Microvessel Density (MVD) in Patients with Osteosarcoma: A Systematic Review and Meta-Analysis.

A meta-analysis was designed and conducted to estimate the effect of tumoral microvessel density (MVD) on the survival of patients with osteosarcoma. There was no difference between high and low MVD regarding the overall (OS) and disease-free (DFS) survival. Low MVD tumors displayed a lower DFS at the third year of follow-up. Although primary metastases did not affect the mean MVD measurements, tumors with a good chemotherapy response had a higher MVD value. Although no significant differences between tumoral MVD, OS and DFS were found, good adjuvant therapy responders had a significant higher vascularization pattern.

Recombinant irisin enhances the extracellular matrix formation, remodeling potential, and differentiation of human periodontal ligament cells cultured in 3D.

BACKGROUND: Irisin is expressed in human periodontal ligament (hPDL), and its administration enhances growth, migration and matrix deposition in hPDL cells cultured in monolayers in vitro. OBJECTIVES: To identify whether irisin affects the gene expression patterns directing the morphology, mechanical properties, extracellular matrix (ECM) formation, osteogenic activity and angiogenic potential in hPDL cell spheroids cultured in 3D. MATERIALS AND METHODS: Spheroids of primary human hPDL cells were generated in a rotational 3D culture system and treated with or without irisin. The gene expression patterns were evaluated by Affymetrix microarrays. The morphology of the spheroids was characterized using histological staining. Mechanical properties were quantified by nanoindentation. The osteogenic and angiogenic potential of spheroids were assessed through immunofluorescence staining for collagen type I, periostin fibronectin and von Willebrand factor (vWF), and mRNA expression of osteogenic markers. The secretion of multiple myokines was evaluated using Luminex immunoassays. RESULTS: Approximately 1000 genes were differentially expressed between control and irisin-treated groups by Affymetrix. Several genes related to ECM organization were differentially expressed, and multiple deubiquitinating enzymes were upregulated in the irisin-exposed samples analyzed. These represent cellular and molecular mechanisms indicative of a role for irisin in tissue remodeling. Irisin induced a rim-like structure on the outer region of the hPDL spheroids, ECM-related protein expression and the stiffness of the spheroids were enhanced by irisin. The expression of osteogenic and angiogenetic markers was increased by irisin. CONCLUSIONS: Irisin altered the morphology in primary hPDL cell-derived spheroids, enhanced its ECM deposition, mechanical properties, differentiation and remodeling potential.

Ovarian Cancer and Glutamine Metabolism.

Cancer cells are known to have a distinct metabolic profile and to exhibit significant changes in a variety of metabolic mechanisms compared to normal cells, particularly glycolysis and glutaminolysis, in order to cover their increased energy requirements. There is mounting evidence that there is a link between glutamine metabolism and the proliferation of cancer cells, demonstrating that glutamine metabolism is a vital mechanism for all cellular processes, including the development of cancer. Detailed knowledge regarding its degree of engagement in numerous biological processes across distinct cancer types is still lacking, despite the fact that such knowledge is necessary for comprehending the differentiating characteristics of many forms of cancer. This review aims to examine data on glutamine metabolism and ovarian cancer and identify possible therapeutic targets for ovarian cancer treatment.

From Classic Whipple to Pylorus Preserving Pancreaticoduodenectomy and Ultimately to Pylorus Resecting - Stomach Preserving Pancreaticoduodenectomy: A Review.

Pancreaticoduodenectomy is the procedure of choice for benign or malignant tumors of the periampullary region. The preservation of the pylorus has been established as the mostly utilized approach during pancreaticoduodenectomy among the majority of specialized, in the surgical treatment of pancreatic cancer, centers worldwide. The factors that influenced this predilection are the shorter operation times, the less intraoperative blood loss, the decreased technical difficulty, and the quite similar short- and long-term outcomes compared to the classic Whipple. However, there is a notable trend in the literature highlighting the increased incidence of delayed gastric emptying following pylorus preserving pancreaticoduodenectomy. Among other factors, pylorus dysfunction attributable to the surgical maneuvers has been implemented in the etiology of this complication. In an attempt to overcome this limitation of the pylorus preserving pancreaticoduodenectomy, pylorus resecting pancreaticoduodenectomy with the preservation of the stomach was proposed. In theory, pylorus resecting pancreaticoduodenectomy could maintain the advantages of organ sparing surgery, but at the same time guarantee a more seamless gastric emptying. Only three RCTs, to date, aimed to evaluate the approach with only one reporting results in favor of the pylorus resecting pancreaticoduodenectomy in regard to the incidence of delayed gastric emptying. Further well-designed prospective randomized studies are needed for an accurate assessment of the true role of each of these surgical alternatives on the treatment of pancreatic cancer.

Milligan-Morgan hemorrhoidectomy vs. hemorrhoid artery ligation and recto-anal repair: a comparative study.

BACKGROUND: Several surgical techniques for the treatment of hemorrhoidal disease (HD) have been proposed. However, the selection of the most proper technique for each individual case scenario is still a matter of debate. The purpose of the present study was to compare the Milligan-Morgan (MM) hemorrhoidectomy and the hemorrhoidal artery ligation and rectoanal repair (HAL-RAR) technique. METHODS: A retrospective analysis of the prospectively collected database of patients submitted to HD surgery in our department was conducted. Patients were divided into two groups, the MM group and the HAL-RAR group. Primary end points were recurrence rates and patients' satisfaction rates. The Unpaired t test was used to compare numerical variables while the x2 test for categorical variables. RESULTS: A total of 124 patients were identified, submitted either to HAL-RAR or MM hemorrhoidectomy. Eight (8) patients were lost to follow up and were excluded from the analysis. Of the remaining 116 patients, 69 patients (54 males and 15 females-male / female ratio: 3.6) with a median age of 47 years old (range 18-69) were included in the HAL-RAR group while 47 patients (40 males and 7 females-male / female ratio: 5.7) with a median age of 52 years old (range 32-71) comprised the MM group. At a median follow up of 41 months (minimum 24 months-maximum 72 months), we recorded 20 recurrences (28.9%) in the HAL-RAR group and 9 recurrences in the MM group (19.1%) (p 0.229). The mean time from the procedure to the recurrence was 14.1 ± 9.74 months in the HAL-RAR group and 21 ± 13.34 months in the MM group. Patients with itching, pain or discomfort as the presenting symptoms of HD experienced statistically significantly lower recurrences (p 0.0354) and reported statistically significantly better satisfaction rates (6.72 ± 2.15 vs. 8.11 ± 1.99-p 0.0111) when submitted to MM. In the subgroup of patients with bleeding as the presenting symptom, patients satisfaction rates were significantly better (8.59 ± 1.88 vs. 6.45 ± 2.70-p 0.0013) in the HAL-RAR group. CONCLUSIONS: In patients with pain, itching or discomfort as the presenting symptoms of HD, MM was associated with less recurrences and better patients satisfaction rates compared to HAL-RAR. In patients with bleeding as the main presenting symptom of HD, HAL-RAR was associated with better patients' satisfaction rates and similar recurrence rates compared to MM.

Maternal serum pregnancy-associated plasma protein-A concentration at 11-14 weeks of gestation and preeclampsia risk of women with common congenital anatomic uterine abnormalities.

To evaluate maternal serum pregnancy-associated plasma protein-A (PAPP-A) levels at 11-14 weeks of gestation and preeclampsia risk in women with common congenital anatomic uterine abnormalities (AUAs). First trimester screening markers were compared between 12 AUA pregnancies, 60 age matched controls and 12 cases of early preeclampsia. PAPP-A level and birth weight were significantly lower in AUA compared to control and early preeclampsia group (p<.001). Preeclampsia was absent in the AUAs pregnancies group. Birth weight were similar in AUA group when we compared AUA and control group regarding weeks of gestation at delivery and lower but not significantly, when we compared AUA and early preeclampsia group. Our findings suggest that AUA pregnancies are associated with low first trimester maternal serum PAPP-A concentrations not predictive of susceptibility to preeclampsia.Impact statementWhat is already known on this subject? During first trimester screening for preeclampsia based on maternal pregnancy-associated plasma protein A (PAPP-A) levels, various parameters are used, such as the somatometric characteristics of pregnant woman, single or multiple pregnancy, smoking status, family history, diabetes, hypertension and measurement of blood pressure and uterine artery Dopplers.What do the results of this study add? Our pioneer study revealed that there is drastic difference in PAPP-A concentration in women with common anatomic uterine abnormalities (AUAs), in comparison with their age matched control women with normal uterus.What are the implications of these findings for clinical practice and further research? Based on our results, uterine anatomical deviations, is another factor which must be taken in account for preeclampsia risk calculation and further clinical consultation and follow up in those pregnancies. Lower PAPP-A levels in AUA cases is a weak predictor of susceptibility to preeclampsia and could be associated to smaller placental size rather than poor placentation and in future research the calculation of the uterine cavity functional dimension may lead to a more accurate clinical assessment.

The role of alginate dressings in wound healing and quality of life after pilonidal sinus resection: A randomised controlled trial.

In this trial, we evaluated the role of alginate dressings in the secondary intention wound healing and quality of life (QoL) after pilonidal sinus resection. The study was designed as a prospective randomised controlled trial (RCT). In the experimental group, alginate dressings with silver and high-G cellulose were introduced after elective pilonidal cyst excision, whereas in the control group, simple gauges were used. The primary end point was the difference in terms of the wound healing period. Blinding existed at the level of the investigator. Overall, 65 patients were included during the study period. Wound healing duration was comparable between the two groups (P = .381). No difference in postoperative pain scores or recovery outcomes was found. The experimental group was associated with reduced wound secretions at specific time end points. Similarly, no effect was identified, on overall Wound-QoL or SF-36 scores. Alginate dressings do not accelerate wound healing or improve QoL. Due to suboptimal sample size and several study limitations, further RCTs are required to confirm our findings.

Bioinformatic Analysis of the BCL-xL/BCL2L1 Interactome in Patients with Pancreatic Cancer.

Objectives: The aim of the present study was to analyze the differential gene expression of BCL-xL/BCL2L and the associated genetic, molecular, and biologic functions in pancreatic ductal adenocarcinoma (PDAC) by employing advanced bioinformatics to investigate potential candidate genes implicated in the pathogenesis of PDAC. Materials and Methods: Bioinformatic techniques were employed to build the gene network of BCL-xL, to assess the translational profile of BCL-xL in PDAC, assess its role in predicting PDAC, and investigate the associated biologic functions and the regulating miRNA families. Results: Microarray data extracted from one dataset was incorporated, including 130 samples (PDAC: 69; Control: 61). In addition, the expression level of BCL-xL was higher in PDAC compared to control samples (p < 0.001). Furthermore, BCL-xL demonstrated excellent discrimination (AUC: 0.83 [95% Confidence Intervals: 0.76, 0.90]; p < 0.001) and calibration (R squared: 0.31) traits for PDAC. A gene set enrichment analysis (GSEA) demonstrated the molecular functions and miRNA families (hsa-miR-4804-5p, hsa-miR-4776-5p, hsa-miR-6770-3p, hsa-miR-3619-3p, and hsa-miR-7152-3p) related to BCL-xL. Conclusions: The current findings unveil the biological implications of BCL-xL in PDAC and the related molecular functions and miRNA families.

Surgical Repair of Iatrogenic Duodenal Injuries with a Roux-en-Y Duodenojejunostomy: A Physiology-oriented Approach.

Introduction: Iatrogenic duodenal injuries represent a condition associated with high morbidity and even mortality. Management is still controversial with a lack of consensus among experts regarding the optimal treatment. The purpose of the present study was to test and assess the results of a certain reconstruction technique. Material and Methods: Four patients (2 males and 2 females) of a mean age of 83 years with iatrogenic duodenal injuries underwent surgical repair of the duodenal perforation, with a two-layer duodenojejunostomy and a Roux-en-Y jejunal loop. Results: Three out of four patients (75%) had a rapid and uncomplicated recovery (13 days mean postoperative length of hospital stay), while the fourth patient died in the ICU due to ARDS three weeks later, without however evidence of anastomotic leak. Conclusion: A variety of surgical repair techniques have been proposed to date; however, with controversial results. A repair using an isolated jejunal Roux-en-Y loop seems to fulfill all the optimal prerequisites for a successful anastomotic outcome and proved efficient in its certain form for the given patient sample.

Intraoperative neuromonitoring in rectal cancer surgery: a systematic review and meta-analysis.

PURPOSE: The aim of this study is to evaluate the role of pelvic intraoperative neuromonitoring (pIONM) in rectal cancer surgery. METHODS: A systematic review of the literature and a meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Overall, nine studies were identified. Quantitative analysis was performed only in three trials. Bilateral pIONM improved postoperative anorectal and urogenital functional outcomes. However, unilateral pIONM displayed a significant effect only on erectile function (p = 0.001). CONCLUSIONS: Our findings suggest a positive effect of pIONM on postoperative functional outcomes and quality of life after rectal cancer surgery. Due to several limitations, further trials are required in order to elucidate the exact role of pIONM.

Cervical Twin Heterotopic Pregnancy: Overview of Ectopic Pregnancies and Scanning Detection Algorithm.

Background: Ectopic pregnancy is the leading cause of gestation-related deaths during the first trimester. Cervical twin heterotopic pregnancies, when ectopic, constitute a small and rare part of gynecological surgery. Case Presentation: A 30-year-old pregnant woman (gravida 3, para 2) presented with mild pain in the lower abdomen and traces of bleeding per vaginum for three days. Transvaginal ultrasonography revealed a balloon-shaped cervical canal with a visible gestational sac measuring 3.5 × 3.9 cm. A second gestational sac was seen in the uterine cavity. The measurements of the gestational sacs corresponded to 7 + 4 weeks' pregnancy. A decision for medical abortion with mifepristone and misoprostol was made. However, due to an incomplete abortion and continuous bleeding, a curettage was performed. Conclusions: Spontaneous heterotopic pregnancy with the ectopic pregnancy located in the cervix is an extremely rare clinical condition requiring urgent treatment in order to reduce maternal mortality and morbidity and preserve fertility.

Reaching the Challenging Diagnosis of Complicated Liver Hydatid Disease: A Single Institution's Experience from an Endemic Area.

Background and Objectives: Hydatid disease (HD) remains a significant public health issue causing morbidity and mortality in many Mediterranean countries. Material and Methods: The present cohort study included 50 consecutive patients with liver hydatid disease who underwent surgery in a tertiary University Hospital. A total of 18 patients (36%) had a case of complicated HD, including simple communication of the cyst with the biliary tree (6 cases), rupture of the cyst into the biliary tree (6 cases), presence of a bronco-biliary fistula (2 cases), rupture of the cyst in the peritoneal cavity (2 cases), and rupture of the cyst and formation of a hepatic abscess (2 cases). Endoscopic retrograde cholangiopancreatography (ERCP) was pre-operatively performed on six patients. Results: The main clinical symptom presented was right upper quadrant pain in 16 patients (88%), which was associated with high fever (>39 °C) in 14 patients (78%). C-reactive protein (CRP) was the primary indicator of a complicated HD (p = 0.003); however, it was only elevated in 67% of cases. CRP was a more sensitive indicator of a rupture in the biliary tree cyst (p = 0.02). Computer tomography (CT) detected more cases (44%) of a complicated HD than ultrasonography (US) (25%); however, the difference was not statistically significant. Conclusions: For prevention and control of HD, a high suspicion of the disease leading to early referral to specialized centers, mainly in endemic areas, is required. Prior to surgical or percutaneous intervention, a combination of imaging and laboratory findings are essential in diagnosing a complicated case and avoiding unnecessary interventions.

Iatrogenic Bile Duct Injuries: A Critical Appraisal of Classification Systems.

Bile duct injuries represent the most dramatic complications after an open or laparoscopic cholecystectomy. The detrimental effects on patient quality of life and overall survival are the most obvious consequences of such injuries. An effective treatment strategy after accurate mapping of the injury type is the only method of averting these morbid consequences. Several classification systems have been proposed in an attempt to accurately describe and categorize bile duct injuries. The critical question is whether we truly need all these systems and whether each of these systems adds value to the existing knowledge base, or further obscures the field. Each classification system has several advantages to base its clinical utility on, but entails a reasonable number of limitations as well. Currently, a tailored approach adopting the classification system which provides the most appropriate guidance - either in terms of diagnosis or treatment decision making - appears to be the most justified option.

Altered expression of 3-betahydroxysterol delta-24-reductase/selective Alzheimer's disease indicator-1 gene in Huntington's disease models.

INTRODUCTION: 3-betahydroxysterol delta-24-reductase (DHCR24), also called selective Alzheimer's disease indicator-1, is a crucial enzyme in cholesterol biosynthesis with neuroprotective properties that is downregulated in brain areas affected by Alzheimer's disease. AIM: In the present study, we investigated modifications of DHCR24 expression in models of Huntington's disease (HD), a neurodegenerative disorder caused by a polyglutamine expansion in huntingtin (Htt) protein that induces degeneration of cerebral cortex and striatum as well as lateral hypothalamic abnormality. METHODS: Basal expression of DHCR24 and its modulation after oxidative stress were evaluated in rat striatal precursors cells (ST14A) transfected with wild-type (Htt) or mutant Htt (mHtt) and in brain tissue of an HD mouse model (R6/2). RESULTS: The results showed that DHCR24 transcript levels were decreased in ST14A cells expressing mHtt and in the brain of symptomatic R6/2 mice, but were significantly increased in ST14A cells overexpressing wild-type Htt. In addition, we demonstrated that, in the striatal precursors, the decrease of DHCR24 expression in response to oxidative stress was modified according to the presence of Htt or of its mutant form. Preliminary results indicated a modification of DHCR24 expression in post-mortem brain samples of HD patients. CONCLUSIONS: In conclusion, these results support the hypothesis of a possible role of DHCR24 in HD.

In need of robust evidence of non-association of pregestational and early pregnancy SARS-CoV-2 infections with congenital anomalies.

SARS-CoV-2 infection during pregestational and early pregnancy periods has an unclear impact on fetal development. Although vertical transmission is rare, potential effects on the developing fetal brain are plausible. However, robust evidence linking maternal SARS-CoV-2 infection to congenital anomalies is limited due to inadequate tracking of infection history and methodological flaws in published studies. This is further complicated by limitations, such as restricted testing access and undiagnosed infections, particularly in low- and middle-income countries. Most data focus on hospitalized women near term, lacking information on first- and second-trimester infections. Thus, an accurate assessment of the impact of COVID-19 on congenital anomalies is essential. It should however be emphasised that we have robust evidence that vaccination against COVID-19 before or during early pregnancy is not associated with malformations, ruling out any role of COVID-19 vaccines in these increased rates of congenital abnormalities. This viewpoint discusses findings from surveillance registries, highlights study limitations, and offers research recommendations to inform clinical guidelines and public health strategies, aiming to mitigate the effects of viral infections on early neurodevelopment.

Protocol to dissect and dissociate the mouse brainstem for single-cell RNA-seq applications.

Processing dissociated cells for transcriptomics is challenging when targeting small brain structures, like brainstem nuclei, where cell yield may be low. Here, we present a protocol for dissecting, dissociating, and cryopreserving mouse brainstem that allows asynchronous sample collection and downstream processing of cells obtained from brainstem tissue in neonatal mice. Although we demonstrate this protocol with the isolated preBötzinger complex and downstream SmartSeq3 cDNA library preparation, it could be readily adapted for other brainstem areas and library preparation approaches.

Pregnant women and measles: we need to be vigilant during outbreaks.

A number of countries including the UK are currently experiencing large outbreaks of measles affecting mainly young children but also adolescents and young adults. Women of childbearing age are a particular group of concern because the 1988 Wakefield Lancet paper, which falsely asserted a connection between the MMR vaccine and autism, was associated with a large and sharp decline in childhood MMR uptake over several years. This has left large cohorts of non-immune adolescents and young adults (born between 1998 and 2004), including young women who are now of childbearing age and remain susceptible to measles as well as rubella. Pregnant mothers are at higher risk of serious complications, such as pneumonia, with adverse pregnancy complications including fetal loss, premature birth, and neonatal death. Measles infection may also result in subacute sclerosing panencephalitis (SSPE), a very rare but very severe and invariably fatal neurodegenerative complication that typically manifests many years after acute measles infection but can have a short-onset latency with a fulminant course in pregnant women. Here, we summarise the epidemiology of measles infection, factors associated with the current measles outbreaks, as well as the risks and outcomes of measles, including SSPE, in pregnancy. We propose an algorithm for clinical management of measles infection in pregnancy. We also highlight the importance of early liaison with local health protection teams for risk assessment, diagnosis and management of suspected measles in pregnancy and close contacts as well as susceptible pregnant women exposed to a person with measles in the community.

Recent increase in infant pertussis cases in Europe and the critical importance of antenatal immunizations: We must do better now.

Recent months have seen an increase in pertussis cases in several countries across the Northern and Southern hemispheres. The lack of immune stimulation during the COVID-19 pandemic due to the reduced circulation of Bordetella pertussis, the pathogen responsible for pertussis, is likely to have led to increased population susceptibility which has been magnified the typical three to five yearly cyclical peaks in activity. Maternal immunization for pertussis proves highly effective in protecting infants under three months of age. It's also critical for immunizers and parents to maintain high and timely immunization uptake to ensure infants receive maximum early protection when they are most at risk of severe disease.