Pancreatic neuroendocrine tumor progression and resistance to everolimus: the crucial role of NF-kB and STAT3 interplay.

PURPOSE: The finding of mTOR overactivation in patients affected by pancreatic neuroendocrine tumors (Pa-NETs) led to their treatment with the mTOR inhibitor everolimus. Unfortunately, the efficacy of everolimus is restricted by the occurrence of resistance. The mechanisms leading to Pa-NETs' progression and resistance are not well understood. Notably, chronic inflammation is implicated in NET development. NF-kB is involved in inflammation and drug resistance mechanisms through the activation of several mediators, including STAT3. In this respect, NF-κB and STAT3 interaction is implicated in the crosstalk between inflammatory and tumor cells. METHODS: We investigated the expression of NF-kB in different Pa-NETs by RT-qPCR and immunohistochemistry. Then, we studied the role of NF-κB and STAT3 interplay in QGP-1 cells. Subsequently, we assessed the impact of NF-κB and STAT3 inhibitors in QGP-1 cell proliferation and spheroids growth. Finally, we evaluated the implication of the NF-kB pathway in everolimus-resistant Pa-NET cells. RESULTS: We found that the increased NF-kB expression correlates  with a higher grade in Pa-NETs. The activation of the STAT3 pathway induced by TNFα is mediated by NF-kB p65. NF-kB p65 and STAT3 inhibitors decrease QGP-1 viability, spheroids growth, and Pa-NETs cell proliferation. These effects are maintained in everolimus-resistant QGP-1R cells. Interestingly, we found that NF-kB, STAT3, IL-8, and SOCS3 are overexpressed in QGP-1R compared to QGP-1. CONCLUSION: Since the NF-kB pathway is implicated in Pa-NETs' progression and resistance to everolimus, these data could explain the potential use of NF-kB as a novel therapeutic target in Pa-NET patients.

SARS-CoV-2 detection in primary thyroid sarcoma: coincidence or interaction?

INTRODUCTION: Thyroid dysfunctions associated with SARS-CoV-2 are emerging in scientific literature. During the second COVID-19 epidemic spread, we evaluated a patient with the suspect of subacute thyroiditis. METHODS AND RESULTS: Specimen from fine-needle aspiration of a hypoechoic undefined area was analyzed for cytology and for SARS-CoV-2 detection. SARS-CoV-2 was retrieved by real-time polymerase chain reaction on the cytologic sample, which was then cultured on Vero E6 cells and demonstrated to be cytopathic. Whole-genome sequence was deposited. Histological exam diagnosed a rare case of primary thyroid sarcoma with diffuse and strong expression of mouse double minute 2 homolog (MDM2) oncoprotein. Ultrastructural examination confirmed, in several neoplastic cells, the presence of viral particles in cytoplasmic vacuoles. CONCLUSIONS: In our hypothesis, SARS-CoV-2 and sarcoma coexistence could represent a synergistic interplay, ultimately favoring both viral persistence and tumor proliferation: the overexpression of MDM2 in tumor cells might have generated a favorable immunological niche for SARS-CoV-2 localization and, in turn, SARS-CoV-2 could have favored tumor growth by inducing MDM2-mediated p53 downregulation. Functional studies are needed to confirm this suggestive pathway.

The Large Uterus Classification System: a prospective observational study.

OBJECTIVE: To investigate the Large Uterus Classification System (LUCS) ability to predict surgical outcomes and complications in total laparoscopic hysterectomies (TLHs) for large uteri. DESIGN: Prospective observational study. SETTING: Two referral centres. POPULATION OR SAMPLE: Three hundred and ninety-two women who underwent TLH for a large uterus (uterine fundus at or over the transverse umbilical line). METHODS: Between 2004 and 2019, the intraoperative LUCS was estimated in all patients. The LUCS considers the uterine and adnexal vascular pedicles displacement. Type 1 is without vascular pedicles displacement. Type 2 has the cephalad displacement of adnexal vascular pedicles. The uterine vessels displacement regardless of adnexal pedicles defines Type 3. MAIN OUTCOME MEASURES: Patients' characteristics with perioperative outcomes were prospectively collected and compared between the three types of large uteri. RESULTS: Two hundred and fifty-one (64%), 82 (20.9%) and 59 (15.1%) women had Type 1, Type 2 and Type 3 uteri, respectively. Women with Type 1 uteri had a lower uterine weight, shorter operative time, less blood loss and lower complication rates than women with Types 2 and 3. The conversion rate to laparotomy in Type 1 was similar to that in Type 2 (odds ratio [OR] 0.98; 95% CI 0.32-3.56) but lower than Type 3 (OR 0.35; 95% CI 0.14-0.97); in Type 2 it was lower than Type 3, although without the conventional statistical significance (OR 0.36; 95% CI 0.13-1.13; P = 0.07). Multivariable analysis showed that the uterine Type (1 versus 2-3) was independently associated with the total complications rate (OR 2.00; 95% CI 1.09-3.68; P = 0.02). CONCLUSIONS: The LUCS appears associated with surgical outcomes and complications, potentially stratifying the surgical risk and guiding the surgical technique in TLHs for large uteri. TWEETABLE ABSTRACT: The Large Uterus Classification System may predict outcomes in total laparoscopic hysterectomy of large uteri.

Predictors of recurrence following laparoscopic radical hysterectomy for early-stage cervical cancer: A multi-institutional study.

OBJECTIVE: To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). METHODS: This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. RESULTS: 428 patients were included in the analysis. With a median follow-up of 56 months (1-162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01-1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34-20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11-0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01-1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58-24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12-0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13-0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39-17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. CONCLUSIONS: In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.

Robotic Single-Port Platform in General, Urologic, and Gynecologic Surgeries: A Systematic Review of the Literature and Meta-analysis.

BACKGROUND: Robotic platforms have recently acquired progressive importance in different surgical fields, such as urology, gynecology, and general surgery. Through the years, new surgical robots have become available as single-port robotic platform. The study is aimed to value the single-port robotic platform characteristics in different surgical specialties. METHODS: The terms "LESS" OR "single port" OR "single site" AND "robot" OR "robotic" were systematically used to search the PubMed and Scopus databases. A total of 57 studies were considered eligible for the present review. The articles included were divided according to the surgical field in which the study was conducted: General surgery (29 articles), Gynecology (18 articles), Urology (10 articles). RESULTS: Most part of the articles showed the feasibility of robotic single-port surgical procedures and described advantages in terms of cosmetic, hospital stay, and in some series even cost reduction. A meta-analysis was conducted, showing a significant increment of complications using RSP if compared with SLPS and a trend (P = 0.008) when RSP was compared with LESS. The comparison of different techniques in terms of conversion to laparotomy did not show any significant difference. CONCLUSION: Robotic single port potentially furnishes an important surgical and post-operatory improvement; however, some limits still prolong the surgical time and complication rate.

Total laparoscopic hysterectomy for enlarged uteri: factors associated with the rate of conversion to open surgery.

A hysterectomy for enlarged uteri is considered a challenge for gynaecologic surgeons, due to the limit of exposure to surgical spaces. Our objective is to investigate the different variables that may have an impact on the risk of conversion to open surgery. This is a retrospective cohort study consisting of 133 women who were submitted to surgery for uterine fibroids and who underwent total hysterectomy by laparoscopic approach attempt. The median uterus weight was 622 grams (range 301-3882) and the median maximum diameter of the bigger fibroid was 74 mm (range 33-148). We registered 13 (9.8%) cases of conversion to laparotomy. Minor and major post-operative complications were recorded in 4 (3%) and in 4 (3%) cases, respectively. After multivariable analysis, the surgeon's experience (OR: 0.24; 95% CI: 0.06-0.94, p = .027) and a maximum diameter of the biggest fibroid ≥10 cm (4.7; 1.39-15.87; p = .046), but not the uterus weight were associated with the risk of conversion to open surgery. IMPACT STATEMENT What is already known on this subject? Laparoscopic procedures for enlarged uteri are well described in literature; however, the only parameters that have been studied for the success of a laparoscopic procedure have been the uterus weight and the surgeon's experience. What do the results of this study add? This study aimed to value all the possible variables related to the successful of laparoscopic procedures; in fact, we investigated not only the uterine weight, but in our multivariate analysis, the position of the fibroids, the trocar's setting, etc. were analysed. What are the implications of these findings for clinical practice and/or further research? This study reported novel data about the feasibility of laparoscopic hysterectomy for enlarged uteri. In opposition to the literature, the uterine weight is not a predictive value for laparotomic conversion. Moreover, we discussed the possible reasons of our novel findings. It opens new perspective to create a predictive value of laparoscopic feasibility for the different types of enlarged uteri.

Transvaginal contained tissue extraction after laparoscopic myomectomy: a cohort study.

OBJECTIVE: To describe the technique and report perioperative outcomes of transvaginal contained extraction of surgical specimens at laparoscopic myomectomy. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Two Italian referral centres for gynaecological minimally invasive surgery. POPULATION: Consecutive patients who underwent laparoscopic myomectomy. METHODS: Tissue extraction was accomplished following laparoscopic myomectomy in a specimen retrieval bag via a posterior colpotomy incision. If morcellation was necessary, this was performed extracorporeally, using a scalpel within the specimen retrieval pouch, whose edges were exteriorised through the vaginal introitus. MAIN OUTCOME MEASURES: Intra- and postoperative complications. RESULTS: A total of 316 women underwent transvaginal specimen retrieval with enclosed manual morcellation. The mean myomectomy specimen weight was 154 ± 128 g, and the mean operative time was 79 ± 26 minutes. No intraoperative complications occurred related to the specimen extraction or morcellation technique, or from rupture of the retrieval bag. Two (0.6%) women had a haemoperitoneum that spontaneously resolved and 16 (5.1%) had fever postoperatively. The final pathological diagnosis was benign in all cases. At the 30-day follow-up, no pelvic infection, vaginal dehiscence, or complaints of dyspareunia were recorded. CONCLUSIONS: Contained transvaginal extraction of fibroid specimens can be performed safely and efficiently in most women undergoing laparoscopic myomectomy. This technique represents a valuable minimally invasive alternative to intracorporeal morcellation. TWEETABLE ABSTRACT: Transvaginal contained morcellation at laparoscopic myomectomy is a valuable alternative to intracorporeal morcellation.

Endometrial cancer cells can express fibrinogen: Immunohistochemistry and RT-PCR analysis.

We investigated whether endometrial cancer (EC) cells can express fibrinogen. Consecutive patients treated for EC were enrolled (cases). A control group of women who had hysterectomy for benign conditions was identified in a case:control ratio of 4:1. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were performed to identify the presence of fibrinogen and the mRNA of its three chains (α, ß, γ) in the tissue specimens from both cases and controls. Sixteen EC cases and 4 benign controls were included. Immunohistochemistry failed in one case of EC. In 12/15 (80%) cases versus 0 controls, a moderate-to-intense positivity for fibrinogen was observed (p = 0.09; OR: 32.1; 95%CI: 1.4-752.9). Six (37.5%) women among the cases versus 0 controls expressed RNA for at least one chain of fibrinogen (p = 0.25). All the cases (6/6, 100%) with positive RT-PCR had moderate-to-intense positive immunohistochemistry. Molecular and immunohistochemistry show that some cases of EC have the capability to express fibrinogen and the mRNA of at least one of its chains.

Mini-laparoscopic Sentinel Node Detection in Endometrial Cancer: Further Reducing Invasiveness for Patients with Early-Stage Disease.

BACKGROUND: Lymphatic mapping and sentinel lymph node (SLN) biopsy have been proposed as a safer and less morbid approach than full lymphadenectomy for patients with early endometrial cancer (EC), through either cervical or corporeal dye injection.1 (-) 4 The advantage of mini-laparoscopy is a further reduction in the overall surgical trauma for the patient. This video aims to show the feasibility of SLN biopsy using a 3-mm mini-laparoscopic approach. METHODS: A 56-year-old woman with grade 2 endometrioid EC underwent mini-laparoscopic pelvic SLN detection plus extrafascial total hysterectomy and bilateral salpingo-oophorectomy (TLH-BSO). A two-sided superficial and deep cervical injection of indocyanine green (2 mL diluted to 1.25 mg/mL) was used for inoculation before the procedure. A 5.8-mm 0° optical camera with a near-infrared high-intensity light source for detection of fluorescence imaging was inserted through the umbilicus. Two ancillary 3-mm trocars were inserted suprapubically. The procedure was accomplished using only 3-mm instruments. RESULTS: Neither intraoperative complications nor conversion to conventional laparoscopy or open surgery occurred. The operative time was 60 min, and the estimated blood loss was 50 mL. SLN was detected bilaterally, and removal of the two identified nodes was achieved through meticulous dissection and preservation of the surrounding structures followed by TLH-BSO. No postoperative complications were registered, and the patient was discharged 24 h after surgery. An SLN ultrastaging exam was negative, and the final pathology showed a International Federation of Gynaecology and Obstetrics (FIGO) stage 1A G2 EC with a 2/21-mm myometrial invasion. CONCLUSION: Mini-laparoscopic SLN detection plus TLH-BSO is a feasible procedure that guarantees minimal surgical trauma to selected patients with early EC.

Interobserver reliability to interpret intrapartum electronic fetal heart rate monitoring: Does a standardized algorithm improve agreement among clinicians?

Our aim was to investigate the accuracy in predicting intrapartum fetal acidaemia and the interobserver reproducibility of a mathematical algorithm for the interpretation of electronic fetal heart rate (FHR) monitoring throughout labour. Eight physicians (blinded to the clinical outcomes of the deliveries) evaluated four randomly selected intrapartum FHR tracings by common visual interpretation, trying to predict umbilical artery base excess at birth. They subsequently were asked to re-evaluate the tracings using a mathematical algorithm for FHR tracing interpretation. Common visual interpretation allowed a correct estimation of the umbilical artery base excess in 34.4% of cases, with a poor interobserver reproducibility (Kappa correlation coefficient = 0.24). After implementation of the algorithm, the proportion of correct estimates significantly increased to 90.6% (p < 0.001), with excellent inter-clinician agreement (κ: 0.85). To conclude, incorporation of a standardised algorithm reduces the interobserver variability and allows a better estimation of fetal acidaemia at birth.

Laparoscopic staging of apparent early stage ovarian cancer: results of a large, retrospective, multi-institutional series.

OBJECTIVE: The aim of this study is to analyze the safety, adequacy, perioperative and survival figures in a large series of laparoscopic staging of patients with apparent early stage ovarian malignancies (ESOM). PATIENTS AND METHODS: Retrospective data from seven gynecologic oncology service databases were searched for ESOM patients undergoing immediate laparoscopic staging or delayed laparoscopic staging after an incidental diagnosis of ESOM. Between May 2000 and February 2014, 300 patients were selected: 150 had been submitted to immediate laparoscopic staging (Group 1), while 150 had undergone delayed laparoscopic staging (Group 2) of ESOM. All surgical, pathologic, and oncologic outcome data were analyzed in each group and a comparison between the two was carried out. RESULTS: Longer operative time, higher blood loss, more frequently spillage/rupture of ovarian capsule and conversion to laparotomy occurred in Group 1. No significant differences of post-operative complications were observed between the two groups. Histological data revealed more frequently serous tumors (0.06), Grade 3 (p=0.0007) and final up-staging (p=0.001) in Group 1. Recurrence and death of disease were documented in 25 (8.3%), and 10 patients (3.3%%), respectively. The 3-year disease free survival (DFS) and overall survival (OS) rates were 85.1%, and 93.6%, respectively in the whole series. There was no difference between Group 1 and Group 2 in terms of DFS (p value=0.39) and OS (p value=0.27). CONCLUSION: In this very large multi-institutional study, it appears that patients with apparent ESOM can safely undergo laparoscopic surgical management.

Herpesviruses and breast milk. / Herpesvirus e latte materno

Breast milk has always been the best source of nourishment for newborns. However, breast milk can carry a risk of infection, as it can be contaminated with bacterial or viral pathogens. This paper reviews the risk of acquisition of varicella-zoster virus (VZV) and cytomegalovirus (CMV), herpesviruses frequently detected in breastfeeding mothers, via breast milk, focusing on the clinical consequences of this transmission and the possible strategies for preventing it. Maternal VZV infections are conditions during which breastfeeding may be temporarily contraindicated, but expressed breast milk should always be given to the infant. CMV infection acquired through breast milk rarely causes disease in healthy term newborns; an increased risk of CMV disease has been documented in preterm infants. However, the American Academy of Pediatrics (AAP) does not regard maternal CMV seropositivity as a contraindication to breastfeeding; according to the AAP, in newborns weighing less than 1500 g, the decision should be taken after weighing the benefits of breast milk against the risk of transmission of infection. The real efficacy of the different methods of inactivating CMV in breast milk should be compared in controlled clinical trials, rigorously examining the negative consequences that each of these methods can have on the immunological and nutritional properties of the milk itself, with a view to establish the best risk-benefit ratio of these strategies before they are recommended for use in clinical practice.

Intake of coffee, caffeine and other methylxanthines and risk of Type I vs Type II endometrial cancer.

BACKGROUND: Coffee and other sources of methylxanthines and risk of Type I vs Type II endometrial cancer (EC) have not been evaluated previously. METHODS: Prospective cohort of 23,356 postmenopausal women with 471 Type I and 71 Type II EC cases. RESULTS: Type I EC was statistically significantly associated with caffeinated (relative risk (RR)=0.65 for 4+ cups per day vs ≤1 cup per month: 95% confidence interval (CI): 0.47-0.89) but not decaffeinated (RR=0.76; 95% CI: 0.50-1.15) coffee intake; there were no associations with tea, cola or chocolate, or for Type II EC. The inverse association with caffeinated coffee intake was specific to women with a body mass index 30+ kg m(-2) (RR=0.56; 95% CI: 0.36-0.89). CONCLUSION: Coffee may protect against Type I EC in obese postmenopausal women.

[Management of outbreaks of nosocomial pathogens in neonatal intensive care unit]. / Gestione degli eventi epidemici in Terapia Intensiva Neonatale.

Outbreaks of nosocomial pathogens are one of the most relevant problems in Neonatal Intensive Care Unit (NICU). Many factors contribute to the onset of an epidemic, including virulence of the pathogen and vulnerability of the infants hospitalized in NICU. Outbreaks are often caused by multidrug-resistant organisms (MDROs). MDROs are defined as microorganisms, predominantly bacteria, that are resistant to one or more classes of antimicrobial agents. MDROs, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and certain gram-negative bacilli (GNB), have important infection control implications. Once MDROs are introduced into a healthcare setting, transmission and persistence of the resistant strain is determined by the availability of vulnerable patients, selective pressure exerted by antimicrobial use, increased potential for transmission from larger numbers of infected or colonized patients ("colonization pressure"), and the impact of adherence to prevention efforts. Often, routine infection control measures are not enough to contain outbreaks, and additional control measures are needed, including implementation of hand hygiene, cohorting of infected/colonized infants, neonatal surveillance cultures, screening of healthcare workers and decolonization of neonates and/or healthcare workers in selected cases. In this review, we report the practices we developed in our NICU to contain an epidemic. These recommendations reflect the experience of the group, as well as the findings of the current literature.

Primary cutaneous interdigitating dendritic cell sarcoma (IDCS): Report of a new case and literature review.

Interdigitating dendritic cell sarcoma is a very rare entity in the spectrum of histiocytic and dendritic cell neoplasms that mostly occurs in lymph nodes, generally presenting as solitary lymphadenopathy, but may affect every organ. Among extra nodal sites, cutaneous interdigitating dendritic cell sarcoma is exceedingly rare; to date, only 9 cases have been described in English literature. The mean age at diagnosis was 60 years, with a male-female ratio of 1,5 to 1; clinically, two different modalities of skin presentation have been reported: solitary, represented by a single red-brownish nodular lesion, or diffuse, characterized by multiple nodular lesions in one or more body districts. The extreme rarity of this sarcoma and its morphological similarity to other poorly differentiated tumors may lead to a delay in diagnosis; in particular, cutaneous localization may be difficult to differentiate from follicular dendritic cell sarcoma, Langerhans cell sarcoma, poorly differentiated squamous cell carcinoma and more generally sarcomatoid carcinoma, atypical fibroxanthoma, malignant melanoma and several sarcomas. Immunohistochemistry plays an important role in identifying this rare entity and formulating a correct histological diagnosis, fundamental requirement for choosing the best therapeutic approach. We report herein a further case of an 81-year-old Caucasian woman who presented to the Dermatology Department to remove an asymptomatic skin papule in the left temporal region, clinically diagnosed as dermatofibroma. The overall pathological and immunohistochemical features supported the diagnosis of a malignant dendritic cell tumor, consistent of interdigitating dendritic cell sarcoma.

Clinical and molecular characterization of diffuse large B-cell lymphomas with 13q14.3 deletion.

BACKGROUND: Deletions at 13q14.3 are common in chronic lymphocytic leukemia and are also present in diffuse large B-cell lymphomas (DLBCL) but never in immunodeficiency-related DLBCL. To characterize DLBCL with 13q14.3 deletions, we combined genome-wide DNA profiling, gene expression and clinical data in a large DLBCL series treated with rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21 days (R-CHOP21). PATIENTS AND METHODS: Affymetrix GeneChip Human Mapping 250K NspI and U133 plus 2.0 gene were used. MicroRNA (miRNA) expression was studied were by real-time PCR. Median follow-up of patients was 4.9 years. RESULTS: Deletions at 13q14.3, comprising DLEU2/MIR15A/MIR16, occurred in 22/166 (13%) cases. The deletion was wider, including also RB1, in 19/22 cases. Samples with del(13q14.3) had concomitant specific aberrations. No reduced MIR15A/MIR16 expression was observed, but 172 transcripts were significantly differential expressed. Among the deregulated genes, there were RB1 and FAS, both commonly deleted at genomic level. No differences in outcome were observed in patients treated with R-CHOP21. CONCLUSIONS: Cases with 13q14.3 deletions appear as group of DLBCL characterized by common genetic and biologic features. Deletions at 13q14.3 might contribute to DLBCL pathogenesis by two mechanisms: deregulating the cell cycle control mainly due RB1 loss and contributing to immune escape, due to FAS down-regulation.

Prediction of fetal base excess values at birth using an algorithm to interpret fetal heart rate tracings: a retrospective validation.

OBJECTIVE: To evaluate whether a standardised algorithm to interpret fetal heart rate (FHR) tracings during the entire length of labour can predict umbilical artery base excess at birth, and to investigate its inter- and intra-observer reproducibility. DESIGN: Retrospective study. SETTING: Obstetrics and gynaecology department at a tertiary referral centre in a university hospital. POPULATION: Group 1: 152 consecutive, generally low-risk, labouring women. Group 2: mixed group of 30 women who delivered a fetus with pH < 7.00 and 30 women who delivered a fetus with pH ≥ 7.00. METHODS: Intrapartum FHR tracings were retrospectively and blindly evaluated by two independent assessors using an algorithm proposed by Ross and Gala to predict fetal base excess at birth. MAIN OUTCOME MEASURES: The accuracy in predicting the base excess values of newborns was expressed as the proportion of FHR tracings in which the operator was able to correctly calculate the actual base excess at birth (approximation of ± 2 mmol/l). Inter- and intra-observer reproducibility were estimated using the Pearson correlation coefficient. RESULTS: In the group of 152 low-risk labouring women, the two assessors correctly predicted the umbilical artery base excess in 73.1 and 76.3% of cases, respectively. Inter-observer (Pearson correlation coefficient = 0.75) and intra-observer (Pearson correlation coefficient = 0.80 and 0.82 for the first and second assessor, respectively) reproducibility was very good. In the 30 fetuses that were acidemic, the first and second observers correctly predicted base excess values in 23 (76.7%) and 21 (70%) cases, respectively (inter-observer reproducibility, Pearson correlation coefficient = 0.72). CONCLUSIONS: The algorithm proposed by Ross and Gala may be a valuable tool to estimate changes in umbilical base excess during active labour, with a high inter- and intra-observer reproducibility.

Dietary and supplemental intake of one-carbon nutrients and the risk of type I and type II endometrial cancer: a prospective cohort study.

BACKGROUND: Type I and II endometrial cancer are biologically and clinically distinct, with type II cancers having a high frequency of p53 mutations and an association with chromosomal instability. This raises the hypothesis that one-carbon nutrients (folate, methionine, and the enzymic cofactors vitamins B2, B6, and B12), which mediate chromosomal stability and DNA methylation, may be protective for type II but not type I endometrial cancer. METHODS: Using a prospective cohort of 23 356 postmenopausal women followed 20 years, we estimated the relative risks (RRs) of type I (N = 471) and II (N = 71) endometrial cancers according to intake of one-carbon nutrients, adjusting for confounders. RESULTS: No associations were observed between dietary or supplemental intake of any one-carbon nutrient and risk of type I cancer. For type II cancer, positive associations were due to supplemental, rather than dietary, intake of these nutrients: supplemental folate (RR = 1.80 for >228.6 versus 0 µg/day; P trend = 0.027) and vitamins B2 (RR = 1.94 for >1.70 versus 0 mg/day; P trend = 0.011), B6 (RR = 2.08 for >2.00 versus 0 mg/day; P trend = 0.012), and B12 (RR = 2.10 for >3.43 versus 0 µg/day; P trend = 0.0060). CONCLUSION: Contrary to our hypothesis, use of supplements containing folate and vitamins B2, B6, and B12 was associated with an increased risk of type II endometrial cancer.

Surgical morbidity of total laparoscopic hysterectomy for benign disease: Predictors of major postoperative complications.

OBJECTIVE: To estimate rate of perioperative complications and to define risk factors of 30-day major (Clavien-Dindo ≥ 2) postoperative complications of total laparoscopic hysterectomy (TLH) for benign disease. STUDY DESIGN: An uncontrolled single-center single-arm retrospective study. Data of consecutive patients who have undergone TLH for pathologically confirmed benign disease between January 2000 and December 2019 have been analyzed. Perioperative surgical outcomes, occurrence of postoperative complications, readmissions, and reoperations within 30 days from surgery were registered. Univariate and multivariable analyses were performed to determine the factors associated with major (Clavien-Dindo ≥ 2) postoperative complications. RESULTS: Over the study period 3090 patients were included in the study. Conversion to open surgery occurred in 54 (1.7%) cases. Mean operative time for TLH was 87.7 (±1.7) minutes while mean estimated blood loss was 119.5 (+7.4) mL. Overall, postoperative complications were registered in 430 (13.9%) patients, and major events were observed in 208 (6.7%) of the cases. Same-hospital readmissions and reoperations within 30-day from surgery occurred in 78 (2.5%) and 28 (0.9%) patients, respectively. At multivariable analysis, endometriosis (odds ratio: 3.51, 95%CI:1.54-8.30, p = 0.02), the need for conversion to open surgery (odds ratio: 1.26, 98%CI:1.03-12.64, p < 0.001), and the occurrence of any intraoperative complication (odds ratio: 3.10, 95%CI: 1.45-21.61, p < 0.001) were found as independent risk factors for major postoperative complications. CONCLUSIONS: Total hysterectomy performed via laparoscopy is associated with acceptable major postoperative complications rate. A huge effort should be made to minimize the occurrence of intraoperative complications and the need for conversion to open surgery. Patients undergoing TLH for endometriosis should be counselled about the increased risk of major postoperative events.

Scoliosis with cognitive impairment in a girl with 8q11.21q11.23 microdeletion and SNTG1 disruption.

Idiopathic scoliosis (IS) is an abnormality of the vertebral column with a spine curvature of at least 10 degrees. It is the most common spinal deformity in children with a prevalence of 2%-3%, and its aetiology is unknown. Genetic factors are known to play a role and a number of linkage analyses showed associations of various loci. Here we describe a new case of a de novo interstitial deletion 8q11.21q11.2 disrupting SNTG1 gene, identified by array-CGH in a girl with cognitive impairment and a scoliosis that 'appears' like to IS. SNTG1 encodes γ-1 Syntrophin protein that is part of the dystrophin associated protein complex and interacts directly with the C-terminal of dystrophin. Its expression is restricted to neurons and particularly in those areas of the brain that have been suggested to affect postural control. The involvement of SNTG1 gene in IS was already been reported in a family with a breakpoint between exons 10 and 11. Mutational analysis of SNTG1 exons in 152 sporadic IS patients had revealed changes in three patients. In conclusion, our data add a further line of evidence suggesting SNTG1 could represent an interesting candidate for its involvement in scoliosis.