Polymer-Tethered Quenched Fluorescent Probes for Enhanced Imaging of Tumor-Associated Proteases.

Fluorescence-based contrast agents enable real-time detection of solid tumors and their neovasculature, making them ideal for use in image-guided surgery. Several agents have entered late-stage clinical trials or secured FDA approval, suggesting they are likely to become the standard of care in cancer surgeries. One of the key parameters to optimize in contrast agents is molecular size, which dictates much of the pharmacokinetic and pharmacodynamic properties of the agent. Here, we describe the development of a class of protease-activated quenched fluorescent probes in which a N-(2-hydroxypropyl)methacrylamide copolymer is used as the primary scaffold. This copolymer core provides a high degree of probe modularity to generate structures that cannot be achieved with small molecules and peptide probes. We used a previously validated cathepsin substrate and evaluated the effects of length and type of linker, as well as the positioning of the fluorophore/quencher pair on the polymer core. We found that the polymeric probes could be optimized to achieve increased overall signal and tumor-to-background ratios compared to the reference small molecule probe. Our results also revealed multiple structure-activity relationship trends that can be used to design and optimize future optical imaging probes. Furthermore, they confirm that a hydrophilic polymer is an ideal scaffold for use in optical imaging contrast probes, allowing a highly modular design that enables efficient optimization to maximize probe accumulation and overall biodistribution properties.

Early change in apparent diffusion coefficient as a predictor of response to neoadjuvant androgen deprivation and external beam radiation therapy for intermediate- to high-risk prostate cancer.

AIM: To determine the role of serial apparent diffusion coefficient (ADC) as a biomarker for response to neoadjuvant androgen deprivation therapy (nADT) followed by external beam radiation therapy (EBRT) in intermediate- to high-risk prostate cancer (PCa) patients. METHODS: This Health Insurance Portability and Accountability Act (HIPAA)-compliant, institutional review board (IRB)-approved prospective study included 12 patients with intermediate- to high-risk PCa patients prior to nADT and EBRT, who underwent serial serum prostate-specific antigen (PSA) and multiparametric prostate magnetic resonance imaging (mpMRI) at baseline (BL), 8-weeks after nADT initiation (time point [TP]1), 6-weeks into EBRT delivery (TP2), and 6-months after nADT initiation (TP3). Tumour volume (tVOL) and tumour and normal tissue ADC (tADC and nlADC) were determined at all TPs. tADC and nlADC dynamics were correlated with post-treatment PSA using Pearson's correlation coefficient. Paired t-tests compared pre/post-treatment ADC. RESULTS: There was a sequential decrease in PSA at all TPs, reaching their lowest values at TP3 post-treatment completion. Mean tADC increased significantly from baseline to TP1 (917.8 ± 107.7 × 10-6 versus 1033.8 ± 139.3 × 10-6 mm2/s; p<0.01), with no subsequent change at TP2 or TP3. Both percentage and absolute change in tADC from BL to TP1 correlated with post-treatment PSA (r=-0.666, r=-0.674; p=0.02). Post-treatment PSA in good responders (<0.1 ng/ml) versus poor responders (≥ 0.1 ng/ml) was associated with a greater increase in tADC from BL to TP1 (169.2 ± 122.4 × 10-6 versus 22.9 ± 75.5 × 10-6 mm2/s, p=0.03). CONCLUSION: This pilot study demonstrates the potential for early ADC metrics as a biomarker of response to nADT and EBRT in intermediate to high-risk PCA.

Biotransformation of 1-nitro-2-phenylethane [Formula: see text] 2-phenylethanol from fungi species of the Amazon biome: an experimental and theoretical analysis.

CONTEXT: Natural products and their biotransformation procedures are a powerful source of new chromophores with potential applications in fields like biology, pharmacology and materials science. Thus, this work discusses about the extraction procedure of 1-nitro-2-phenylethane (1N2PE) from Aniba canelilla, its biotransformation setup into 2-phenylethanol (2PE) using four fungi, Lasiodiplodia caatinguensis (phytopathogenic fungus from Citrus sinensis), Colletotrichum sp. (phytopathogenic fungus from Euterpe oleracea), Aspergillus flavus and Rigidoporus lineatus isolated from copper mining waste located in the interior of the Brazilian Amazon. A detailed experimental and theoretical vibrational analysis (IR and Raman) have allowed us to perform some charge transfer effects on the title compounds (push-pull effect) by monitoring specific vibrational modes of their electrophilic and nucleophilic molecular sites. The solvent interactions promote molecular conformations that affect the vibrational spectra of the donor and acceptor groups, as can be seen comparatively in the gas and aqueous solution spectra, an effect possibly related to the bathochromic shift in the calculated optical spectrum of the compounds. The nonlinear optical behavior shows that while the solvent reduces the response of 1N2PE, the response of 2PE increases the optical parameters, which presents low refractive index (n) and first hyperpolarizability. ([Formula: see text]) is almost eight times that reported for urea (42.79 a.u.), a common nonlinear optical material. Furthermore, the bioconversion goes from an electrophilic to a nucleophilic compound, affecting its molecular reactivity. METHODS: 1N2PE was obtained from Aniba canelilla, whose essential oil is constituted of [Formula: see text] of 2PE. The A. canelilla essential oil was extracted under hydrodistillation. The biotransformation reactions were performed in autoclaved liquid media (100 mL) composed of malt extract (2%) in 250 mL Erlenmeyer flask. Each culture was incubated in an orbital shaker (130 rpm) at [Formula: see text]C during 7 days and after that, 50 mg of 1N2PE (80%) were diluted in 100 [Formula: see text]L of dimethylsulfoxide (DMSO) and added to the reactions flasks. Aliquots (2 mL) were removed using ethyl acetate (2 mL) and analyzed by GC-MS (fused silica capillary col1umn, Rtx -5MS 30 m [Formula: see text] 0.25 mm [Formula: see text] 0.25 [Formula: see text]m) in order to determine the amount of 1N2PE biotransformation. FTIR 1N2PE and 2PE spectra were obtained by attenuated total reflectance (ATR), using a Agilent CARY 630 spectrometer, in the spectral region 4000-650 cm[Formula: see text]. The quantum chemical calculations were carried out in the Gaussian 09 program while the DICE code was used to perform the classical Monte Carlo simulations and generate the liquid environment using the classical All-Atom Optimized parameters for Liquid Simulations (AA-OPLS). All nonlinear optical properties, reactive parameters, and electronic excitations were calculated using the Density Functional Theory framework coupled to the standard 6-311++G(d,p) basis set.

Protease Activated Probes for Real-Time Ratiometric Imaging of Solid Tumors.

Surgery is the preferred treatment option for most solid tumors. However, inaccurate detection of cancer borders leads to either incomplete removal of malignant cells or excess excision of healthy tissue. While fluorescent contrast agents and imaging systems improve tumor visualization, they can suffer from low signal-to-background and are prone to technical artifacts. Ratiometric imaging has the potential to eliminate many of these issues such as uneven probe distribution, tissue autofluorescence, and changes in positioning of the light source. Here, we describe a strategy to convert quenched fluorescent probes into ratiometric contrast agents. Conversion of the cathepsin-activated probe, 6QC-Cy5, into a two-fluorophore probe, 6QC-RATIO, significantly improved signal-to-background in vitro and in a mouse subcutaneous breast tumor model. Tumor detection sensitivity was further enhanced using a dual-substrate AND-gate ratiometric probe, Death-Cat-RATIO, that fluoresces only after orthogonal processing by multiple tumor-specific proteases. We also designed and built a modular camera system that was coupled to the FDA-approved da Vinci Xi robot, to enable real-time imaging of ratiometric signals at video frame rates compatible with surgical workflows. Our results demonstrate that ratiometric camera systems and imaging probes have the potential to be clinically implemented to improve surgical resection of many types of cancer.

Pilot study for low-cost model validation in laparoscopic pediatric pyeloplasty simulation. / Estudio piloto para la validación de un modelo de bajo coste en la simulación de la pieloplastia laparoscópica pediátrica.

OBJECTIVE: To describe the creation of an original 3D-printed liquid latex model designed for laparoscopic pyeloplasty (LP) simulation in infants, and to assess its usefulness. MATERIALS AND METHODS: A 3D model of a dilated pelvis and a ureter with ureteropelvic junction obstruction (UPJO) was designed. It was covered in liquid latex, which allowed flexible models to be achieved in order to conduct pyeloplasty in a pelvitrainer. The total price of each model was 6 euros. A nearly-experimental, non-randomized, blind study was carried out, while measuring operating times and OSATS (Objective Structured Assessment of Technical Skills) scores. Following simulation completion, a survey based on Likert scale was conducted to assess overall appearance, texture, usefulness, and probability of recommending the model for regular training. RESULTS: 8 pediatric surgeons spent a median of 71.5 minutes (range: 50-86), and rated the model with a median 20.1/30 (range: 17-24) OSATS score. The model received a 4.25 (range: 3-5) score in terms of overall appearance, a 4.37 (range: 3-5) score in terms of texture, a 4.5 (range: 4-5) score in terms of usefulness, and a 4.6 (range: 4-5) score in terms of probability of recommending the model for regular training. CONCLUSIONS: Our liquid latex model for laparoscopic pyeloplasty simulation is feasible, with favorable preliminary results. Its usefulness in laparoscopic pyeloplasty training is promising.

OBJETIVOS: Describir la creación de un modelo original de látex líquido diseñado para la simulación de la pieloplastia laparoscópica (PL) en lactantes, construido a partir de una impresión tridimensional (3D), y valorar su utilidad. MATERIAL Y METODOS: Se diseñó un modelo 3D de una pelvis dilatada y un uréter con estenosis pieloureteral (EPU), que fue recubierto por látex líquido obteniendo modelos flexibles para realizar la pieloplastia en un pelvitrainer. El precio total de cada modelo fue de 6 euros. Se realizó un estudio cuasiexperimental, ciego y no aleatorizado, midiendo el tiempo quirúrgico y la puntuación OSATS (Objective Structured Assessment of Technical Skills). Tras completar la simulación, se realizó una encuesta utilizando la escala de Likert, en la cual se valoró el aspecto general, la textura, la utilidad del modelo y el grado de recomendación en el entrenamiento habitual. RESULTADOS: 8 cirujanos pediátricos dedicaron una mediana de 71,5 minutos (R 50-86), y puntuaron una mediana de 20,1/30 (R 17-24) en la escala OSATS. El modelo obtuvo una valoración de 4,25 (R3-5) en aspecto general, 4,37 (R3-5) en textura, 4,5 (R 4-5) en utilidad y 4,6 (R 4-5) en recomendación para incorporar al entrenamiento habitual. CONCLUSIONES: El uso de nuestro modelo de látex líquido para la simulación de la pielopalstia laparoscópica es factible y los resultados preliminares han sido favorables. Su utilidad como herramienta en el entrenamiento de la pieloplastia laparoscópica es prometedora.

The normal and fibrotic mouse lung classified by spatial proteomic analysis.

Single cell classification is elucidating homeostasis and pathology in tissues and whole organs. We applied in situ spatial proteomics by multiplex antibody staining to routinely processed mouse lung, healthy and during a fibrosis model. With a limited validated antibody panel (24) we classify the normal constituents (alveolar type I and II, bronchial epithelia, endothelial, muscular, stromal and hematopoietic cells) and by quantitative measurements, we show the progress of lung fibrosis over a 4 weeks course, the changing landscape and the cell-specific quantitative variation of a multidrug transporter. An early decline in AT2 alveolar cells and a progressive increase in stromal cells seems at the core of the fibrotic process.

The pathological growth of the prostate gland in atherogenic contexts.

The human prostate is an androgen-dependent gland where an imbalance in cell proliferation can lead to benign prostatic hyperplasia (BPH), which results in voiding lower urinary tract symptoms in the elderly. In the last decades, novel evidence has suggested that BPH might represent an element into the wide spectrum of disorders conforming the Metabolic Syndrome (MS). The dyslipidemic state and the other atherogenic factors of the MS have been shown to induce, maintain and/or aggravate the pathological growth of different organs, with data regarding the prostate being still limited. We here review the available epidemiological and experimental studies about the association of BPH with dyslipidemias. In particular, we have focused on Oxidized Low-Density Lipoproteins (OxLDL) as a potential trigger for vascular disease and cellular proliferation in atherogenic contexts, analyzing their putative molecular mechanisms, including the induction of specific extracellular vesicles (EVs)-derived miRNAs. In addition to the epidemiological evidence, OxLDL is proposed to play a fundamental role in the upregulation of prostatic cell proliferation by activating the Rho/Akt/p27Kip1 pathway in atherogenic contexts. miR-21, miR-141, miR-143, miR-145, miR-155, and miR-221 would be involved in the transcription of genes related to the proliferative process. Although much remains to be investigated regarding the impact of OxLDL, its receptors, and molecular mechanisms on the prostate, it is clear that EVs and miRNAs represent a promising target for proliferative pathologies of the prostate gland.

Clinical outcomes of FOLFIRINOX and gemcitabine-nab paclitaxel for metastatic pancreatic cancer in the real world setting.

BACKGROUND/OBJECTIVES: The incidence of pancreatic cancer is increasing in developed countries. The incorporation of new therapies, to the first-line treatment of patients with good performance status led to better survival in clinical trials. However, there is a wide variability in their use and some concerns about the treatment of elderly patients who were not included in the clinical trials. METHODS: This is a retrospective multicenter study. Data from consecutive patients diagnosed with metastatic pancreatic cancer (mPC) treated with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) were analysed to evaluate efficacy (overall survival-OS) and toxicity. RESULTS: A total of 119 patients were included. 49.6% were treated with FFX and 50.4% with GNP in first-line. The median OS was 12 months with no statistically significant differences between both regimens (12.7 m for FFX vs 10.2 m for GnP). Elevated Ca 19.9 levels and neutrophil-lymphocyte ratio (NLR) increased the risk of death. Patients who received both regimens in first/second line had a median OS longer than 15 months whichever the sequence. 32 patients (27%) were older than 70-y. 54% patients received a second-line treatment, 56% in the FFX group and 44% in the GnP group. The median OS for patients older than 70 was 9.5 m versus 12.3 m for patients younger than 70. Progression of the disease was the cause of death in 67.6% of the patients. CONCLUSIONS: In our setting, the use of FFX and GnP for treating mPC is quite similar, but superiority could not be demonstrated for any of the schemes in the first line. OS was determined by basal levels of Ca 19.9 and NLR. Patients receiving both regimens in first/second line whichever the sequence, exhibited the best survival rates. In our series, elderly patients had poorer survival rates.

GEANT4 Monte Carlo simulations for virtual clinical trials in breast X-ray imaging: Proof of concept.

Virtual clinical trials (VCT) are in-silico reproductions of medical examinations, which adopt digital models of patients and simulated devices. They are intended to produce clinically equivalent outcome data avoiding long execution times, ethical issues related to radiation induced risks and huge costs related to real clinical trials with a patient population. In this work, we present a platform for VCT in 2D and 3D X-ray breast imaging. The VCT platform uses Monte Carlo simulations based on the Geant4 toolkit and patient breast models derived from a cohort of high resolution dedicated breast CT (BCT) volume data sets. Projection images of the breast and three-dimensional glandular dose maps are generated for a given breast model, by simulating both 2D full-field digital mammography (DM) and 3D BCT examinations. Uncompressed voxelized breast models were derived from segmented patient images. Compressed versions of the digital breast phantoms for DM were generated using a previously published digital compression algorithm. The Monte Carlo simulation framework has the capability of generating and tracking ~105 photons/s using a server equipped with 16-cores and 3.0 GHz clock speed. The VCT platform will provide a framework for scanner design optimization, comparison between different scanner designs and between different modalities or protocols on computational breast models, without the need for scanning actual patients as in conventional clinical trials.

Radiofrequency ablation of functioning and non-functioning thyroid nodules: a single institution 12-month survey.

PURPOSE: Radiofrequency (RF) treatment has played an increasing role in the management of benign thyroid nodules in recent years. The aim of this retrospective study was to evaluate the efficacy of RF treatment on volume reduction in functioning and non-functioning thyroid nodules. PATIENTS AND METHODS: We reviewed the medical records of patients who had thyroid nodule RF ablation at our department between August 2017 and May 2018. Patients underwent a periodical follow-up with ultrasound examinations and thyroid function tests at 1, 3, 6 and 12 months from RF. Complications were assessed using the reporting standards of Interventional societies. RESULTS: 43 patients were submitted to thyroid nodule RF ablation treatment. Patients were subdivided into two groups, those with functioning (17 patients) or non-functioning nodules. At baseline (i.e. pre-RF treatment), the two groups of patients were superimposable for gender, age, BMI, nodule volume and maximum nodule diameter. The volume reduction of all 43 nodules was 69.1 ± 17.3% (range 26.0-94.5%) with no difference between functioning and non-functioning lesions (72.9 ± 18.1% vs 66.7 ± 16.7%, p = 0.254). A total energy delivered per nodule was 16.5 ± 6.8 kJ, with no difference between functioning and non-functioning lesions (14.5 ± 7.2 kJ vs. 18.2 ± 6.3 kJ, p = 0.083, respectively). No major complications were observed. CONCLUSIONS: Radiofrequency ablation is a clinically effective and safe outpatient treatment in patients with benign nodules. In particular, we showed that a single treatment is effective in restoring euthyroidism in patients with autonomously functioning thyroid nodules.

Rotational radiotherapy of breast cancer with polyenergetic kilovoltage X-ray beams: An experimental and Monte Carlo phantom study.

PURPOSE: We investigated the feasibility of kilovoltage rotational radiotherapy for breast cancer (kV-EBRT) via Monte Carlo simulations and measurements on phantoms. METHODS: We derived the dose distributions for X-ray beams at 150 kV, 300 kVp and 320 kV irradiating breast cylindrical phantoms of 14 cm diameter, mimicking the pendant breast. Simulations were based on the Geant4 toolkit. The point-like X-ray source was rotated either over a full circle or on a limited arc around the phantom. We studied the influence on the surface dose of the distance between the tumor lesion to the skin, of the irradiation protocol (full scan or partial scan) and of the X-ray tube current modulation. RESULTS: Rotational kV-EBRT permitted a periphery-to-center dose ratio from 13% to 9% in homogeneous breast phantoms. Dose distributions in phantoms with off-center simulated lesions, showed a skin-to-tumor dose ratio of 16% and 34% for lesions at 3.25 and 5.25 cm from cylinder axis, respectively. Simulation of the X-ray tube current modulation during the rotation, permits to reach a dose ratio of 20% for the lesion located at 5.25 cm from phantom axis. CONCLUSIONS: We showed the possibility of using low-energy X-ray spectra for kV-EBRT with collimated beams, for obtaining a periphery-to-center dose ratio in the same order of conventional accelerator based megavoltage radiotherapy, when the irradiated area is localized in the center of the breast. For tumors localized near the breast border, we showed that the tube current modulation can be a good solution in order to reduce the skin-to-tumor dose ratio.

Monte Carlo calculation of monoenergetic and polyenergetic DgN coefficients for mean glandular dose estimates in mammography using a homogeneous breast model.

We computed normalized glandular dose (DgN) coefficients for mean glandular dose estimates in contemporary 2D mammography units, taking into account a homogeneous model for the breast which reflects recent literature reports. We developed a Monte Carlo code based on the simulation toolkit GEANT4 ver. 10.00. The breast was modelled as a cylinder with a semi-cylindrical section with a radius of 10 cm, enveloped in a 1.45 mm thick skin layer, as found out in recent reports in the analysis of breast computed tomography clinical scans. The compressed breast thickness was between 3 cm and 8 cm. The DgN coefficients were calculated for monoenergetic x-ray beams between 4.25 keV and 49.25 keV and were fitted with polynomial curves. Polyenergetic DgN coefficients were then computed for spectra obtained for various anode/filter combinations as adopted in routine clinical practice: Mo/Mo 30 µm (25-40 kV), Mo/Rh 25 µm (25-40 kV), Rh/Rh 25 µm (25-40 kV), W/Ag 50 µm (26-34 kV), W/Al 500 µm (26-38 kV), W/Al 700 µm (28-40 kV) and W/Rh 50 µm (24-35 kV). Monoenergetic DgN curve fit coefficients and polyenergetic DgNp coefficients were released for research and clinical work. Polyenergetic DgNp coefficients were 6% higher than those provided in the recent literature, on average. The differences range between -18% and 30%; up to 50% of the computed coefficients differed by less than 10%. The dataset of DgN coefficients are provided as tables for varying glandular fraction by mass and compressed breast thickness. Moreover, a computer code has been developed for generating user specific coefficients DgNp for user defined x-ray spectra up to 49 kV, calculated by spectral weighting from the dataset of monoenergetic DgN coefficients.

Nano-TiO2 stability in medium and size as important factors of toxicity in macrophage-like cells.

TiO2 along with nano-TiO2 are commonly found in consumer products. In vivo studies have observed an accumulation of nano-TiO2 in macrophages. However, characteristics of nano-TiO2 determining toxicity remain unclear. In our study, the cytotoxic effects of 14 diverse nano-TiO2 on THP-1 macrophage-like cells were measured by 3 cytotoxicity assays (MTS, WST-1 and LDH). Total averaged cytotoxicity was calculated using principal component analysis. Characteristics of all 14 nano-TiO2 included hydrodynamic diameter, zeta potential, shape, polydispersity index (PDI) and concentration; moreover, crystal form, specific surface area and crystallite size were measured for 10 nano-TiO2.The variables affecting cytotoxicity were chosen using LASSO (least absolute shrinkage and selection operator). Except for concentration, PDI in media measured within 1 h after preparation of the nanomaterial dispersion was selected as a variable affecting cytotoxicity: stable dispersion resulted in higher cytotoxic effects. Crystallite size has been shown to have nonlinear effects (particles of sizes between 20 and 60 nm were cytotoxic while smaller and larger ones were not) and thus it has been excluded from LASSO. The shape (particles/fibre) and crystal form did not affect the cytotoxicity. PDI and the nonlinear effect of size could be an explanation for the inconsistencies of the cytotoxicity of nano-TiO2 in various studies.

Clinical utility of plasma-based digital next-generation sequencing in patients with advance-stage lung adenocarcinomas with insufficient tumor samples for tissue genotyping.

BACKGROUND: Approximately 30% of tumor biopsies from patients with advanced-stage lung adenocarcinomas yield insufficient tissue for successful molecular subtyping. We have analyzed the clinical utility of next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) in patients with inadequate tumor samples for tissue genotyping. PATIENTS AND METHODS: We conducted the study in a multi-institutional prospective cohort of clinically unselected patients with advanced-stage lung adenocarcinomas with insufficient tissue for EGFR, ALK or ROS1 genotyping across 12 Spanish institutions (n = 93). ctDNA NGS was carried out by Guardant Health (Guardant360, Redwood City, CA), using a hybrid-capture-based 73-gene panel. Variants were deemed actionable if they were part of the OncoKB precision oncology knowledge database and classified in four levels of actionability based on their clinical or preclinical evidence for drug response. RESULTS: Eighty-three out of 93 patients (89%) had detectable levels of ctDNA. Potentially actionable level 1-4 genomic alterations were detected in 53 cases (57%), of which 13 (14%) had level 1-2A alterations (Food and Drug Administration-approved and standard-care biomarkers according to lung cancer guidelines). Frequencies of each genomic alteration in ctDNA were consistent with those observed in unselected pulmonary adenocarcinomas. The majority of the patients (62%), particularly those with actionable alterations (87%), had more than one pathogenic variant in ctDNA. The median turnaround time to genomic results was 13 days. Twelve patients (13%) received genotype-matched therapies based on ctDNA results, deriving the expected clinical benefit. Patients with co-occurring pathogenic alterations had a significantly shorter median overall survival as compared with patients without co-occurring pathogenic alteration (multivariate hazard ratio = 5.35, P = 0.01). CONCLUSION: Digital NGS of ctDNA in lung cancers with insufficient tumor samples for tissue sequencing detects actionable variants that frequently co-occur with other potentially clinically relevant genomic alterations, allowing timely initiation of genotype-matched therapies.

'True Day Case' Laparoscopic Cholecystectomy in a High-Volume Specialist Unit and Review of Factors Contributing to Unexpected Overnight Stay.

INTRODUCTION: Laparoscopic cholecystectomy (LC) is the gold standard treatment for gallstones. British Association of Day Case Surgery recommends at least 60% of LCs be performed as day cases. The aim of this study was to assess our rate of true day case LCs and review factors preventing same-day discharge. METHODS: We prospectively collected data of all elective LCs performed in a district general hospital over 32 months. RESULTS: 500 patients underwent LC during this period; 438 (88.2%) patients were planned day cases and 59 patients (11.8%) planned overnight stays. Of the planned day cases, 75.8% (n=332) were discharged on the same day and 106 (24.2%) had unexpected overnight stay (UOS). Most patients with BMI >35 and ASA3 planned day case patients were successfully discharged. Drain insertion, longer operations, and late recovery departure were the main reasons for UOS. There were more complications in this group compared to day cases. CONCLUSIONS: This unit has a high 'true day case' rate of 75.8%. High BMI and ASA3 should not be absolute contraindications to day case surgery. The majority of unexpected overnight stays are unavoidable but may be reduced by patient selection, stringent preoperative assessment, operation scheduling, and reduction in unnecessary drain insertion.

Elective "True Day Case" Laparoscopic Inguinal Hernia Repair in a District General Hospital: Lessons Learned from 1000 Consecutive Cases.

INTRODUCTION: Laparoscopic inguinal hernia repair (LIHR) is ideal for day case surgery. It is recommended that at least 70% should be day cases as a measure of cost-effectiveness. The aims of this study were to (i) assess the rate of true day case (TDC) surgery and (ii) identify predictors associated with unexpected overnight stay (UOS). METHODS: Data was collected prospectively on 1000 consecutive elective LIHR performed in a District General Hospital (DGH) over a 7-year period. Data was collected on baseline patient demographics, ASA grade, and intraoperative details. A multivariate analysis was performed in order to identify predictors of UOS. RESULTS: 1000 patients (927 males) underwent elective LIHR. Mean age was 57.3±15.2 years. 915 patients were planned as day case procedures. 822/915 day cases (89.8%) were discharged on the same day and 93 (10.2%) stayed overnight unexpectedly. Patient age, duration of procedure, and patient slot in the operating list were found to be independent predictors (p<0.05) of UOS. CONCLUSION: Our results demonstrate that LIHR is a "true" day case procedure in a DGH. Although some factors associated with UOS cannot be altered, careful patient selection and operating list planning are of paramount importance in order to minimise the burden on healthcare resources.

Adult T-Cell Leukemia/Lymphoma. Review of the Literature. / Leucemia/linfoma de células T del adulto. Revisión de la literatura científica.

Adult T-cell Leukemia/Lymphoma (ATLL) is an aggressive neoplasm of T lymphocytes associated with Human T-lymphotropic virus type1 (HTLV-1) infection. HTLV-1 is a public health problem because it is endemic in native groups in Latin America, and its infection leads to several chronic diseases as ATLL. We aimed to review current literature of ATLL in order to consider it as a differential diagnosis in front of patients with compatible symptoms. Prognosis is still poor in aggressive and indolent variants, with survival rates from months to few years. Treatment based on chemotherapy, antiretroviral, and allogenic stem cell transplantation are currently improving survival rates, but with limited results.

Respiratory Profile in Patients After Liver Transplantation.

BACKGROUND: Patients in the immediate post-operative liver transplantation (LxT) period can develop respiratory and functional complications. In the postoperative months, these functions tend to improve. Nevertheless, there are few studies that evaluate precisely and specifically respiratory function in post-LxT long-term after surgery. The objective of the study was to describe the respiratory profile of patients 1 to 6 months after LxT, accompanied by LxT outpatients. METHODS: We included patients between 25 and 60 years old. We excluded patients with chronic renal or cerebrovascular impairment, severe heart disease, and history of lung surgery or liver re-transplantation. Evaluations were carried out on 3 occasions: 1 month, 3 months, and 6 months after LxT. The following evaluations were submitted: respiratory muscle strength (manuvacuometer), value flows and lung volumes (spirometer), and surface electromyography analyzing root mean square in the right (RMS-R) and left (RMS-L) diaphragm. We analyzed MELD (Model for End-Stage Liver Disease). After normality tests, we used the Friedman test (non-parametric values) and ANOVA (parametric values), P ≥ .5 with the use of SPSS 21.0. RESULTS: Patients (n = 15) had a mean age of 53.0 ± 7.5 years and 25.9 ± 4.6 MELD score. The statistically significant value obtained at the 3 occasions of evaluation was RMS-R, with a decline during periods of evaluation. This can be caused by removal of the liver, resulting in a denervation and reduction in compliance of this portion of the muscle. CONCLUSIONS: Patients between 1 and 6 months after transplantation have a specific respiratory profile, close to normal values. However, there are few studies on this subject, and we suggest that more research be done.

Characterization of Streptococcus suis through serotyping, SE-AFLP and virulence profile / Caracterização de Streptococcus suis por sorotipagem, SE-AFLP e perfil de virulência

Streptococcus suis is one of most important pathogens in the swine industry worldwide. Despite its importance, studies of S. suis characterization in South America are still rare. This study evaluates S. suis isolates from distinct Brazilian states, from 1999 to 2004, and its molecular and serological characterization. A total of 174 isolates were studied. S. suis identification was confirmed by PCR and isolates were further serotyped and genotyped by SE-AFLP and amplification of virulence markers. Serotype 1, 2, 3, 4, 7, 18, 22 and 32 were identified among the studied isolates, and only 4% were characterized as non-typeable. The mrp+/epf+/sly+ genotype was the most frequent. The SE-AFLP analysis resulted in 29 patterns distributed in three main clusters with over 65% of genetic similarity. Isolates presented a slight tendency to cluster according to serotype and origin; however, no further correlation with virulence genotypes was observed.(AU)

Streptococcus suis é um dos patógenos de maior importância para indústria suinícola mundial. Apesar de sua importância, a caracterização de isolados de S. suis na América do Sul ainda é pouco descrita. O presente estudo descreve a avaliação de isolados de S. suis provenientes de diferentes Estados brasileiros, e sua caracterização sorológica e molecular. Foram avaliados 174 isolados de S. suis e os mesmos foram submetidos a SE-AFLP e pesquisa de marcadores de virulência. Os sorotipos 1, 2, 3, 4, 7, 18, 22 e 32 foram identificados dentre os isolados estudados e apenas 4% foram caracterizados como não tipáveis. O perfil de virulência mrp+/epf+/sly+ foi o mais frequente. A análise do SE-AFLP resultou em 29 perfis distribuídos em três grupos principais com mais de 65% de similaridade genética. Os isolados apresentaram tendência de se agrupar segundo origem e sorotipo; no entanto, não foi observada correlação entre os grupamentos e os perfis de virulência.(AU)

Walking Capacity Is Positively Related with Heart Rate Variability in Symptomatic Peripheral Artery Disease.

OBJECTIVES: The aim was to investigate the association between walking capacity and HRV in patients with symptomatic peripheral artery disease (PAD). METHODS: This was a cross sectional study. Ninety-five patients were recruited. Patients undertook a supine position for 20 minutes, with the final 10 minutes used to examine for resting HRV. Time domain, frequency domain, and non-linear indices were evaluated. A maximal treadmill test (Gardner protocol) was performed to assess maximal walking distance (MWD) and claudication distance (CD) in groups of PAD patients based upon their walking abilities (low, moderate, high). Differences between PAD patient groups were examined using non-parametric analyses, and Spearman rank correlations identified the relationship between MWD and CD, and HRV parameters. RESULTS: Symptomatic PAD patients with high MWD exhibited significantly greater HRV than patients with low MWD. Furthermore, MWD was positively associated with time domain and non-linear indices of HRV (all p < .05). However, no statistically significant correlations were observed between CD and HRV parameters or between PAD groups. CONCLUSION: A greater walking capacity is associated with better HRV in symptomatic PAD patients.