Minimally invasive surgery versus standard posterior approach in the treatment of adolescent idiopathic scoliosis: a 2-year follow-up retrospective study.

PURPOSE: This is a monocentric retrospective controlled study that compares the safety and efficacy of posterior minimally invasive surgery (MISS) to standard posterior spinal fusion (PSF) surgery in adolescent idiopathic scoliosis (AIS). METHODS: We retrospectively collected 111 patients with Lenke type 1-6 AIS who were treated with MIS (n = 47) or PSF (n = 64) between February 2019 and January 2021 with a 2-year clinical and radiological follow-up. MIS technique was applied via two midline noncontiguous skin incisions ranging from 3 to 7 cm in length, so we obtained the arthrodesis only in the exposed tract, passing the rods below the fascia, avoiding the complete muscular sparing. Values of Cobb angles degrees were collected to study the correction rate of the structural major curve. Postoperative AP direct radiography and preoperative AP direct radiography were compared with the last follow-up examination. Operative time, preoperative hemoglobin (Hb) and second postoperative day Hb, full length of hospitalization, time to achieve verticalization and time to remove the drainage were recorded. NRS medium score was assessed immediately after surgery and during the whole postoperative rehabilitation treatment to estimate pain reduction. Complications were collected postoperatively and throughout the whole follow-up period. RESULTS: There was no significant difference between the two groups in terms of radiographic and clinical features. The correction rates of the structural curve resulted to be not significantly different between MISS and PSF (64.6 ± 11.7 vs 60.9 ± 13.2, p = 0.1292) as well as for the correction rate of the secondary curve between the two compared techniques (59.1 ± 13.2 vs 59.2 ± 12.4, p = 0.9865). The two groups had comparable operative time (210 min vs 215 min). The MIS group had a significantly lower reduction of postoperative Hb in comparison with PSF group (2.8 ± 1.3 mg/dl vs 4.3 ± 1.5 mg/dl, p < 0.0001). The postoperative NRS score was lower in MIS group (1.9 ± 0.8 vs 3.3 ± 1.3). PSF group was observed to have a significantly longer period of hospitalization than MIS (5.2 ± 1.4 days vs 6.3 ± 2.9 days, p = 0.206). Complications were more frequent in PSF group rather than in MFS group. CONCLUSIONS: MISS is a safe and capable alternative to PSF for AIS patients with curves < 70°, with analogue capacity of scoliosis correction and same operative time and with advantages in blood loss, length of stay and postoperative pain.

Exclusive Neurogenic Bladder and Fecal Incontinency in an Achondroplasic Child Successfully Treated with Lumbar Foraminal Decompression.

INTRODUCTION: Achondroplasia is a genetic disorder characterized by defects in the development of endochondral bone resulting in skeletal abnormalities like stenosis of the foramen magnum and of the spine, shortened limb bones, and macrocephaly. Congenital spinal stenosis is frequent and due to premature fusion of the pedicles to the laminae. CASE PRESENTATION: We report a case of neurogenic bladder and fecal incontinence due to lumbar stenosis successfully treated with L1-L5 partial laminectomy and foraminotomy in a 7-year-old achondroplasic child. DISCUSSION/CONCLUSION: To our knowledge, this is the first case report of exclusive neurogenic bladder and fecal incontinence in an achondroplasic child. Neurogenic bladder and fecal incontinence without motor impairment may be early and exclusive clinical findings of lumbar stenosis in children with achondroplasia.

Robot-assisted extravesical ureteral reimplantation (revur) for unilateral vesico-ureteral reflux in children: results of a multicentric international survey.

PURPOSE: This multicentric international retrospective study aimed to report the outcome of robot-assisted extravesical ureteral reimplantation (REVUR) in patients with unilateral vesico-ureteral reflux (VUR). METHODS: The medical records of 55 patients (35 girls, 20 boys) underwent REVUR in four international centers of pediatric robotic surgery for primary unilateral VUR were retrospectively reviewed. Patients' average age was 4.9 years. The preoperative grade of reflux was III in 12.7%, IV in 47.3% and V in 40%. Twenty-six patients (47.3%) presented a loss of renal function preoperatively and 10 (18.1%) had a duplex system. RESULTS: Average robot docking time was 16.2 min (range 5-30). Average total operative time was 92.2 min (range 50-170). No conversions or intra-operative complications were recorded. All patients had a bladder Foley catheter for 24 h post-operatively. Average hospital stay was 2 days (range 1-3). Average follow-up length was 28 months (range 9-60). We recorded three (5.4%) postoperative complications: 1 small urinoma resolved spontaneously (II Clavien) and 2 persistent reflux, only one requiring redo-surgery using endoscopic injection (IIIb Clavien). CONCLUSION: REVUR is a safe and effective technique for treatment of primary unilateral VUR. The procedure is easy and fast to perform thanks to the 6° of freedom of robotic arms. The learning curve is short and it is useful to begin the robotics experience with a surgeon expert in robotic surgery as proctor on the 2nd robot console. The high cost and the diameter of instruments remain the main challenges of robotics applications in pediatric urology.

Redox control of viral carcinogenesis: The human papillomavirus paradigm.

BACKGROUND: Cervical cancer is the second most common neoplastic disease among women worldwide. The initiating event of such cancer is the infection with certain types of human papillomavirus (HPV), a very common condition in the general population. However, the majority of HPV infections is subclinical and transitory and is resolved spontaneously. Intriguingly, viral oncogene expression, although necessary, is not per se sufficient to promote cervical cancer and other factors are involved in the progression of infected cells to the full neoplastic phenotype. In this perspective it has been suggested that the redox balance and the oxidative stress (OS) may represent interesting and under-explored candidates as promoting factors in HPV-initiated carcinogenesis. SCOPE OF THE REVIEW: The current review discusses the possible interplay between the viral mechanisms modulating cell homeostasis and redox sensitive mechanisms. Experimental data and indirect evidences are presented on the activity of viral dependent functions on i) the regulation of enzymes and compounds involved in OS; ii) the protection from oxidation of detoxifying/antiapoptotic enzymes and redox-sensitive transcription factors; iii) the suppression of apoptosis; and iv) the modulation of host microRNAs regulating genes associated with antioxidant defense. MAJOR CONCLUSIONS: The resulting tangled scenario suggests that viral hosting cells adapt their metabolisms in order to support their growth and survival in the increasingly oxidant micro-environment associated with HPV tumor initiation and progression. GENERAL SIGNIFICANCE: HPV can modulate the host cell redox homeostasis in order to favor infection and possibly tumor transformation. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.

Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain.

Down syndrome (DS) is the most frequent genetic cause of intellectual disability characterized by the presence of three copies of chromosome 21 (Chr21). Individuals with DS have sufficient neuropathology for a diagnosis of Alzheimer's disease (AD) after the age of 40years. The aim of our study is to gain new insights in the molecular mechanisms impaired in DS subjects that eventually lead to the development of dementia. We evaluate the PI3K/Akt/mTOR axis in the frontal cortex from DS cases (under the age of 40years) and DS with AD neuropathology compared with age-matched controls (Young and Old). The PI3K/Akt/mTOR axis may control several key pathways involved in AD that, if aberrantly regulated, affect amyloid beta (Aß) deposition and tau phosphorylation. Our results show a hyperactivation of PI3K/Akt/mTOR axis in individuals with DS, with and without AD pathology, in comparison with respective controls. The PI3K/Akt/mTOR deregulation results in decreased autophagy, inhibition of IRS1 and GSK3ß activity. Moreover, our data suggest that aberrant activation of the PI3K/Akt/mTOR axis acts in parallel to RCAN1 in phosphorylating tau, in DS and DS/AD. In conclusion, this study provides insights into the neuropathological mechanisms that may be engaged during the development of AD in DS. We suggest that deregulation of this signaling cascade is already evident in young DS cases and persist in the presence of AD pathology. The impairment of the PI3K/Akt/mTOR axis in DS population might represent a key-contributing factor to the neurodegenerative process that culminates in Alzheimer-like dementia.

Impairment of proteostasis network in Down syndrome prior to the development of Alzheimer's disease neuropathology: redox proteomics analysis of human brain.

DS is the most frequent genetic cause of intellectual disability characterized by the anomalous presence of three copies of chromosome 21. One of the peculiar features of DS is the onset of Alzheimer's disease neuropathology after the age of 40years characterized by deposition of senile plaques and neurofibrillary tangles. Growing studies demonstrated that increased oxidative damage, accumulation of unfolded/damaged protein aggregates and dysfunction of intracellular degradative system are key players in neurodegenerative processes. In this study, redox proteomics approach was used to analyze the frontal cortex from DS subjects under the age of 40 compared with age-matched controls, and proteins found to be increasingly carbonylated were identified. Interestingly, our results showed that oxidative damage targets specifically different components of the intracellular quality control system such as GRP78, UCH-L1, V0-ATPase, cathepsin D and GFAP that couples with decreased activity of the proteasome and autophagosome formation observed. We also reported a slight but consistent increase of Aß 1-42 SDS- and PBS-soluble form and tau phosphorylation in DS versus CTR. We suggest that disturbance in the proteostasis network could contribute to the accumulation of protein aggregates, such as amyloid deposits and NFTs, which occur very early in DS. It is likely that a sub-optimal functioning of degradative systems occur in DS neurons, which in turn provide the basis for further accumulation of toxic protein aggregates. The results of this study suggest that oxidation of protein members of the proteostatis network is an early event in DS and might contribute to neurodegenerative phenomena.

Modified PATIO technique for urethrocutaneous fistula after hypospadias repair: Experience from a tertiary referral hospital.

INTRODUCTION: Urethrocutaneous fistula (UCF) is a common complication after hypospadias repair with an incidence of 5-10%. Several techniques are described for its repair: small UCFs are frequently corrected by isolation, excision, and closure with apposition of a protective second layer. In 2008 Malone described the PATIO technique: the fistula tract is turned inside out in the urethral lumen preventing contact with passing urine without direct urethral sutures. OBJECTIVE: Aim of our study is to present our outcomes using a modified version of the PATIO technique, with a more reproducible isolation of the tract and without its fixation at the urethral meatus. STUDY DESIGN: We retrospectively reviewed all cases of UCFs corrected with a modified PATIO technique at our center between 2016 and 2020. Data collected from electronical clinical notes were age at UCF closure, location of UCF, presence of meatal stenosis and clinical outcomes. Data are presented as median and IQR. RESULTS: In the study period we performed 425 urethroplasties for distal and mid penile hypospadias. The incidence of UCFs was 7% (30/425) and 25 patients underwent UCF correction with modified PATIO. Median age at repair was 4.5 years (IQR: 2.5-6.2). At a median follow-up of 3 years (IQR: 2-4) recurrence was observed in 5 cases out of 24 with one patient who was lost at follow-up (20.8%). One case was corrected successfully with re-do modified PATIO technique, while 4 are awaiting repair. One cases was lost at follow-up. UFC-recurrence was homogeneously distributed along the study period. DISCUSSION: Risk factors for UCF recurrence are mostly the type of hypospadias, neo-urethral length, and quality of the urethral plate. Among the many existing techniques, we propose a modified version of Malone's PATIO repair. We believe that the use of four stay-suture to isolate the fistula allows a well-defined dissection of the tract along its surface, compared to the use of a single stay-suture. In our experience, there is no need to keep and fix the traction on the fistula tract to the urethral meatus, probably reflecting the efficacy of the fistula closure during the introflection, which is then maintained without traction. Limitations to our study include the retrospective nature of the review, the small sample size of the cohort and the absence of control groups. CONCLUSIONS: Our results appear consistent with literature regarding the efficacy of PATIO principles in treating UCF. Modified PATIO seem to be particularly reproducible, showing encouraging results.

Biliverdin reductase--a protein levels and activity in the brains of subjects with Alzheimer disease and mild cognitive impairment.

Biliverdin reductase-A is a pleiotropic enzyme involved not only in the reduction of biliverdin-IX-alpha into bilirubin-IX-alpha, but also in the regulation of glucose metabolism and cell growth secondary to its serine/threonine/tyrosine kinase activity. Together with heme oxygenase, whose metabolic role is to degrade heme into biliverdin-IX-alpha, it forms a powerful system involved in the cell stress response during neurodegenerative disorders. In this paper, an up-regulation of the biliverdin reductase-A protein levels was found in the hippocampus of the subjects with Alzheimer disease and arguably its earliest form, mild cognitive impairment. Moreover a significant reduction in the phosphorylation of serine, threonine and tyrosine residues of biliverdin reductase-A was found, and this was paralleled by a marked reduction in its reductase activity. Interestingly, the levels of both total and phosphorylated biliverdin reductase-A were unchanged as well as its enzymatic activity in the cerebella. These results demonstrated a dichotomy between biliverdin reductase-A protein levels and activity in the hippocampus of subjects affected by Alzheimer disease and mild cognitive impairment, and this effect likely is attributable to a reduction in the phosphorylation of serine, threonine and tyrosine residues of biliverdin reductase-A. Consequently, not just the increased levels of biliverdin reductase-A, but also its changed activity and phosphorylation state, should be taken into account when considering potential biomarkers for Alzheimer disease and mild cognitive impairment.

Sex differences in brain proteomes of neuron-specific STAT3-null mice after cerebral ischemia/reperfusion.

Signal transduction and activator of transcription-3 (STAT3) plays an important role in neuronal survival, regeneration and repair after brain injury. We previously demonstrated that STAT3 is activated in brain after cerebral ischemia specifically in neurons. The effect was sex-specific and modulated by sex steroids, with higher activation in females than males. In the current study, we used a proteomics approach to identify downstream proteins affected by ischemia in male and female wild-type (WT) and neuron-specific STAT3 knockout (KO) mice. We established four comparison groups based on the transgenic condition and the hemisphere analyzed, respectively. Moreover, the sexual variable was taken into account and male and female animals were analyzed independently. Results support a role for STAT3 in metabolic, synaptic, structural and transcriptional responses to cerebral ischemia, indeed the adaptive response to ischemia/reperfusion injury is delayed in neuronal-specific STAT3 KO mice. The differences observed between males and females emphasize the importance of sex-specific neuronal survival and repair mechanisms, especially those involving antioxidant and energy-related activities, often caused by sex hormones.

Endoscopic treatment of ureterocele in children: Results of a single referral tertiary center over a 10 year-period.

INTRODUCTION: The management of UCs remain controversial, especially for UCs with duplex collecting systems that still represent a great challenge in paediatric urology. Several approaches have been used and a shared management is not yet validated. STUDY AIM: Aim of our study is to evaluate the results of the endoscopic treatment of UC comparing ortothopic single-system UC and ectopic duplex-system UC over a 10-year period in a single referral tertiary center. Success was defined as resolution of dilation, lack of urinary infections and preservation of renal function. STUDY DESIGN: We retrospectively reviewed medical records of children with a diagnosis of UC who underwent endoscopic puncture at our division from January 2009 to January 2019. Patients were divided in two groups: Group A composed of patients with ectopic UC associated with renal duplex system and Group B with orthotopic UC in single collecting system. RESULTS: We identified 48 paediatric patients treated with transurethral primary endoscopic incision. Groups result homogeneous for clinical and pathological characteristics. The only statistical significative difference between the two samples was the age at diagnosis (p value with Yates correction = 0.01). DISCUSSION: We considered as a therapeutic success infections control and the elimination of obstruction with preservation of global kidney function. Based on that, our success rate after single (77%) or double (92%) endoscopic treatment is higher than data reported in literature. Differently from previous studies, vescico-ureteral reflux without UTIs was not considered as a failure of the procedure. The present study has some limitations: it is a retrospective and monocentric serie and it lacked a longer follow-up; on the other hand, it has been conducted on a quite large sample size and it is one of the few studies that compares the endoscopic treatment between orthotopic and ectopic UC. CONCLUSION: Our data report primary endoscopic puncture of ureterocele as a simple, effective, and safe procedure also in long-term follow up. This technique avoids the need for additional surgery in the majority of the patients, also in the case of an ectopic UC associated to a duplex system.

Treatment of ureteropelvic junction obstruction and urolithiasis in children with minimally invasive surgery.

BACKGROUND: Ureteropelvic Junction Obstruction (UPJO) is the most common congenital ureteral anomaly. Nowadays, according to the increasing incidence of urolithiasis, 20% of children with UPJO presents urolithiasis. Open pyeloplasty was the standard treatment before the introduction of minimally invasive surgery (MIS). Nevertheless, only scattered experiences on MIS were previously described and universal agreement on the treatment of UPJO plus urolithiasis is still missing. OBJECTIVE: The study aim was to describe our experience with a series of pediatric patients affected by UPJO and urolithiasis treated with robot-assisted pyeloplasty (RAP) and endoscopic removal of stones using a flexible cystoscope and a stones basket in a singular tertiary referral center. MATERIAL AND METHODS: We retrospectively reviewed our data from pediatric patients affected by UPJO and urolithiasis undergoing RAP between April 2013 and December 2019. The analysis was conducted on seven patients. All procedures were performed by one expert robotic surgeon and one endoscopic surgeon skilled in the management of urolithiasis. RESULTS: The mean age was 7 years (IQR 4-16). The median stone area was 77.7 mm two (IQR 50.2-148.4). Most of them (71.4%) presented preoperative symptoms. The median operative time was 110 min (IQR 104-125) with a console time of 90 (IQR 90-105). The median length of stay was 5 days (IQR 4-5). Median follow-up was 16 months (IQR 10-25). CONCLUSION: RAP with concomitant flexible ureteroscope is a safe and effective option for the simultaneous management of UPJO with urolithiasis with excellent outcomes in children.

Ureteral Reimplantation for Primary Obstructive Megaureter in Pediatric Patients: Is It Time for Robot-Assisted Approach?

Objective: To compare open and robotic approach for treatment of Primary Obstructive Megaureter (POM) in a series of pediatric patients. Materials and Methods: Medical records of all patients who had undergone ureteral reimplantation for POM at our institution, between January 2016 and December 2019, were retrospectively collected and analyzed. Open (Group B) and robotic (Group A) approach were compared. Success was defined as reduction of anteroposterior diameter of pelvis and ureter on postoperative ultrasound scan. Surgical complications were reported according to the Clavien-Dindo Classification. Esthetic results were compared through the Vancouver Scar Scale. Results: Out of 23 patients, 11 belonged to Group A (5M and 6F) and 12 to Group B (9M and 3F). Median age at diagnosis was 38 months in Group A and 46 months in Group B (P = .69). Operative times were comparable (150' Group A and 140' Group B; P = .35), but the hospital stay was significantly shorter in the robotic group (P < .01). Success rate was comparable: 90.9% in Group A and 91.7% in Group B, respectively (P = .95). Incidence of early complications was 9.1% in Group A (grade IIIB) and 8.3% in Group B (grade II) (P = .95). Esthetic evaluation obtained a median score of 1 in Group A and 3 in Group B (P < .01). Conclusions: Our preliminary experience shows that robotic reimplantation can be a safe option in the treatment of POM in pediatric patients with clinical outcomes comparable to the open technique.

Is preoperative ultrasound tumor size a prognostic factor in endometrial carcinoma patients?

Objective: We aimed to assess the prognostic value of preoperative ultrasound tumor size in EC through a single center, observational, retrospective, cohort study. Methods: Medical records and electronic clinical databases were searched for all consecutive patients with EC, preoperative ultrasound scans available to ad hoc estimate tumor size, and a follow-up of at least 2-year, at our Institution from January 2010 to June 2018. Patients were divided into two groups based on different dimensional cut-offs for the maximum tumor diameter: 2, 3 and 4 cm. Differences in overall survival (OS), disease specific survival (DSS) and progression-free survival (PFS) were assessed among the groups by using the Kaplan-Meier estimator and the log-rank test. Results: 108 patients were included in the study. OS, DSS and PFS did not significantly differ between the groups based on the different tumor diameter cut-offs. No significant differences were found among the groups sub-stratified by age, BMI, FIGO stage, FIGO grade, lymphovascular space invasion status, myometrial invasion, lymph nodal involvement, histotype, and adjuvant treatment. Conclusions: Preoperative ultrasound tumor size does not appear as a prognostic factor in EC women.

Renal pseudoaneurysm after blunt trauma in a 10-year-old girl: A case report.

INTRODUCTION: Renal trauma is a relevant cause of morbidity in children older than 1 year. Most patients are currently managed conservatively, even in case of high-grade traumas; nevertheless, harmful complications may occur even in hemodynamically stable patients. We present a case of grade IV blunt renal trauma complicated by post-traumatic pseudoaneurysm. CASE DESCRIPTION: A 10-year-old girl was referred to our institution for grade IV trauma of the right kidney. During observation she had persistent hematuria that caused anemia. A second contrast-enhanced computed tomography scan revealed a posttraumatic pseudoaneurysm that was successfully treated by angiographic embolization. CONCLUSIONS: Although extremely rare after blunt renal trauma, post-traumatic renal pseudoaneurysm may cause severe blood loss and anemia, and angioembolization is therefore indicated. This condition should be suspected and move physicians to investigate further.

Check cystoscopy in the management of anterior urethral valves in a cohort of pediatric patients.

INTRODUCTION: Anterior urethral valves (AUV) are a rare cause of lower urinary tract obstruction which could progress to renal damage, Clinical presentation varies according with patient's age and severity of obstruction, but, in most cases, diagnosis is based on voiding cysto-urethrogram (VCUG). To date, the treatment of choice is endoscopic ablation even if approved guidelines about the overall management of AUVs, including the recognition and treatment of residual valves, are not available. OBJECTIVE: We describe our protocol for AUV treatment based on primary endoscopic valve ablation followed by check cystoscopy 15 days later. STUDY DESIGN: Medical records of 5 patients with AUVs admitted from 2008 to 2018 to our Pediatric Urology Unit were retrospectively reviewed. Blood tests, urinalysis, renal US and VCUG were performed in all children, while urodynamic evaluation was performed in the 3/5 patients who could void spontaneously. All patients underwent endoscopic valves ablation and after 15 days after a second look cystoscopy was performed. Follow up was based on clinical and radiological evaluation with US, urinalysis and blood tests. Postoperative non-invasive urodynamic studies were performed in the 3/5 patient toilet-trained patients and VCUG was performed in 1/5 patient. RESULTS: and Discussion: At primary endoscopic ablation cystoscopy revealed AUVs in the penile urethra in three patients, in the penoscrotal urethra in one case, in the bulbar urethra in another case. In 3/5 patients check cystoscopy found residual valves and a second endoscopic ablation was performed. All patients achieved symptoms release and improved urodynamic parameters. No intra or post-operative complication were reported. The assessment of residual valves is variable in literature and it is usually described for posterior urethral valves (PUVs). Few series report the use of VCUG within the first week after valve ablation, our experience instead suggests that performing a second look cystoscopy, is very effective to evaluate the presence of residual AUVs and eventually proceed with further ablation. CONCLUSION: Endoscopic ablation is the gold standard treatment for AUV, but residual valves management is not clearly defined. According to our experience, a check cystoscopy 15 days after primary ablation allows to identify and treat possible residual valves showing good results in terms of safety and efficacy.

The wheat germ agglutinin-fractionated proteome of subjects with Alzheimer's disease and mild cognitive impairment hippocampus and inferior parietal lobule: Implications for disease pathogenesis and progression.

Lectin affinity chromatography is a powerful separation technique that fractionates proteins by selectively binding to specific carbohydrate moieties characteristic of protein glycosylation type. Wheat germ agglutinin (WGA) selectively binds terminal N-acetylglucosamine (O-GlcNAc) and sialic acid moieties characteristic of O-linked glycosylation. The current study utilizes WGA affinity chromatography to fractionate proteins from hippocampus and inferior parietal lobule (IPL) from subjects with Alzheimer's disease (AD) and arguably its earliest form, mild cognitive impairment (MCI). Proteins identified by proteomics that were fractionated from MCI and AD hippocampus by WGA affinity chromatography with altered levels compared with age-matched controls included GP96, γ-enolase, glutamate dehydrogenase, glucosidase IIα, 14-3-3ϵ, 14-3-3γ, 14-3-3ζ, tropomyosin-2, calmodulin 2, gelsolin, ß-synuclein, α1-antichymotrypsin, and dimethylguanosine tRNA methyltransferase. Proteins identified by proteomics that were fractionated from MCI and AD IPL by WGA affinity chromatography showing altered levels compared with age-matched controls included protein disulfide isomerase, calreticulin, and GP96. The proteins described in this study are involved in diverse processes, including glucose metabolism, endoplasmic reticulum (ER) functions, chaperoning, cytoskeletal assembly, and proteolysis, all of which are affected in AD. This study, the first to use proteomics to identify WGA-fractionated proteins isolated from brains from subjects with MCI and AD, provides additional information about the active proteome of the brain throughout AD progression.

Effects of UVB-induced oxidative stress on protein expression and specific protein oxidation in normal human epithelial keratinocytes: a proteomic approach.

BACKGROUND: The UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS), which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes. RESULTS: The expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins and heat shock response - were differentially regulated in UVB-exposed cells, indicating that an appropriate response is developed in order to counteract/neutralize the toxic effects of UVB-raised ROS. On the other side, the redox proteomics approach revealed that seven proteins - involved in cellular adhesion, cell-cell interaction and protein folding - were selectively oxidized. CONCLUSIONS: Despite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional) proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis.

Could surgical experience of adult endourologist overcome the learning curve of retrograde intrarenal surgery in children?

With the increasing of the prevalence of pediatric urolithiasis (1-5%), retrograde intrarenal surgery (RIRS) is emerging as preferred option for the management of stones in pediatric patients. Although the principles of RIRS developed in adults can be applied in children, also expert adult endourologists feel uncomfortable to approach young patients due to long learning curve that usually is expected to be required in this particular setting. The aim of the study was to compare peri- and postoperative outcomes of RIRS in pediatric and adult patients performed by a single surgeon expert in adult endourology (> 500 RIRS) with no experience in pediatric urology. Data on patient characteristics of 30 consecutive patients (15 adults and 15 children) undergoing RIRS at our institution were collected retrospectively from January 2016 to October 2018. Mean age for the pediatric group was 11.8 years (IQR 8-16) and for the adult group was 56 years (IQR 49-58). No significative differences between the two groups in terms of peri- and postoperative outcomes were found. The most common complication was hematuria in 2/30 patients (1 children vs 1 adults) and fever 2/30 (1 pediatric patient vs 1 adult) (p = 1.00) that required antibiotic treatment (Clavien Dindo 2). Median length of stay was 1 day (IQR 1-1 days) in both groups (p = 1.00). Stone-free rate was 86.7% in children and 80% in adults (p = 0.624). Our preliminary experience suggests that expert adult endourologist can manage successfully also pediatric cases with results comparable to adults and low complication rate.

Robot-assisted laparoscopic pyeloplasty in children: a systematic review.

INTRODUCTION: Open pyeloplasty has been the first-line treatment for uretero-pelvic junction obstruction for decades. In the last years, minimally-invasive surgery (MIS) has gained popularity in the pediatrics field. Furthermore, recently, a great extension of Robot-assisted laparoscopic pyeloplasty (RALP) has been seen in younger and lighter-weight children as well as in redo cases. Herein we provided a comprehensive review of primary and redo RALP performed in children, particularly focusing on the different distribution of outcomes among the ages. EVIDENCE ACQUISITION: A systematic review of the literature was performed according to PRISMA recommendations and was conducted on surgical indication and technique, intraoperative nuances, peri- and postoperative outcomes of primary and redo RALP. EVIDENCE SYNTHESIS: Overall, 33 studies with 1448 patients were included for primary RALP and 7 studies with 101 patients for redo cases between 2000 and 2019. In particular, 4 studies aimed to compare RALP in different cohorts of children grouped on ages or weight and 4 studies evaluated technical feasibility and safety of RALP over laparoscopic and open approach in very young populations. Success rate for primary RALP was found >90% in all studies but one, with low complication rate and preoperative indication. In redo series, 96% of patients revealed a decreased hydronephrosis on postoperative imaging. CONCLUSIONS: RALP offers excellent outcomes in the pediatric population. However, there is still a strong need for higher quality evidence in the form of prospective observational studies and clinical trials. The rising of new robotic systems, such as single-port platform, might further enhance the applications of RALP in children.