Publications by authors named "Alvaro Morales"

108 Publications

At a time of global BCG shortage, attempts at optimizing BCG dose and schedule is no longer the answer.

Urol Oncol 2021 02 17;39(2):137-138. Epub 2020 Nov 17.

Department of Urology, Queen's University, Kingston, Ontario, Canada; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada; Cancer Biology and Genetics Division, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.

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http://dx.doi.org/10.1016/j.urolonc.2020.10.009DOI Listing
February 2021

Total Sacrectomy for the Treatment of Advanced Pelvic Chondrosarcoma.

Indian J Surg Oncol 2020 Sep 3;11(Suppl 1):27-32. Epub 2019 Dec 3.

Universidad Complutense de Madrid, Madrid, Spain.

Primary tumors of sacrum are rare. The most common malignant tumors are metastasis, and only 6% of all malignant tumors arise from the sacrum. Chondrosarcoma is the third most common primary bone malignancy following myeloma and osteosarcoma. Surgery is usually the most important therapeutic modality; the wide en bloc excision remains the treatment of choice. These technically demanding procedures require a multidisciplinary expert team (neurosurgery, surgical and orthopedic oncology, colorectal surgery, and plastic surgery) involvement. We present in this article a case of a 52-year-old man who presented less infrequent symptoms, and the diagnosis was made in a very advanced stage. The wide surgical excision of the mass was performed by two different anterior and posterior approaches in one stage. The free surgical margins were difficult to achieve because it presented a voluminous tumor with invasion of the rectum, bone, and sacral plexus, but the age, low histological grade, and extensive experience in extreme pelvic surgery of our multidisciplinary team allowed approaching the patient with debulking surgery en bloc, successfully. Total hospital stay was 20 days. The patient was discharged without any complications. At the 6-months' follow-up, the patient showed no local recurrence.
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http://dx.doi.org/10.1007/s13193-019-01009-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534767PMC
September 2020

Letter to Editor.

Authors:
Alvaro Morales

Can J Urol 2020 10;27(5):10347

Department of Urology, Health Sciences Center, Queen's University, Kingston, Ontario, Canada.

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October 2020

Testosterone and prostate health: Have the paradigms truly shifted?

Can Urol Assoc J 2020 Aug;14(8):230-234

Department of Urology, Queen's University, Kingston, ON, Canada.

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http://dx.doi.org/10.5489/cuaj.6549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402689PMC
August 2020

Phenotypical, Clinical, and Molecular Aspects of Adults and Children With Homozygous Familial Hypercholesterolemia in Iberoamerica.

Arterioscler Thromb Vasc Biol 2020 10 6;40(10):2508-2515. Epub 2020 Aug 6.

Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal (A.C.A., A.M.M., M.B.).

Objective: Characterize homozygous familial hypercholesterolemia (HoFH) individuals from Iberoamerica. Approach and Results: In a cross-sectional retrospective evaluation 134 individuals with a HoFH phenotype, 71 adults (age 39.3±15.8 years, 38.0% males), and 63 children (age 8.8±4.0 years, 50.8% males) were studied. Genetic characterization was available in 129 (96%). The majority (91%) were true homozygotes (true HoFH, n=79, 43.0% children, 46.8% males) or compound heterozygotes (compound heterozygous familial hypercholesterolemia, n=39, 51.3% children, 46.2% males) with putative pathogenic variants in the . True HoFH due to variants had higher total (=0.015) and LDL (low-density lipoprotein)-cholesterol (=0.008) compared with compound heterozygous familial hypercholesterolemia. Children with true HoFH (n=34) tended to be diagnosed earlier (=0.051) and had a greater frequency of xanthomas (=0.016) than those with compound heterozygous familial hypercholesterolemia (n=20). Previous major cardiovascular events were present in 25 (48%) of 52 children (missing information in 2 cases), and in 43 (67%) of 64 adults with variants. Children who are true HoFH had higher frequency of major cardiovascular events (=0.02), coronary heart (=0.013), and aortic/supra-aortic valve diseases (=0.022) than compound heterozygous familial hypercholesterolemia. In adults, no differences were observed in major cardiovascular events according to type of variant. From 118 subjects with variants, 76 (64%) had 2 likely pathogenic or pathogenic variants. In 89 subjects with 2 variants, those with at least one null allele were younger (=0.003) and had a greater frequency of major cardiovascular events (=0.038) occurring at an earlier age (=0.001).

Conclusions: There was a high frequency of cardiovascular disease even in children. Phenotype and cardiovascular complications were heterogeneous and associated with the type of molecular defect.
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http://dx.doi.org/10.1161/ATVBAHA.120.313722DOI Listing
October 2020

BCG vaccine and COVID-19: implications for infection prophylaxis and cancer immunotherapy.

J Immunother Cancer 2020 07;8(2)

Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.

The COVID-19 pandemic has killed over 400 000 people globally. Ecological evidence indicates that countries with national universal BCG vaccination programs for tuberculosis (TB) prevention have a much lower incidence of severe COVID-19 and mortality compared with those that do not have such programs. BCG is a century old vaccine used for TB prevention via infant/childhood vaccination in lowto middle-income countries with high infection prevalence rate and is known to reduce all-cause neonatal mortality. BCG remains the standard immunotherapy treatment for patients with high-risk non-muscle invasive bladder cancer globally for more than 44 years. Several trials are, therefore, investigating BCG as a prophylactic against COVID-19 in healthcare workers and the elderly. In this commentary, we discuss the potential mechanisms that may underlie BCG associated heterologous protection with a focus on tertiary lymphoid structure (TLS) organogenesis. Given the significance of TLSs in mucosal immunity, their association with positive prognosis and response to immune checkpoint blockade with a critical role of Type I interferon (IFN-1) in inducing these, we also discuss potentiating TLS formation as a promising approach to enhance anti-tumor immunity. We propose that lessons learned from BCG immunotherapy success could be applied to not only augment such microbe-based therapeutics but also lead to similar adjunctive IFN-1 activating approaches to improve response to immune checkpoint blockade therapy in cancer.
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http://dx.doi.org/10.1136/jitc-2020-001119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342862PMC
July 2020

Anticancer potential of new 3-nitroaryl-6-(N-methyl)piperazin-1,2,4-triazolo[3,4-a]phthalazines targeting voltage-gated K channel: Copper-catalyzed one-pot synthesis from 4-chloro-1-phthalazinyl-arylhydrazones.

Bioorg Chem 2020 08 19;101:104031. Epub 2020 Jun 19.

Department of Chemistry, University of Florida, Gainesville, FL, United States. Electronic address:

A series of six 3-aryl-6-(N-methylpiperazin)-1,2,4-triazolo[3,4-a]phthalazines were prepared through a facile and efficient one-pot copper-catalyzed procedure from 4-chloro-1-phthalazinyl-arylhydrazones with relatively good yields (62-83%). The one-pot copper-catalytic procedure consists of two simultaneous reactions: (i) a direct intramolecular dehydrogentaive cyclization between ylidenic carbon and adjacent pyrazine nitrogen to form 1,2,4-triazolo ring and, (ii) a direct N-amination on carbon-chlorine bond. Then, an in vitro anticancer evaluation was performed for the synthesized compounds against five selected human cancer cells (A549, MCF-7, SKBr3, PC-3 and HeLa). The nitro-derivatives were significantly more active against cancer strains than against the rest of tested compounds. Specifically, compound 8d was identified as the most promising anticancer agent with significant biological responses and low relative toxicities on human dermis fibroblast. The cytotoxic effect of compound 8d was more significant on PC3, MCF-7 and SKBr3 cancer cells with low-micromolar IC value ranging from 0.11 to 0.59 μM, superior to Adriamycin drug. Mechanistic experimental and theoretical studies demonstrated that compounds 8d act as a K channel inhibitor in cancer models. Further molecular docking studies suggest that the EGFR Tyrosine Kinase enzyme may be a potential target for the most active 3-aryl-6-(N-methylpiperazin)-1,2,4-triazolo[3,4-a]phthalazines.
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http://dx.doi.org/10.1016/j.bioorg.2020.104031DOI Listing
August 2020

Prognostic impact of renal failure recovery in patients with newly diagnosed multiple mieloma.

Rev Med Chil 2019 Nov;147(11):1374-1381

Nephrology Department, Hospital del Salvador, Santiago, Chile.

Background Renal failure (RF) is a common complication in patients with newly diagnosed multiple myeloma (NDMM). Aim To evaluate the frequency of RF in NDMM patients, and the prognostic impact of its reversibility. Material and Methods A retrospective study evaluating demographic and clinical characteristics of 154 consecutive patients with NDMM was carried out. Estimated glomerular filtration rate (eGFR) was calculated at the beginning and at the end of the induction therapy. In addition, we evaluated renal responses (RR) according to the International Myeloma Working Group (IMWG) criteria. The induction regimen was based on thalidomide in all cases. Results Fifty-three patients had RF (34.4%). Complete renal response (RR) was achieved in 51%. Three years overall survival in patients without RF, with RF and complete RR, and patients with RF and any other RR, was 66, 47 and 13%, respectively. Median survival was 53, 27 and 6 months, respectively (p < 0.01). In the multivariate analysis, RF and hypercalcemia were independent predictors of a worse outcome. Conclusions Achieving a complete RR in patients with NDMM, is associated with a better survival.
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http://dx.doi.org/10.4067/S0034-98872019001101374DOI Listing
November 2019

Diurnal Concentration of Urinary Nitrogen and Rumen Ammonia Are Modified by Timing and Mass of Herbage Allocation.

Animals (Basel) 2019 Nov 13;9(11). Epub 2019 Nov 13.

Animal Science Institute, Faculty of Veterinary Sciences, Universidad Austral de Chile, PO Box 567, Valdivia, Chile.

The objective of this work was to evaluate whether changes in time of herbage allocation and herbage mass (HM) (low (L) or medium (M)) modify the diurnal pattern of urinary nitrogen (N) concentration and ruminal ammonia (NH) of lactating dairy cows. Four Holstein-Friesian cows fitted with rumen cannula were randomly allocated to one of four treatments: 1) low herbage mass in the morning (L-AM) (Access to new herbage allocation after morning milking with a herbage mass (HM) of 2000 kg DM/ha); 2) low herbage mass in the afternoon (L-PM) (Access to new herbage allocation after afternoon milking with a HM of 2000 kg DM/ha); 3) medium herbage mass in the morning (M-AM) (Access to new herbage allocation after morning milking with a HM of 3000 kg DM/ha); and 4) medium herbage mass in the afternoon (M-PM) (Access to new herbage allocation after afternoon milking with a HM of 3000 kg DM/ha). A four by four Latin Square design with four treatments, four cows, and four experimental periods was used to evaluate treatment effects. Rumen NH concentration was greater for L-AM compared to L-PM and M-PM at 13:00 and 16:00 h. Urine urea and N concentrations were lower for M-AM compared to L-AM. Urine N concentration was greater for L-AM than other treatments at 10:00 hours and greater for M-PM compared to M-AM at 16:00 hours. Results suggest that maintaining the cows in the holding pen at the milking parlor for two hours after morning grass silage supplementation for L-AM and for two hours after afternoon grass silage supplementation for M-PM, could allow collection of urine from cows at the holding pen and storage of urine in the slurry pit during the time of peak N concentration, returning cows to the pasture at a time of day when urinary N concentration is decreased.
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http://dx.doi.org/10.3390/ani9110961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912627PMC
November 2019

Comprehensive Characterization of a Porcine Model of The "Small-for-Flow" Syndrome.

J Gastrointest Surg 2019 11 7;23(11):2174-2183. Epub 2019 Feb 7.

Transplant and Hepatobiliopancreatic Surgery Unit, Department of General and Digestive Surgery, Hospital General Universitario Gregorio Marañón - IiSGM, Madrid, Spain.

Introduction: The term "Small-for-Flow" reflects the pathogenetic relevance of hepatic hemodynamics for the "Small-For-Size" syndrome and posthepatectomy liver failure. We aimed to characterize a large-animal model for studying the "Small-for-Flow" syndrome.

Methods: We performed subtotal (90%) hepatectomies in 10 female MiniPigs using a simplified transection technique with a tourniquet. Blood tests, hepatic and systemic hemodynamics, and hepatic function and histology were assessed before (Bas), 15 min (t-15 min) and 24 h (t-24 h) after the operation. Some pigs underwent computed tomography (CT) scans for hepatic volumetry (n = 4) and intracranial pressure (ICP) monitoring (n = 3). Postoperative care was performed in an intensive care unit environment.

Results: All hepatectomies were successfully performed, and hepatic volumetry confirmed liver remnant volumes of 9.2% [6.2-11.2]. The hepatectomy resulted in characteristic hepatic hemodynamic alterations, including portal hyperperfusion, relative decrease of hepatic arterial blood flow, and increased portal pressure (PP) and portal-systemic pressure gradient. The model reproduced major diagnostic features including the development of cholestasis, coagulopathy, encephalopathy with increased ICP, ascites, and renal failure, hyperdynamic circulation, and hyperlactatemia. Two animals (20%) died before t-24 h. Histological liver damage was observed at t-15 min and at t-24 h. The degree of histological damage at t-24 h correlated with intraoperative PP (r = 0.689, p = 0.028), hepatic arterial blood flow (r = 0.655, p = 0.040), and hepatic arterial pulsatility index (r = 0.724, p = 0.066). All animals with intraoperative PP > 20 mmHg presented liver damage at t-24 h.

Conclusion: The present 90% hepatectomy porcine experimental model is a feasible and reproducible model for investigating the "Small-for-Flow" syndrome.
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http://dx.doi.org/10.1007/s11605-019-04130-2DOI Listing
November 2019

Identification of dehydroxy isoquine and isotebuquine as promising anticancer agents targeting K+ channel.

Chem Biol Drug Des 2019 04 19;93(4):638-646. Epub 2019 Feb 19.

Laboratorio de Biotecnología Clínica Santa María, Cevalfes, Caracas, Venezuela.

Traditional antimalarial drugs based on 4-aminoquinolines have exhibited good antiproliferative activities against human tumor cells; however, their low relative efficacy has limited their corresponding clinical uses. In order to identify new potent anticancer agents based on 4-aminoquinoline, we evaluated the antiproliferative activity of a series of dehydroxy isoquines and isotebuquines against five human cancer lines. HeLa and SKBr3 were significantly more sensitive to the action of tested quinolines than the A549, MCF-7, and PC-3 cancer lines. Compound 2h was by far the most potent derivative against four of the tested lines (except to PC3 line), exhibiting low micromolar or nanomolar IC values superior to adriamycin reference, low toxicities on dermis human fibroblasts (LD  > 250 μM), and excellent selectivity indexes against the mentioned cancer cells. A structure-activity relationship analysis put in evidence that a pyrrolidine or morpholine moiety as N-alkyl terminal substitution and the incorporation of the extra phenyl attached to aniline ring are pharmacophore essentials for improvement the anticancer activity of the studied dehydroxy isoquines and isotebuquines. From the results, compound 2h emerged as a promising anticancer candidate for further in vitro assays against resistant-strain and in vivo studies as well as pharmacokinetic and genotoxicity studies. Mechanistic assays suggested that the most active quinoline 2h act as calcium-activated potassium channel activator.
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http://dx.doi.org/10.1111/cbdd.13461DOI Listing
April 2019

1 Gb/s chaotic encoded W-band wireless transmission for physical layer data confidentiality in radio-over-fiber systems.

Opt Express 2018 Aug;26(17):22296-22306

Physical layer encryption methods are emerging as effective, low-latency approaches to ensure data confidentiality in wireless networks. The use of chaotic signals for data masking is a potential solution to prevent a possible eavesdropper to distinguish between noise and sensitive data. In this work, we experimentally demonstrate the W-band wireless transmission of a 1 Gb/s chaotic signal over 2 m in a radio-over-fiber architecture. The chaos encoding scheme is based on the transition between different states of a Duffing oscillator system, digitally implemented. The bit error rate achieved in all cases was below the forward error correction limit for 7 % overhead. The presented results validate the proposed chaos-based physical layer encoding solution for gigabit data transmissions in hybrid millimeter-wave/photonic networks.
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http://dx.doi.org/10.1364/OE.26.022296DOI Listing
August 2018

Higher pharmaceutical public expenditure after direct price control: improved access or induced demand? The Colombian case.

Cost Eff Resour Alloc 2018 2;16. Epub 2018 Mar 2.

4Ministerio de Salud y Protección Social, Carrera 13 # 32-76, Bogotá, Colombia.

Background: High pharmaceutical expenditure is one of the main concerns for policymakers worldwide. In Colombia, a middle-income country, outpatient prescription represents over 10% of total health expenditure in the mandatory benefits package (POS), and close to 90% in the complementary government fund (No POS). In order to control expenditure, since 2011, the Ministry of Health introduced price caps on inpatient drugs reimbursements by active ingredient. By 2013, more than 400 different products, covering 80% of public pharmaceutical expenditure were controlled. This paper investigates the effects of the Colombian policy efforts to control expenditure by controlling prices.

Methods: Using SISMED data, the official database for prices and quantities sold in the domestic market, we estimate a Laspeyres price index for 90 relevant markets in the period 2011-2015, and, then, we estimate real pharmaceutical expenditure.

Results: Results show that, after direct price controls were enacted, price inflation decreased almost - 43%, but real pharmaceutical expenditure almost doubled due mainly to an increase in units sold. Such disproportionate increase in units sold maybe attributable to better access to drugs due to lower prices, and/or to an increase in marketing efforts by the pharmaceutical industry to maintain profits.

Conclusions: We conclude that pricing interventions should be implemented along with a strong market monitoring to prevent market distortions such as inappropriate and unnecessary drug use.
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http://dx.doi.org/10.1186/s12962-018-0092-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833155PMC
March 2018

Testosterone Replacement in a Man with Intermediate-risk Prostate Cancer.

Authors:
Alvaro Morales

Eur Urol Focus 2017 10 30;3(4-5):319-320. Epub 2017 Jun 30.

Urology Department, Queen's University, Kingston, Canada. Electronic address:

In brief, a hypogonadal man with successfully treated localized prostate cancer deserves testosterone therapy (TTh) regardless of grade. The evidence is not conclusive but compelling. The story is different for those with intermediate-risk disease who, for a variety of reasons, need TTh but cannot or elect not to have treatment of their primary malignancy, but still desire androgen supplementation.
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http://dx.doi.org/10.1016/j.euf.2017.06.010DOI Listing
October 2017

Taking the first steps in establishing recommendations for testosterone monitoring in men with prostate cancer on androgen-deprivation therapy.

Authors:
Alvaro Morales

Can Urol Assoc J 2017 Jun;11(6):210-211

Department of Urology, Queen's University, Kingston, ON, Canada.

The paper by Shayegan et al in this issue of represents an important initial step in establishing recommendations for hormonal monitoring in men with prostate cancer on androgen-deprivation therapy (ADT). As with most subjects related to the actions of testosterone, the survey adds to the controversies, but also opens the opportunity to explore several of the concerns relevant to the hormonal management of prostate cancer.
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http://dx.doi.org/10.5489/cuaj.4652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472468PMC
June 2017

BCG: A throwback from the stone age of vaccines opened the path for bladder cancer immunotherapy.

Authors:
Alvaro Morales

Can J Urol 2017 Jun;24(3):8788-8793

Queen's University, Kingston, Ontario, Canada.

Introduction: It is 40 years since the initial documentation of the efficacy of bacille Calmette-Guérin (BCG) in the management of non-muscle invasive bladder cancer (NMIBC) and probably an opportune a time as any to retrace the origins of this development and to reflect on the progress that has occurred on the use of immune modifiers in the treatment of NMIBC.

Materials And Methods: A PubMed search for publications on the history of BCG was conducted, and those related to the development of the vaccine for protection against tuberculosis as well as those published in the last 40 years related to its use for treatment for NMIBC were selected for review. A manual search was also carried out for recent articles on immunotherapy for NMIBC failing to respond to BCG. Publications were selected for their usefulness in exemplifying the development of BCG as an antineoplastic agent, elucidating its mechanisms of action of BCG or introducing significant modifications in treatment regimens resulting in enhancement of its efficacy. Alternative innovative immunotherapeutic approaches were chosen to illustrate current trends in the management of this disease.

Results: Well thought-out modifications of the original protocol resulted in enhanced efficacy of the vaccine, which currently ranks as the best-known and most-used and investigated agent for high risk NMIBC. Despite its efficacy, a considerable number (30%-40%) of these tumors fail to respond to BCG. In addition, as a live bacterium it carries the potential for serious adverse effects and some patients are unable to tolerate it. These shortcomings have created the need for new agents. These range from other mycobacteria and viruses to monoclonal antibodies alone or in combination with other agents currently at various stages of development.

Conclusion: After 4 decades of use, BCG remains the most effective agent against high risk NMIBC, but it still holds substantial drawbacks. The enduring use of immunotherapy for NMIBC has created a propitious environment to search for better alternatives. There are an increasing number of promising in vitro, animal and early human clinical trials to anticipate a significant therapeutic alternative in the foreseeable future.
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June 2017

Administration of Mycobacterium phlei cell wall-nucleic acid complex in the immediate postoperative period for the treatment of non-muscle-invasive bladder cancer.

Authors:
Álvaro Morales

Can Urol Assoc J 2016 Sep-Oct;10(9-10):328-332

Queens University, Kingston, ON, Canada.

Introduction: This review sought to investigate the safety of intravesical administration of Mycobacterium phlei cell wall-nucleic acid (MCNA) in the immediate postoperative period after biopsy/resection for non-muscle-invasive bladder cancer (NMIBC).

Methods: Patients with NMIBC who failed bacillus Calmette-Guérin (BCG) therapy and at high risk of recurrence and progression participated in this study. Treatment involved an induction phase of six weeks and maintenance of three weekly instillations every six months for two years. Biopsies were mandatory at six months and resections/biopsies as indicated. Of the 129 patients enrolled, 18 (14%) received one or more instillations of MCNA within 24 hours of an endoscopic procedure for a total of 32 instillations.

Results: Fourteen patients (78%) received MCNA in the immediate postoperative period. Two (11%) received treatment the day after surgery, but a second treatment immediately after a transurethral resection of the bladder tumour (TURBT). The remaining two patients received an instillation each the day after surgery. Adverse events (AEs) occurred in 31.3% of those treated immediately after the procedure; they were mild, limited to the lower urinary tract, and not drug-related. Only one patient experienced systemic symptoms of moderate severity. None of the AEs resulted in postponement of treatment. There were no AEs among those receiving MCNA the day after surgery.

Conclusions: The dual mechanism of action of MCNA suggests that early treatment would take advantage of its chemotherapeutic (pro-apoptotic) activity. Concerns about early administration due to the presence of live bacteria are circumvented with this sterile preparation. These preliminary results warrant further investigation to confirm the safety of perioperative administration of MCNA.
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http://dx.doi.org/10.5489/cuaj.3568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085912PMC
November 2016

Addressing the pressing issues related to testosterone administration to men with prostate cancer.

Authors:
Alvaro Morales

Can Urol Assoc J 2016 May-Jun;10(5-6):185-186

Department of Urology, Queen's University, Kingston, ON, Canada.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045344PMC
http://dx.doi.org/10.5489/cuaj.3824DOI Listing
October 2016

[The debate on regulating biotechnology drugs: Colombia in the international context].

Rev Panam Salud Publica 2016 Aug;40(1):40-47

In September 2014, Colombia issued standards for the evaluation of biological drugs within the framework of the marketing authorization process. The Colombian approach explicitly includes a fast track for evaluating competing biologicals, which caused great national and international controversy. This article explains the context that justifies the need for this fast-track approach, critically analyzes comparability as a paradigm for the evaluation of biogenerics, and shows that Colombia's position is not isolated and is based on global regulatory trends.
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August 2016

[Survival of older patients starting hemodialysis in Chile].

Rev Med Chil 2016 Jun;144(6):697-703

Departamento de Medicina Oriente, Universidad de Chile, Santiago, Chile.

Unlabelled: The proportion of older people with end stage renal disease is increasing. Their prognosis is characterized by a high mortality and poor quality of life.

Aim: To analyze the survival of patients starting chronic hemodialysis (CHD) according to their age.

Material And Methods: Patients admitted to CHD in the East Metropolitan Health Service of Santiago in a 2-year period were analyzed. Four age groups were created, separating patients older than 70 years in a special group.

Results: During the study period, 459 patients were admitted to CHD and were followed for an average of 27 months. The frequency of cardiovascular comorbidity, cancer, and chronic renal disease of unknown cause (attributed to nephrosclerosis) increased along with age. Mortality was higher at older ages. There was a significant association between starting CHD with a catheter, Charlson comorbidity index and increasing age with mortality. For those aged over 80 years, mortality at three months and one year was 25 and 43% respectively.

Conclusions: Age, Charlson index and vascular access are predictors of mortality in older adults entering hemodialysis. This study suggests the importance of considering comorbidities, assessment by specialists and creating an arteriovenous fistula in this age group.
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http://dx.doi.org/10.4067/S0034-98872016000600002DOI Listing
June 2016

Mycobacterium phlei cell wall-nucleic acid complex in the treatment of nonmuscle invasive bladder cancer unresponsive to bacillus Calmette-Guerin.

Expert Opin Biol Ther 2016 ;16(2):273-83

b Clinical Research , Telesta Therapeutics Inc ., Pointe-Claire , Québec , Canada.

Introduction: Current guidelines recommend cystectomy in patients with high risk NMIBC who fail to respond to BCG. However due to the significant morbidity and mortality of the procedure, many are not candidates or refuse it. No new treatments for this indication have been approved by the US FDA since 1998.

Areas Covered: A cell wall-nucleic acid complex (MCNA) from M. phlei has been investigated for possible application in patients with BCG refractory NMIBC. The development of this biological from the original studies is reviewed, together with the clinical trials leading to a submission to the FDA. Its efficacy and safety are presented together with comparative analysis of alternative treatments, most of which are used off-label. In addition, new combinations of standard therapies are described as well as single agents exhibiting activity against these tumors.

Expert Opinion: MCNA has shown activity against high risk BCG refractory bladder cancer and offers an alternative to current treatments. The clinical experience remains limited and the optimal therapeutic regimen (dose, frequency) have not been firmly established. Patients and clinicians would welcome the introduction of a compound that may delay or prevent the risks and negative impact in quality of life of cystectomy and urinary diversion.
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http://dx.doi.org/10.1517/14712598.2016.1134483DOI Listing
September 2016

Effects of Seasonal Upwelling on Inorganic and Organic Matter Dynamics in the Water Column of Eastern Pacific Coral Reefs.

PLoS One 2015 11;10(11):e0142681. Epub 2015 Nov 11.

Leibniz Center for Tropical Marine Ecology, Bremen, Germany.

The Gulf of Papagayo at the northern Pacific coast of Costa Rica experiences pronounced seasonal changes in water parameters caused by wind-driven coastal upwelling. While remote sensing and open water sampling already described the physical nature of this upwelling, the spatial and temporal effects on key parameters and processes in the water column have not been investigated yet, although being highly relevant for coral reef functioning. The present study investigated a range of water parameters on two coral reefs with different exposure to upwelling (Matapalo and Bajo Rojo) in a weekly to monthly resolution over one year (May 2013 to April 2014). Based on air temperature, wind speed and water temperature, three time clusters were defined: a) May to November 2013 without upwelling, b) December 2013 to April 2014 with moderate upwelling, punctuated by c) extreme upwelling events in February, March and April 2014. During upwelling peaks, water temperatures decreased by 7°C (Matapalo) and 9°C (Bajo Rojo) to minima of 20.1 and 15.3°C respectively, while phosphate, ammonia and nitrate concentrations increased 3 to 15-fold to maxima of 1.3 μmol PO43- L-1, 3.0 μmol NH4+ L-1 and 9.7 μmol NO3- L-1. This increased availability of nutrients triggered several successive phytoplankton blooms as indicated by 3- (Matapalo) and 6-fold (Bajo Rojo) increases in chlorophyll a concentrations. Particulate organic carbon and nitrogen (POC and PON) increased by 40 and 70% respectively from February to April 2014. Dissolved organic carbon (DOC) increased by 70% in December and stayed elevated for at least 4 months, indicating high organic matter release by primary producers. Such strong cascading effects of upwelling on organic matter dynamics on coral reefs have not been reported previously, although likely impacting many reefs in comparable upwelling systems.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142681PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641702PMC
June 2016

Diagnosis and management of testosterone deficiency syndrome in men: clinical practice guideline.

CMAJ 2015 Dec 26;187(18):1369-1377. Epub 2015 Oct 26.

Department of Urology (Morales), Queen's University, Kingston, Ont.; Division of Endocrinology and Department of Urologic Sciences (Bebb), University of British Columbia and St. Paul's Hospital, Vancouver, BC; Division of Endocrinology (Manjoo), University of British Columbia, and Department of Medicine (Manjoo), Vancouver Island Health Authority, Vancouver, BC; McGill University and Jewish General Hospital (Assimakopoulos), Montréal, Que.; Department of Family and Community Medicine (Axler), University of Toronto, Toronto, Ont.; Department of Pathology and Molecular Medicine (Collier), Queen's University, Kingston, Ont.; Departments of Psychiatry (Elliott) and Urologic Sciences (Elliott, Goldenberg), University of British Columbia, Vancouver, BC; Canadian Men's Health Foundation (Goldenberg), Vancouver, BC; Faculty of Medicine (Gottesman), University of Toronto, Credit Valley Hospital, Toronto, Ont.; Division of Urology (Grober), Department of Surgery, University of Toronto, Mount Sinai Hospital and Women's College Hospital, Toronto, Ont.; Departments of Clinical Epidemiology and Biostatistics and of Medicine (Guyatt), McMaster University, Hamilton, Ont.; Department of Pathology and Laboratory Medicine (Holmes), University of British Columbia and St. Paul's Hospital, Vancouver, BC; Division of Urology (Lee), Department of Surgery, University of Calgary, Calgary, Alta.

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http://dx.doi.org/10.1503/cmaj.150033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674408PMC
December 2015

Beyond a Simple Anesthetic Effect: Lidocaine in the Diagnosis and Treatment of Interstitial Cystitis/bladder Pain Syndrome.

Urology 2015 May;85(5):1025-1033

Department of Anesthesiology and Perioperative Care, University of California Irvine, Irvine, CA.

Intravesical local anesthetics, in a wide variety of combinations, are increasingly used to treat patients with interstitial cystitis-bladder pain syndrome (IC/BPS). Lidocaine has demonstrated properties that block the neuroinflammatory cycle associated with IC/BPS at many of the interactive points in this cycle. Intravesical lidocaine has been shown to assist in identifying the bladder as the source of pain in patients with pelvic pain. An appreciation of these anti-inflammatory effects and of the pharmacokinetics of intravesical lidocaine in patients with IC/BPS could lead to a safe and effective diagnosis and treatment for an as yet unidentified subset of patients in the IC/BPS spectrum.
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http://dx.doi.org/10.1016/j.urology.2015.01.021DOI Listing
May 2015

Tubing erosion of an inflatable penile prosthesis long after implantation.

Authors:
Alvaro Morales

Sex Med 2014 Jun;2(2):103-6

Department of Urology, Queen's University Kingston, ON, Canada.

Introduction: Erosion through skin of connecting tubing of an inflatable penile prosthesis (IPP) has not been previously reported.

Aim: The aim of this study was to present a case of tubing erosion, review the pertinent literature, and discuss the possible causes and management options, including preservation of the device and its components.

Methods: A 42-year-old male failing to respond to medical treatment for erectile dysfunction underwent insertion of an AMS 700 IPP in 1986. Six years later, a revision was necessary because of a leak in the right cylinder and 4 years after, the pump was replaced. Fourteen years after the original implant, he presented with a portion of the tube connecting the pump to the right cylinder eroding through the skin. There was no infection. The skin area involved was resected and the original pump and tubing were buried in a new scrotal pocket after thorough irrigation.

Results: The IPP remained in place, allowing vaginal penetration and without infection for another 11 years. Three years later, it was de-functionalized, converted into a fixed volume device. It eventually was replaced 25 years after originally implanted with a semirigid prosthesis because it did not provide sufficient rigidity and because of concerns about the presence of "screws" detected during pelvic imaging.

Conclusions: Mechanical failures in the early IPP models, as illustrated in this case, were expected. However, the long survival of the device is remarkable. Erosion of the connecting tubing through the skin is unique and, under exceptional circumstances, may be managed conservatively without replacing components of the IPP. Clinicians unfamiliar with procedures involving inflatable devices need to be aware of "foreign bodies" visible in radiological examinations in men who have had revisions of an IPP. Morales A. Tubing erosion of an inflatable penile prosthesis long after implantation. Sex Med 2014;2:103-106.
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http://dx.doi.org/10.1002/sm2.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184680PMC
June 2014

Efficacy and safety of MCNA in patients with nonmuscle invasive bladder cancer at high risk for recurrence and progression after failed treatment with bacillus Calmette-Guérin.

J Urol 2015 Apr 5;193(4):1135-43. Epub 2014 Oct 5.

University of Texas M.D. Anderson Cancer Center, Houston, Texas. Electronic address:

Purpose: Patients with high risk recurrences after bacillus Calmette-Guérin failure have limited options. We performed an open label study to evaluate the efficacy and safety of intravesical MCNA in this setting.

Materials And Methods: Patients were treated intravesically with 8 mg MCNA weekly for 6 weeks followed by 3 weekly instillations at months 3, 6, 12, 18 and 24. Cystoscopy and cytology were performed every 3 months for 2 years with mandatory biopsy at 6 months and as clinically indicated thereafter. The primary efficacy end point was the disease-free survival rate at 1 year.

Results: A total of 129 patients were enrolled in study, including 91 with carcinoma in situ with or without papillary disease and 38 with papillary only tumors. Most patients had high risk disease. A total of 107 cases were bacillus Calmette-Guérin refractory and 2 or more prior bacillus Calmette-Guérin induction courses had been given in 68. Median followup in all patients was 34.7 months. The overall disease-free survival rate was 25.0% at 1 year and 19.0% at 2 years. In patients with papillary only tumors the disease-free survival rate was 35.1% and 32.2% at 1 and 2 years, respectively. The median disease-free duration in the 30 responders was 32.7 months. The progression-free survival rate was 87.3%, 79.8% and 77.7% at 1, 2 and 3 years, respectively, with a progression event in 28 patients. MCNA was well tolerated and few adverse events led to treatment discontinuation.

Conclusions: Intravesical MCNA achieved significant activity in patients at high risk with nonmuscle invasive bladder cancer in whom bacillus Calmette-Guérin treatment failed, especially those with papillary only tumors and those with bacillus Calmette-Guérin relapse. A durable response was seen, particularly in patients with a response at 1 year. MCNA offers an option for patients who are not candidates for or who refuse cystectomy.
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http://dx.doi.org/10.1016/j.juro.2014.09.109DOI Listing
April 2015

Relation between ultra-sensitive C-reactive protein, diabetes and periodontal disease in patients with and without myocardial infarction.

Arq Bras Endocrinol Metabol 2014 Jun;58(4):362-8

Department of Internal Medicine and Department of Clinical Epidemiology, School of Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia.

Objective: The purpose of this study was to evaluate the impact of diabetes and periodontal disease in us-CRP, an inflammatory marker in patients with and without acute myocardial infarction (AMI).

Subjects And Methods: A case-control study was conducted in 401 subjects aged between 30 and 75 years, living in Bogotá D.C. (Colombia). Patients arriving at the emergency room of the San Ignacio University Hospital with AMI were included into the case group. The control group was defined as those subjects without AMI. The following blood tests were performed: complete blood count (CBC), glycemia, total cholesterol, triglycerides, cHDL, cLDL, and us-CRP. Patients with infections or antibiotic treatment within the last three months, who had received periodontal treatment within the six months prior to the study entry, had oral ulcerations, or less than seven teeth were excluded from the study. Periodontal disease was diagnosed based on the 1999 Armitage's classification.

Results: The mean us-CRP value found in diabetic patients with severe chronic periodontitis was 5.31 mg/L (SD 6.82), and 2.38 mg/L (SD 4.42) in non-diabetic patients, being statistically significant (p = 0.000).

Conclusion: Diabetes had an impact in periodontal disease and us-CRP. In patients with AMI, DM and PD considerably increased the us-CRP.
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http://dx.doi.org/10.1590/0004-2730000002899DOI Listing
June 2014

Testosterone deficiency syndrome and cardiovascular health: Looking carefully at the evidence.

Authors:
Alvaro Morales

Can Urol Assoc J 2014 Jan-Feb;8(1-2):34-5

Emeritus Professor of Urology, Queen's University, Kingston, ON.

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http://dx.doi.org/10.5489/cuaj.1906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929477PMC
February 2014