Learning curve in flexible ureteroscopy for renal stones: A propensity score-matched study.

OBJECTIVE: To assess the learning curve and evaluate the impact of surgical experience related to the outcomes of flexible ureteroscopy (fURS) for upper urinary tract stones. METHOD: We evaluated retrospectively lithiasis fURS performed in our institution between January 2004 and December 2020. Patients were divided into two groups by the number of procedures performed by surgeon. Group 1 (G1) included the first 50 procedures, and group 2 (G2) the next cases. These groups were matched on baseline characteristics by a propensity score. Stones free rate (SFR) and complication rate (CR) were compared. Learning curves were realized using logistic curve with 95% confidence interval. RESULTS: After criteria exclusion and propensity score matching, 1548 procedures were analyzed (1:1, G1 and G2, n=774 procedures). A total of 29 surgeons were evaluated. The overall SFR was 68.4% without statistical difference between the two groups (G1=67.9% vs. G2=68.8%, P=0.72). The surgeon's experience was not associated with SFR (OR=1.15, 95% CI: 0.90-1.47), except in subgroup stones>2cm (OR=2.89, 95% CI: 1.29-6.46). The overall CR was 12.5%, mainly Clavien-Dindo grade I-II complications (96.2%). Surgical experience was not associated with CR (OR=1.06, 95% CI: 0.77-1.45). The overall logistic curves for probability of stone clearance and complication tended to be a flat slope. CONCLUSION: Impact of surgical experience on fURS for UUTS was not associated with SFR and CR. However, for stones larger than 2cm, surgeon's experience tended to be associated with SFR, but without impact on overall complications.

SARS-CoV-2 Igg seroprevalence in IBD patients treated with biologics: first vs. second pandemic wave in a prospective study.

OBJECTIVE: In a prospective study, SARS-CoV-2 IgG seroprevalence was assessed during the second pandemic wave (W2) in a cohort of Inflammatory Bowel Disease (IBD) patients using biologics. The secondary aim was to compare, in the same cohort, the frequency of seropositivity and of COVID-19 during the second vs. the first (W1) wave. PATIENTS AND METHODS: From November 2020 to March 2021, SARS-CoV-2 IgG seropositivity and the prevalence of COVID-19 were assessed in a cohort of IBD patients using biologics already studied at W1. INCLUSION CRITERIA: age ≥ 18 years; diagnosis of IBD; follow-up; written consent. EXCLUSION CRITERIA: SARS-CoV-2 vaccination. Risk factors for infection, compatible symptoms, history of infection or COVID-19, nasopharyngeal swab test were recorded. Data were expressed as median [range]. The χ2 test, Student's t-test, logistic regression analysis was used. RESULTS: IBD cohort at W1 and W2 included 85 patients: 45 CD (52.9%), 40 UC (47.1%). When comparing the same 85 patients at W2 vs. W1, a higher SARS-CoV-2 seroprevalence at W2 was at the limit of the statistical significance (9.4% vs. 2.3%; p=0.05). The prevalence of COVID-19 at W2 vs. W1 was 3.5% (3/85) vs. 0% (0/85) (p=0.08). Contacts with COVID-19 patients and symptoms compatible with COVID-19 were more frequent at W2 vs. W1 (18.8 % vs. 0%; p=0.0001; 34.1% vs. 15.3%; p=0.004). At W2, history of contacts and new onset diarrhea were more frequent in seropositive patients [4/8 (50%) vs. 12/77 (15.6%); p=0.01 and 4/8 (50%) vs. 2/77 (2.6%); p=0.0001]. At W2, the risk factors for seropositivity included cough, fever, new onset diarrhea, rhinitis, arthromyalgia, dysgeusia/anosmia at univariate (p<0.05), but not at multivariate analysis. History of contacts was the only risk factor for seropositivity at univariate (p=0.03), but not at multivariate analysis (p=0.1). CONCLUSIONS: During W2, characterized by a high viral spread, IBD and biologics appeared not to increase the prevalence of SARS-CoV-2 infection or COVID-19 disease. New onset diarrhea mimicking IBD relapse may be observed in patients with SARS-CoV-2 infection.

Impact of blood transfusion on survival after nephrectomy for localized or locally advanced renal cancer.

OBJECTIVE: Several studies have reported blood transfusion were associated with a decrease of survival after oncological surgery. For kidney cancer, the effect of blood transfusion is still debated. The objective of this study was to determine the effect of blood transfusion after oncological nephrectomy on overall, specific and recurrence-free survival in a retrospective cohort of localized or locally advanced kidney cancer. MATERIAL AND METHODS: We performed a monocentric retrospective analysis of all patients managed by surgery for localized or locally advanced renal cancer between January 2000 and December 2016. We compared overall and specific survival and recurrence-free survival between two groups: patients transfused and not transfused. Demographic, surgical and tumor characteristics were compared. Survival analyses were performed using univariate Cox regression and multivariate Cox proportional regression test. RESULTS: We included 382 patients in this study: 320 (83.8%) were not transfused and 62 (16.2%) were transfused. Transfused patients were significantly older (P=0.001) and had a lower pre-operative hemoglobin level (P=0.008). Operative and oncological characteristics were also different between both groups. In univariate analysis, we showed that blood transfusion was associated with lower overall survival (P<0.001), specific survival (P<0.001), and recurrence-free survival (P<0.001). In multivariate analysis, we found that blood transfusion was not associated with overall survival, or specific survival, but it was associated with lower recurrence-free survival (HR: 1.967, CI95% [1.024-3.780], P=0.042). CONCLUSIONS: Perioperative blood transfusion is an independent risk factor that increases tumor recurrence among patients treated with nephrectomy for renal cancer.

Low testosterone levels and high estradiol to testosterone ratio are associated with hyperinflammatory state and mortality in hospitalized men with COVID-19.

OBJECTIVE: Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex hormones [total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D [25(OH)D] and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19. PATIENTS AND METHODS: We conducted an exploratory retrospective study including symptomatic men with confirmed SARS-CoV-2 infection who were consecutively admitted to our Institution between April 1 and May 31, 2020. RESULTS: Patients were divided into survivors (n=20) and non-survivors (n=39). As compared to survivors, non-survivors showed significantly higher median neutrophil-to-lymphocyte ratio (NLR) values, D-dimer and procalcitonin (PCT) levels, along with significantly lower median 25(OH)D levels and total testosterone levels. Non-survivors exhibited significantly higher median values of E2/T ratio (a marker of aromatase activity). Spearman's correlation analysis revealed that total testosterone levels were significantly and inversely correlated with NLR, high-sensitivity C-reactive protein (hsCRP), interleukin-6, D-dimer and PCT. Conversely, E2/T ratio values were significantly and positively correlated with the aforementioned markers and with white blood cell (WBC) count. In a multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, body mass index, hypertension and cardiovascular disease, diabetes mellitus and malignancy), total testosterone levels were significantly and inversely associated with risk of COVID-19-related in-hospital mortality. CONCLUSIONS: Low total testosterone levels and elevated E2/T ratio values at admission are associated with hyperinflammatory state in hospitalized men with COVID-19. Low total testosterone levels at admission represent an independent risk factor for in-hospital mortality in such patients. Therefore, total testosterone and E2/T ratio may serve as prognostic markers of disease severity in this population.

Low prevalence of SARS-CoV-2 infection in inflammatory bowel disease.

OBJECTIVE: Treatments used in Inflammatory Bowel Disease (IBD) have been associated with enhanced risk of viral infections and viral reactivation, however, it remains unclear whether IBD patients have increased risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The aim of the study was to examine the prevalence of SARS-CoV-2 IgG positivity in IBD patients followed at our referral center. The role of treatments for IBD and risk factors for infection were also evaluated. PATIENTS AND METHODS: In a prospective study, all IBD patients followed at our referral centre between May 27th and July 21st, 2020 and fulfilling the inclusion criteria were tested for SARS-CoV-2 IgG. Specific IgG antibodies were evaluated by a commercial ELISA kit and SARS-CoV-2 nasopharyngeal swab was performed in seropositive patients. RESULTS: Two-hundred and eighteen patients, 128 Crohn's disease (CD) and 90 Ulcerative colitis (UC) [age 44, (19-77) years; ongoing biologics in 115 (52.7%)] were enrolled. No patient had major SARS-CoV-2-related symptoms. SARS-CoV-2 IgG were detected in 3 out of 218 (1.37%) patients with IBD (2 CD and 1 UC), all on biologics (2.6%). In all of the 3 seropositive patients, the nasopharyngeal swab was negative. There was no relationship between SARS-CoV-2 seroprevalence and the demographic/clinical characteristics of IBD patients. In contrast, history of recent travel was more frequent in the SARS-CoV-2 seropositive patients (2/3; 66.6%) than in SARS-CoV-2 seronegative patients [7/215 (3.25%); p<0.0001]. CONCLUSIONS: The prevalence of SARS-CoV-2 IgG seropositivity in IBD patients appears to be comparable to the non-IBD population and not influenced by ongoing treatments. Risk factors for infection common to the general non-IBD population should be considered when managing patients with IBD.

The Von Willebrand Factor Antigen Plasma Concentration: a Monitoring Marker in the Treatment of Aortic and Mitral Valve Diseases.

Von Willebrand disease is a commonly inherited bleeding disorder caused by defects of von Willebrand factor (vWF). In the most common valve diseases, aortic valve stenosis (AVS) and mitral valve regurgitation (MVR), a bleeding tendency has been described in a number of patients. This has been associated to a high turbulence of blood flow through the compromised valve, promoting degradation of vWF with loss of high-molecular-weight multimers of vWF (HMWM), leading to an acquired von Willebrand syndrome (AvWS). We analysed three groups of patients, one affected by AVS, treated with transcatheter aortic valve implantation (TAVI), the second group of patients affected by MVR, treated with Mitraclip® mitral valve repair. The third group was represented by patients also affected by AVS, but not eligible for TAVI and treated with standard surgery. A fourth group of patients that underwent percutaneous coronary intervention (PCI) with stenting was used as a control. Our results demonstrated that the level of vWF measured as antigen concentration (vWF:Ag) increases in all cohorts of patients after treatment, while in control PCI patients, no modification of vWF:Ag has been registered. Western blot analysis showed only a quantitative loss of vWF in the pre-treatment time, but without significant HMWM modification. The monitoring of the vWF:Ag concentration, but not the quality of HMWM, can indicate the status of blood flow in the treated patients, thus introducing the possibility of using the vWF antigen detection in monitoring the status of replaced or repaired valves.

[Concordances and predictors of biopsies in renal tumors]. / Concordances et facteurs prédictifs des biopsies dans les tumeurs rénales.

AIM: Evaluate the concordance between the renal lesions biopsy's histology and the final histology of the surgical specimen according to histological subtype, and search for predictive factors of non-concordance. MATERIAL: We performed a monocentric retrospective study that included 156 patients suffering from a renal tumor that benefited a lesion biopsy before surgical treatment. Sensibility and specificity of the renal lesion's biopsy for histological diagnostic of the different renal tumors where calculated. RESULTS: One hundred and fifty-eight renal tumor biopsies were realized between 2001 and 2016. One hundred and forty-three renal cell carcinoma were found on the surgical piece, 135 were diagnosed on prior biopsy. Global concordance rate was 88%. For the establishment of the nuclear Fuhrmann grade, the concordance rate (low vs. high grade) was 72.9%. The cohort was divided into 2 groups according to the existence (group 1, n=139) or the absence (group 2, n=19) of concordance. Group 1 and 2 differed by the predominance of men in group 1 (66% vs. 37%, P=0.013), distance between the sinus and the tumor above 4mm (65% vs. 42%, P=0.05). CONCLUSION: In renal tumor care, renal biopsy is a reliable testing. However, some factors most likely linked to the tumor anatomy (intra-sinusal tumor) and their histological composition were involved in the lack of non-contribution to the diagnosis. LEVEL OF EVIDENCE: 4.

Role of the TAp63 Isoform in Recurrent Nasal Polyps.

The pathogenic molecular mechanisms underlying the insurgence of nasal polyps has not been completely defined. In some patients, these lesions can have a recurrence after surgery removal, and the difference between recurrent and not recurrent patients is still unclear. To molecularly characterize and distinguish between these two classes, a cohort of patients affected by nasal polyposis was analysed. In all patients we analysed the p63 isoform expression using fresh tissues taken after surgery. Moreover, confocal immunofluorescence analysis of fixed sections was performed. The results show high ΔNp63 expression in samples from the nasal polyps of patients compared to the normal epithelia. Analysis of the expression level of the TAp63 isoform shows differential expression between the patients with recurrence compared to those not recurring. The data, considered as the ΔN/TAp63 ratio, really discriminate the two groups. In fact, even though ΔNp63 is expressed in non-recurrent patients, the resulting ratio ΔN/TAp63 is significantly lower in these patients. This clearly indicates that the status of TAp63 expression, represented by the ΔN/TAp63 ratio, could be considered a prognostic marker of low recurrence probability. In these samples we also investigated the expression of OTX2 transcription factor, known to be a selective activator of TAp63, detecting a significant correlation. Database analysis of HNSCC patients showed increased survival for the patients presenting OTX2 amplification and/or overexpression. These results, together with the fact that TAp63 can be selectively upregulated by HDAC inhibitors, open the possibility to consider local treatment of recurrent nasal polyps with these molecules.

Aging and Adherence to the Mediterranean Diet: Relationship with Cardiometabolic Disorders and Polypharmacy.

OBJECTIVES: To investigate the association between adherence to the Mediterranean Diet (Med-Diet), cardiometabolic disorders and polypharmacy. DESIGN: Cross-sectional study. SETTING: Geriatrics outpatient clinic, Policlinico Umberto I, Sapienza University of Rome. PARTICIPANTS: 508 patients (219 male, 289 female) aged 50 to 89 who were evaluated for cardiovascular and metabolic disorders. METHODS AND MEASUREMENTS: Patients underwent a comprehensive medical assessment including medical history and the use of medications. Adherence to Med-Diet was assessed using the validated Med-Diet 14-item questionnaire; for the analysis, patients were divided in high (≥8) and medium-low (<8) adherence. Polypharmacy was defined as taking ≥5 medications. RESULTS: 476 patients completed the study. Mean age was 70.4 years; 58% female. Median Med-Diet score was 8 (interquartile range, 6-9). Patients with medium-low adherence had higher body mass index (p=0.029) and higher prevalence of arterial hypertension (p<0.001), previous coronary (p=0.002) and cerebrovascular events (p=0.011), diabetes, (p<0.001) and dyslipidemia (p=0.001) compared to those at high adherence. Med-Diet score decreased with the number of cardiometabolic disorders (p<0.001). The prevalence of polypharmacy was 39%. Consumption of olive oil (p=0.005), vegetables, (p<0.001), wine (p=0.017), legumes (p=0.028), fish (p=0.046) and nuts (p=0.045) were all inversely associated with the overall number of medications. In a multivariable regression model, medium-low adherence to Med-Diet was independently associated to polypharmacy (O.R.:1.859; 95% CI 1.142 to 3.025; p=0.013), after adjusting for possible confounding factors. CONCLUSION: Med-Diet was inversely associated with cardiometabolic disorders and with polypharmacy, suggesting that improved Med-Diet adherence might potentially delay the onset of age-related health deterioration and reduce the need of multiple medications.

[Flexible ureterorenoscopy vs percutaneous nephrolithotomy for renal stone management: Retrospective study]. / Étude rétrospective comparant la néphrolithotomie percutanée et l'uréterorénoscopie souple pour le traitement des calculs intrarénaux.

PURPOSE: The aim of this study was to evaluate the efficacy and tolerance of renal stone fragmentation by flexible ureterorenoscopy (URS), compared to percutaneous nephrolithotomy (PCNL). MATERIAL AND METHODS: Patients treated between 1998 and 2010 by URS and PCNL for intrarenal stone were reviewed. Patients' and stones' characteristics were analyzed. The preoperative parameters were reported as well as the procedure's efficiency and its complications. Success was defined by the absence of residual lithiasis visualized on renal imaging at 6 months of follow-up. RESULTS: Among 531 patients included, there were 159 PCNL and 372 URS. The mean duration of hospitalization after PCNL was 8±4.6 days and 3±1.7 days after URS. The mean stones' size was higher in the PCNL group (19.9±7.5mm) than for the URS group (9.7±5.6mm; P<0.0001). The stone-free rate was significantly better in the PCNL group for stones measuring between 10 and 20mm (P<0.0001) and for stones of more than 20mm (P=0.017). Postoperative complications were significantly more frequent (27 %) and more severe (8.8 % vs Clavien III and IV) in the PCNL, than in the URS group, respectively (P=0.0001). CONCLUSION: PCNL is a successful technique for renal stone fragmentation. However, URS seemed more tolerated despite a lower stone-free rate. LEVEL OF EVIDENCE: 4.

[Impact of obesity on pathologic outcomes and biochemical reccurence after radical prostatectomy]. / Effets de l'obesité sur les résultats anatomopathologiques de la prostatectomie totale et sur la survie sans recidive biologique.

OBJECTIVE: To determine whether obesity is associated with adverse pathologic characteristics, positive surgical margins and the biochemical recurrence free survival (bRFS) after primary treatment with radical prostatectomy (RP). PATIENTS AND METHODS: Medical charts of patients managed with RP between 1999 and 2011 for localized prostate cancer (PCa) were retrospectively reviewed. Population study was split into two groups according to the body mass index (BMI): non obese (BMI< 30 kg/m(2)) and obese (BMI ≥ 30 kg/m(2)). Correlations between obesity and adverse pathological features or bRFS were assessed using univariable and multivariable analyses. RESULTS: Overall, 328 patients were included in the present study: 278 (84.8%) obese and 50 (15.2%) non obese. In multivariable analysis, obesity was associated with positive surgical margins (P=0.014), extracapsular extension (P=0.004) and pathologic Gleason score ≥ 7 (P=0.048). Obesity was not associated with seminal vesicle invasion (P=0.636) and lymph node metastasis (P=0.132). After a mean follow-up of 60.51 ± 28.82 months, no statistical difference in terms of bRFS was observed between the two groups (P=0.186). Furthermore, obesity was not an independent predictor of bFS in multivariable analysis. CONCLUSION: Obesity was associated with adverse pathologic characteristics and positive surgical margins but no statistical correlation was found with bRFS. LEVEL OF EVIDENCE: 5.

[Flexible ureterorenoscopy in obese patients: results from a large monocenter cohort]. / Urétérorénoscopie souple avec laser Holmium-YAG dans la prise en charge des lithiases urinaires chez le patient obèse: résultats d'une cohorte monocentrique.

OBJECTIVE: To analyze results and morbidity after flexible ureterorenoscopy (fURS) in patients with a body mass index (BMI)>30 kg/m² and to compare with results obtained in a large cohort of non-obese patients. METHODS: We conducted a retrospective monocenter study including all fURS for urinary lithiasis performed in our institution between January 2004 and December 2010. During the study period, 497 procedures were performed. Twenty-three had to be excluded because of missing data on BMI. Thus, a total of 474 procedures were included in the final analysis, 93 for obese patients (OP) and 381 for non-obese patients (NOP). Characteristics of the patients, stones and procedures were analyzed. Success was defined as clear imaging (completely stone-free) on renal tomography and ultrasonography. RESULTS: Mean BMI was 33.5 ± 0.3 in OP vs 23.9 ± 0.1 kg/m² in NOP (P<0.0001). Mean stone size, location, and composition were not significantly different between groups. Technical aspects (operative time, ureteral dilatation, access sheath, monobloc extraction) were also similar in OP and NOP. The immediate (63.5% for OP vs 66.1% in NOP, P=0.62) and follow-up (65.1% for OP vs 71% in NOP, P=0.26) stone-free rate were not significantly different between the groups. For stone size<1cm, SFR raised to 77% in OP vs 83% in NOP (P=0.28). The rate of minor complications Clavien II was similar in OP (7.5%) and NOP (12%). No major complication (Clavien III or IV) was observed. CONCLUSION: fURS is a safe and efficient option for the management of urinary lithiasis in obese patients.

[Existence of pattern 5 on radical prostatectomy: poor prognostic factor associated with a lower biochemical recurrence-free survival]. / Existence de grade 5 sur pièce de prostatectomie totale: facteur de mauvais pronostic associé à une moindre survie sans récidive biologique.

OBJECTIVES: To analyze the impact of the existence of Gleason grade 5 on the adverse pathology and biochemical recurrence-free survival of patients. PATIENTS: Three hundred and seventy-two prostatectomies were performed between 1999 and 2011 in our institution for localised prostate adenocarcinoma. We examined the existence of grade 5 of the specimen to determine the reliability of prostate biopsies in the diagnosis of grade 5 and the association of grade 5 with other histoprognostic factors. Biochemical recurrence-free survival was analyzed according to the presence of grade 5 in the final specimen. RESULTS: In total, all histological data and biochemical recurrence-free survival were available for 321 patients who were included in the study. Sixty-eight had Gleason grade 5 (majority or third minority pattern) on the specimen while 253 had not. Grade 5, rarely diagnosed on biopsy (sensitivity=26.47 %) was correlated independently with the extracapsular extension (OR=2.1; CI 95 [1.1-3.9]), the seminal vesicle invasion (OR=3.8; CI 95 [1.7-8.7]) and positive surgical margins (OR=2.0; CI 95 [1.1-3.6]). Overall survival was similar in both groups but the biochemical recurrence-free survival was statistically lower in the presence of grade 5 (HR=3.7; CI 95 [1.8-7.6]). Biochemical recurrence-free survival was not different than grade 5 is predominant or third minority pattern (HR=1.01; CI 95 [0.3-2.8]). On multivariate analysis, grade 5 was an independent risk factor for biochemical recurrence (P=0.005) as well as seminal vesicle invasion (P=0.047). CONCLUSION: The existence of grade 5 in the surgical specimen whatever the percentage was a poor prognostic factor associated with increased tumor aggressiveness and reduced biochemical recurrence-free survival. LEVEL OF EVIDENCE: 5.

[Evaluation of the activity of a urological emergency unit in university hospital]. / Évaluation de l'activité d'une unité d'urgences urologiques en centre hospitalier universitaire.

AIM OF THE STUDY: To determine the epidemiology of urological emergencies in a university hospital and the interest of a dedicated urological emergency unit. PATIENTS AND METHODS: In 2008, a dedicated urological emergency unit was individualized in our department of urology. We conducted a retrospective study including all patients consulting in this unit in 2009 with epidemiological, clinical and therapeutic data. RESULTS: During 2009, 1257 patients consulted in this unit. Main diagnoses were acute urinary retention (303, 24.11%), renal colic (219, 17.42%), urinary infections (278, 22.11%), postoperative complications (141, 11.22%), symptomatic benign prostate hyperplasia (65, 5.17%), genitourinary cancers (61, 4.85%), trauma of urinary apparel (41, 3.26%), and spermatic cords torsion (10, 0.8%). In 99 cases (7.88%) diagnosis did not involved the urinary system. The treatment was surgical in 213 (17.7%) cases, technical procedure under local anesthesia in 368 (29.3%) and a medical treatment in 675 (53.7%) cases. Six hundred and sixty (52.5%) patients were managed ambulatory whereas 596 (47.5%) needed hospitalization. CONCLUSION: The opening of a dedicated urological emergency unit lead to 1257 emergency consultations. Frequent etiologies were acute urinary retention, renal colic and urinary infection. The creation of this unit allowed to register and to valorize this emergency activity through the ATU emergency amount.

Proline oxidase-adipose triglyceride lipase pathway restrains adipose cell death and tissue inflammation.

The nutrient-sensing lipolytic enzyme adipose triglyceride lipase (ATGL) has a key role in adipose tissue function, and alterations in its activity have been implicated in many age-related metabolic disorders. In adipose tissue reduced blood vessel density is related to hypoxia state, cell death and inflammation. Here we demonstrate that adipocytes of poorly vascularized enlarged visceral adipose tissue (i.e. adipose tissue of old mice) suffer from limited nutrient delivery. In particular, nutrient starvation elicits increased activity of mitochondrial proline oxidase/dehydrogenase (POX/PRODH) that is causal in triggering a ROS-dependent induction of ATGL. We demonstrate that ATGL promotes the expression of genes related to mitochondrial oxidative metabolism (peroxisome proliferator-activated receptor-α, peroxisome proliferator-activated receptor-γ coactivator-1α), thus setting a metabolic switch towards fat utilization that supplies energy to starved adipocytes and prevents cell death, as well as adipose tissue inflammation. Taken together, these results identify ATGL as a stress resistance mediator in adipocytes, restraining visceral adipose tissue dysfunction typical of age-related metabolic disorders.

MicroRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 locus, regulate proliferation, apoptosis, migration and invasion in metastatic prostate cancer cells.

miRNAs act as oncogenes or tumor suppressors in a wide variety of human cancers, including prostate cancer (PCa). We found a severe and consistent downregulation of miRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 region in metastatic cell lines as compared with normal prostatic epithelial cells (PrEC). In specimens of human prostate (28 normals, 99 primary tumors and 13 metastases), lower miRNA levels correlated significantly with a higher incidence of metastatic events and higher prostate specific antigen (PSA) levels, with similar trends observed for lymph node invasion and the Gleason score. We transiently transfected 10 members of the 14q32.31 cluster in normal prostatic epithelial cell lines and characterized their affect on malignant cell behaviors, including proliferation, apoptosis, migration and invasion. Finally, we identified FZD4, a gene important for epithelial-to-mesenchymal transition in (PCa), as a target of miR-377.

Triazene compounds in the treatment of acute myeloid leukemia: a short review and a case report.

Acute myeloid leukemia (AML) is a highly lethal disease, especially in old patients. Chemoresistance and the absence of host immune responses against autochthonous malignancy play a major role in the poor prognosis of AML. The triazene compounds Dacarbazine and Temozolomide are monofunctional alkylators that donate methyl groups to many sites in DNA, including the O(6)-position of guanine producing O(6)-methylguanine (O(6)-MeG). If not repaired, O(6)-MeG frequently mispairs with thymine during DNA duplication. O(6)-MeG:T mismatches can be recognized by the mismatch repair (MMR) system which activates a cascade of molecular events leading to cell cycle arrest and cell death. If MMR is defective, cells continue to divide and GC → AT transition mutations occur. In preclinical models, such mutations can lead to the appearance of abnormal proteins containing non-self peptides ("chemical xenogenization" CX) that can be recognized by host cell-mediated immunity. Repair of O(6)-MeG is achieved by the DNA repair protein, O(6)-methylguanine-DNA methyltransferase (MGMT), which removes the methyl adduct in an autoinactivating stoichiometric reaction. High MGMT levels attenuate the pharmacodynamic effects of triazenes. In the last few years, triazenes, alone or with MGMT inhibitors, have been tested in AML. In view of their potential activity as CX inducers, triazenes could offer the additional advantage of host anti-leukemia immune responses. The present paper describes several studies of leukemia treatment with triazenes and a case of acute refractory leukemia with massive skin infiltration by malignant cells. Treatment with Temozolomide and Lomeguatrib, a potent MGMT inhibitor, produced a huge, although transient, blastolysis and complete disappearance of all skin lesions.

DNA methylation silences miR-132 in prostate cancer.

Silencing of microRNAs (miRNAs) by promoter CpG island methylation may be an important mechanism in prostate carcinogenesis. To screen for epigenetically silenced miRNAs in prostate cancer (PCa), we treated prostate normal epithelial and carcinoma cells with 5-aza-2'-deoxycytidine (AZA) and subsequently examined expression changes of 650 miRNAs by megaplex stemloop reverse transcription-quantitative PCR. After applying a selection strategy, we analyzed the methylation status of CpG islands upstream to a subset of miRNAs by methylation-specific PCR. The CpG islands of miR-18b, miR-132, miR-34b/c, miR-148a, miR-450a and miR-542-3p showed methylation patterns congruent with their expression modulations in response to AZA. Methylation analysis of these CpG islands in a panel of 50 human prostate carcinoma specimens and 24 normal controls revealed miR-132 to be methylated in 42% of human cancer cases in a manner positively correlated to total Gleason score and tumor stage. Expression analysis of miR-132 in our tissue panel confirmed its downregulation in methylated tumors. Re-expression of miR-132 in PC3 cells induced cell detachment followed by cell death (anoikis). Two pro-survival proteins-heparin-binding epidermal growth factor and TALIN2-were confirmed as direct targets of miR-132. The results of this study point to miR-132 as a methylation-silenced miRNA with an antimetastatic role in PCa controlling cellular adhesion.

Outcomes of renal transplantation in obese recipients.

PURPOSE: Although obesity has been shown to paradoxically increase dialysis patient survival, its impact has not been clearly defined on renal transplantation. We assessed outcomes of obesity renal transplant patients by evaluating graft and patient survivals. PATIENTS AND METHODS: A single-institution, retrospective study was performed on 202 renal transplant recipients from January 2004 to December 2008 excluding two combined kidney and liver transplantations. Recipients were classified based on body mass index (BMI) at the time of transplantation: obese (BMI ≥ 30 kg/m(2)) and nonobese recipients (BMI < 30 kg/m(2)). The comparative analysis included surgical complications, hospital stay, onset of delayed graft function (DGF), acute rejection episodes and graft patient survivals. RESULTS: Twenty-one renal transplants were performed in obese recipients versus 179 in the control group. Obese patients were older (53.3 ± 11.2 versus 46.4 ± 14.4 years old; P = .035) and more often diabetic (29% ± 0.46 versus 60% ± 0.24, P = .001), but there were no differences among other combidities of high blood pressure, arteriopathy, thrombophilia, and smoking. Obesity did not appear to be a risk factor for urinary or vascular as well as parietal complications, but did tend to augment lymphatic complications (14.3% ± 0.36 versus 4.5% ± 0.21; P = .065). DGF occurred more frequently in obese patients (38% ± 0.50 versus 14% ± 0.34; P = .004) and hospital stays were therefore longer in this group (24.9 ± 23.53 days versus 15.6 ± 13.67 days; P = .008). Graft (hazard ratio [HR] 1.22; 95% confidence interval [CI] [0.25-6.0], P = .63) and patient survivals (HR:0,81; 95% CI [0.12- 5.3], P = .83) were comparable between the groups. CONCLUSION: Obese patients seeking renal transplantation are usually older and more often diabetic compared with nonobese recipients. The higher rate of lymphatic complications and DGF lead to longer hospital stays among the group with BMI ≥ 30 kg/m(2). However, long-term results showed similar graft and patient survivals as nonobese patients. Consequently, there seemed to be no reason to avoid renal transplantation in obese recipients.