X-linked retinoschisis: mutation spectrum and genotype-phenotype relationship in an Italian pediatric cohort.

BACKGROUND: X-linked juvenile retinoschisis (×LRS) is an X-linked vitreoretinal degenerative disease that consists of variable phenotypes ranging from severe early-onset defects to subtle abnormalities diagnosed in elderly patients. XLRS is caused by a loss of function of the protein Retinoschisin (RS1), which is essential to preserve retinal integrity and function of photoreceptor-bipolar synapse. The literature data so far mostly agree on the absence of a clear genotype-phenotype correlation in XLRS. We reviewed clinical and molecular characteristics of a cohort of Italian pediatric XLRS patients to assess the presence of a correlation between genotype and phenotype severity. MATERIALS AND METHODS: We retrospectively examined clinical and genetic features of a cohort of 27 XLRS patients. In this study we included patients with a diagnosis of XLRS confirmed by fundus photography, spectral domain optical coherence tomography, and molecular analysis and with an onset of less than 10 years of age. We sorted RS1 variants according to their effect of RS1 structure and function in three separate groups. RESULTS: According to previous studies, we did not observe a conclusive genotype-phenotype correlation in our cohort; nevertheless, we noticed that patients harboring RS1 variants leading to RS1-secreted mutants show a more homogeneous phenotype, with an overall good visual acuity, compared to the other two groups. CONCLUSIONS: Our data support the hypothesis that secretion profile of RS1 could influence the severity of the phenotype. More extensive and functional studies are needed to acquire notions in view of the opportunity of gene replacement therapy for XLRS patients.

Epidemiological characteristics of COVID-19 cases in non-Italian nationals notified to the Italian surveillance system.

BACKGROUND: International literature suggests that disadvantaged groups are at higher risk of morbidity and mortality from SARS-CoV-2 infection due to poorer living/working conditions and barriers to healthcare access. Yet, to date, there is no evidence of this disproportionate impact on non-national individuals, including economic migrants, short-term travellers and refugees. METHODS: We analyzed data from the Italian surveillance system of all COVID-19 laboratory-confirmed cases tested positive from the beginning of the outbreak (20th of February) to the 19th of July 2020. We used multilevel negative-binomial regression models to compare the case fatality and the rate of admission to hospital and intensive care unit (ICU) between Italian and non-Italian nationals. The analysis was adjusted for differences in demographic characteristics, pre-existing comorbidities, and period of diagnosis. RESULTS: We analyzed 213 180 COVID-19 cases, including 15 974 (7.5%) non-Italian nationals. We found that, compared to Italian cases, non-Italian cases were diagnosed at a later date and were more likely to be hospitalized {[adjusted rate ratio (ARR)=1.39, 95% confidence interval (CI): 1.33-1.44]} and admitted to ICU (ARR=1.19, 95% CI: 1.07-1.32), with differences being more pronounced in those coming from countries with lower human development index (HDI). We also observed an increased risk of death in non-Italian cases from low-HDI countries (ARR=1.32, 95% CI: 1.01-1.75). CONCLUSIONS: A delayed diagnosis in non-Italian cases could explain their worse outcomes compared to Italian cases. Ensuring early access to diagnosis and treatment to non-Italians could facilitate the control of SARS-CoV-2 transmission and improve health outcomes in all people living in Italy, regardless of nationality.

Increased incidence of invasive meningococcal disease of serogroup C / clonal complex 11, Tuscany, Italy, 2015 to 2016.

We report an increase of serogroup C Neisseria meningitidis invasive meningococcal disease in Tuscany. From January 2015 to end February 2016, 43 cases were reported, among which 10 were fatal, compared to two cases caused by serogroup C recorded in 2014 and three in 2013. No secondary cases occurred. Thirty-five strains belonged to C:P1.5-1,10-8:F3-6:ST-11(cc11). Control measures have been adopted and immunisation campaigns implemented. Studies on risk factors and carriage are ongoing.

Sensitive detection of transitional cell carcinoma of the bladder by microsatellite analysis of cells exfoliated in urine.

Transitional cell carcinoma (TCC) is the most common bladder tumor. Urine cytology can identify most high-grade tumors but sensitivity is lower if one includes lesions of all grades. Microsatellite marker alterations have been found in many tumor types including bladder cancer and have been used to detect cancer cells in body fluids including urine. The aim of our study is to further evaluate feasibility and sensitivity of microsatellite analysis to detect bladder cancer cells in urine. We studied 55 individuals: 21 with symptoms suggestive of bladder cancer, 23 patients with previous history of TCC and 11 healthy subjects. Genomic DNA was extracted from blood lymphocytes, urine sediment, bladder washings and tumor or normal bladder mucosa. Twenty highly informative microsatellite markers were analyzed for loss of heterozigosity (LOH) and microsatellite instability (MIN) by polymerase chain reaction. Microsatellite analysis of urine identified 33 of 34 (97%) patients with either primary or tumor recurrence, whereas urine cytology identified 27 of 34 (79%) patients (p = 0.0001). Detection of microsatellite abnormalities improved the sensitivity of detecting low-grade and/or stage bladder tumor: from 75-95% for grades G1-G2 and from 75-100% for pTis-pTa tumors. Bladder washings from 25 patients were also analyzed, and in all cases results were identical to those obtained from voided urine. None of the 16 patients without evidence of TCC showed LOH and/or MIN in urine samples or bladder washings. Interestingly, in a patient with persistent bladder mucosa abnormalities, microsatellite alterations were demonstrated 8 months before the histopathologic diagnosis of tumor recurrence. These results further indicate that microsatellite marker analysis is more sensitive than conventional urine cytology in detecting bladder cancer cells in urine and represents a potential clinical tool for monitoring patients with low-grade/stage TCC.

Diagnosis and therapy of the female urethral diverticula.

The various diagnostic and therapeutic modalities currently in use for urethral diverticula are reviewed. Various radiographic techniques have been reported, but only voiding cystourethrography (VCUG) and positive-pressure urethrography (PPU) are currently utilized. Urethroscopy is another suitable technique for diagnosis. Various sonographic techniques have been proposed, but their sensitivity is improved only by the transvaginal approach and magnetic resonance imaging (MRI). Various treatment methods have been proposed. The standard operative approach is surgical, through the vagina. The techniques currently in use to treat urethral diverticula are the Spence procedure, the typical urethral diverticulectomy, and the Tancer partial ablation technique. A full history, and physical examination is the first step in screening. When the diagnosis is suspected ultrasound and radiological imaging is necessary. Sonography is the first non-invasive examination to be performed. In negative cases it is imperative to perform a PPU or MRI. Symptomatic and very large diverticula must be treated in the easiest way possible. The best treatment, except for complicated and infected diverticula, is excision.

Extracorporeal shock wave lithotripsy in ureteral and kidney malformations.

INTRODUCTION: Extracorporeal shock wave lithotripsy (SWL) has long been accepted worldwide in the treatment of kidney stone disease. Upper ureter calculi in ureteral and kidney malformations are rather frequent (10-25%). The aims of this retrospective study were to determine whether malformations might impair fragment expulsion. MATERIAL AND METHODS: From 1986 to 1995, 203 patients with ureteral and kidney malformations were treated and followed up for a minimum of 1 year to a maximum of 9 years. Malformations included: ureteropelvic junction stenosis, horseshoe kidney, renal malrotation, renal ectopia, duplicated ureter, nonobstructive megaureter, medullary sponge kidney and caliceal diverticula. As pretreatment workup, all patients underwent conventional studies prior to SWL treatment: X-rays, renal ultrasound, intravenous pyelography, routine blood tests and urinalysis. All examinations were repeated at regular intervals for the first 6 months. Patients with metabolic disorders were excluded from the study. We also excluded patients with a follow-up of under 1 year. We considered three groups of patients: (1) stone-free patients at plain X-rays and ultrasound; (2) >90% elimination, i.e. stone-free patients at plain X-rays and positive at ultrasound; (3) patients with residual fragments at plain X-rays and ultrasound. RESULTS: 96 (55%) patients were in group 1 (stone free), 40 (19%) were in group 2 (>90% elimination) and 67 (26%) were in group 3 (residual). Residual stones were more frequent in patients with medullary sponge kidney (82%). In patients with renal ectopia the residual stone rate accounted for only 13% of cases. CONCLUSIONS: There is evidence that SWL should always be offered to patients with ureteral and kidney malformations. These patients should however be considered at high risk for recurrences and so they need to be carefully followed up.

Abdominal sacral colpopexy with prolene mesh.

The objective was to evaluate abdominal colposacropexy using Prolene mesh to correct total vaginal vault prolapse or total procidentia. Between 1994 and 1997 we performed colposacropexy on 15 patients for simple vaginal vault prolapse (in 7 cases after hysterectomy) and for total uterine prolapse in 8 cases. In these cases a simple abdominal hysterectomy was performed. We simultaneously performed colposacropexy with colposuspension according to the Burch technique for urinary stress incontinence in 6 cases. The colposacropexy technique consisted of isolating the vaginal apex and creating a retroperitoneal tunnel from the vagina to the sacral promontory. Between the vaginal cul de sac and the sacrum, a mesh of Prolene is inserted and fixed with non-absorbable sutures. The Foley catheter was removed after 4-12 days (average 5). Average follow-up was 15 months. No intraoperative complications occurred, and all patients who were sexually active have resumed normal sexual activity; no infections or rejections of the prostheses have been verified. We believe that it is very important to restore the normal anatomic support of the vaginal vault after prolapse. This strong support is assured by fixing the vaginal apex to the periosteum of the sacrum using Prolene mesh. Colposacropexy with Prolene mesh is a safe and effective technique for the surgical therapy of vaginal vault prolapse.

Transurethral electrovaporization of the prostate vs. transurethral resection. Results of a multicentric, randomized clinical study on 150 patients.

AIM OF THE STUDY: To evaluate clinical, urodynamic efficacy and safety of TURP and TVP in patients with symptoms due to obstructive benign prostatic hypertrophy with a prospective multicentric randomized study. MATERIALS AND METHODS: 150 patients with BPH, urodynamically obstructed, were randomized to receive TURP or TVP. At the end of the recruitment phase, 80 patients underwent TURP and 70 patients underwent TVP. Patients were clinically evaluated by the I-PSS score at months 0, 1, 3, 6 and 12. Preoperative evaluation included complete blood routine examination, PSA, transrectal ultrasound and pressure/flow studies. Pressure/flow studies were also performed after 3 months. RESULTS: There was no statistical difference between groups in any of the preoperative parameters. All patients were considered urodynamically obstructed at preoperative pressure studies. As for catheter days and hospitalization days, statistical differences between TVP and TURP were found; catheter days were 2.71 days (SE 0.12) in the TURP group vs. 1.9 (SE 0.24) in the TVP group (p < 0.000). Hospitalization was 4.7 days (SE 0.22) after TURP and 3.9 days (SE 0.24) after TVP (p < 0.000). Mean preoperative I-PSS score was 18.84 and 18.19 in the TVP and TURP groups, respectively. At 3, 6 and 12 months, IPSS was 5.52 and 5.50, 3.77 and 4.94, 3.52 and 4.04 for TURP and TVP, respectively. Mean preoperative peak flow rate (PFR) was 8.78 and 7.26 ml/s for TURP and TVP, respectively; after 3, 6 and 12 months, PFR was 19.21 and 18.8, 20.77 and 20.13, 20.30 and 20.31 ml/s, respectively. After 3 months, 6 patients in the TURP group (7.5%) and 7 patients in the TVP group (10%) were borderline obstructed. 1 patient in the TVP group (1.4%) was still obstructed and underwent TURP. As for complications, 4 patients (5.7%) in the TVP group had stress urinary incontinence after 12 months vs. 1 (1.25%) in the TURP group. DISCUSSION: The present study clearly demonstrates that TVP is as effective as TURP in relieving urinary obstruction due to BPH, it offers some advantages in terms of catheterization and hospital stay, but at the price of a higher incidence of postoperative urine incontinence. Technical improvements might solve this problem in the future, perhaps combining TVP with TURP of the apical tissue.

Management of hemorrhage after percutaneous renal surgery.

Percutaneous renal surgery is routine therapy for a number of renal pathologies. It is a technique not without complications, often serious ones, of which the worst is bleeding. We reviewed our experience of the incidence, etiology, and management of this serious complication to determine a protocol of treatment that will minimize the consequences. Between 1984 and 1996, we carried out 976 percutaneous operations for reno-calix stones, pyeloureteral junction stenosis, neoplasia of the renal pelvis, diagnosis, and ureteral prostheses. In all cases, the percutaneous access was achieved through a lower calix in the posterior axillary line with the patient in a prone position. The lithotripsy was performed with ultrasound and balistic energy lithotripters. Antegrade endopyelotomy was performed according to our technique. At the end of the procedure, a nephrostomy tube was positioned, 24F for lithotripsy and 16F for endopyelotomy. The nephrostomy tube was removed after 24 to 48 hours. In this series, 146 patients (15%) presented significant perioperative bleeding. In 97 cases (10%), this complication was resolved with the repositioning of the nephrostomy tube, bedrest in a supine position, and observation, whereas in 49 cases (5%), clamping of the nephrostomy tube for 24 hours was necessary. In 56 patients (5.7%), two blood transfusions were necessary, and three patients (0.3%) had bleeding 10, 12, and 20 days after the operation, which was resolved by embolization of the lacerated vessel.

Diverticula of the female urethra.

OBJECTIVE: To determine the optimum procedure for the diagnosis and therapy of diveticula of the female urethra. PATIENTS AND METHODS: The study included 18 patients with urethral diverticula treated at the Cristo Re Hospital in Rome between 1987 and 1995. Most of the patients were suffering from cystitis (eight), dysuria (seven) and recurring urinary infections (11). Less frequently, more specific symptoms were present such as post-voiding dribbling (two) and anterior vaginal mass (three). The pre-operative evaluation included a history, physical examination, voiding and positive pressure voiding cysto-urethrography (VCUG) and urodynamic tests. A 'typical' surgical excision of the diverticula was carried out in all cases. Surgical excision was combined with cystopexis (Raz operation) in four patients with urinary stress incontinence and three with detrusor instability were treated postoperatively with anticholinergics for 3 months. The outcome was evaluated by a physical examination and urodynamic tests at 3, 6 and 12 months postoperatively; the mean (range) follow-up was 34 (2-80) months. RESULTS: All the urethral diverticula were in the distal two-thirds of the urethra, along the posterolateral wall. The VCUG was sufficient for diagnosis in eight patients while the other 10 required a positive-pressure VCUG. Fifteen patients were evaluated; complications included a urinary tract infection for 2 months in four patients and stress incontinence for 2 months in two. There were no recurrences or urethrovaginal fistulae. CONCLUSIONS: Diverticula in the female urethra are difficult to diagnose because the symptoms can be misleading; the positive-pressure VCUG is useful in doubtful cases. However, a detailed history and physical examination are mandatory.

Transurethral electrovaporization of the prostate with the Vaportrode VE-B. Preliminary results.

UNLABELLED: Transurethral resection of the prostate (TURP) is still considered the 'gold standard' in the treatment of benign prostatic hyperplasia (BPH). However, it is possible to replace this technique in particular situations (advanced age, serious cardiovascular, respiratory and metabolic disorders). OBJECTIVE: The aim of this study is to propose an alternative treatment to TURP with a minimal invasiveness, rapid discharge of the patient and lower costs achieving the same results as TURP. We have used electrovaporization of the prostatic tissue to investigate the outcome of electrovaporization in the treatment of patients with BPH. METHODS: A grooved rolling electrode with a large surface contact was used (Vaportrode VE-B; Circon Acmi, USA), mounted on a common resectoscope connected to a normal high-frequency discharge unit. This concentration of high energy produces an area of high current density at the point of contact with the prostatic tissue and a consequent thermal reaction which causes the tissue temperature to rise rapidly until vaporization. In the period ranging from January 1995 to June 1995, 35 patients with BPH were treated. RESULTS: The average maximal flow increased from 9.8 +/- 3.18 to 13.6 +/- 5.9 ml/s at 2 days and to 20.74 +/- 9.8 ml/s at 28 days (p < or = 0.01); the average symptom score decreased from 18.17 +/- 4.5 to 10.4 +/- 3.3, 28 days after surgery with an average improvement of 52% (p < or = 0.01). Voiding pressure at 28 days was 22.9 +/- 2 cm H2O (p < or = 0.01). Sixteen patients were obstructed preoperatively while 19 patients were unobstructed postoperatively and 3 were equivocal as shown in the Abrams-Griffiths nomogram. Postvoiding residual urine was 0 ml at the follow-up at 2 and 28 days. The average reduction in weight of the prostatic adenoma, measured with transrectal ultrasound and the ellipsoid formula, was 84% (range 50-90%). CONCLUSION: We think that this technique represents an interesting alternative in the treatment of symptomatic BPH.