Linking genotype to trophoblast phenotype in preeclampsia and HELLP syndrome associated with STOX1 genetic variants.

Preeclampsia is a major hypertensive pregnancy disorder with a 50% heritability. The first identified gene involved in the disease is STOX1, a transcription factor, whose variant Y153H predisposes to the disease. Two rare mutations were also identified in Colombian women affected by the hemolysis, elevated liver enzyme, low platelet syndrome, a complication of preeclampsia (T188N and R364X). Here, we explore the effects of these variants in trophoblast cell models (BeWo) where STOX1 was previously invalidated. We firstly showed that STOX1 knockout alters response to oxidative stress, cell proliferation, and fusion capacity. Then, we showed that mutant versions of STOX1 trigger alterations in gene profiles, growth, fusion, and oxidative stress management. The results also reveal alterations of the STOX interaction with DNA when the mutations affected the DNA-binding domain of STOX1 (Y153H and T188N). We also reveal here that a major contributor of these effects appears to be the E2F3 transcription factor.

Maturation of the vertebral ring apophysis is delayed in girls with adolescent idiopathic scoliosis compared to the normal population.

PURPOSE: The ring apophysis is a secondary ossification center on both sides of each vertebral body, to which the annulus of the intervertebral disc inserts. Recently, its pattern of ossification and fusion to the vertebral body was described for the normal growing spine. The aim of the present study was to investigate the ossification and fusion of the ring apophysis in patients with adolescent idiopathic scoliosis (AIS) and compare it to the normal growing population. METHODS: Ring apophysis maturation along the entire thoracic and lumbar spine was analyzed on CT scans of 99 female, pre-operative AIS patients and compared to 134 CT scans of non-scoliotic girls, aged 12 to 20. RESULTS: The ring apophysis maturation in AIS patients was delayed at all spinal levels in AIS patients compared to non-scoliotic controls. Ossification starts at T4-T11 at age 12, followed by T1-T5 and L3-S1 at age 15. The fusion process in AIS patients continues longer in the midthoracic region as compared to the other regions and as compared to non-scoliotic controls, with many incomplete fusions still at age 20. CONCLUSION: The ring apophysis maturation in AIS is delayed compared to that in the normal population and lasts longer in the mid/low thoracic spine. Delayed maturation of the spine's most important stabilizer, while the body's dimensions continue to increase, could be part of the patho-mechanism of AIS.

Exploring the Antioxidant and Anti-Inflammatory Potential of Saffron (Crocus sativus) Tepals Extract within the Circular Bioeconomy.

Repurposing saffron (Crocus sativus) waste presents a sustainable strategy for generating high-value products within the bioeconomy framework. Typically, flower components are discarded after stigma harvest, resulting in significant waste-350 kg of tepals per kilogram of stigmas. This research employed a comprehensive approach, integrating bioactivity studies (in vitro and in silico) with Life Cycle Assessment (LCA) evaluations, to extract and assess bioactive compounds from C. sativus tepals sourced in Tuscany, Italy. Phytochemical characterization using UPLC-MS/MS revealed a high abundance and variety of flavonoids in the hydro-ethanolic extract (CST). The antioxidant capacity was validated through various assays, and the ability to mitigate H2O2-induced oxidative stress and enhance fermentation was demonstrated in Saccharomyces cerevisiae. This study reports that C. sativus tepals extract reduces oxidative stress and boosts ethanol fermentation in yeast, paving the way for applications in the food and biofuels sectors. Further validation in RAW 264.7 macrophages confirmed CST's significant anti-inflammatory effects, indicating its potential for pharmaceutical, cosmeceutical, and nutraceutical applications. In silico studies identified potential targets involved in antioxidant and anti-inflammatory processes, shedding light on possible interaction mechanisms with Kaempferol 3-O-sophoroside (KOS-3), the predominant compound in the extract. The integration of LCA studies highlighted the environmental benefits of this approach. Overall, this research underscores the value of using waste-derived extracts through "green" methodologies, offering a model that may provide significant advantages for further evaluations compared to traditional methodologies and supporting the circular bioeconomy.

Incidence, Risk Factors, and Management of Incisional Hernias After Kidney Transplant: A 20-Year Single Center Experience.

BACKGROUND: Incisional hernias (IH) constitute a complication after kidney transplant (KT). Patients may be particularly at risk because of comorbidities and immunosuppression. The study aim was to assess the incidence, risk factors, and treatment of IH in patients undergoing KT. METHODS: This retrospective cohort study included consecutive patients who underwent KT between January 1998 and December 2018. Patient demographics, comorbidities, perioperative parameters, and IH repair characteristics were assessed. Postoperative outcomes included morbidity, mortality, need for reoperation, and length of stay (LOS). Patients who developed IH were compared with those who did not develop one. RESULTS: Forty-seven patients (6.4%) developed an IH after a median delay of 14 months (IQR, 6-52 months) in 737 KTs. On uni- and multivariate analyses, body mass index (odds ratio [OR], 1.080; P = .020), pulmonary diseases (OR, 2.415; P = .012), postoperative lymphoceles (OR, 2.362; P = .018), and LOS (OR, 1.013; P = .044) were independent risk factors. Thirty-eight patients (81%) underwent operative IH repair, and 37 (97%) were treated with a mesh. The median LOS was 8 days (IQR, 6-11 days). Three patients (8%) developed surgical site infections, and 2 patients (5%) presented hematomas requiring surgical revision. After IH repair, 3 patients (8%) had a recurrence. CONCLUSIONS: The incidence of IH after KT seems rather low. Overweight, pulmonary comorbidities, lymphoceles, and LOS were identified as independent risk factors. Strategies focusing on the modifiable patient-related risk factors and early detection and treatment of lymphoceles may help to decrease the risk of IH formation after KT.

The three-dimensional coupling mechanism in scoliosis and its consequences for correction.

INTRODUCTION: In idiopathic scoliosis, the anterior spinal column has rotated away from the midline and has become longer through unloading and expansion of the intervertebral discs. Theoretically, extension of the spine in the sagittal plane should provide room for this longer anterior spinal column, allowing it to swing back towards the midline in the coronal and axial plane, thus reducing both the Cobb angle and the apical vertebral rotation. METHODS: In this prospective experimental study, ten patients with primary thoracic adolescent idiopathic scoliosis (AIS) underwent MRI (BoneMRI and cVISTA sequences) in supine as well as in an extended position by placing a broad bolster, supporting both hemi-thoraces, under the scoliotic apex. Differences in T4-T12 kyphosis angle, coronal Cobb angle, vertebral rotation, as well as shape of the intervertebral disc and shape and position of the nucleus pulposus, were analysed and compared between the two positions. RESULTS: Extension reduced T4-T12 thoracic kyphosis by 10° (p < 0.001), the coronal Cobb angle decreased by 9° (p < 0.001) and vertebral rotation by 4° (p = 0.036). The coronal wedge shape of the disc significantly normalized and the wedged and lateralized nucleus pulposus partially reduced to a more symmetrical position. CONCLUSION: Simple extension of the scoliotic spine leads to a reduction of the deformity in the coronal and axial plane. The shape of the disc normalizes and the eccentric nucleus pulposus partially moves back to the midline.

Combination of transjugular intrahepatic portosystemic shunt and antegrade through-the-TIPS coil embolization for bleeding mixed-type ectopic ileal varices.

A 61-year-old man with alcoholic cirrhosis and a history of severe cholecystitis leading to secondary thrombosis of the recanalized paraumbilical vein was admitted to our hospital for recurrent gastrointestinal bleeding and severe anemia. Capsule endoscopy and CT angiography detected profuse bleeding in the proximal ileum from ectopic ileal varices. Hepatic venous-portal gradient (HVPG) measurement was consistent with severe portal hypertension. Persistent bleeding despite transjugular intrahepatic portosystemic shunt (TIPS) placement required a combined approach with antegrade through-the-TIPS coil embolization of the ileal varices.

GERD surgery in non-neurologic patients: Modified Laparoscopic Hill-Snow Repair is a valid alternative to Nissen fundoplication. Results of a 20 years of follow-up.

Nowadays laparoscopic Nissen fundoplication represents the gold standard in surgical treatment of complicated Gastro-Esophageal-Reflux Disease (GERD), above all in cerebral palsy patients. In non-neurological patients without gastrostomy Nissen fundoplication can create some problems (gas bloat syndrome, dysphagia). Laparoscopic Hill-Snow repair is an established surgical alternative, but it is reported only in adult population. We describe our modification of Hill-Snow technique and our experience in a large series of non-neurological children in order to report its effectiveness and applicability in pediatric patients affected by complicated GERD. Between 2000 and 2022, 319 children underwent surgical correction of gastro-esophageal reflux at our Department. All were affected by complicated gastro-esophageal reflux unresponsive to PPI (Proton Pump Inhibitors). 251 underwent laparoscopic Nissen fundoplication; 68 non-neurological patients underwent laparoscopic Hill-Snow repair. Of these 68 children 48 were males (71%) and 20 females (29%); median age was 5years (3 months-11 years). Weight range was 4-37kg. 52 patients (76.5%) presented the following symptoms: retrosternal pain, dysphagia, regurgitation, coughing, failure to thrive, persisting reflux esophagitis. 16 (23.5%) had chronic respiratory problems (aspiration, apneic-spells, dysphagia, coughing, choking, gagging). For 8 (11.8%) symptoms were expression of chronic recurrent gastric volvulus. All underwent modified-laparoscopic-Hill-Snow repair. Contrast study showed sliding hiatal hernia in 55 patients (81%), while endoscopy demonstrated 16 cases of histologically severe esophagitis (23.5%) and 52 of mild esophagitis (76.5%). No intraoperative/postoperative complications were recorded. 60patients had a complete follow-up (range 1-20 years). 60/68 patients were evaluated with barium-swallow-study at 6-12 months; 40/68 patients with upper-gastrointestinal-endoscopy at 12months. No relapse was reported. 50 patients (73.7%) were symptom-free. 18 (26.3%) referred occasional epigastric pain, associated with vomit in 2 cases. 64 (94.1%) referred ability to vomit; 4 temporary difficulty to swallow (average 30 days). All patients reported being able to burp. 3(4.5%) presented episodes of gas-air-bloat during the first 2 months with spontaneous resolution. No case of dumping syndrome was recorded. This technique's modification yields excellent results in term of relapse and side effects at long-term follow-up. We reported the first and largest pediatric series in non-neurological children with encouraging results.

Acute pancreatitis after pancreatoduodenectomy: A prospective study of diffusion-weighted magnetic resonance imaging, serum biomarkers, and clinical features.

BACKGROUND: Postpancreatectomy acute pancreatitis is challenging to diagnose and poorly characterized in its early phases. However, it represents the ideal target for novel therapeutic opportunities possibly gleaned from medical acute pancreatitis. This study aims to systematically investigate early radiologic, biochemical, and clinical features of postpancreatectomy acute pancreatitis. METHODS: This was a prospective observational study of patients undergoing pancreatoduodenectomy from September 2019 to January 2021. Diffusion-weighted magnetic resonance imaging was performed on postoperative day 3. Serum pancreatic amylase and lipase were assessed daily until postoperative day 5. Postoperative serum hyperamylasemia and postpancreatectomy acute pancreatitis were defined based on the International Study Group for Pancreatic Surgery definition. RESULTS: A total of 65 patients were enrolled according to the sample size calculation. Patients with postoperative serum hyperamylasemia and postpancreatectomy acute pancreatitis had significantly lower apparent diffusion coefficient values at diffusion-weighted magnetic resonance imaging but no macroscopic features consistent with acute pancreatitis. Subsequently, 21 patients (32.3%) underwent computed tomography imaging for clinical worsening, and 6 had radiologic features of acute pancreatitis. All these latter patients had postoperative serum hyperamylasemia and worse outcomes, characterized by local (postoperative pancreatic fistula: 83%) and systemic morbidity (sepsis: 66.7%). The postoperative serum hyperamylasemia incidence was 21.5% (n = 14), and postpancreatectomy acute pancreatitis occurred in 6 patients (9.2%), with 4 grade B (6.1%) and 2 grade C (3%). CONCLUSION: Postpancreatectomy acute pancreatitis is characterized by early serum hyperamylasemia and hyperlipasemia. Although pancreatic changes may appear at postoperative day 3 diffusion-weighted magnetic resonance imaging, its standard use has no impact on postoperative management. Macroscopic radiologic features appear later and correlate with worse clinical scenarios. This paper paves the ground for including postpancreatectomy acute pancreatitis in the spectrum of acute pancreatitis, promoting the transfer of treatment strategies for acute pancreatitis into managing postpancreatectomy acute pancreatitis.

Pediatric Gastric Volvulus: Is Laparoscopic Hill-Snow-Modified Gastropexy the Effective Long-Term Minimally Invasive Solution?

Introduction: Gastric volvulus (GV) is a rare and life-threatening condition if not promptly diagnosed and treated. Extreme rotation can cause obstruction cutting off blood supply to stomach and distal organs, leading to ischemia and necrosis. It is a clinically significant cause of acute/recurrent abdominal pain and chronic vomiting in children. GV can be classified into the following: primary, secondary, organoaxial, mesenteroaxial, or combined, acute, or chronic. Materials and Methods: Six neonates (5 males-1 female) were admitted to our department for recurrent postprandial vomiting associated with paleness, hyporeactivity, transitory abdominal distension, failure to thrive, and respiratory infections (only-1). Median age: 6 months (range 2-9 months). Patients metabolic and neurological evaluations were normal. A barium-swallow-study (upper gastrointestinal [UGI]) allowed definitive diagnosis. Results: UGI and esophagogastroduodenoscopy (EGDS) showed a gastric abnormal dilatation (gastric fundus), hiatal hernia (HH) in 5 patients, a large/small curvature discrepancy in 3 patients. Four were chronic-organoaxial-GV, 2 chronic-mesenteroaxial-GV. All underwent Laparoscopic-Hill-Snow-gastropexy (LHSG) with HH correction. No intraoperative/postoperative complications were recorded. Refeeding started in first postoperative day. Average hospital stay: 6-days. At long-term follow-up, all patients were symptoms free (able to vomit/burp); 2 referred occasionally epigastric pain sometimes with vomit. At 10-12 years follow-up UGI and EGDS confirmed correct gastric position revealing gastroduedenitis. Discussion: GV is a rare clinical entity in children considering etiology and management with an important morbidity and mortality rate. Its diagnosis could be missed simply. Vomiting or HH on imaging studies should suggest GV regardless patient's stable appearance. Conclusions: Chronic GV can manifest with atypical chest, abdominal, and gastrointestinal symptoms. Early diagnosis and treatment reduce the risk of developing acute form. LHSG is a long-term effective and safe solution with a very low complication rate, and no symptoms correlated to Nissen procedure.

Reply to Weiss, H.-R. Comment on "Costa et al. The Effectiveness of Different Concepts of Bracing in Adolescent Idiopathic Scoliosis (AIS): A Systematic Review and Meta-Analysis. J. Clin. Med. 2021, 10, 2145".

We would like to thank you for the opportunity to reply to the comments in regard of the letter by Dr. Weiss [...].

Disc and Vertebral Body Morphology From Birth to Adulthood.

STUDY DESIGN: Cross-sectional. OBJECTIVE: The aim of this study was to describe the morphology of intervertebral discs and vertebral bodies during growth in asymptomatic children and adolescents. SUMMARY OF BACKGROUND DATA: Earlier studies demonstrated that spinal growth occurs predominantly in vertebral bodies. This axiom introduced a vertebral-body-focus for unravelling etiological questions and achieve growth-modulation in young spinal deformity patients. Recent studies show the importance of the intervertebral discs in the early phases and possible etiology of pediatric spinal deformities. There is presently a paucity of 3D morphometric data of spinal elements during growth. METHODS: A database of 298 patients aged 0 to 21 that have received a computed tomography scan for indications not related to the spine was analyzed. Custom made software was used to semi-automatically measure intervertebral disc and vertebral body morphology, corrected for orientation in all 3 planes. RESULTS: Vertebral body height increased from birth up to adulthood, from 4-to-14 mm in the cervical, 6 to 20 mm in the thoracic, and 9 to 28 mm in the lumbar spine. This increase was 0.70 mm/year in males, more pronounced than females with 0.62 mm/year (P = 0.001). Lumbar discs increased throughout growth from 4.4 to 9.0 mm, whereas thoracic discs only increased from 3.5 to 4.9 mm at age 4 and remained stable afterwards, similarly for cervical discs. The disc transverse surface area increased greatly and consistently throughout growth. Disc slenderness was stable in the lumbar spine during growth, but decreased in the thoracic and cervical spine. Overall, discs were more slender in females, especially around early adolescence. CONCLUSION: The spine grows predominantly in the vertebral bodies. Thoracic discs increase in height only during the first years, whereas the transverse surface area continues to increase throughout growth, thus discs slenderness decreases. Relatively, female discs remained slenderer around growth-spurt. These measurements may assist future studies on the role of disc morphology in the etiology and treatment of spinal deformity.Level of Evidence: 4.

Torsion of cecal appendix. Report of the first Italian case and review of the literature.

In pediatric patients appendicitis is the most common cause of abdominal pain and surgery. Torsion of vermiform appendix is a rare cause, clinically indistinguishable from appendicitis with usually an intraoperative diagnosis. The first description of vermiform appendix torsion was made by Payne in 1918. Clinical presentation is similar to acute appendicitis. Preoperative investigations play a minimal role. Etiology of this condition is unclear, but is possible to distinguish a primary and a secondary torsion. We report a case of 5-years-old boy who presented with right lower quadrant abdominal pain. His clinical signs, symptoms and investigations mimicked an acute appendicitis. Intraoperatively we found a 720° appendix torsion on its base with its mesentery rotated in counter-clockwise direction. The appendix was gangrenous in appearance. A video-assisted trans-umbilical appendectomy was performed. We describe clinical presentation and management of this rare condition reviewing the literature.

Ossification and Fusion of the Vertebral Ring Apophysis as an Important Part of Spinal Maturation.

In scoliosis, most of the deformity is in the disc and occurs during the period of rapid growth. The ring apophyses form the insertion of the disc into the vertebral body, they then ossify and fuse to the vertebrae during that same crucial period. Although this must have important implications for the mechanical properties of the spine, relatively little is known of how this process takes place. This study describes the maturation pattern of the ring apophyses in the thoracic and lumbar spine during normal growth. High-resolution CT scans of the spine for indications not related to this study were included. Ossification and fusion of each ring apophysis from T1 to the sacrum was classified on midsagittal and midcoronal images (4 points per ring) by two observers. The ring apophysis maturation (RAM) was compared between different ages, sexes, and spinal levels. The RAM strongly correlated with age (R = 0.892, p < 0.001). Maturation differed in different regions of the spine and between sexes. High thoracic and low lumbar levels fused earlier in both groups, but, around the peak of the growth spurt, in girls the mid-thoracic levels were less mature than in boys, which may have implications for the development of scoliosis.

The Effectiveness of Different Concepts of Bracing in Adolescent Idiopathic Scoliosis (AIS): A Systematic Review and Meta-Analysis.

Brace treatment is the most common noninvasive treatment in adolescent idiopathic scoliosis (AIS); however it is currently not fully known whether there is a difference in effectiveness between brace types/concepts. All studies on brace treatment for AIS were searched for in PubMed and EMBASE up to January 2021. Articles that did not report on maturity of the study population were excluded. Critical appraisal was performed using the Methodological Index for Non-Randomized Studies tool (MINORS). Brace concepts were distinguished in prescribed wearing time and rigidity of the brace: full-time, part-time, and night-time, rigid braces and soft braces. In the meta-analysis, success was defined as ≤5° curve progression during follow-up. Of the 33 selected studies, 11 papers showed high risk of bias. The rigid full-time brace had on average a success rate of 73.2% (95% CI 61-86%), night-time of 78.7% (72-85%), soft braces of 62.4% (55-70%), observation only of 50% (44-56%). There was insufficient evidence on part-time wear for the meta-analysis. The majority of brace studies have significant risk of bias. No significant difference in outcome between the night-time or full-time concepts could be identified. Soft braces have a lower success rate compared to rigid braces. Bracing for scoliosis in Risser 0-2 and 0-3 stage of maturation appeared most effective.

The Use of Endoclips in Thoracoscopic Correction of Esophageal Atresia: Advantages or Complications?

Background: Thoracoscopic correction of esophageal atresia (EA) with tracheoesophageal fistula (TEF) has been increasingly widespread, but is still one of the most advanced pediatric surgical skills. This procedure has a challenging learning curve, and usually initially requires a longer operative time than the open approach; furthermore to perform this intervention, the surgeon must be very experienced in endocorporeal knotting. In our opinion, standardization of the technique and the application of "tricks" (including the use of titanium endoclips for TEF closure) to make surgical steps easier, faster, and safe would be useful to the surgeon and to the patient above all. Materials and Methods: We present our experience in thoracoscopic treatment of EA/TEF over the past 12 years; during this period, we have treated 32 neonates. We reviewed all patient clinical records evaluating demographics, surgical technique, postoperative period, and long-term follow-up. Results: Thirty-one patients were affected by type C EA (five presented with a long-gap defect); one by type E EA. Mean gestational age was 36 + 5 weeks (29-41). Mean weight at surgery was 2340 g (990-3715 g). Through a transpleural thoracoscopic approach, after Azygos vein division, TEF was closed by sutures (silk/polydioxanone [PDS]) in 4 patients while in the remaining 28 two 5 mm titanium endoclips were applied. Esophageal anastomosis was then performed with 8-12 interrupted 5/0 absorbable sutures. We had two intraoperative complications in endoclips application (migration and misplacement), which were immediately resolved. After a contrast study on sixth to seventh postoperative day (average eighth), in the absence of leakage, oral feeding was started and chest tube removed. Four to six weeks after surgery, patients underwent endoscopic evaluation. At a follow-up of 9 years, we had no postoperative complications due to endoclips: neither TEF recurrence, nor problems due to clips dislocation. Conclusions: Although the benefits of thoracoscopic correction of EA/TEF are still discussed, we agree with this part of recent literature that considers thoracoscopic approach as a feasible, safe, and advantageous alternative to the traditional open approach. We also want to emphasize that in our experience, TEF closure by titanium endoclips is fast, reducing operative time, and effective, with no reported long-term complications in our case series. Overall success rate after clips application is, in our series, 100%. The only limit we have found, above all for low-weight patients, is the diameter of the clip applier which needs a 5 mm access even if the surgeon uses 3 mm operative instruments.

Torsion of huge epididymal cyst in a 16-year-old boy: case report and review of the literature.

Epididymal cysts (ECs) are relatively common in adults, rare in children. Normally their treatment is conservative. They may be situated anywhere in the organ, frequently in the region of the head. Torsion of these cysts is extremely rare in both children and adults, causing acute scrotal swelling. The diagnosis is intraoperative. A 16-year-old boy was referred to our Divisional Clinic by the treating physician for scrotal swelling appeared 4 months earlier. Absence of a history of minor scrotal trauma. Ultrasonography showed a 40×50 mm fluid-filled right para-testicular mass. We performed surgery finding a large black cyst connected to the head of the epididymis with 720°-degrees rotation. Histology revealed an acquired EC. The particularity of our case is due to the absence of symptoms in association with a big EC twisted of 720° degrees. This is the only case reported in literature. All patients with EC torsion reported presented symptoms related to acute scrotum.

Duodenal Atresia: Open versus MIS Repair-Analysis of Our Experience over the Last 12 Years.

Objective. Duodenal atresia (DA) routinely has been corrected by laparotomy and duodenoduodenostomy with excellent long-term results. We revisited the patients with DA treated in the last 12 years (2004-2016) comparing the open and the minimally invasive surgical (MIS) approach. Methods. We divided our cohort of patients into two groups. Group 1 included 10 patients with CDO (2004-09) treated with open procedure: 5, DA; 3, duodenal web; 2, extrinsic obstruction. Three presented with Down's syndrome while 3 presented with concomitant malformations. Group 2 included 8 patients (2009-16): 1, web; 5, DA; 2, extrinsic obstruction. Seven were treated by MIS; 1 was treated by Endoscopy. Three presented with Down's syndrome; 3 presented with concomitant malformations. Results. Average operating time was 120 minutes in Group 1 and 190 minutes in Group 2. In MIS Group the visualization was excellent. We recorded no intraoperative complications, conversions, or anastomotic leakage. Feedings started on 3-7 postoperative days. Follow-up showed no evidence of stricture or obstruction. In Group 1 feedings started within 10-22 days and we have 1 postoperative obstruction. Conclusions. Laparoscopic repair of DA is one of the most challenging procedures among pediatric laparoscopic procedures. These patients had a shorter length of hospitalization and more rapid advancement to full feeding compared to patients undergoing the open approach. Laparoscopic repair of DA could be the preferred technique, safe, and efficacious, in the hands of experienced surgeons.