Objective
Radical cystectomy with permanent urinary diversion is the gold standard treatment for invasive muscle bladder cancer. Hydronephrosis is common in these patients, but Ultrasound (US) or ...Computed Tomography Urography (CTU) scan are unable to discriminate obstructive from non-obstructive hydronephrosis. We used Diuresis Renography (DR) with F + 10 in seated position (sp) method in the identification of patients with a Uretero-ileal Anastomosis Stricture (UAS) who would benefit from surgical therapy.
Methods
We studied 39 asymptomatic patients, who underwent radical cystectomy and urinary diversion. Based on radiological findings (US, CTU) 44 kidneys were hydronephrotic. All patients underwent a
99m
Tc-MAG3 DR with F + 10(sp) method. We acquired a DR for 20 min with the patient in a seated position. Patient drank 400–500 mL of water at 5 min after tracer injection and received a 20 mg bolus of Furosemide at 10 min during dynamic acquisition. The indices Time to peak, diuretic half time, and 20 min/peak ratio have been evaluated. Retrograde pyelography confirmed UAS in all patients with DR obstructive findings. We repeated DR as follow-up in two subgroups of patients.
Results
DR with F + 10(sp) method showed obstructive findings in 36 out of 44 hydronephrotic kidneys. 6 patients showed non-obstructive findings. 32 patients showed obstructive findings (20 out of 32 developed UAS within 12 months after surgery). Fifteen pts underwent a surgical treatment of UAS. In 1 patient with equivocal findings, we observed an ileo-ureteral reflux.
Conclusions
The DR with F + 10(sp) method in the seated position has a lower uncertain diagnostic rate, compared to the radiological findings of US or CTU, in management of bladder cancer patients with urinary diversion. The semiquantitative indices diuretic half time and 20 min/peak ratio evaluated in a condition of favorable gravity reduce uncertain responses improving interobserver concordance.
Collection of an adequate amount of autologous haematopoietic stem progenitor cells (HSPC) is required for ex vivo manipulation and successful engraftment for certain inherited disorders. Fifty-seven ...paediatric patients (age 0.5-11.4 years) underwent a bone marrow harvest for the purpose of HSPC gene therapy (GT), including adenosine deaminase-severe combined immunodeficiency (ADA-SCID), Wiskott-Aldrich syndrome (WAS) and metachromatic leukodystrophy (MLD) patients. Total nucleated cells and the percentage and absolute counts of CD34+ cells were calculated at defined steps of the procedure (harvest, CD34+ cell purification, transduction with the gene transfer vector and infusion of the medicinal product). A minimum CD34+ cell dose for infusion was 2 × 10
/kg, with an optimal target at 5-10 × 10
/kg. Median volume of bone marrow harvested was 34.2 ml/kg (range 14.2-56.6). The number of CD34+ cells collected correlated inversely with weight and age in all patients and particularly in the MLD children group. All patients reached the minimum target dose for infusion: median dose of CD34+ cells/kg infused was 10.3 × 10
/kg (3.7-25.9), with no difference among the three groups. Bone marrow harvest of volumes > 30 ml/kg in infants and children with ADA-SCID, WAS and MLD is well tolerated and allows obtaining an adequate dose of a medicinal product for HSPC-GT.
Background
Improved survival in ADA-SCID patients is revealing new aspects of the systemic disorder. Although increasing numbers of reports describe the systemic manifestations of adenosine deaminase ...deficiency, currently there are no studies in the literature evaluating genital development and pubertal progress in these patients.
Methods
We collected retrospective data on urogenital system and pubertal development of 86 ADA-SCID patients followed in the period 2000–2017 at the Great Ormond Street Hospital (UK) and 5 centers in Italy. In particular, we recorded clinical history and visits, and routine blood tests and ultrasound scans were performed as part of patients’ follow-up.
Results and Discussion
We found a higher frequency of congenital and acquired undescended testes compared with healthy children (congenital, 22% in our sample, 0.5–4% described in healthy children; acquired, 16% in our sample, 1–3% in healthy children), mostly requiring orchidopexy. No urogenital abnormalities were noted in females. Spontaneous pubertal development occurred in the majority of female and male patients with a few cases of precocious or delayed puberty; no patient presented high FSH values. Neither ADA-SCID nor treatment performed (PEG-ADA, BMT, or GT) affected pubertal development or gonadic function.
Conclusion
In summary, this report describes a high prevalence of cryptorchidism in a cohort of male ADA-SCID patients which could represent an additional systemic manifestation of ADA-SCID. Considering the impact urogenital and pubertal abnormalities can have on patients’ quality of life, we feel it is essential to include urogenital evaluation in ADA-SCID patients to detect any abnormalities, initiate early treatment, and prevent long-term complications.
Hemophagocytic inflammatory syndrome (HIS) is a rare form of secondary hemophagocytic lymphohistiocytosis caused by an impaired equilibrium between natural killer and cytotoxic T-cell activity, ...evolving in hypercytokinemia and multiorgan failure. In the context of inborn errors of immunity, HIS occurrence has been reported in severe combined immunodeficiency (SCID) patients, including two cases of adenosine deaminase deficient-SCID (ADA-SCID). Here we describe two additional pediatric cases of ADA-SCID patients who developed HIS. In the first case, HIS was triggered by infectious complications while the patient was on enzyme replacement therapy; the patient was treated with high-dose corticosteroids and intravenous immunoglobulins with HIS remission. However, the patient required HLA-identical sibling donor hematopoietic stem cell transplantation (HSCT) for a definitive cure of ADA-SCID, without HIS relapse up to 13 years after HSCT. The second patient presented HIS 2 years after hematopoietic stem cell gene therapy (GT), secondarily to Varicella-Zoster vaccination and despite
and
lymphocytes' reconstitution in line with other ADA SCID patients treated with GT. The child responded to trilinear immunosuppressive therapy (corticosteroids, Cyclosporine A, Anakinra). We observed the persistence of gene-corrected cells up to 5 years post-GT, without HIS relapse. These new cases of children with HIS, together with those reported in the literature, support the hypothesis that a major dysregulation in the immune system can occur in ADA-SCID patients. Our cases show that early identification of the disease is imperative and that a variable degree of immunosuppression could be an effective treatment while allogeneic HSCT is required only in cases of refractoriness. A deeper knowledge of immunologic patterns contributing to HIS pathogenesis in ADA-SCID patients is desirable, to identify new targeted treatments and ensure patients' long-term recovery.
The aim of this study is to investi-gate the association between the urinary metabolic milieu and kidney stone recurrence with a validated papillary evaluation score (PPLA).
We prospectively enrolled ...30 stone for-mers who underwent retrograde intrarenal surgery procedures. Visual inspection of the accessible renal papillae was performed to calculate PPLA score, based on the characterization of ductal plugging, surface pitting, loss of papillary contour and Randall's plaque extension. Stone compositions, 24h urine collections and kidney stone events during follow-up were collected. Relative supersaturation ratios (RSS) for calcium oxalate (CaOx), brushite and uric acid were calculated using EQUIL-2. PPLA score > 3 was defined as high.
Median follow-up period was 11 months (5, 34). PPLA score was inversely correlated with BMI (OR 0.59, 95% CI 0.38, 0.91, p = 0.018), type 2 diabetes (OR 0.04, 95% CI 0.003, 0.58, p = 0.018) and history of recurrent kidney stones (OR 0.17, 95%CI 0.04, 0.75, p = 0.019). The associations between PPLA score, diabetes and BMI were not confirmed after excluding patients with uric acid stones. Higher PPLA score was associated with lower odds of new kidney stone events during follow-up (OR 0.15, 95% CI 0.02, 1.00, p = 0.05). No other significant correla-tions were found.
Our results confirm the lack of efficacy of PPLA score in phenotyping patients affected by kidney stone disease or in predicting the risk of stone recurrence. Larger, long-term studies need to be performed to clarify the role of PPLA on the risk of stone recurrence.
Vaccination with Bacillus Calmette-Guérin (BCG) can be harmful to patients with combined primary immunodeficiencies. We report the outcome of BCG vaccination in a series of twelve patients affected ...by adenosine deaminase deficiency (ADA-SCID). BCG vaccination resulted in a very high incidence of complications due to uncontrolled replication of the mycobacterium. All patients who developed BCG-related disease were treated successfully and remained free from recurrence of disease. We recommend the prompt initiation of enzyme replacement therapy and secondary prophylaxis to reduce the risk of BCG-related complications in ADA-SCID patients.
The world of complementary and alternative medicine (CAM) encompasses a wide range of practices, treatments, and products that fall outside the realm of conventional (mainstream) medicine. The use of ...complementary and CAM has become increasingly popular in Western nations. People are turning to CAM for a variety of reasons, including managing chronic diseases, relieving symptoms of various conditions, and improving their overall health and well-being. There’s a growing trend of people using and showing interest in complementary and alternative medicine therapies, especially in Western countries. CAM encompasses a wide range of treatments, some offering complete alternatives to conventional medicine, while others aim to complement existing medical approaches. Urologists should stay informed about CAM to guide their patients effectively to treat patients in a modern and personalized way. The aim of review is to analyze the scenario of complimentary and alternative medicine with a specific focus in the urological field.
Mitomycin C (MMC) as an intravesical chemotherapeutic agent is a well-known option for treatment of nonmuscle invasive bladder cancer (NMIBC) recurrence; it is probably the most commonly used agent ...given its low rate of side effects and its efficacy.
Both the American Urologic Association (AUA) and European Association of Urology (EAU) consider MMC as a standard treatment for immediate single-dose postoperative treatment and for adjuvant therapy in low and intermediate-risk NMIBC.
Despite the popularity of this agent in the treatment of NMIBCs, many questions regarding the optimal approach to MMC therapy remain unanswered and the schedule widely used is empirical.
Nevertheless, even when the current optimal approaches to MMC administration are used, a large proportion of NMIBCs recur.
This apparent treatment resistance might be overcome by an optimization of standard MMC therapy or with a combination of MMC with other agents that have different mechanisms of action.
Strategies to enhance passive delivery of MMC have been well studied and multiple measures are recommended for implementation of use in routine clinical practice.
A modified scheme of instillation seems to be an easy and inexpensive alternative to increase efficacy of intravesical MMC and to also use this agent with an ablative intent.
Enhancing tumor response with a sequential therapy is another option that has been investigated, mostly for chemo-immunotherapy wherein the different mechanisms of action of Bacillus of Calmette and Guerìn (BCG) and MMC are combined to achieve a higher response.
Effective treatment for metachromatic leukodystrophy (MLD) remains a substantial unmet medical need. In this study we investigated the safety and efficacy of atidarsagene autotemcel (arsa-cel) in ...patients with MLD.
This study is an integrated analysis of results from a prospective, non-randomised, phase 1/2 clinical study and expanded-access frameworks. 29 paediatric patients with pre-symptomatic or early-symptomatic early-onset MLD with biochemical and molecular confirmation of diagnosis were treated with arsa-cel, a gene therapy containing an autologous haematopoietic stem and progenitor cell (HSPC) population transduced ex vivo with a lentiviral vector encoding human arylsulfatase A (ARSA) cDNA, and compared with an untreated natural history (NHx) cohort of 31 patients with early-onset MLD, matched by age and disease subtype. Patients were treated and followed up at Ospedale San Raffaele, Milan, Italy. The coprimary efficacy endpoints were an improvement of more than 10% in total gross motor function measure score at 2 years after treatment in treated patients compared with controls, and change from baseline of total peripheral blood mononuclear cell (PBMC) ARSA activity at 2 years after treatment compared with values before treatment. This phase 1/2 study is registered with ClinicalTrials.gov, NCT01560182.
At the time of analyses, 26 patients treated with arsa-cel were alive with median follow-up of 3·16 years (range 0·64–7·51). Two patients died due to disease progression and one due to a sudden event deemed unlikely to be related to treatment. After busulfan conditioning, all arsa-cel treated patients showed sustained multilineage engraftment of genetically modified HSPCs. ARSA activity in PBMCs was significantly increased above baseline 2 years after treatment by a mean 18·7-fold (95% CI 8·3–42·2; p<0·0001) in patients with the late-infantile variant and 5·7-fold (2·6–12·4; p<0·0001) in patients with the early-juvenile variant. Mean differences in total scores for gross motor function measure between treated patients and age-matched and disease subtype-matched NHx patients 2 years after treatment were significant for both patients with late-infantile MLD (66% 95% CI 48·9–82·3) and early-juvenile MLD (42% 12·3–71·8). Most treated patients progressively acquired motor skills within the predicted range of healthy children or had stabilised motor performance (maintaining the ability to walk). Further, most displayed normal cognitive development and prevention or delay of central and peripheral demyelination and brain atrophy throughout follow-up; treatment benefits were particularly apparent in patients treated before symptom onset. The infusion was well tolerated and there was no evidence of abnormal clonal proliferation or replication-competent lentivirus. All patients had at least one grade 3 or higher adverse event; most were related to conditioning or to background disease. The only adverse event related to arsa-cel was the transient development of anti-ARSA antibodies in four patients, which did not affect clinical outcomes.
Treatment with arsa-cel resulted in sustained, clinically relevant benefits in children with early-onset MLD by preserving cognitive function and motor development in most patients, and slowing demyelination and brain atrophy.
Orchard Therapeutics, Fondazione Telethon, and GlaxoSmithKline.
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