architect and Cobas were the only immunoassay methods able to identify patients with deficiencies consistent with the findings of the reference method LC-MS/MS. On the other hand, using a cut-off of 37.5 nmol/L for Liaison and 75 nmol/L for IDS-iSYS, while maintaining the value of 50 nmol/L for the LC-MS/MS method, kappa values of 0.80 and 0.83 respectively were obtained. CONCLUSIONS: Choosing the best method for each laboratory is challenging due to methodological differences between them and 50 nmol/L cannot be considered as a general cut-off for defining hypovitaminosis.

Do PHI and PHI density improve detection of clinically significant prostate cancer only in the PSA gray zone?

OBJECTIVES: Prostate health index (PHI) is a predictive biomarker of positive prostate biopsy. The majority of evidence refers to its use in the PSA gray zone (4-10 ng/mL) and negative digital rectal exam (DRE). We aim to evaluate and compare the predictive accuracy of PHI and PHI density (PHId) with PSA, percentage of free PSA and PSA density, in a wider range of patients for the detection of clinically significant prostate cancer (csPCa). METHODS: Multicenter prospective study that included patients suspicious of harboring prostate cancer. Non-probabilistic convenience sampling, where men who attended the urology consultation were tested for PHI before prostate biopsy. To evaluate and compare diagnostic accuracy AUC and decision curve analysis (DCA) were calculated. All these procedures were performed for the overall sample and the following subsamples: PSA < 4 ng/ml; PSA 4-10 ng/ml; PSA 4-10 ng/ml plus negative DRE and PSA > 10 ng/ml. RESULTS: Among the 559 men included, 194 (34.7%) were diagnosed of csPCa. PHI and PHId outperfomed PSA in all subgroups. PHI best diagnostic performance was found in PSA 4-10 ng/ml with negative DRE (sensitivity 93.33, NPV 96.04). Regarding AUC, significant differences were found between PHId and PSA in the subgroup of PSA 4-10 ng/ml, whatever DRE status. In DCA, PHI density shows the highest net benefit. CONCLUSIONS: PHI and PHId outperfom PSA in csPCa detection, not only in the PSA grey zone with negative DRE, but also in a wider range of PSA values. There is an urgent need of prospective studies to established a validated threshold and its incorporation in risk calculators.

Prophylactic Treatment of Intestinal Ischemia-Reperfusion Injury Reduces Mucosal Damage and Improves Intestinal Absorption.

Purpose: Intestinal ischemia-reperfusion injury (i-IRI) involves a blood flow interruption in an intestinal segment followed by blood flow restoration. When blood flow is restored, oxidative and inflammatory molecules are distributed throughout the bloodstream, triggering both local and systemic damage. Our goal was to evaluate the potential of three antioxidant and/or anti-inflammatory compounds (curcumin, dexmedetomidine and α-tocopherol) to prevent or reverse local and systemic damage induced by i-IRI. Methods: i-IRI was induced by placing a microvascular clip in the superior mesenteric artery of female WAG/RijHsd rats; the clip was removed after 1h and reperfusion was allowed for 4h. Curcumin (200 mg/kg, orally), α-tocopherol (20 mg/kg, i.p.), and dexmedetomidine (5 or 20 µg/kg, s.c.; DEX5 and DEX20, respectively) were administered. Blood and terminal ileum specimens were collected for biochemical and histological determination. Furthermore, D-xylose absorption test was performed to evaluate intestinal absorption; after completing the 1-hour ischemia and 4-hour reperfusion period, 1 mL of aqueous D-xylose solution (0.615 mg/mL) was administered orally, and one hour later, plasma D-xylose levels were quantified. Results: The histological injury degree (HID) measured by the Chiu scale was significantly reduced when the treatments were applied (non-treated rats, 2.6 ± 0.75; curcumin, 1.54 ± 0.8; DEX5, 1.47 ± 0.7; DEX20 1.14 ± 0.5; and α-tocopherol, 1.01 ± 0.6); intestinal absorptive capacity also improved in all cases healthy rats (2.06 ± 0.07 µg/mL; non-treated, 1.18 ± 0.07 µg/mL; curcumin 1.76 ± 0.3 µg/mL; DEX5, 2.29 ± 0.2 µg/mL; DEX20, 2.25 ± 0.26 µg/mL; and α-tocopherol 1.66 ± 0.21 µg/mL). However, it failed to reduce liver enzyme levels. Finally, only dexmedetomidine significantly reduced urea and creatinine levels compared to non-treated animals. Conclusion: All drugs were effective in reducing HID, although α-tocopherol was effective to a greater extent. Only dexmedetomidine reverted intestinal absorption to normal values of healthy animals.

CT Enterography for Preoperative Evaluation of Peritoneal Carcinomatosis Index in Advanced Ovarian Cancer.

To compare the diagnostic performance of routine CT (rCT), CT enterography (CTE) and intraoperative quantification of PCI to surgical and pathological reference standards in patients with advanced ovarian cancer, a retrospective study of 122 patients who underwent cytoreduction surgery for ovarian peritoneal carcinomatosis was conducted. Radiological, surgical, and pathological PCIs were obtained from the corresponding reports, and the latter two were considered reference standards. The radiological techniques used were rCT: 64 MDCT (32 × 1 mm) (100 mL iopromide 370 i.v., 800 mL water p.o.), and CTE: 64 MDCT (64 × 0.5 mm) (130 mL iopromide 370 i.v., 1800 mL mannitol solution p.o., 20 mg buscopan i.v.). Data were grouped by imaging technique and analyzed using total PCI and stratified by tumor burden (low-PCI < 10, high-PCI > 20). Agreement, diagnostic performance and degree of cytoreduction were evaluated. Disappointing results for rCT and CTE were obtained when using a surgical referent, but better diagnostic performance and concordance (0.86 vs. 0.78 vs. 0.62, p < 0.05) was observed when using a pathological referent-surgical PCI overestimates and overstaged patients. PCI is underestimated by rCT rather than CTE. For high-PCI, the ROC curve was mediocre for CTE and useless for rCT, as it failed to identify any cases. For low-PCI, the ROC was excellent (86% CTE vs. 75% rCT). In four cases with low-PCI as determined by rCT, cytoreduction was suboptimal. CTE has a better diagnostic performance than rCT in quantifying PCI in patients with advanced ovarian cancer, suggesting that CTE should be used as the initial technique. Surgical-PCI could be considered as an imperfect standard reference.

The Prevention of Ischemia-Reperfusion Injury in Elderly Rats after Lower Limb Tourniquet Use.

Background: Lower limb ischemia-reperfusion injury (IRI-LL) is a common major complication of orthopedic surgery, especially in elderly patients. It has previously been demonstrated that folinic acid (FA) reduced IRI-LL damage in 3−4-month-old rats. This current work analyses the effect of FA in the prevention of IRI-LL in elderly animals. Methods: Forty-two 18-month-old male WAG/RijHsd rats were subjected to 3 h of ischemia. Eighteen animals received FA (2.5 mg/kg, ip) 20 min before the end of the ischemia period, while the other half received the same volume of saline solution. The animals were sacrificed after 3 h, 24 h, and 14 days of reperfusion for biochemical (tissue damage markers and electrolytes), histopathological studies of the gastrocnemius muscle and the daily assessment of the limb function by the Rota Rod test, respectively. Results: The administration of FA prior to the end of the ischemia period reduced the increase in LDH and CK observed in non-treated animals by 30−40% (p < 0.0001). When the histological sections were analyzed, FA was found to have reduced the number of damaged muscle fibers per field by 20% (60 ± 17.1 vs. 80.7 ± 16.4, p < 0.0001). The functional test revealed that FA also led to an improvement in the muscle function, assessed by the length of time that the animals kept running on the rod, compared to untreated animals. Conclusions: The administration of FA, prior to the end of the ischemic period, decreases the damage induced by IRI-LL, also achieving a faster recovery of mobility.

Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats.

Liver resection remains the gold standard for hepatic metastases. The future liver remnant (FLR) and its functional status are two key points to consider before performing major liver resections, since patients with less than 25% FLR or a Child-Pugh B or C grade are not eligible for this procedure. Folinic acid (FA) is an essential agent in cell replication processes. Herein, we analyze the effect of FA as an enhancer of liver regeneration after selective portal vein ligation (PVL). Sixty-four male WAG/RijHsd rats were randomly distributed into eight groups: a control group and seven subjected to 50% PVL, by ligation of left portal branch. The treated animals received FA (2.5 m/kg), while the rest were given saline. After 36 h, 3 days or 7 days, liver tissue and blood samples were obtained. FA slightly but significantly increased FLR percentage (FLR%) on the 7th day (91.88 ± 0.61%) compared to control or saline-treated groups (86.72 ± 2.5 vs. 87 ± 3.33%; p < 0.01). The hepatocyte nuclear area was also increased both at 36 h and 7days with FA (61.55 ± 16.09 µm2, and 49.91 ± 15.38 µm2; p < 0.001). Finally, FA also improved liver function. In conclusion, FA has boosted liver regeneration assessed by FLR%, nuclear area size and restoration of liver function after PVL.

Proposal of New Safety Limits for In Vivo Experiments of Magnetic Hyperthermia Antitumor Therapy.

BACKGROUND: Lately, major advances in crucial aspects of magnetic hyperthermia (MH) therapy have been made (nanoparticle synthesis, biosafety, etc.). However, there is one key point still lacking improvement: the magnetic field-frequency product (H × f = 4.85 × 108 Am-1s-1) proposed by Atkinson-Brezovich as a limit for MH therapies. Herein, we analyze both local and systemic physiological effects of overpassing this limit. METHODS: Different combinations of field frequency and intensity exceeding the Atkinson-Brezovich limit (591-920 kHz, and 10.3-18 kA/m) have been applied for 21 min to WAG/RijHsd male rats, randomly distributed to groups of 12 animals; half of them were sacrificed after 12 h, and the others 10 days later. Biochemical serum analyses were performed to assess the general, hepatic, renal and/or pancreatic function. RESULTS: MH raised liver temperature to 42.8 ± 0.4 °C. Although in five of the groups the exposure was relatively well tolerated, in the two of highest frequency (928 kHz) and intensity (18 kA/m), more than 50% of the animals died. A striking elevation in liver and systemic markers was observed after 12 h in the surviving animals, independently of the frequency and intensity used. Ten days later, liver markers were almost recovered in all of the animals. However, in those groups exposed to 591 kHz and 16 kA/m, and 700 kHz and 13.7 kA/m systemic markers remained altered. CONCLUSIONS: Exceeding the Atkinson-Brezovich limit up to 9.59 × 109 Am-1s-1 seems to be safe, though further research is needed to understand the impact of intensity and/or frequency on physiological conditions following MH.

Factor Structure of the Escala de Autoeficacia para la Depresión en Adolescentes (EADA).

The current concept and measures of self-efficacy for depression in adolescents do not consider developmental and cultural aspects essential to understand and assess this construct in Latino youth. We examined the factor structure of the Escala de Autoeficacia para la Depresión en Adolescentes (EADA): a Spanish instrument designed to assess this construct as experienced by this population. Participants were 116 Puerto Rican adolescents aged 13 to 17 years who completed the EADA and two other self-report measures. An exploratory factor analysis yielded a two-factor solution (Personal Self-Efficacy for Depression and Interpersonal Self-Efficacy for Depression) accounting for 37.57% of the total variance. Results revealed that EADA factors have excellent internal consistency as well as concurrent and construct validity, supporting its adequacy to assess Latino adolescents' self-efficacy for depression. The conceptual meaning of the factors was consistent with the distinction between aspects of this construct hypothesized to be important among Latino youth.

Curcumin Reduces Colorectal Cancer Cell Proliferation and Migration and Slows In Vivo Growth of Liver Metastases in Rats.

BACKGROUND: New therapeutic approaches are an essential need for patients suffering from colorectal cancer liver metastases. Curcumin, a well-known plant-derived polyphenol, has been shown to play a role in the modulation of multiple signaling pathways involved in the development and progression of certain cancer cells in vitro. This study aims to assess the anti-tumor effect of curcumin on CC531 colorectal cancer cells, both in vitro and in vivo. METHODS: On CC531 cultures, the cell viability and cell migration capacity were analyzed (wound healing test) 24, 48, and 72 h after treatment with curcumin (15, 20, 25, or 30 µM). Additionally, in WAG/RijHsd tumor-bearing rats, the total and individual liver lobe tumor volume was quantified in untreated and curcumin-treated animals (200 mg/kg/day, oral). Furthermore, serum enzyme measurements (GOT, GPT, glucose, bilirubin, etc.) were carried out to assess the possible effects on the liver function. RESULTS: In vitro studies showed curcumin's greatest effects 48h after application, when all of the tested doses reduced cell proliferation by more than 30%. At 72 h, the highest doses of curcumin (25 and 30 µM) reduced cell viability to less than 50%. The wound healing test also showed that curcumin inhibits migration capacity. In vivo, curcumin slowed down the tumor volume of liver implants by 5.6-fold (7.98 ± 1.45 vs. 1.41 ± 1.33; p > 0.0001). CONCLUSIONS: Curcumin has shown an anti-tumor effect against liver implants from colorectal cancer, both in vitro and in vivo, in this experimental model.

Biochemical and Metabolomic Changes after Electromagnetic Hyperthermia Exposure to Treat Colorectal Cancer Liver Implants in Rats.

BACKGROUND: Hyperthermia (HT) therapy still remains relatively unknown, in terms of both its biological and therapeutic effects. This work aims to analyze the effects of exposure to HT, such as that required in anti-tumor magnetic hyperthermia therapies, using metabolomic and serum parameters routinely analyzed in clinical practice. METHODS: WAG/RigHsd rats were assigned to the different experimental groups needed to emulate all of the procedures involved in the treatment of liver metastases by HT. Twelve hours or ten days after the electromagnetic HT (606 kHz and 14 kA/m during 21 min), blood samples were retrieved and liver samples were obtained. 1H-nuclear-magnetic-resonance spectroscopy (1H-NMR) was used to search for possible diagnostic biomarkers of HT effects on the rat liver tissue. All of the data obtained from the hydrophilic fraction of the tissues were analyzed and modeled using chemometric tools. RESULTS: Hepatic enzyme levels were significantly increased in animals that underwent hyperthermia after 12 h, but 10 d later they could not be detected anymore. The metabolomic profile (main metabolic differences were found in phosphatidylcholine, taurine, glucose, lactate and pyruvate, among others) also showed that the therapy significantly altered metabolism in the liver within 12 h (with two different patterns); however, those changes reverted to a control-profile pattern after 10 days. CONCLUSIONS: Magnetic hyperthermia could be considered as a safe therapy to treat liver metastases, since it does not induce irreversible physiological changes after application.

Autopsy findings from the first known death from Severe Acute Respiratory Syndrome SARS-CoV-2 in Spain.

The new coronavirus SARS-CoV-2, first identified in Wuhan, China in December, 2019, can cause Severe Acute Respiratory Syndrome (SARS) with massive alveolar damage and progressive respiratory failure. We present the relevant autopsy findings of the first patient known to have died from COVID19 pneumonia in Spain, carried out on the 14th of February, 2020, in our hospital (Hospital Arnau de Vilanova-Lliria, Valencia). Histological examination revealed typical changes of diffuse alveolar damage (DAD) in both the exudative and proliferative phase of acute lung injury. Intra-alveolar multinucleated giant cells, smudge cells and vascular thrombosis were present. The diagnosis was confirmed by reverse real-time PCR assay on a throat swab sample taken during the patient's admission. The positive result was reported fifteen days subsequent to autopsy.

Ultrasound Tumor Size Assessment, Histology and Serum Enzyme Analysis in a Rat Model of Colorectal Liver Cancer.

During tumor development, tissue necrosis appears as a natural phenomenon directly associated with an increase in tumor size. The aim of this study was to assess the use of ultrasound (US) for predicting natural tumor necrosis in a rat liver implant model of colorectal cancer. To achieve this goal, we sought to establish a correlation between US-measured tumor volume, serum enzyme levels and histopathological findings, particularly those regarding necrosis phenomena in liver implants. Under US guidance, CC531 colorectal cancer cells were injected into the left liver lobe of WAG/RijHsd rats. Twenty-eight days after cell inoculation, tumor volume was measured by US, and rats were sacrificed to obtain samples of tumor tissue as well as blood serum. In hematoxylin and eosin-stained tumor samples, the percentage of tumor that was necrotic was estimated. The association between percentage tumor necrosis and US-measured tumor volume was assessed by univariate logistic regression analysis, and a linear regression equation was obtained. Serum enzyme levels did not differ significantly between tumor-bearing and tumor-free rats. Tumor implants appeared as well-defined hyper-echoic regions with a mean volume of 0.61 ± 0.39 mL and tumor necrosis percentage of 8.6 ± 7.7%. Linear regression analysis revealed a very strong relationship (Pearson correlation coefficient r = 0.911) between US-measured tumor volume and tumor necrosis percentage; the regression equation was tumor necrosis percentage = 21 × US-measured tumor volume (in mL) - 3.1. The study found US to be a useful tool in animal-based trials. Tumors inside the liver (ranging in volume from 0.24-1.37 mL) can be observed by US, and moreover, US-measured tumor volume on day 28 can be used to estimate tumor necrosis occurring as the natural evolution of tumor implants.

N-Benzyl-indolo carboxylic acids: Design and synthesis of potent and selective adipocyte fatty-acid binding protein (A-FABP) inhibitors.

Small molecule inhibitors of adipocyte fatty-acid binding protein (A-FABP) have gained renewed interest following the recent publication of pharmacologically beneficial effects of such inhibitors. Despite the potential utility of selective A-FABP inhibitors within the fields of metabolic disease, inflammation and atherosclerosis, there are few examples of useful A-FABP inhibitors in the public domain. Herein, we describe the optimization of N-benzyl-tetrahydrocarbazole derivatives through the use of co-crystal structure guided medicinal chemistry efforts. This led to the identification of a potent and selective class of A-FABP inhibitors as illustrated by N-benzyl-hexahydrocyclohepta[b]indole 30.

Individual and group CBT and IPT for Puerto Rican adolescents with depressive symptoms.

This study compared individual (I) to group (G) formats of cognitive-behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for the treatment of depression in adolescents. One hundred and 12 Puerto Rican adolescents were randomized to four conditions (CBT-I, CBT-G, IPT-I, IPT-G). Participants were assessed at pretreatment and posttreatment with structured interviews to establish diagnosis and with self-report measures to assess treatment outcome. The results suggest that CBT and IPT are robust treatments in both group and individual formats. However, CBT produced significantly greater decreases in depressive symptoms and improved self-concept than IPT. The implications of these findings are discussed.

Hepatic epithelioid hemangioendothelioma: A great mimicker.

INTRODUCTION: Epithelioid hemangioendothelioma is a malignant mesenchymal tumor of unknown etiology. They tend to be asymptomatic or with non-specific symptoms. The lesion is usually multiple and variable size. PRESENTATION OF CASE: We describe a clinical case of a 23-years-old patient diagnosed with a pelvic mass, a possible uterine fibroid or adnexal mass, and multiple liver lesions that seemed an advanced ovarian cancer presentation and after liver biopsy turned out to be a hepatic epithelioid hemangioendothelioma. DISCUSSION: It may be confused with a metastatic process in diagnostic imaging. There have been described some possible risk factors but the etiology remains unknown. The prognosis is usually lethal in 50% of cases. The surgical removal of the lesion and liver transplant appear to be the only hope for these patients. CONCLUSION: Epithelioid hemangioendothelioma must be part of our differential diagnosis when we find a liver tumour, especially in young women. Treatment is excision of the tumour in limited disease. In the case of unresectable disease are candidates for liver transplantation.