Current Therapeutic Strategies in Clinical Urology.

The field of urology encompasses all benign and malignant disorders of the urinary tract and the male genital tract. Urological disorders convey a huge economic and patient quality-of-life burden. Hospital acquired urinary tract infections, in particular, are under scrutiny as a measure of hospital quality. Given the prevalence of these pathologies, there is much progress still to be made in available therapeutic options in order to minimize side effects and provide effective care. Current drug delivery mechanisms in urological malignancy and the benign urological conditions of overactive bladder (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS), and urinary tract infection (UTI) will be reviewed herein. Both systemic and local therapies will be discussed including sustained release formulations, nanocarriers, hydrogels and other reservoir systems, as well as gene and immunotherapy. The primary focus of this review is on agents which have passed the preclinical stages of development.

Poor immune reconstitution is associated with symptomatic BK polyomavirus viruria in allogeneic stem cell transplant recipients.

BACKGROUND: BK polyomavirus (BKPyV) infections are known indicators of immune suppression in hematopoietic stem cell transplant (HSCT) recipients; they can lead to hemorrhagic cystitis, ureteral stenosis, renal dysfunction, and prolonged hospital stays. In this study, we determined transplant-associated variables and immune parameters that can predict for the risk of BKPyV viruria. We hypothesized that BKPyV infection is a marker of poor immune recovery. METHODS: We analyzed all engrafted patients undergoing first allogeneic HSCT at MD Anderson Cancer Center in Houston between January 2004 and December 2012. We evaluated their immune parameters and their transplant-associated factors. BKPyV positivity was defined as BKPyV detection in urine by polymerase chain reaction testing. Cox proportional hazards model, as well as competing risk analysis method using subdistribution hazard models with death as competing risk, were applied to assess risk of BKPyV viruria. RESULTS: We identified a total of 2477 patients with a median age of 52 years. BKPyV viruria was manifest in 25% (n=629) of the patients. The median time from transplantation to BKPyV viruria development was 42 days among the patients who had BKPyV viruria. On multivariate analysis, tumor type, acute GVHD, chronic GVHD, myeloablative conditioning regimen, cord blood as the graft source, CD3+ , CD4+ , CD8+ , CD56+ , NK counts, and low platelet count were shown to be significantly associated with BKPyV infection. These finding were further confirmed when models incorporating the competing risk of death yielded similar findings. CONCLUSION: In this study, we report significant associations between BKPyV reactivation following allogeneic HSCT and suppressed immune variables. In addition, this study provides valuable information on the immune status of HSCT recipients as a predictor of BKPyV infections that may in turn help us formulate plans for more effective prevention and treatment of this infection.

Glutamine-enriched enteral nutrition in very low birthweight infants and allergic and infectious diseases at 6 years of age.

In a previous randomised controlled trial, we found that glutamine-enriched enteral nutrition in 102 very low birthweight (VLBW) infants decreased both the incidence of serious infections in the neonatal period and the risk of atopic dermatitis during the first year of life. We hypothesised that glutamine-enriched enteral nutrition in VLBW infants in the neonatal period influences the risk of allergic and infectious disease at 6 years of age. Eighty-eight of the 102 infants were eligible for the follow-up study (13 died, 1 chromosomal abnormality). Doctor-diagnosed allergic and infectious diseases were assessed by means of validated questionnaires. The association between glutamine-enriched enteral nutrition in the neonatal period and allergic and infectious diseases at 6 years of age was based on univariable and multivariable logistic regression analyses. Seventy-six of the 89 (85%) infants participated, 38 in the original glutamine-supplemented group and 38 in the control group. After adjustment, we found a decreased risk of atopic dermatitis in the glutamine-supplemented group: adjusted odds ratio (aOR) 0.23 [95% CI 0.06, 0.95]. No association between glutamine supplementation and hay fever, recurrent wheeze and asthma was found. A decreased risk of gastrointestinal tract infections was found in the glutamine-supplemented group (aOR) 0.10 [95% CI 0.01, 0.93], but there was no association with upper respiratory, lower respiratory or urinary tract infections. We concluded that glutamine-enriched enteral nutrition in the neonatal period in VLBW infants decreased the risk of atopic dermatitis and gastrointestinal tract infections at 6 years of age.

Urological manifestations of the disease related to immunoglobulin G4.

Immunoglobulin G4 related disease (IgG4-RD) is a fibro-inflammatory disease of unknown etiology, characterized by lesions in the form of tumors, elevated serum IgG4 levels, plasma cells with significant IgG4 infiltration, accompanied by phlebitis obliterans and fibrosis. This disease usually has multiorgan disease, including pancreas, biliary tract, salivary glands, peri orbital tissues, kidneys, lungs, lymph nodes and retro peritoneum. IgG4-RD mainly affects men with a predominance of age by young adults until old age. The clinical manifestations of IgG4-RD, depend mainly on the organs affected and the response to steroids. His forecast is not yet clear. Within the affected urogenital organs can be observed kidney, retroperitoneum, ureter, bladder, urachus, testis/epididymis, paratesticular region, prostate and urethra.

La enfermedad relacionada con la inmunoglobulina G4 (ER-IgG4) es una enfermedad fibroinflamatoria de etiología desconocida, la cual se caracteriza por presentar lesiones en forma de tumoraciones, concentraciones séricas aumentadas de IgG4 y células plasmáticas con una infiltración importante de IgG4, junto con flebitis obliterante y fibrosis. Esta enfermedad suele tener afección multiorgánica, incluyendo el páncreas, el tracto biliar, las glándulas salivares, los tejidos periorbitarios, los riñones, los pulmones, los ganglios linfáticos y el retroperitoneo. La ER-IgG4 afecta principalmente a hombres, con un predominio de edad por los adultos jóvenes y hasta la vejez. Las manifestaciones clínicas de la ER-IgG4 dependen principalmente de los órganos afectados y de la respuesta a los esteroides. Su pronóstico aún no es del todo claro. Dentro de los órganos urogenitales afectados pueden incluirse el riñón, el retroperitoneo, el uréter, la vejiga, el uraco, el testículo/epidídimo, la región paratesticular, la próstata y la uretra.

IgG4-related disease: what urologists should know.

INTRODUCTION: IgG4-related disease (IgG4-RD) is a recent nosological entity defined as a chronic immune-mediated fibro-inflammatory condition characterized by a tendency to form tumefactive, tissue-destructive lesions or by organ failure. Urologic involvement in IgG4-RD has been described in some short series of patients and in isolated case reports. AIM: The aim of the present study was to review urologic involvement in IgG4-RD with the purpose of providing urologists with the proper background necessary for a preliminary assessment of possible urologic localization of this recent clinical entity. Indeed, patients are typically referred for immunologic management, often right after a differential diagnosis of urologic disease. MATERIALS AND METHODS: A systematic search of PubMed® for both original and review articles published up until October 2015 was performed using keywords relating to IgG4 and to single specific urologic organs, structures, or anatomic sites. The search was then extended to Google® using the same search criteria in order to identify articles not indexed in PubMed®. RESULTS: IgG4-RD is a systemic condition potentially involving every urologic site. It can mimic malignancies and is often misdiagnosed due to its rarity. CONCLUSIONS: A multidisciplinary approach to IgG4-RD should be required because it occasionally mimics other urologic diseases, including malignancies. Therefore, urologists should perform preliminary assessments to avoid inappropriate urologic treatments.

Relationship of lower urinary tract signs to seropositivity for feline immunodeficiency virus in cats.

A group of 41 cats with signs of lower urinary tract disease was compared to a group of 41 cats without any history of disease for prevalence of seropositivity for feline immunodeficiency virus (FIV). The group of healthy cats was similar in age and gender to the group of cats with signs of lower urinary tract disease. Three of the cats with lower urinary tract disease and one control cat were seropositive for FIV. This difference was not statistically significant. The most common cause of lower urinary tract signs was idiopathic. Only 7 cats had urinary tract infection, most associated with perineal urethrostomy or catheterization. Six of the cats with bacterial urinary tract infections were FIV negative.

IgG antibodies to papillomavirus genus-antigens in adult men with cancer of the urinary bladder.

Forty-five sera from men with bladder cancer were examined in a micro solid-phase enzyme-linked immunosorbent assay (ELISA) and in a Western-blotting (WB) assay for the presence of IgG antibodies to papillomavirus (PV) genus-antigens of bovine origin. The ELISA detected PV antibodies in 75.6% of cancer patients. This antibody frequency was significantly higher than that found in both healthy males (22.7%) and patients with urological disorders (24%). A similar correlation among the PV antibody frequencies of the three groups was found with WB assay: 60% of the neoplastic group showed PV antibodies versus 17.3% in healthy males and 32.6% in non-neoplastic patients. Within the same group, 78% to 87% sera showed the same reactivity to both assays. Of these concordant sera, PV positive sera were 55.6% in cancer patients, 13.3% in healthy adults and 19.6% in patients with urological disorders. ELISA PV antibody level in the cancer group was higher than in each of the two control groups. The meaning of the humoral response to PV genus-antigens in men with bladder cancer is discussed.

[A clinical study of bacteremia in urology].

We investigated 32 patients with bacteremia that occurred in the Department of Urology, School of Medicine, Kanazawa University between April, 1983 and March, 1989. This incidence represented 1.9% of the total number of inpatients. The study group comprised 29 males and 3 females, and their age varied from 25 to 82 years with a mean age of 61.7 years. Twenty-two (75%) of the 32 patients had urologic malignancies. The majority of patients were compromised hosts who had one or more (average, 3.8) factors that promoted bacteremia. Urinary tract infections existed in 26 (86.0%) patients before the bacteremic episode and urine cultures revealed a species identical to that simultaneously isolated from the blood in 19 (73.1%) of the 26 patients. Out of the 26 patients, there were 22 (84.6%) with complicated pyelonephritis and 22 (84.6%) with an indwelling urinary tract catheter. In blood cultures, the most common isolate was Staphylococcus epidermidis and gram-positive cocci were cultured at a rate of 43.9% which was higher than that (39.0%) of gram-negative rods. In contrast, in urine cultures, gram-negative rods were isolated predominantly. S. epidermidis and Corynebacterium spp. isolated less frequently in blood than in urine, indicated contaminants. However, Enterococcus spp. and Candida albicans were recognized as causative organisms of bacteremia via the urinary tract, because the urine culture demonstrated a species identical to that obtained from blood in these bacteremic patients. Antibiotic sensitivity tests demonstrated that isolates from blood tended to show tolerance to beta-lactam antibiotics, but had good sensitivity to aminoglycosides.(ABSTRACT TRUNCATED AT 250 WORDS)

[Malakoplakia]. / La malakoplakie.

Malakoplakia is a fairly rare disease, normally found in women (four out of every five cases). It mainly attacks the urinary system, but may spread to the other viscera. The symptoms are not clinically specific. The main interest of the disease is its pathogenesis, from which its treatment is derived. It is in fact an immunological dysfunction of the phagocytes, leading to chemical disorders in the macrophages. Its treatment is based on the use of cholinergic agonists and vitamin C therapy.

[The use of plasmapheresis in treating urology patients]. / Ispol'zovanie plazmafereza v lechenii urologicheskikh bol'nykh.

The paper presents the results of plasmapheresis inclusion into a combined therapy of pyelonephritis. Out of 79 patients treated, 42 had urosepsis, 25 developed pyelonephritis in pregnancy, 12 had complicating chronic renal failure. Uroseptic patients were examined for hemostasis, the rest for immune status. There were symptoms of DIC syndrome in the former and immunity suppression in the latter. After the combined therapy with plasmapheresis, latent hypercoagulation and intoxication disappeared, uroseptic manifestations reduced. The above treatment of pregnancy pyelonephritis stopped inflammation, promoted activation of the immune system. In patients with chronic renal failure adjuvant plasmapheresis enhanced cellular and humoral immunity, neutrophil function, the number of middle-size molecules in the blood diminished. The latter improved renal function in decreasing uremia.