First urinary tract infections in children: the role of the risk factors proposed by the Italian recommendations.

AIM: In 2009, the Italian society for paediatric nephrology suggested the need for cystography, following a first febrile urinary tract infection (UTI), only in children at high risk for dilating vesicoureteral reflux or in the event of a second infection. The aim of this study was to evaluate the adequacy of the risk factors proposed by the Italian guidelines. METHODS: Children aged 2-36 months, managed by 10 Italian hospitals between 2009 and 2013, with a first febrile UTI were retrospectively evaluated. RESULTS: Four hundred and fourteen children were included: 51% female, mean age eight months. Escherichia coli was responsible of 84% UTIs. 269 children (65%) presented at least one risk factor, thus were further investigated: 44% had a reflux. The presence of a pathogen other than E. coli significantly predicted high-grade reflux, both in the univariate (Odd Ratio 2.52, 95% Confidence Interval 1.32-4.81, p < 0.005) and multivariate analysis (OR 2.74, 95% CI: 1.39-5.41, p: 0.003). 26/145 children (18%) with no risk factors experienced a second UTI, which prompted the execution of cystography, showing a dilating reflux in 11. CONCLUSION: Among the risk factors proposed by the Italian guidelines, only the presence of a pathogen other than E. coli significantly predicted reflux. Cystography can be postponed in children with no risk factors.

Alport syndrome: impact of digenic inheritance in patients management.

Alport syndrome (ATS) is a genetically heterogeneous nephropathy with considerable phenotypic variability and different transmission patterns, including monogenic (X-linked/autosomal) and digenic inheritance (DI). Here we present a new series of families with DI and we discuss the consequences for genetic counseling and risk assessment. Out of five families harboring variants in more than one COL4 gene detected by next generation sequencing (NGS), minigene-splicing assay allowed us to identify four as true digenic. Two families showed COL4A3/A4 mutations in cis, mimicking an autosomal dominant inheritance with a more severe phenotype and one showed COL4A3/A4 mutations in trans, mimicking an autosomal recessive inheritance with a less severe phenotype. In a fourth family, a de novo mutation (COL4A5) combined with an inherited mutation (COL4A3) triggered a more severe phenotype. A fifth family, predicted digenic on the basis of silico tools, rather showed monogenic X-linked inheritance due to a hypomorphic mutation, in accordance with a milder phenotype. In conclusion, this study highlights the impact of DI in ATS and explains the associated atypical presentations. More complex inheritance should be therefore considered when reviewing prognosis and recurrence risks. On the other side, these findings emphasize the importance to accompany NGS with splicing assays in order to avoid erroneous identification of at risk members.

Unbiased next generation sequencing analysis confirms the existence of autosomal dominant Alport syndrome in a relevant fraction of cases.

The mode of inheritance of Alport syndrome (ATS) has long been controversial. In 1927, the disease was hypothesized as a dominant condition in which males were more severely affected than females. In 1990, it was considered an X-linked (XL) semidominant condition, due to COL4A5 mutations. Later on, a rare autosomal recessive (AR) form due to COL4A3/COL4A4 mutations was identified. An autosomal dominant (AD) form was testified more recently by the description of some large pedigrees but the real existence of this form is still questioned by many and its exact prevalence is unknown. The introduction of next generation sequencing (NGS) allowed us to perform an unbiased simultaneous COL4A3-COL4A4-COL4A5 analysis in 87 Italian families (273 individuals) with clinical suspicion of ATS. In 48 of them (55%), a mutation in one of the three genes was identified: the inheritance was XL semidominant in 65%, recessive in 4% and most interestingly AD in 31% (15 families). The AD form must therefore be seriously taken into account in all pedigrees with affected individuals in each generation. Furthermore, a high frequency of mutations (>50%) was shown in patients with only 1 or 2 clinical criteria, suggesting NGS as first-level analysis in cases with a clinical suspicion of ATS.

Is retroperitoneoscopic renal ablative surgery easier and safer using a new hemostatic device compared with clips and monopolar coagulation? A comparative study.

AIM: The aim of study was to retrospectively analyze our series of total and partial retroperiotoneoscopic nephrectomies performed in the last 5 years. METHODS: Twenty-two procedures were performed, 20 patients underwent nephrectomy and 2 patients underwent partial nephrectomy. The 20 patients who underwent nephrectomy were divided in 2 groups: group 1 (G1) patients-1-10, for whom we performed the procedure using monopolar coagulation, and group 2 (G2) patients 11-20 for whom we used a new hemostatic device to perform dissection and hemostasis. The results were analyzed using χ2 test. The results of partial nephrectomies were analyzed separately. RESULTS: No conversion were reported. We analyzed 6 parameters to compare the results: operative time (OT), estimated blood loss (EBL), need for transfusion (NT), complications, time to oral intake (TOI), hospital stay (HS). OT in G1 was in median 85 minutes, in G2 65 minutes (P=0.004); EBL was 15 mL for G1 and 5 mL for G2 (P=0.000.), NT was not necessary in both, in G1 we had 2 complications and 1 complication in G2; TOI was day 1 for both groups; median HS was 3 days for both. As for heminephrectomy, OT was 120 and 140 min, EBL 30 mL in both, NT not necessary, TOI was 1 day and HS 4 and 5 days respectively. CONCLUSION: Our study shows that the use of a new hemostatic devices reduce significantly OT and EBL in children underwent renal ablative surgery for benign pathologies compared with the use of monopolar coagulation.

What hides beneath the scar: sexuality and breast cancer what women don't say: A single-center study.

Background: Breast is a symbol of femininity, motherhood and sexuality. Breast cancer (BC) is the leading cause of cancer death in women worldwide and most frequent cancer in Italy: in 2019, 53.500 new cases were diagnosed. BC and its treatment, the disturbances of body image, and mental health problems such as anxiety and depression could influence sexuality. Very often the aspect of sexuality in BC is likely not to be fully investigated: cultural barriers may also contribute to lack of attention to these issues. In Italy, there are very few Breast Units that provide the figure of the sexologist and psycho-oncologist. Methods: We enlisted 141 BC patients (pts), mean age was 54 years afferent to Breast Unit S. Maria Goretti Hospital, Latina, from March 2019 to March 2020. All pts had undergone surgical intervention. Participants were invited to complete a structured questionnaire, which included four close-up questions regarding self-image, sexual activity, sexual satisfaction, analyzing these aspects before and after BC and its treatments. Finally the participants were asked if they needed the sexologist and psycho-oncologist. Results: Only 2/141 pts (1.41%) refused to participate in our study. Of 139 participants, 68 (48.92%) had disturbances of body image, 26 (18.7%) had sexuality greatly negatively affected, and 103 (74.1%) every kind of sexual dissatisfaction after BC. 38 pts (27.3%) would require the help of the sexologist. 135 ( 97%) would require the help of the psycho-oncologist. Despite the negative influence in their body-image and sexuality, few pts require the help of the sexologist, but nearly all pts require the help of the psycho-oncologist. Conclusion: In our study nearly all pts require the help of the psycho-oncologist, but few pts of the sexologist. Further studies will be needed to understand the reasons for this disparity: at the moment we are carrying out another project following this illustration, with the aim of understanding why this disparity.

Effect of prepartum energetic supplementation on productive and reproductive characteristics, and metabolic and hormonal profiles in dairy cows under grazing conditions.

The effect of cracked corn grain supplementation (3.5 kg/day) during 3 weeks before the expected calving date on milk production and composition, body condition score (BCS), metabolic and hormonal profiles and length of postpartum anoestrus was evaluated in multiparous Holstein dairy cows under grazing conditions (Energy supplemented group, n = 10; Control group, n = 10). Body condition score was weekly recorded during the peripartum period, from days -21 to +35 (parturition = day 0). Non-esterified fatty acids, beta-hydroxybutyrate, cholesterol, urea, insulin, insulin-like growth factor I (IGF-I), leptin, thyroxine (T(4)) and 3,3''5-triiodothyroinine (T(3)) were weekly determined in plasma from days -21 to +35. The reinitiation of ovarian cyclicity was twice weekly determined by ovarian ultrasonography and confirmed by plasma progesterone concentrations. Cows fed energy concentrate prepartum had higher BCS during the prepartum and postpartum and produced more milk. Non-esterified fatty acids plasma concentrations were significantly higher in the energy group, while cholesterol was higher in the control group. Treated cows had higher levels of plasma insulin, IGF-I and leptin pre-calving. IGF-I, leptin and T(4) were diminished during the early postpartum period in both groups. Insulin levels were also diminished in the control group, but levels remained high in the energy-supplemented group. Treated cows ovulated sooner after parturition than controls. We conclude that Energetic supplementation prepartum in cows under grazing conditions increased milk production and reduced the reinitiation of ovarian activity, consistent with a better EB (BCS), higher prepartum levels of IGF-I, leptin and insulin, and higher insulin levels during early postpartum.

'Frequently recurring' nocturnal polyuria is predictive of response to desmopressin in monosymptomatic nocturnal enuresis in childhood.

INTRODUCTION: The nocturnal polyuria is considered a significant predictive value for response to desmopressin. The cutoff value useful to define nocturnal polyuria is still a matter of debate. Moreover, it is current notion that maximal voided volume (MVV) could be used as a predictor for desmopressin response. OBJECTIVE: The objective of this study was to assess the impact of different definitions of nocturnal polyuria (and of its frequency) and MVV in predicting the response to desmopressin. STUDY DESIGN: A total of 103 patients with frequent monosymptomatic nocturnal enuresis (≥4 wet nights/week) were enrolled. A bladder diary over a 4-day period was collected. The MVV was defined as the highest micturition volume detected at bladder diary. Nocturnal diuresis was measured in 5 wet nights. Then, patients were administered with 120 mcg of sublingual desmopressin. After 2 months, if there was no complete response, the dose was increased to 240 mcg. Nocturnal polyuria was defined as follows: 1.Definition 1: nocturnal urine production >130% of the expected bladder capacity (EBC). 2. Definition 2: >100% EBC. 3. Definition 3: > 20×(age + 9) mL. The primary outcome was 'response to desmopressin' after 3 months of treatment. RESULTS: Fifty-three patients responded to desmopressin. Comparing the responses to desmopressin on the basis of the three definitions of nocturnal polyuria, no significant difference was found. There was no cutoff value of nocturnal polyuria expressed as %EBC useful in providing a significant receiver-operating characteristic (ROC) curve. The area under the ROC curve for MVV expressed as %EBC was 0.67 (95% confidence interval [CI], 0.54-0.80; p = 0.01). A MVV >103.1% of EBC had 78.8% (95% CI, 61.1-91.0) sensitivity and 47.5% (95% CI, 31.5-63.9) specificity for predicting response to desmopressin. Among the patients with nocturnal polyuria according to definition 1, a higher percentage of subjects with nocturnal polyuria in 4 out of 5 or 5 out of 5 nights responded to desmopressin, compared with other patients. Patients presenting with nocturnal polyuria according to definition 3 in 5 out of 5 nights showed a 100% of response to desmopressin. At multivariate analysis, the only significant odds ratio (OR) to respond to desmopressin was that of patients with nocturnal polyuria according to definition 1 in >3 nights (OR = 7.1, 95% CI, 1.3-40.3). DISCUSSION AND CONCLUSIONS: The presence or absence of nocturnal polyuria-according to all three definitions-in at least one night was not effective in predicting the response to desmopressin. Predictors of desmopressin response were nocturnal polyuria in >3 out of 5 wet nights according to definition 1 and in 5 out of 5 wet nights according to definition 3.

Verification of silage type using near-infrared spectroscopy combined with multivariate analysis.

The ability to authenticate the feed given to animals has become a major challenge in animal production, where the diet fed to the animal is one of the most important production factors affecting the composition of milk and meat from cattle, sheep, and goats. Hence, there is currently an increased consumer demand for information on herbivore production factors and particularly the animal diet. The aim of this study was to evaluate the reliability and accuracy of near-infrared (NIR) reflectance spectroscopy as a tool to verify and authenticate the type of silage used as fed for ruminants. Grain silage (GrS, n = 94), grass and legume silage (GLegS, n = 121), and sunflower silage (SunS, n = 50) samples were collected from commercial farms and analyzed in the visible and NIR regions (400-2500 nm) in a monochromator instrument in reflectance. Principal component analysis (PCA), partial least-squares discriminant analysis (PLS1-DA), and linear discriminant analysis (LDA) models were used as methods to verify the different silage types. The classification models based on the NIR data correctly classified more than 90% of the silage samples according to their type. The results from this study showed that NIR spectra combined with multivariate analysis could be used as a tool to objectively authenticate silage samples used as a feed for ruminants.

Thrombectomy and distal protection devices.

Visible distal embolization is a relatively rare complication during percutaneous coronary interventions but it may occur in 15-20% of angioplasties in saphenous vein grafts (SVG) and in thrombus containing lesions of native coronary arteries, especially in the setting of acute myocardial infarction (AMI). Mechanical thrombectomy devices and distal protection devices have been introduced to reduce the incidence of distal embolisation. Angiojet thrombectomy has shown positive outcomes in thrombus containing lesions when compared with intracoronary thrombolysis but a randomised trial failed to show benefit in the context of AMI. The X-Sizer, Excimer LASER and various simple aspiration thrombectomy catheters show promise in treatment of AMI with improvement shown in surrogate end-points such as resolution of ST-elevation but there have been no randomised trials large enough to demonstrate changes in hard clinical end-points. Distal protection devices have come to be routinely used during SVG treatment and, after the results of the SAFER and FIRE trials; they became a treatment recommendation in the recently issued European Society of Cardiology (ESC) guidelines. For AMI, these devices showed great promise in early single-centre studies which have been offset by the lack of clinical benefit in the multi-centre EMERALD trial. Proximal occlusion devices may further decrease the incidence of distal embolisation, especially in the treatment of totally occluded SVGs or native arteries, by reversing the blood flow and offering protection at a very early stage of the procedure before wire passage. Despite continuous technical improvement and a growing number of miniaturised thrombectomy devices and filters, because of the paucity of controlled large studies, it remains unclear whether these devices will remain limited to niche' applications or will become a regular companion to balloons and stents in mainstream angioplasty procedures.

The Ultimaster® coronary stent system: state of the art.

Percutaneous coronary intervention (PCI) has been a mainstay in the management of coronary artery disease since its introduction in the late 1970s. Bare-metal stent (BMS) and then first- and second-generation drug-eluting stents (DES) have enhanced the results of PCI by improving early results and reducing the risk of restenosis and stent thrombosis (ST). The delay of re-endothelialization and recovery of endothelial function after stenting as well as inhibition of vascular repair after DES implantation, in part related to permanent polymers, are consider important part of ST pathophysiology mechanism. Several progresses have been made to overcome this issue, among them the development of new more biocompatible - first - and completely biodegradable - then - polymer coatings. A third-generation DES using a biodegradable polymer and eluting sirolimus (Ultimaster®, Terumo Corporation, Tokyo, Japan) has been recently introduced to overcome the long-term adverse vascular reactions. Thanks to the polymer coating applied to the outside surface only (abluminal side), the total drug dose applied on the stent platform has been reduced, leaving the luminal side of the stent free from drug and polymer to enhance endothelial coverage. Indeed, 3-4 months after implantation, the Ultimaster® DES has lost most of its coating, acquiring a profile similar to conventional BMS. This article reviews the recent publications investigating the safety and effectiveness of the bioresorbable polymer sirolimus-eluting Ultimaster® stent (BP-SES), for the treatment of coronary artery lesions.

60 reoperations on 890 patients after gastric restrictive surgery.

BACKGROUND: Since 1988 we performed gastric restriction operations on 890 patients; 60 required subsequent re-operation. METHODS: The Molina non-adjustable band was discontinued early because of a high percentage of re-operations. Between 1992 and 1995, we performed the Mason vertical banded gastroplasty (VBG) using a 9-cm long vertical staple-line, with a re-operation rate of 15%. Since 1996, we have been performing a 6-cm long vertical staple-line, with a re-operation rate of 0.7%. The MacLean VBG also had a low re-operation rate (0.9%), but the seriousness of its most dangerous complication, perioperative cardia fistula, limited our use of this method to specifically selected cases. With adjustable banding, we have used the Swedish band which produced a low re-operation rate (2.1%), consisting of relatively simple corrective procedures. RESULTS: The re-operations produced results similar to those of first-time operations in terms of weight loss and nutritional status. In particular, after 3 years, re-operated patients had similar weight to those who had been operated upon with the same method initially. CONCLUSIONS: When the surgical procedure was selected with greater astuteness and modified appropriately, the re-operation rate decreased from 17% in the period 1992 to 1995, to 1% in the period 1996 to 2000.

Swedish adjustable gastric banding: a preliminary experience.

BACKGROUND: The authors have been performing bariatric surgery for 15 years; since February 1992 they have carried out laparoscopic gastric banding (LGB) with a silastic band. Good experience with the LGB combined with everyday laparoscopic activity in their institution persuaded them to try laparoscopic placement of the Swedish adjustable gastric band (SAGB). METHODS: The surgical procedure is the same as that for laparoscopic gastric banding except for the use of a 15 mm trocar that is required to introduce the band, and the need to place a port that is connected to the band via a wide loop tube; the port is place subcutaneously and is supported by the lower part of the sternum. The authors do not use any abdominal drain nor a naso-gastric tube. At surgery the band is left empty, and filling is usually not started until 4 weeks after surgery. The patient is immediately mobilized and begins a liquid diet the evening after the operation. The patients are usually discharged from hospital on the first postoperative day. RESULTS: Over 8 months, 24 patients underwent SAGB, with mean BMI 44.69 and mean operating time 45 minutes (range 30-75). No early complications occurred. Preliminary results in this small series show BMIs of 38.65 and 34.60 at 3 and 6 months postoperation. CONCLUSION: SAGB appears for be a good method for obesity surgery. It is easy to perform and is associated with a low operative risk. Provided that the band is put in the right place, weight loss can be adjusted to patient comfort.

Press-coated tablets for time-programmed release of drugs.

A new dry-coated device for the release of drug after a programmable period of time is proposed. It is intended to be used mainly in the therapy of those diseases which depend on circadian rhythms. Some core formulations, characterized by different release rates and mechanisms (containing diltiazem hydrochloride or sodium diclofenac as model drugs), were coated by compression with different polymeric barrier layers (press-coated systems). The shell formulations tested contained either gellable or erodible polymers. The dissolution profiles of uncoated cores and press-coated devices were compared. The gellable and/or erodible characteristics (properties) of the barrier formulations were also examined by means of a penetrometer. The coatings prevent drug release from the core until the polymeric shell is completely eroded or swollen. This delay in release start is not influenced by the core composition and depends only on the shell formulation. Except for the time-lag, the release kinetics of the drug contained in the core are not significantly influenced by the presence of the erodible barrier, but can be widely modulated using a swellable polymeric shell.

Swelling-activated drug delivery systems.

A previous paper dealt with the preparation of an in vitro programmable zero-order drug delivery system in which the area of the surface exposed to the dissolution medium and the macromolecular relaxation of polymer controlled the release of the drug. In the present study, the preparation of similar delivery systems is described, in which differing drugs and polymers were used to ascertain the mechanism governing the drug-release kinetics. The movement of the interfaces between solvent and system was measured during drug release in systems with varying composition. The results indicate that the synchronization of the movement of swelling and eroding fronts at the solvent-system interface determines the achievement of the linear-release kinetics of such swelling activated systems and that the swelling and dissolution characteristics of the polymer employed for core preparation govern front movement.

Disintegrating force as a new formulation parameter.

Some coated aspirin tablet formulations were evaluated by relating their properties to disintegrating force development patterns. The treatment of disintegrating force-time curves was effected using the Weibull distribution as proposed for dissolution. Such parameters as the maximum disintegrating force developed, the time needed to reach 63.2% maximum disintegrating force (tau d) the shape parameter, the lag time, and the input value were used for evaluating the formulas examined. It was concluded that the input values, the integrating force development rate at tau d, can be employed as a new formulation parameter since, when correlated with the crushing strength, it allows an overall evaluation of the formula examined.

Modification of the dissolution behaviour of a water-insoluble drug, naftazone, for zero-order release matrix preparation.

The preparation of hydrophilic matrix tablets able to release naftazone, a water-insoluble drug, into an aqueous medium at a constant rate (zero-order dissolution) is described. Enhancement of dissolution rate of the drug was achieved using cross-linked carmellose sodium, beta-cyclodextrin or hydroxypropyl-beta-cyclodextrin. Hypromellose was used as a water-gelling polymer. Tablets could be prepared that released naftazone at a constant rate over 16 h.

Delayed pubertal growth spurt and normal adult height attainment in boys receiving long-term alternate-day prednisone therapy.

Statural growth to age > or = 20 years was studied in 10 boys with glomerulonephritis who received alternate-day prednisone (mean 1.2 mg/kg) for at least 2 consecutive years during pubertal age. Peak growth velocity was delayed after age 15 years in six patients and it was less than 7 cm/year in five. However, after age 16, growth velocity was significantly (p = 0.02) higher than expected and allowed patients to ultimately reach their genetic height potential.

Renal calyceal microlithiasis: clinical presentation may precede sonographic evidence.

Calyceal microlithiasis (CM) is characterized by the sonographic finding of hyperechogenic spots less than 3 mm in diameter in renal calyces, and it may be the first step in calculus formation. From January 1992 to January 1998, we have observed 216 children with CM. The present report deals with 34 of them in whom renal sonography was negative at first observation and the diagnosis of CM was made only on repeated sonographic examinations. The presenting symptoms were recurrent abdominal pain, dysuria, and hematuria occurring alone or in combination. Half of the patients had hypercalciuria. A history of urolithiasis in at least one first- or second-degree relative was present in 85% of patients. Renal sonography was repeated after 6-22 months (mean 11) and showed unilateral CM in 16 subjects and bilateral in 18. The finding of CM may be preceded by a period of time when symptoms and/or signs are present while microcalculi are not yet detectable. Repeated ultrasound examinations may be needed not only in patients with hypercalciuria but also in those with recurrent abdominal pain, dysuria, and/or hematuria not associated with hypercalciuria.

Bone mineral content in nephrotic children on long-term, alternate-day prednisone therapy.

Bone mineral content (BMC) was measured by single-photon absorptiometry in 24 children with steroid-dependent, minimal-lesion nephrotic syndrome after 1 to 6.3 years of alternate-day prednisone therapy and in a sex- and age-matched control group. Bone mineral content was -0.002 +/- 1.2 standard deviation scores in patients and 0.3 +/- 1.4 in controls (t = 1.17; P = 0.25). No significant relation was found between BMC in patients and the amount of prednisone taken or the duration of therapy. Alternate-day prednisone therapy at doses usually needed to keep children with steroid-dependent nephrotic syndrome under control does not significantly affect BMC.