The best management of superficial bladder tumours: Comparing TUR alone versus TUR combined with intravesical chemotherapy modalities?

To compare retrospectively the recurrence rates of TUR alone versus different intravesical chemotherapy modalities in superficial bladder cancer cases, 187 patients with stage Ta and T₁ bladder tumours were treated with transurethral resection followed by adjuvant intravesical chemotherapy with mitomycin, BCG or epirubicin or by transurethral resection alone. All patients in this study had historically proven transurethrally resectable primary, category Ta and T₁ transitional cell carcinoma (TCC) of the bladder. Group I included transurethral resection alone, and the other groups included intravesical mitomycin-C(Group II), BCG (Group III) and epirubicin (Group IV) therapies after transurethral resection. 146 male and 41 female patients (78% male and 22% female patients) in this study were diagnosed as primary TCC bladder tumours. Only 52 of them were stage Ta and 135 of them were stage T₁ bladder tumours. Examining the histological grade of the bladder tumours, 88 (47%) of the patients had grade I, 53 (28%) had grade IIa, 30 (16%) had grade IIb and remaining 16 (9%) had grade III bladder cancers. The recurrence rates were 25% for Group I, 23.8% for Group II, 26.2% for Group III and 22.7% for Group IV. These values were given with disregarding the grade and volume of the bladder tumours. For solitary, less than 3 cm low grade tumours (grade I, IIa) recurrence rates were 16% for Group I, 15.4% for Group II, 17.8% for Group III, 17.2% for Group IV (p> 0.05). As a result of this retrospective study, for patients with low grade, stage Ta and T₁ tumours TUR alone may be the best treatment modality. Although intravesical chemotherapy is effective in decreasing short-term incidences of tumour recurrence, it has not decreased long-term incidences of tumour recurrence. The high cost and adverse side effects of intravesical chemotherapy should also be taken into consideration in superficial, single, low grade tumours of bladder. This revised version was published online in August 2006 with corrections to the Cover Date.     

Molecular Epidemiology of SARS-CoV-2 in Tunisia (North Africa) through Several Successive Waves of COVID-19

Documenting the circulation dynamics of SARS-CoV-2 variants in different regions of the world is crucial for monitoring virus transmission worldwide and contributing to global efforts towards combating the pandemic. Tunisia has experienced several waves of COVID-19 with a significant number of infections and deaths. The present study provides genetic information on the different lineages of SARS-CoV-2 that circulated in Tunisia over 17 months. Lineages were assigned for 1359 samples using whole-genome sequencing, partial S gene sequencing and variant-specific real-time RT-PCR tests. Forty-eight different lineages of SARS-CoV-2 were identified, including variants of concern (VOCs), variants of interest (VOIs) and variants under monitoring (VUMs), particularly Alpha, Beta, Delta, A.27, Zeta and Eta. The first wave, limited to imported and import-related cases, was characterized by a small number of positive samples and lineages. During the second wave, a large number of lineages were detected; the third wave was marked by the predominance of the Alpha VOC, and the fourth wave was characterized by the predominance of the Delta VOC. This study adds new genomic data to the global context of COVID-19, particularly from the North African region, and highlights the importance of the timely molecular characterization of circulating strains.     

Predictive value of the international prostate symptom score for positive prostate needle biopsy in the low-intermediate prostate-specific antigen range

PURPOSE: Serum prostate-specific antigen (PSA) has a restricted predictive value for prostate cancer in the low-intermediate PSA range (2.5-10 ng/ml). Our aim was to determine the predictive value of the International Prostate Symptom Score (IPSS) for positive prostate needle biopsy (PNB) in patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy with a low-intermediate PSA level. PATIENTS AND METHODS: Between 2001 and 2004, the data of 389 consecutive patients applying for any urologic complaint to our department and who underwent TRUS-guided prostate biopsy due to an elevated serum PSA and/or abnormal digital rectal examination (DRE) were retrospectively analyzed. A total of 158 eligible patients with a low-intermediate PSA level were included in the study. The patient's age, PSA, free PSA, free/total PSA, prostate volume, PSA density (PSAD), pre-biopsy IPSS were compared in the positive and negative biopsy groups. RESULTS: Fifty-eight of 158 patients (37%) who underwent TRUS-guided prostate biopsy had positive PNBs. Forty-eight patients (30%) had abnormal DREs. In the positive PNB group, the mean age was older and PSAD was higher, but the means of the prostate volumes and total IPSS were lower (p<0.05). Multivariate analysis demonstrated that age and IPSS were independent predictors of a positive PNB (p<0.05). The odds ratio of mild IPSS for positive PNB controlled for age was 3.0 (95% CI 1.5-6.7). Receiver-operating characteristics analysis revealed a mild IPSS (AUC=0.640) and was a considerable predictor for positive PNB as well as PSAD (AUC=0.648). The sensitivity and specificity of IPSS with a cutoff value of 7.5 points were 31 and 87% for prediction of prostate cancer detection. CONCLUSION: In the low-intermediate PSA range, mild IPSS may be a predictive factor for positive PNB with a similar specificity of PSAD.     

Determination of <Emphasis Type="Italic">arylsulfatase A pseudodeficiency</Emphasis> allele and haplotype frequency in the Tunisian population

Arylsulfatase A (ASA) is a lysosomal enzyme involved in the catabolism of cerebroside sulfate. ASA deficiency is associated with metachromatic leukodystrophy (MLD). Low ASA activities have also been reported in a more common condition with no apparent clinical consequences termed ASA pseudo-deficiency (ASA-PD) which is associated with two linked mutations in the ASA gene (c.1049A>G and c.*96A>G). This study aimed to investigate the frequency of the two ASA-PD variants and their linkage disequilibrium (LD) among Tunisians. ASA-PD variants were detected in 129 healthy Tunisians and their frequencies were compared to those described worldwide. The frequency of the PD allele was estimated at 17.4 % for the overall sample, with c.1049A>G and c.*96A>G frequencies of 25.6 and 17.4 %, respectively. This study also revealed a high LD between the two ASA-PD variants (r ² = 0.61). Inter-population analysis revealed similarities in the ASA-PD genetic structure between Tunisians and populations from Middle East with c.*96A>G frequencies being the highest in the world. A significant North vs. South genetic differentiation in the ASA-PD frequency was also observed in Tunisian population who seems genetically intermediate between Africans, Middle-Easterners and Europeans. This is the first report on the allele frequency of the ASA-PD in North Africa, revealing a relatively high frequency of the PD allele among Tunisians. This study gives also evidence on the importance of discriminating ASA-PD allele from pathological mutations causing MLD and supporting enzymatic activity testing with both sulfatiduria determination and genetic testing in the differential diagnosis of MLD in the Tunisian population.     

ATP13A2 variability in Parkinson disease

Recessively inherited mutations in ATP13A2 result in Kufor‐Rakeb syndrome (KRS), whereas genetic variability and elevated ATP13A2 expression have been implicated in Parkinson disease (PD). Given this background, ATP13A2 was comprehensively assessed to support or refute its contribution to PD. Sequencing of ATP13A2 exons and intron‐exon boundaries was performed in 89 probands with familial parkinsonism from Tunisia. The segregation of mutations with parkinsonism was subsequently assessed within pedigrees. The frequency of genetic variants and evidence for association was also examined in 240 patients with nonfamilial PD and 372 healthy controls. ATP13A2 mRNA expression was also quantified in brain tissues from 38 patients with nonfamilial PD and 38 healthy subjects from the United States. Sequencing analysis revealed 37 new variants; seven missense, six silent, and 24 that were noncoding. However, no single ATP13A2 mutation segregated with familial parkinsonism in either a dominant or recessive manner. Four markers showed marginal association with nonfamilial PD, prior to correction for multiple testing. ATP13A2 mRNA expression was marginally decreased in PD brains compared with tissue from control subjects. In conclusion, neither ATP13A2 genetic variability nor quantitative gene expression in brain appears to contribute to familial parkinsonism or nonfamilial PD. Hum Mutat 0, 1–5, 2008. © 2008 Wiley‐Liss, Inc.     

Variable cardiac involvement in Tunisian siblings harboring FKRP gene mutations

Mutations in the gene encoding fukutin-related protein (FKRP) cause limb-girdle muscular dystrophy 2I (LGMD2I) and congenital muscular dystrophy (MDC1C). Cardiac involvement was frequently reported with numerous mutations including C826A and 1364C > A mutations. The original Tunisian family with LGMD2I included 12 patients sharing the LGMD phenotype and homozygous to the 1486T > A mutation but who did not display any cardiac involvement. In this study, we report the clinical data, cardiac assessment and mutation analysis in four sibs belonging to a second Tunisian LGMD2I family. All patients showed the LGMD phenotype, the oldest brother and sister had mild cardiac involvement, whereas two twin sisters displayed severe cardiomyopathy leading to death. The patients shared the compound heterozygous 1486T > A, 1364C > A mutation in the FKRP gene suggesting that the association of a compound heterozygous state of mutation responsible for LGMD2I and the MDC1C phenotype could lead to cardiac involvement.