Clinical Usefulness of Prostate-specific Membrane Antigen-ligand Positron Emission Tomography/Computed Tomography for the Detection of Prostate Cancer Biochemical Recurrence after Primary Radiation Therapy in Patients with Prostate-specific Antigen Below the Phoenix Threshold: Systematic Review and Meta-analysis.

AIMS: After primary radiotherapy, biochemical recurrence is defined according to the Phoenix criteria as a prostate-specific antigen (PSA) value >2 ng/ml relative to the nadir. Several studies have shown that prostate-specific membrane antigen (PSMA)-ligand positron emission tomography/computed tomography (PET/CT) can help in detecting recurrence in patients with low PSA values. This study aimed to assess the detection rate and patterns of PSMA-ligand PET/CT uptake in patients with suspected biochemical recurrence after primary radiotherapy and with PSA levels below the Phoenix threshold. MATERIALS AND METHODS: The meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Articles providing data on patients with suspected prostate cancer recurrence after primary radiotherapy with a PSA value below the Phoenix threshold and who underwent PSMA-ligand PET/CT were included. Quality assessment was carried out using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). RESULTS: In total, five studies were included, recruiting 909 patients (202 with PSA ≤2 ng/ml). The PSMA-ligand detection rate in the patients with ≤2 ng/ml ranged from 66 to 83%. The most frequent source of PSMA-ligand PET/CT uptake was local recurrence, followed by lymph node metastasis and bone metastasis. PSMA-ligand PET/CT uptake due to local-only recurrence was more likely in patients with PSA ≤2 ng/ml compared with PSA > 2 ng/ml: risk ratio 0.72 (95% confidence interval 0.58-0.89), P = 0.003. No significant differences were observed in the detection of PSMA-ligand uptake in other areas. Limitations include a lack of biopsy confirmation, cohort reports with small sample sizes and a potentially high risk of bias. CONCLUSION: A significant detection of PSMA-ligand-avid disease was observed in patients with PSA levels below the Phoenix threshold. There was a higher likelihood of detecting local-only uptake when the PSA value was ≤2 ng/ml. The findings suggest that a critical review of the Phoenix criteria may be warranted in the era of PSMA-ligand PET/CT and highlight the need for further prospective trials.

Cryotherapy versus high-intensity focused ultrasound for treating prostate cancer: Oncological and functional results. / Crioterapia frente a high intensity focused ultrasound en el tratamiento del cáncer de próstata: resultados oncológicos y funcionales.

CONTEXT AND OBJECTIVE: The increasingly early diagnosis of prostate cancer requires a search for therapeutic alternatives with good oncological results that in turn facilitate a good long-term quality of life. This review analyses 2 minimally invasive therapies for treating localised prostate cancer in terms of oncological and functional results, as well as the complications resulting from the therapies. ACQUISITION OF EVIDENCE: A systematic literature review was conducted of the treatment of localised prostate cancer with 2 ablative techniques as the primary therapy: cryosurgery or cryotherapy and high intensity focused ultrasound (HIFU). We included patients who underwent procedures that included the entire gland, with hemiablation or focal therapy, which were indicated for low to intermediate-risk prostate cancer according to the D'Amico criteria. We excluded patients with high-risk prostate cancer and those who underwent any prior treatment for prostate cancer. SYNTHESIS OF THE EVIDENCE: After conducting the literature search and excluding the studies that did not meet the protocol criteria, we reviewed a total of 14 studies, with a total of 350 patients treated using cryotherapy and 1107 treated with HIFU. All studies were either prospective or retrospective and were not randomised. The patients' mean age was younger than 75 years. Overall, the rate of disease recurrence in the patients treated with cryotherapy varied between 13.2% and 26%, while the rate for those treated with HIFU varied between 7.3% and 67.9%. The overall demonstrated continence at 12 months was 97.6-100% for cryotherapy and 96-100% for HIFU. In terms of sexual potency rates, cryotherapy showed complete potency at 12 months for 86-100% of the patients treated with focal cryotherapy and slightly lower rates for hemiablation (76.9-100%) and total therapy (39%). HIFU showed potency rates of 89%, 52-80% and 33-78% for focal therapy, hemiablation and total therapy, respectively. CONCLUSIONS: Both techniques have comparable functional results, although the somewhat poorer oncological results for HIFU reflect a steeper learning curve, which could lead to its use in centres with high volumes of patients.

Influence of practitioner expertise during early pregnancy diagnosis on pregnancy loss rate: A controlled, blinded trial.

A controlled field trial was conducted to assess the potential influence of practitioner inexperience during early pregnancy diagnosis with ultrasound (PD-US) on the risk of pregnancy loss. A veterinarian with more than 10 years' experience in PD-US (Vet-A) and a veterinarian with fewer than 12 months' experience at the start of the study (Vet-B) visited the same dairy farm once a week for 33 and 26 weeks, respectively. The two veterinarians did not interact with each other at any time during the study, nor did they know that their data would later be used in this study. Using the same farm scanner, they performed PD-US at 28-34 day after breeding, together diagnosing 915 pregnancies. All cows were re-checked at 49-56 day after artificial insemination, and cows no longer pregnant were recorded as having suffered pregnancy loss. Although Vet-A and Vet-B diagnosed a similar proportion of pregnancies (58.44 ± 16% vs 56.96 ± 18%, p > .05), the rate of pregnancy loss was significantly higher among cows diagnosed by Vet-B (10.41 ± 11.2% vs 4.87 ± 9.0, p = .029). In addition, among cows diagnosed by Vet-B, the rate of pregnancy loss was significantly higher among cows diagnosed, while he had fewer than 12 months' PD-US experience (11.17 ± 12.14%) than among cows that he diagnosed later (7.14 ± 11.01%, p = .038); in fact, this latter loss rate was comparable to that among cows diagnosed by Vet-A during the same period (3.51 ± 9.83%, p = .620). These results suggest that inexperience with PD-US during the late embryonic period can increase risk of early pregnancy loss, supporting the need for proper training.

Neuroinvasive St. Louis Encephalitis Virus Infection in Solid Organ Transplant Recipients.

In summer 2015, three unrelated solid organ transplant recipients in Phoenix, Arizona, had meningoencephalitis suggestive of West Nile virus (WNV) infection. Testing was inconclusive but was later confirmed as St. Louis encephalitis (SLE). We retrospectively reviewed clinical manifestations, treatment, and outcomes of these transplant recipients. Common symptoms were fever, rigors, diarrhea, headache, and confusion. One patient died 3 days after hospitalization. Therapy for the other two patients was initiated with interferon α-2b (IFN) and intravenous IgG (IVIG; IFN plus IVIG in combination). Both patients tested positive for WNV by serologic assay, but SLE virus (SLEV) infection was later confirmed by plaque reduction neutralization test at a reference laboratory. Clinical improvement was observed within 72 h after initiation of IFN plus IVIG. SLEV has been an uncommon cause of neuroinvasive disease in the United States. Accurate, timely diagnosis is hindered because of clinical presentation similar to neuroinvasive WNV and SLE, serologic cross-reactivity, and lack of a commercially available serologic assay for SLEV. There is currently no approved therapy for flaviviral neuroinvasive disease. Anecdotal reports indicate varying success with IFN, IVIG, or IFN plus IVIG in WNV neuroinvasive disease. The same regimen might be of value for immunocompromised persons with neuroinvasive SLEV infection.

Searching for genes responsible for patulin degradation in a biocontrol yeast provides insight into the basis for resistance to this mycotoxin.

Patulin is a mycotoxin that contaminates pome fruits and derived products worldwide. Basidiomycete yeasts belonging to the subphylum Pucciniomycotina have been identified to have the ability to degrade this molecule efficiently and have been explored through different approaches to understand this degradation process. In this study, Sporobolomyces sp. strain IAM 13481 was found to be able to degrade patulin to form two different breakdown products, desoxypatulinic acid and (Z)-ascladiol. To gain insight into the genetic basis of tolerance and degradation of patulin, more than 3,000 transfer DNA (T-DNA) insertional mutants were generated in strain IAM 13481 and screened for the inability to degrade patulin using a bioassay based on the sensitivity of Escherichia coli to patulin. Thirteen mutants showing reduced growth in the presence of patulin were isolated and further characterized. Genes disrupted in patulin-sensitive mutants included homologs of Saccharomyces cerevisiae YCK2, PAC2, DAL5, and VPS8. The patulin-sensitive mutants also exhibited hypersensitivity to reactive oxygen species as well as genotoxic and cell wall-destabilizing agents, suggesting that the inactivated genes are essential for tolerating and overcoming the initial toxicity of patulin. These results support a model whereby patulin degradation occurs through a multistep process that includes an initial tolerance to patulin that utilizes processes common to other external stresses, followed by two separate pathways for degradation.

Superiority of entangled measurements over all local strategies for the estimation of product coherent states.

It is shown that the ensemble {P(alpha),|alpha|alpha;{*}}, where P(alpha) is a Gaussian distribution of finite variance and |alpha is a coherent state, can be better discriminated with an entangled measurement than with any local strategy supplemented by classical communication. Although this ensemble consists of products of quasiclassical states without any squeezing, it thus exhibits a purely quantum feature. This remarkable effect is demonstrated experimentally by implementing the optimal local strategy on coherent states of light together with a global strategy that yields a higher fidelity.

Long-term outcome of a phase II study of weekly docetaxel with a short course of estramustine and enoxaparine in hormone-resistant prostate cancer patients.

OBJECTIVE: The objective was to define the toxicity and activity of weekly docetaxel administered with a short course of estramustine and enoxaparine in patients with hormone-resistant prostate cancer (HRPC). PATIENTS AND METHODS: Twenty-four patients were treated with the next regimen: weekly docetaxel 36 mg/m(2) iv for three consecutive weeks every 28 days, and estramustine 280 mg three times a day for three consecutive days beginning the day before docetaxel (days 1-3, 8-10 and 15-17). In order to prevent thromboembolic events, 40 mg of subcutaneous enoxaparine was administered daily sc on the same days as estramustine. Primary endpoints were: toxicity, especially the presence of thromboembolic events, PSA response rate and response in measurable disease. Secondary endpoints were: time to PSA progression and overall survival. RESULTS: Nineteen of 24 patients (79.1%, 95% CI 71-87%) had a PSA response = or >50%. Four of the eleven patients with measurable disease had a partial response. The median time to PSA progression was 7 months (CI 95%: 6.5-9) and the median survival was 19 months (IC 95%: 11-24). Toxicity was manageable with no treatment- related mortality. Only two patients had grade 4 neutropenia. Two patients had thrombotic events, one deep venous thrombosis and one stroke. The main grade 3 non-haematologic toxicity was diarrhoea and asthenia, both in 25% of patients. CONCLUSIONS: Weekly docetaxel with a short course of estramustine and enoxaparine is active and tolerable in HRPC patients. The observed incidence of thrombosis was lower than previously reported but the association of enoxaparine was not enough to completely prevent the thromboembolic events.

[Renal synchronous tumor: association of renal adenocarcinoma and transitional tumor of renal pelvis, in the same kidney, an exceptional discovery]. / Tumor sincrónico renal: asociación de adenocarcinoma renal y tumor transicional de pelvis renal, en el mismo riñón, un hallazgo excepcional.

The renal cell tumour supposes 1% of the adult's tumors, while the transitional carcinoma has an incidence of 7%. The simultaneous appearance of a carcinoma of renal cells, and a transitional tumour of pelvis in the same kidney, they suppose an exceptional fact not existing but of 30 cases published in the world, presenting an approximate incidence of 0.14% of the pathology renal tumoral. We present a new case of this unusual association that supposes the 4 case indexed in the literature in Spanish.

[Benign retroperitoneal schwannoma. Incidental diagnostic in patient with hematuria of the percusionist]. / Schwannoma retroperitoneal benigno. Diagnostico incidental en paciente con hematuria del percusionista.

The incidence of retroperitoneal primitive tumour varies from the 0.3 to 3%. The sarcomas suppose the group but it frequents of retroperitoneal tumour, being the Schwannoma an unusual tumour with an incidence from 1% to 50% of the retroperitoneal primary tumours. The schwannoma also denominated neurinoma or neurolenoma, it is a derived tumour of the cells of Schwann of the outlying nerves. It is characterized by their clinical and radiological inespecify, being the diagnose pathological, with intense positive inmunohistoquimics to the protein S-100. The election treatment is the surgical remove, with wide margins; not being described cases of malignización neither of metastasis at distance, but if the recurrence existence at probably secondary local level to incomplete resection.

Proposal for a loophole-free Bell test using homodyne detection.

We propose a feasible optical setup allowing for a loophole-free Bell test with efficient homodyne detection. A non-Gaussian entangled state is generated from a two-mode squeezed vacuum by subtracting a single photon from each mode, using beam splitters and standard low-efficiency single-photon detectors. A Bell violation exceeding 1% is achievable with 6 dB squeezed light and a homodyne efficiency around 95%. A detailed feasibility analysis, based upon the recent experimental generation of single-mode non-Gaussian states, suggests that this method opens a promising avenue towards a complete experimental Bell test.

[Primary testicular lymphoma. Report of a new case and review of the literature]. / Linfoma testicular primario. Aportación de un nuevo caso y revisión de la literatura.

Primary testicular lymphoma is an uncommon testicular tumour that accounts for no more than 9% of all testicular tumours in those series with higher incidence; testicular lymphoma as haematopoietic tumours are also rare accounting for just 1% of all lymphomas; but due to their highly malignant histopathology they may become highly aggressive tumours. Patient age at presentation is over 60 years old which makes it the most frequent tumour for this age group. There is no standard protocol to treat this malignancy due to lack of extensive series. We contribute one case and make a literature review discussing the current therapeutic trends for this disease.

[Sarcomatoid carcinoma of the kidney. Report of a new case and review of the bibliography]. / Carcinoma sarcomatoide de riñón. Aportación de un nuevo caso, y revisión de la bibliografía.

We report a new case of sarcomatoid renal cell carcinoma, in a male of 67 years old, with locoregional recidive four months after first surgery, with two episodes of retroperitoneal hemorrhage after second surgery. The objective of this work is to contribute a new case and of doing one revision.

The putative role of botrydial and related metabolites in the infection mechanism of Botrytis cinerea.

Phytotoxic assays, performed both in vitro and in vivo on leaves of Phaseolus vulgaris, with metabolites excreted by the fungus B. cinerea are evaluated. Exogenous application of the phytotoxin botrydial has been found to produce severe chlorosis and cell collapse and facilitated fungal penetration and colonization of plant tissue. The results also show a light-dependent action mechanism for the phytotoxin and seem to indicate that botrydial is a non-host-specific toxin involved in fungal infection of B. cinerea.

Pharmacokinetic Interaction between amprenavir and rifabutin or rifampin in healthy males.

The objective of this study was to determine if there is a pharmacokinetic interaction when amprenavir is given with rifabutin or rifampin and to determine the effects of these drugs on the erythromycin breath test (ERMBT). Twenty-four healthy male subjects were randomized to one of two cohorts. All subjects received amprenavir (1,200 mg twice a day) for 4 days, followed by a 7-day washout period, followed by either rifabutin (300 mg once a day [QD]) (cohort 1) or rifampin (600 mg QD) (cohort 2) for 14 days. Cohort 1 then received amprenavir plus rifabutin for 10 days, and cohort 2 received amprenavir plus rifampin for 4 days. Serial plasma and urine samples for measurement of amprenavir, rifabutin, and rifampin and their 25-O-desacetyl metabolites, were measured by high-performance liquid chromatography. Rifabutin did not significantly affect amprenavir's pharmacokinetics. Amprenavir significantly increased the area under the curve at steady state (AUC(ss)) of rifabutin by 2.93-fold and the AUC(ss) of 25-O-desacetylrifabutin by 13.3-fold. Rifampin significantly decreased the AUC(ss) of amprenavir by 82%, but amprenavir had no effect on rifampin pharmacokinetics. Amprenavir decreased the results of the ERMBT by 83%. The results of the ERMBT after 2 weeks of rifabutin and rifampin therapy were increased 187 and 156%, respectively. Amprenavir plus rifampin was well tolerated. Amprenavir plus rifabutin was poorly tolerated, and 5 of 11 subjects discontinued therapy. Rifampin markedly increases the metabolic clearance of amprenavir, and coadministration is contraindicated. Amprenavir significantly decreases clearance of rifabutin and 25-O-desacetylrifabutin, and the combination is poorly tolerated. Amprenavir inhibits the ERMBT, and rifampin and rifabutin are equipotent inducers of the ERMBT.

[Repetition of ultrasonography-guided prostatic biopsy for the detection of cancer. Study of a series of 192 re-biopsied patients]. / Repetición de la biopsia prostática ecodirigida para la detección de cáncer. Estudio de una serie de 192 pacientes re-biopsiados.

PURPOSE: We reviewed the result of transrectal ultrasound (TRUS)-guided needle biopsies to find the re-biopsy criteria, emphasizing on the Focal Glandular Atypia (FGA) histological changes. MATERIAL AND METHOD: 192 cases were selected, from a total of 1957 patients older than 50, re-biopsied because of high PSA levels and/or abnormal DRE, or because of the histological findings on initial biopsies (high grade PIN and/or FGA). The results are related to the serum PSA levels and DRE characteristics. RESULTS: A 38.83% global positivity for cancer was obtained and 27.08% for re-biopsy. When the first biopsy was negative, the positivity of the re-biopsies was 19.37%; if it was negative for cancer but had high grade PIN and/or FGA changes, the positivity was 65.62%, being higher in FGA changes than in the PIN cases (68.00% vs. 57.14%). The abnormal DRE raised the positivity rate from 17.82% to, 35.75%. CONCLUSIONS: The positivity was especially related to abnormal DRE and/or PSA > or = 10 ng/ml. The tumor rate detected at second and third or successive biopsies was similar (19.28% vs 21.74%). The FGA changes (3.47% globally) had a cancer predictive value of 65.62%. We recommend re-biopsy in all patients with FGA changes.

Biosynthetic studies on the tropane ring system of the tropane alkaloids from Datura stramonium.

Isotopic labelling experiments have been carried out in Datura stramonium root cultures with the following isotopically labelled precursors; [2H3]- [2-13C, 2H3]-, [1-13C, 18O2]-acetates, 2H2O, [2H3-methyl]-methionine, [2-13C]-phenyllactate, [3-2H]-tropine and [2'-13C, 3-2H]-littorine. The study explored the incorporation of isotope into the tropane ring system of littorine 1 and hyoscyamine 2 and revealed that deuterium from acetate is incorporated only into C-6 and C-7, and not into C-2 and C-4 as previously reported. Oxygen-18 was not retained at a detectable level into the C(3)-O bond from [1-13C, 18O2]-acetate. The intramolecular nature of the rearrangement of littorine 1 to hyoscyamine 2 is revealed again by a labelling study using [2'-13C, 3-2H]-littorine, [2-13C]-phenyllactate and [3-2H]-tropine.

Secobotrytriendiol and related sesquiterpenoids: new phytotoxic metabolites from Botrytis cinerea.

Six new sesquiterpenoid metabolites (1, 3-7) have been isolated from Botrytis cinerea. Their structures were elucidated by means of MS and extensive NMR studies. The phytotoxic activities of these new products have been evaluated.

Biotransformation of (4E,8R)-caryophyll-4(5)-en-8-ol by Botrytis cinerea.

Biotransformation of (4E,8R)-caryophyll-4(5)-en-8-ol (1) with Botrytis cinerea afforded 14 products (3-16). Thirteen of these (4-16) are described here for the first time. The main reaction paths involved the isomerization of the double bond at C-4/C-5 and hydroxylation of methyl groups.

Combinations of vancomycin and beta-lactams are synergistic against staphylococci with reduced susceptibilities to vancomycin.

Evidence of synergism between combinations of vancomycin and beta-lactam antibiotics against 59 isolates of methicillin-resistant staphylococci (Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus) for which vancomycin MICs ranged from 1 to 16 microg/ml were tested by broth microdilution checkerboard, disk diffusion, agar dilution, and time-kill antimicrobial susceptibility tests. The combination of vancomycin and oxacillin demonstrated synergy by all test methods against 30 of 59 isolates; no antagonism was seen. Synergy with vancomycin was also found by modified disk diffusion testing for ceftriaxone, ceftazidime, cefpodoxime, and amoxicillin-clavulanate but not for aztreonam. Evidence of synergy correlated directly with vancomycin MICs. The efficacy of vancomycin given alone and in combination with nafcillin was tested in the rabbit model of experimental endocarditis caused by three clinical isolates of glycopeptide-intermediate-susceptible S. aureus (GISA) (isolates HIP5827, HIP5836, and MU50). Two of the GISA isolates (isolates MU50 and HIP5836) were extremely virulent in this model, with 27 of 42 (64%) animals dying during the 3-day trial. Therapy with either vancomycin or nafcillin given as a single agent was ineffective for animals infected with HIP5827 or MU50. However, the combination of vancomycin and nafcillin resulted in a mean reduction of 4.52 log10 CFU/g of aortic valvular vegetations per g compared to the reduction for controls for animals infected with HIP5827 and a reduction of 4. 15 log10 CFU/g for animals infected with MU50. Renal abscesses caused by HIP5827 were sterilized significantly better with the combination of vancomycin and nafcillin than by either treatment alone. We conclude that the combination of vancomycin and beta-lactams with antistaphylococcal activity is an effective regimen for the treatment of infections with clinical strains of staphylococci which demonstrate reduced susceptibility to glycopeptides.

Lysostaphin treatment of experimental aortic valve endocarditis caused by a Staphylococcus aureus isolate with reduced susceptibility to vancomycin.

The rabbit model of endocarditis was used to test the effectiveness of vancomycin and two different lysostaphin dosing regimens for the treatment of infections caused by a Staphylococcus aureus strain with reduced susceptibility to vancomycin (glycopeptide-intermediate susceptible S. aureus [GISA]). Vancomycin was ineffective, with no evidence of sterilization of aortic valve vegetations. However, rates of sterilization of aortic valve vegetations were significantly better for animals treated with either a single dose of lysostaphin (43%) or lysostaphin given twice daily for 3 days (83%) than for animals treated with vancomycin. Rabbits given a single dose of lysostaphin followed by a 3-day drug-free period had mean reductions in aortic valve vegetation bacterial counts of 7.27 and 6.63 log10 CFU/g compared with those for untreated control rabbits and the vancomycin-treated group, respectively. We conclude that lysostaphin is an effective alternative for the treatment of experimental aortic valve endocarditis caused by a clinical VISA strain.