Antenatal Determinants of Postnatal Renal Function in Fetal Megacystis: A Systematic Review.

Introduction: To evaluate the clinical usefulness of demographic data, fetal imaging findings and urinary analytes were used for predicting poor postnatal renal function in children with congenital megacystis. Materials and methods: A systematic review was conducted in MEDLINE's electronic database from inception to December 2023 using various combinations of keywords such as "luto" [All Fields] OR "lower urinary tract obstruction" [All Fields] OR "urethral valves" [All Fields] OR "megacystis" [All Fields] OR "urethral atresia" [All Fields] OR "megalourethra" [All Fields] AND "prenatal ultrasound" [All Fields] OR "maternal ultrasound" [All Fields] OR "ob-stetric ultrasound" [All Fields] OR "anhydramnios" [All Fields] OR "oligohydramnios" [All Fields] OR "renal echogenicity" [All Fields] OR "biomarkers" [All Fields] OR "fetal urine" [All Fields] OR "amniotic fluid" [All Fields] OR "beta2 microglobulin" [All Fields] OR "osmolarity" [All Fields] OR "proteome" [All Fields] AND "outcomes" [All Fields] OR "prognosis" [All Fields] OR "staging" [All Fields] OR "prognostic factors" [All Fields] OR "predictors" [All Fields] OR "renal function" [All Fields] OR "kidney function" [All Fields] OR "renal failure" [All Fields]. Two reviewers independently selected the articles in which the accuracy of prenatal imaging findings and fetal urinary analytes were evaluated to predict postnatal renal function. Results: Out of the 727 articles analyzed, 20 met the selection criteria, including 1049 fetuses. Regarding fetal imaging findings, the predictive value of the amniotic fluid was investigated by 15 articles, the renal appearance by 11, bladder findings by 4, and ureteral dilatation by 2. The postnatal renal function showed a statistically significant relationship with the occurrence of oligo- or anhydramnion in four studies, with an abnormal echogenic/cystic renal cortical appearance in three studies. Single articles proved the statistical prognostic value of the amniotic fluid index, the renal parenchymal area, the apparent diffusion coefficient (ADC) measured on fetal diffusion-weighted MRI, and the lower urinary tract obstruction (LUTO) stage (based on bladder volume at referral and gestational age at the appearance of oligo- or anhydramnios). Regarding the predictive value of fetal urinary analytes, sodium and ß2-microglobulin were the two most common urinary analytes investigated (n = 10 articles), followed by calcium (n = 6), chloride (n = 5), urinary osmolarity (n = 4), and total protein (n = 3). Phosphorus, glucose, creatinine, and urea were analyzed by two articles, and ammonium, potassium, N-Acetyl-l3-D-glucosaminidase, and microalbumin were investigated by one article. The majority of the studies (n = 8) failed to prove the prognostic value of fetal urinary analytes. However, two studies showed that a favorable urinary biochemistry profile (made up of sodium < 100 mg/dL; calcium < 8 mg/dL; osmolality < 200 mOsm/L; ß2-microglobulin < 4 mg/L; total protein < 20 mg/dL) could predict good postnatal renal outcomes with statistical significance and urinary levels of ß2-microglobulin were significantly higher in fetuses that developed an impaired renal function in childhood (10.9 ± 5.0 mg/L vs. 1.3 ± 0.2 mg/L, p-value < 0.05). Conclusions: Several demographic data, fetal imaging parameters, and urinary analytes have been shown to play a role in reliably triaging fetuses with megacystis for the risk of adverse postnatal renal outcomes. We believe that this systematic review can help clinicians for counseling parents on the prognoses of their infants and identifying the selected cases eligible for antenatal intervention.

Utility of Functional Lumen Imaging Probe in Long-Term Follow-Up of Children with Esophageal Atresia: A Single-Center Retrospective Study.

Long term follow-up of patients with esophageal atresia (EA) may be hampered by esophageal dysmotility, which affects quality of life and might lead to late complications. The endoluminal functional lumen imaging probe (EndoFlip™ Medtronic, Crospon Inc.) is an innovative diagnostic tool that assesses esophageal distensibility. Our aim was to report the use of EndoFlip™ in an EA follow-up, in order to describe distensibility patterns and to determine its possible role for functional evaluation of patients. We retrospectively collected data of EA patients, with a minimum follow-up of 9 years, who required endoscopic evaluation and underwent EndoFlip™. An adaptation of the Medtronic EF-322 protocol was applied and distensibility data were compared to those reported by Pandolfino et al. Nine patients (median age 13 years) were included in the study. The median minimum distensibility was 2.58 mm2/mmHg. Signs of peristalsis were observed in three patients. In one case, the esophagogastric junction (EGJ) after Toupet fundoplication showed low distensibility. EGJ distensibility values of 2.58 mm2/mmHg (median) confirmed both good esophagogastric continence and compliance. Esophagitis and absent peristalsis were found in one patient together with partial stenosis of the fundoplication, confirming the importance of surgical adaptation. Esophageal body distensibility was higher than that of the EGJ. Considering the presence of symptoms, the EndoFlip™ results seem to correlate better with the clinical picture. EndoFlip™ use was safe and feasible in children. It allowed for the measurement of esophageal distensibility and diameter and the acquisition of indirect information on motility with clinical implications. The routine use of EndoFlip™ could be part of EA follow-up, although considerable research is needed to correlate Endoflip™ system measurements to EA patient outcomes.

Minimally invasive vascular hitch to treat pediatric extrinsic ureteropelvic junction obstruction by crossing polar vessels: A systematic review and meta-analysis.

INTRODUCTION: Vascular hitch (VH) gained an increasing success in treating ureteropelvic junction obstruction (UPJO) by crossing vessels (CV) in pediatrics. AIMS OF THE STUDY: We aimed: (i) to compare laparoscopic VH versus laparoscopic dismembered pyeloplasty (DP) to treat UPJO by CV; (ii) to review possible amelioration given by a robot-assisted procedure. METHODS: Using defined search strategy, three investigators identified all studies on laparoscopic VH. Those studies comparing VH versus DP or versus robot-assisted VH were included in the meta-analysis. The meta-analysis was conducted using RevMan 5.3. Data are mean ± SD. RESULTS: Systematic review - Of 2783 titles/abstracts screened, 43 full-text articles were analyzed. Twelve studies on laparoscopic VH (298 pts) reported 98.3% success rate, with 1.3% intra-operative complications. Meta-Analysis - Five studies compared laparoscopic VH versus laparoscopic DP (277 pts). Operative time was reduced in VH (102.5 ± 47.5min) compared to DP (165.7 ± 53.7min; p < 0.00001). Complications were similar (VH 4/119 pts, 3.4 ± 1.2% versus DP 15/158 pts, 9.5 ± 6.8%; p = ns). Hospital stay was shortened in VH (1.1 ± 0.9dd) versus DP (3.3 ± 3.2dd; p < 0.0001; Summary Figure). The success rate was comparable (VH 115/118 pts, 97.5 ± 1.6% versus DP 157/158 pts, 99.4 ± 0.5%; p = ns). Two prospective studies compared robot-assisted VH to laparoscopic VH (53 pts). No differences were found among complications (robot-assisted VH 0/13 pts, 0% versus laparoscopic VH 1/40 pts, 2.5%; p = ns) and success rate (robot-assisted VH 13/13 pts, 100% versus laparoscopic VH 39/40 pts, 97.5%; p = ns). DISCUSSION: Several studies have been reported long-term results of laparoscopic VH in children. However, few papers demonstrated its superiority over laparoscopic DP to treat extrinsic UPJO. In the present study, we found similar incidence of complications and success rates when comparing VH versus DP. Nonetheless, the operative time and the length of hospital stay were significantly reduced in VH compared to DP. An increasing number of surgeons performed robotic-assisted VH, reporting promising outcomes. However, only a couple of studies compared robot-assisted VH to laparoscopic VH, with a similar incidence of complications and success rate in both procedures. The main limitations of the study were related to the slight number of papers included and to their quality, since all of them were retrospective studies or prospectively followed-up cohort of patients. CONCLUSIONS: Laparoscopic VH seems to be a safe and reliable procedure to treat UPJO by CV. The procedure appeared quicker than laparoscopic DP, with shortened hospital stay. Further studies are needed to corroborate these results and to establish amelioration given by a robot-assisted procedure.

Secondary hydrosalpinx in adolescents: a challenging decision-making process for surgical choice and future fertility preservation.

Hydrosalpinx in pre-pubertal children and non-sexually active adolescents is a rare finding with several etiology and negative impact on future female fertility. The therapeutic approach in these specific populations is debated and it must consider its etiology and adult guidelines focused on fertility issues, which suggest laparoscopic salpingectomy. We described two adolescent cases (15 years asymptomatic and 13 years with abdominal pain) presenting a monolateral hydrosalpinx secondary to surgery for Hirschsprung's disease and complicated appendicitis, respectively. Both patients underwent to uncomplicated robotic-assisted salpingectomy, with uneventful follow-up and preserved ovarian function. Robotic-assisted salpingectomy for hydrosalpinx secondary to previous surgical conditions is a safe and careful approach for adolescents in order to preserve ovarian vascularization, function and future fertility.

Esophageal Atresia and Associated Duodenal Atresia: A Cohort Study and Review of the Literature.

INTRODUCTION: Esophageal atresia (EA) is associated with duodenal atresia (DA) in 3 to 6% of cases. The management of this association is controversial and literature is scarce on the topic. MATERIALS AND METHODS: We aimed to (1) review the patients with EA + DA treated at our institution and (2) systematically review the English literature, including case series of three or more patients. RESULTS: Cohort study: Five of seventy-four patients with EA had an associated DA (6.8%). Four of five cases (80%) underwent primary repair of both atresia, one of them with gastrostomy placement (25%). One of five cases (20%) had a delayed diagnosis of DA. No mortality has occurred. Systematic Review: Six of six-hundred forty-five abstract screened were included (78 patients). Twenty-four of sixty-eight (35.3%) underwent primary correction of EA + DA, and 36/68 (52.9%) underwent staged correction. Nine of thirty-six (25%) had a missed diagnosis of DA. Thirty-six of sixty-eight underwent gastrostomy placement. Complications were observed in 14/36 patients (38.9 ± 8.2%). Overall mortality reported was 41.0 ± 30.1% (32/78 patients), in particular its incidence was 41.7 ± 27.0% after a primary treatment and 37.0 ± 44.1% following a staged approach. CONCLUSION: The management of associated EA and DA remains controversial. It seems that the staged or primary correction does not affect the mortality. Surgeons should not overlook DA when correcting an EA.

Challenges, constraints and failures that are related to the posterior sagittal anorectoplasty approach to anorectal malformations in a low-resource context: An experience from a sudanese tertiary referral centre.

BACKGROUND: Anorectal malformations (ARMs) in the sub-Saharan Africa are a common cause of neonatal referral for intestinal obstruction, and the posterior sagittal anorectoplasty (PSARP) approach is rapidly spreading. The small number of paediatric surgeons and the low-resource context limit children's access to care and constrain the quality of results. A retrospective, observational study has been done on a consecutive series of ARM cases admitted to a Sudanese tertiary paediatric surgical centre within the framework of a partnership between Italian and Sudanese academic institutions addressed to review and upgrade the standard of care of major congenital anomalies. MATERIALS AND METHODS: The authors collected 94 ARM cases in a 3 years' period. Conditions on referral, operative procedures, post-operative course and follow-up were recorded and examined. Their correlations with complications and outcome were analysed. RESULTS: The male/female ratio was 47/47. Eighty patients presented with an untreated ARM; 66 had a divided stoma and 14 had already a PSARP procedure, followed by a poor outcome or sequelae. In 25% of the cases, colostomy required re-doing. In 57 cases, a staged PSARP (primary or re-do) was done. Surgical-site infections occurred in nine patients. Some patients were lost to follow-up after preliminary colostomy. Post-operative dilatation programme suffered from the lack of systematic follow-up, and colostomy closure was possible in 46% of the cases due to problems in travelling and accessing hospital care. Anal stenosis was frequently observed among unfollowed patients. CONCLUSION: Despite PSARP's widespread adoption in Africa, the risk of complications and failures is high. Primary management is often inappropriate, and a high rate of colostomy-related complications is observed. Poverty and lack of transportation reduce attendance to follow-up, hampering the final results. Investments in healthcare facilities and retention of trained health providers are needed to improve the standard of care.

A Rare Case of Giant Mesenteric Lipoblastoma in a 6-Year-Old Child and Review of the Literature.

Giant mesenteric lipoblastoma is a rare benign tumor arising from the adipocytes. It can mimic malignant tumors, and its diagnosis is difficult before surgery. Imaging studies could lead the diagnosis but not confirm it. Those tumors arising in the abdomen are usually larger and can cause symptoms of compression. Surgical excision is the treatment of choice, and a long-term follow-up is necessary to detect local recurrences. Only a few cases of lipoblastomas arising from the mesentery are reported in literature. We present a case of a rare giant lipoblastoma arising from the mesentery of a 6-year-old girl, with a history of postprandial abdominal pain.

Management of Spontaneous Pneumothorax in Children: A Systematic Review and Meta-Analysis.

INTRODUCTION: Management of primary spontaneous pneumothorax (PSP) is mainly based on adults. Data are controversial with regards to its management in children. We aimed to assess: (1) the length of hospital stay (LOS) between conservative management (i.e., observation with O2 administration), aspiration/chest drain, and surgical management; (2) the risk of recurrence after nonsurgical treatment versus surgery; (3) the risk of recurrence in the presence of bullae. MATERIALS AND METHODS: Using a defined search strategy, three independent investigators identified all the studies on the management of PSP in children. Case reports, opinion articles, and gray literature publications were excluded. The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A meta-analysis was performed using RevMan 5.3. Data are expressed as mean ± SD. RESULTS: Of 3,089 abstracts screened, 95 full-text were analyzed, 23 were included in the quantitative analysis, and 16 were included in the meta-analysis (1,633 patients). LOS was similar between conservative and surgical management (6.2 ± 0.8 days vs. 5.9 ± 1.4 days; p = ns). Recurrence of PSP was significantly higher among children with a nonsurgical management (32%) versus those surgically treated (18%; p = 0.002). The incidence of recurrence was slightly higher in patients managed by aspiration/chest drain (34%) compared with those with a conservative management (27%; p = 0.05). Risk of recurrence in patients with or without documented bullae was not significantly different (26 vs. 38%, respectively; p = ns). CONCLUSION: Given the lack of a standardized management of pediatric PSP, the present study seems to demonstrate a better outcome in children treated with surgery as first-line of management. LEVEL OF EVIDENCE: This is a Level III study.

Neurodevelopmental impairment in children with congenital diaphragmatic hernia: Not an uncommon complication for survivors.

PURPOSE: To evaluate neurodevelopmental impairment (NDI) in children born with congenital diaphragmatic hernia (CDH). METHODS: Using a defined search strategy, a systematic review was conducted to define the incidence and types of NDI, to report abnormal neuroimaging findings and to evaluate possible NDI predictors. A meta-analysis was performed on comparative studies reporting risk factors for NDI, using RevMan 5.3. RESULTS: Of 3541 CDH children (33 studies), 829 (23%) had NDI, with a higher incidence in CDH survivors who received ECMO treatment (49%) vs. those who had no ECMO (22%; p<0.00001). NDI included neuromuscular hypotonia (42%), hearing (13%) and visual (8%) impairment, neurobehavioral issues (20%), and learning difficulties (31%). Of 288 survivors that had postnatal neuroimaging, 49% had abnormal findings. The main risk factors for NDI were severe pulmonary hypoplasia, large defect size, ECMO use. CONCLUSIONS: NDI is a relevant problem for CDH survivors, affecting 1 in 4. The spectrum of NDI covers all developmental domains and ranges from motor and sensory (hearing, visual) deficits to cognitive, language, and behavioral impairment. Further studies should be designed to better understand the pathophysiology of NDI in CDH children and to longitudinally monitor infants born with CDH to correct risk factors that can be modifiable. LEVEL OF EVIDENCE: Level III.

Activation of metabotropic glutamate receptor 5 improves recovery after spinal cord injury in rodents.

OBJECTIVE: Activation of metabotropic glutamate receptor 5 (mGluR5) has neuroprotective properties in vitro and has been reported to limit postischemic lesion volume in vivo. Previously, mGluR5 has been identified on microglia in vitro, but the effects of mGluR5 activation on inflammation in vivo or on recovery after spinal cord injury is unknown. METHODS: Rats received intrathecal infusion of the selective mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) for 7 days after moderate impact spinal cord injury at T9. Complementary studies examined CHPG effects on activated spinal microglia cultures. RESULTS: Functional motor recovery was significantly increased by CHPG treatment up to 28 days after injury, with improvements in weight bearing, step taking, and coordination of stepping behavior. CHPG treatment significantly reduced lesion volume and increased white matter sparing at 28 days after injury. Administration of CHPG attenuated microglial-associated inflammatory responses in a dose-dependent fashion, including expression of ED1, Iba-1, Galectin-3, NADPH oxidase components, tumor necrosis factor-alpha, and inducible nitric oxide synthase. Because mGluR5 is expressed by microglial cells in the rat spinal cord, such effects may be mediated by direct action on microglial cells. mGluR5 stimulation also reduced microglial activation and decreased microglial-induced neurotoxicity in spinal cord microglia cultures; the latter effects were blocked by the selective mGluR5 antagonist MTEP. INTERPRETATION: These data demonstrate that mGluR5 activation can reduce microglial-associated inflammation, suggesting that the protective effects of mGluR5 agonists may reflect this action. Ann Neurol 2009;66:63-74.

Metabotropic glutamate receptor 5 activation inhibits microglial associated inflammation and neurotoxicity.

The Group I metabotropic glutamate receptor 5 (mGluR5) can modulate addiction, pain, and neuronal cell death. Expression of some mGluRs, such as Group II and III mGluRs, has been reported in microglia and may affect their activation. However, the expression and role of mGluR5 in microglia is unclear. Using immunocytochemistry and Western blot, we demonstrate that mGluR5 protein is expressed in primary microglial cultures. Activation of mGluR5 using the selective agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) significantly reduces microglial activation in response to lipopolysaccharide, as indicated by a reduction in nitric oxide, reactive oxygen species, and TNFalpha production. Microglial induced neurotoxicity is also markedly reduced by CHPG treatment. The anti-inflammatory effects of CHPG are not observed in microglial cultures from mGluR5 knockout mice and are blocked by selective mGluR5 antagonists, suggesting that these actions are mediated by the mGluR5 receptor. Anti-inflammatory actions of mGluR5 activation are attenuated by phospholipase C and protein kinase C inhibitors, as well as by calcium chelators, suggesting that the mGluR5 activation in microglia involves the G(alphaq)-protein signal transduction pathway. These data indicate that microglial mGluR5 may represent a novel target for modulating neuroinflammation, an important component of both acute and chronic neurodegenerative disorders.