A novel mortality risk score for emphysematous pyelonephritis: A multicenter study of the Global Research in the Emphysematous Pyelonephritis group.

Background: Emphysematous pyelonephritis (EPN) is a necrotizing infection of the kidney and the surrounding tissues associated with considerable mortality. We aimed to formulate a score that classifies the risk of mortality in patients with EPN at hospital admission. Materials and methods: Patients diagnosed with EPN between 2013 and 2020 were retrospectively included. Data from 15 centers (70%) were used to develop the scoring system, and data from 7 centers (30%) were used to validate it. Univariable and multivariable logistic regression analyses were performed to identify independent factors related to mortality. Receiver operating characteristic curve analysis was performed to construct the scoring system and calculate the risk of mortality. A standardized regression coefficient was used to quantify the discriminating power of each factor to convert the individual coefficients into points. The area under the curve was used to quantify the scoring system performance. An 8-point scoring system for the mortality risk was created (range, 0-7). Results: In total, 570 patients were included (400 in the test group and 170 in the validation group). Independent predictors of mortality in the multivariable logistic regression were included in the scoring system: quick Sepsis-related Organ Failure Assessment score ≥2 (2 points), anemia, paranephric gas extension, leukocyte count >22,000/µL, thrombocytopenia, and hyperglycemia (1 point each). The mortality rate was <5% for scores ≤3, 83.3% for scores 6, and 100% for scores 7. The area under the curve was 0.90 (95% confidence interval, 0.84-0.95) for test and 0.91 (95% confidence interval, 0.84-0.97) for the validation group. Conclusions: Our score predicts the risk of mortality in patients with EPN at presentation and may help clinicians identify patients at a higher risk of death.

Prognosis of Extended-Spectrum-Beta-Lactamase-Producing Agents in Emphysematous Pyelonephritis-Results from a Large, Multicenter Series.

BACKGROUND: Emphysematous pyelonephritis (EPN) is a necrotizing infection of the kidney and surrounding tissues with significant mortality. We aimed to assess the clinical factors and their influence on prognosis in patients being managed for EPN with and without ESBL-producing bacteria and to identify if those with EPN due to ESBL infections fared any different. METHODS: A retrospective analysis was performed on patients with EPN diagnosis from 22 centers across 11 countries (between 2013 and 2020). Demographics, clinical presentation, biochemical parameters, radiological features, microbiological characteristics, and therapeutic management were assessed. Univariable and multivariable analyses were performed to determine the independent variables associated with ESBL pathogens. A comparison of ESBL and non-ESBL mortality was performed evaluating treatment modality. RESULTS: A total of 570 patients were included. Median (IQR) age was 57 (47-65) years. Among urine cultures, the most common isolated pathogen was Escherichia coli (62.2%). ESBL-producing agents were present in 291/556 urine cultures (52.3%). In multivariable analysis, thrombocytopenia (OR 1.616 95% CI 1.081-2.413, p = 0.019), and Huang-Tseng type 4 (OR 1.948 95% CI 1.005-3.778, p= 0.048) were independent predictors of ESBL pathogens. Patients with Huang-Tseng Scale type 1 had 55% less chance of having ESBL-producing pathogens (OR 1.616 95% CI 1.081-2.413, p = 0.019). Early nephrectomy (OR 2.3, p = 0.029) and delayed nephrectomy (OR 2.4, p = 0.015) were associated with increased mortality in patients with ESBL infections. Conservative/minimally invasive management reported an inverse association with mortality (OR 0.314, p = 0.001). CONCLUSIONS: ESBL bacteria in EPN were not significantly associated with mortality in EPN. However, ESBL infections were associated with poor prognosis when patients underwent nephrectomy compared conservative/minimally invasive management.

Phimosis: A rare complication of immunotherapy with durvalumab.

We present a case of a 69 year old man with phimosis associated with immunotherapy with durvalumab for metastatic non-small-cell lung cancer. The patient developed vitiligo like dermatosis after the induction dose of durvalumab, subsequent administration of the immunotherapy the patient developed a fibrous ring of the foreskin. Immune-mediated adverse reactions have been described after the use of durvalumab, but, to our knowledge, there are no reports of phimosis and vitiligo like reactions.

Genetic association of monocyte chemoattractant protein 1 (MCP-1)-2518 polymorphism in Mexican patients with transitional cell carcinoma of the bladder.

OBJECTIVE: To investigate the role of MCP-1-2518, stromal cell-derived factor-1 (SDF-1)-G801A and chemokine receptors CCR5-Delta32, CCR5-59 029, and CCR2-64I gene polymorphisms in transitional cell carcinoma of the bladder in Mexican Mestizo patients. METHODS: Forty-seven unrelated consecutive patients with non-muscle-invasive transitional cell carcinoma (TCC) and 126 unrelated healthy individuals were studied. Genomic extraction was carried out from complete blood samples using the salting out method. The PCR-RFLP method was used to amplify the following polymorphisms: MCP-1-2518, SDF-1-G801A, CCR5-Delta32, CCR5-59 029, and CCR2-64I. RESULTS: The patients were divided according to low, intermediate, and high risk of progression and treated accordingly with surveillance or immunotherapy with BCG. SDF-1-G801A, CCR5-Delta32, CCR5-59 029, and CCR2-64I polymorphisms were not associated with the genetic susceptibility to non-muscle-invasive TCC of the bladder in Mexican patients. The distribution of AA, AG, and GG genotypes of MCP-1-2518 was significantly different in bladder cancer patients compared with controls (P = .006). There was a significant decrease both in the frequency of the G mutant allele (P = .021, OR = 1.752; C 95% CI 1.088-2.828) and in the GG genotype (P = .001, OR = 6.097 95% CI 1.885-19.570) in TCC patients, compared with controls. CONCLUSIONS: This preliminary study shows that MCP-1 polymorphism is associated with TCC.

[The bacillus Calmette-Guérin as immunomodulator in bladder cancer]. / Il bacilo de Calmette-Guérin como inmunomodulador en el cáncer de vejiga.

The bacillus Calmette-Guérin (BCG) is regarded as the most successful immunotherapy against superficial bladder carcinoma recurrences to date. BCG intravesical therapy for superficial bladder cancer has shown its efficacy and advantage over classical therapeutic strategies. This efficacy is based on complex and long lasting immune activation. The initial step is the binding of mycobacteria to the urothelial lining, which depends on the interaction of a fibronectin attachment protein on the bacteria surface with fibronectin in the bladder wall. Granulocytes and other immunocompetent mononuclear cells became attracted to the bladder wall and a cascade of proinflammatory cytokines sustains the immune response. In the bladder wall a largely TH1 based cytokine milieu and granuloma-like cellular foci are established. Within this scenario, the most important effector mechanisms might be the direct antitumor activity of interferons and the cytotoxic activity of NK cells. Current treatment consists of an induction phase of 6 weeks and a maintenance dose schedule of 3 weeks every three months up to 36. The majority of patients present adverse events related to dose administration due to bladder inflammatory response and on only a few occasions, there are mayor complications like granulomatous prostatitis. Among all the neoplasms only in superficial bladder cancer the BCG is proved to be effective.

El bacilo de Calmette-Guérin como inmunomodulador en el cáncer de vejiga / The bacillus Calmette-Guérin as immunomodulator in bladder cancer

The bacillus Calmette-Guérin (BCG) is regarded as the most successful immunotherapy against superficial bladder carcinoma recurrences to date. BCG intravesical therapy for superficial bladder cancer has shown its efficacy and advantage over classical therapeutic strategies. This efficacy is based on complex and long lasting immune activation. The initial step is the binding of mycobacteria to the urothelial lining, which depends on the interaction of a fibronectin attachment protein on the bacteria surface with fibronectin in the bladder wall. Granulocytes and other immunocompetent mononuclear cells became attracted to the bladder wall and a cascade of proinflammatory cytokines sustains the immune response. In the bladder wall a largely TH1 based cytokine milieu and granuloma-like cellular foci are established. Within this scenario, the most important effector mechanisms might be the direct antitumor activity of interferons and the cytotoxic activity of NK cells. Current treatment consists of an induction phase of 6 weeks and a maintenance dose schedule of 3 weeks every three months up to 36. The majority of patients present adverse events related to dose administration due to bladder inflammatory response and on only a few ocassions, there are mayor complications like granulomatous prostatitis. Among all the neoplasms only in superficial bladder cancer the BCG is proved to be effective.

El bacilo de Calmette-Guérin (BCG) es considerado como la inmunoterapia más exitosa en contra del carcinoma de vejiga superficial recidivante hasta la fecha. La terapia intravesical con el BCG para el cáncer superficial de vejiga ha mostrado su eficacia y ventaja sobre otras estrategias terapéuticas; esta eficacia está basada en una compleja y larga duración de la activación inmunológica. El paso inicial es la unión de la micobacteria al urotelio, la cual depende de la interacción con la fibronectina de la bacteria con la fibronectina del urotelio. Los granulocitos y otras células mononucleares inmunocompetentes son atraídos hacia la pared vesical, así activando una cascada inmunológica a través de secreción de diversas citocinas, quienes estimulan a las células asesinas naturales (NK) activadas por el BCG, las cuales son capaces de diferenciar células neoplásicas y del epitelio urinario normal. En la pared vesical se encuentra un medio ambiente de citocinas principalmente del tipo TH1 y se forman focos celulares similares a granulomas. Dentro de este escenario los mecanismos efectores más importantes parecen ser la actividad antitumoral directa de los interferones y la actividad citotóxicas de las células NK. El tratamiento actual consiste en la administración intravesical del bacilo en una primera fase de inducción de seis semanas y posteriormente dosis de mantenimiento cada tres meses hasta los 36 meses. La mayoría de los pacientes presentan efectos adversos locales secundarios a la reacción inflamatoria y en un porcentaje muy pequeño se presentan complicaciones mayores como prostatitis y orquiepididimitis granulomatosa. De entre todas estas neoplasias sólo en el cáncer superficial de vejiga se han demostrado resultados satisfactorios con el empleo del BCG.

In vivo IL-10 and TGF-beta production by PBMC from long-term kidney transplant recipients with excellent graft function: a possible feedback mechanism participating in immunological stability.

BACKGROUND: Interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) are Th2-derived multifunctional cytokines that exhibit potent immunoregulatory and anti-inflammatory properties which might prolong graft survival. The aim of this study was to explore whether spontaneous production of IL-10 and TGF-beta by blood mononuclear cells correlates with excellent long-term graft function. METHODS: A cross-sectional study was carried out in 32 kidney transplant recipients, without albuminuria, treated with azathioprine and prednisone. Spontaneous IL-10 and TGF-beta were measured by enzyme-linked immunosorbent assay in supernatants from 24 h cultured unstimulated peripheral blood mononuclear cells. Both cytokines were also determined in 10 healthy kidney donors. RESULTS: There was no correlation between IL-10 or TGF-beta with any variable tested, namely age, SCr, histocompatibility, and post-transplant follow-up. In vivo IL-10 production displayed a statistical trend to be higher in transplant recipients than in controls (362.3 +/- 465, range 12.5-1929.3 pg/ml, and 189 +/- 170, range 4.17-485.7 pg/ml, respectively; p = 0.08), whereas no difference was observed in TGF-beta among the same groups (134.7 +/- 79.2, range 68-421 pg/ml, and 121.4 +/- 25.8, range 75-151 pg/ml, respectively). Interestingly, a statistically significant inverse correlation was observed between IL-10 and TGF-beta in kidney transplant recipients (p = 0.03). CONCLUSIONS: The higher IL-10 production observed in long-term kidney transplant recipients supports the notion that this cytokine contributes in decreasing allogenic immune responses and allows prolongation of allograft survival. The balance between TGF-beta and IL-10 may be of paramount importance in graft acceptance.