Machine learning-enabled maternal risk assessment for women with pre-eclampsia (the PIERS-ML model): a modelling study.

BACKGROUND: Affecting 2-4% of pregnancies, pre-eclampsia is a leading cause of maternal death and morbidity worldwide. Using routinely available data, we aimed to develop and validate a novel machine learning-based and clinical setting-responsive time-of-disease model to rule out and rule in adverse maternal outcomes in women presenting with pre-eclampsia. METHODS: We used health system, demographic, and clinical data from the day of first assessment with pre-eclampsia to predict a Delphi-derived composite outcome of maternal mortality or severe morbidity within 2 days. Machine learning methods, multiple imputation, and ten-fold cross-validation were used to fit models on a development dataset (75% of combined published data of 8843 patients from 11 low-income, middle-income, and high-income countries). Validation was undertaken on the unseen 25%, and an additional external validation was performed in 2901 inpatient women admitted with pre-eclampsia to two hospitals in south-east England. Predictive risk accuracy was determined by area-under-the-receiver-operator characteristic (AUROC), and risk categories were data-driven and defined by negative (-LR) and positive (+LR) likelihood ratios. FINDINGS: Of 8843 participants, 590 (6·7%) developed the composite adverse maternal outcome within 2 days, 813 (9·2%) within 7 days, and 1083 (12·2%) at any time. An 18-variable random forest-based prediction model, PIERS-ML, was accurate (AUROC 0·80 [95% CI 0·76-0·84] vs the currently used logistic regression model, fullPIERS: AUROC 0·68 [0·63-0·74]) and categorised women into very low risk (-LR <0·1; eight [0·7%] of 1103 women), low risk (-LR 0·1 to 0·2; 321 [29·1%] women), moderate risk (-LR >0·2 and +LR <5·0; 676 [61·3%] women), high risk (+LR 5·0 to 10·0, 87 [7·9%] women), and very high risk (+LR >10·0; 11 [1·0%] women). Adverse maternal event rates were 0% for very low risk, 2% for low risk, 5% for moderate risk, 26% for high risk, and 91% for very high risk within 48 h. The 2901 women in the external validation dataset were accurately classified as being at very low risk (0% with outcomes), low risk (1%), moderate risk (4%), high risk (33%), or very high risk (67%). INTERPRETATION: The PIERS-ML model improves identification of women with pre-eclampsia who are at lowest and greatest risk of severe adverse maternal outcomes within 2 days of assessment, and can support provision of accurate guidance to women, their families, and their maternity care providers. FUNDING: University of Strathclyde Diversity in Data Linkage Centre for Doctoral Training, the Fetal Medicine Foundation, The Canadian Institutes of Health Research, and the Bill & Melinda Gates Foundation.

Incidence of vasa praevia: a systematic review and meta-analysis.

OBJECTIVES: To derive accurate estimates of the incidence of vasa praevia (VP) in a routine population of unselected pregnancies. DESIGN: Systematic review and meta-analysis. DATA SOURCES: A search of MEDLINE, EMBASE, CINAHL and the Cochrane database was performed to review relevant citations reporting outcomes in pregnancies with VP from January 2000 until 5 April 2023. ELIGIBILITY CRITERIA FOR SELECTION OF STUDIES: Prospective or retrospective cohort or population studies that provided data regarding VP cases in routine unselected pregnancies during the study period. We included studies published in the English language after the year 2000 to reflect contemporary obstetric and neonatal practice. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened the retrieved citations and extracted data. The methodological quality of studies was assessed using the Newcastle-Ottawa Scale, and Preferred Reporting Items for Systematic reviews and Meta-Analyses was used to ensure standardised reporting of studies. RESULTS: A total of 3847 citations were screened and 82 full-text manuscripts were retrieved for analysis. There were 24 studies that met the inclusion criteria, of which 12 studies reported prenatal diagnosis with a systematic protocol of screening. There were 1320 pregnancies with VP in a total population of 2 278 561 pregnancies; the weighted pooled incidence of VP was 0.79 (95% CI: 0.59 to 1.01) per 1000 pregnancies, corresponding to 1 case of VP per 1271 (95% CI: 990 to 1692) pregnancies. Nested subanalysis of studies reporting screening for VP based on a specific protocol identified 395 pregnancies with VP in a population of 732 654 pregnancies with weighted pooled incidence of 0.82 (95% CI: 0.53 to 1.18) per 1000 pregnancies (1 case of VP per 1218 (95% CI: 847 to 1901) pregnancies). CONCLUSION: The incidence of VP in unselected pregnancies is 1 in 1218 pregnancies. This is higher than is previously reported and can be used as a basis to assess whether screening for this condition should be part of routine clinical practice. Incorporation of strategies to screen for VP in routine clinical practice is likely to prevent 5% of stillbirths. PROSPERO REGISTRATION NUMBER: CRD42020125495.

Fibular hemimelia.

Fibular hemimelia is defined as a partial or complete absence of the fibula. Alongside fibular deformities, there is a wide spectrum of anomalies, foot deformities, and absent rays. A literature review showed only a handful of cases of prenatal diagnosis of fibular hemimelia. It is a rare disorder that might be isolated or associated with visceral anomalies.

The role of novel poly (ADP-ribose) inhibitors in the treatment of locally advanced and metastatic Her-2/neu negative breast cancer with inherited germline BRCA1/2 mutations. A review of the literature.

The use of the PARP inhibitors (PARPi) in the treatment of breast cancer (BC) with germine mutations has evolved over the years, and further research has been done in order to broaden the horizon of this treatment strategy. Therefore the aim of this paper is to review the efficiency of PARPi in the treatment of BRCA 1/2-mutated locally advanced and metastatic Her-2/net negative BC mentioning their side effects, mechanism of resistance and future directions. Inhibition of PARP transforms single-strand breaks into double-strand breaks (DBS), the accumulation of the latter causing cell death (cell apoptosis). The Olympia AD phase III trial demonstrated a statistically significant progression-free survival rate (PFS) when using the PARPi olaparib in metastatic BC with germline BRCA1/2 mutations without any benefit of the overall survival rate. PARPi therapy is associated with acceptable responsive rates and progression-free survival rates in locally advanced and metastatic BRCA1/2 associated BC through mechanisms that enhance and increase the sensitivity to chemotherapeutic or target agents as they induce a synthetic lethality and cell apoptosis. The side effects are not significant, the most adverse effects being related to the hematological and gastrointestinal systems. Olaparib is currently approved in the first-line treatment of BRCA1/2 mutated Her-2/neu negative metastatic BC at an oral dose of 300 mg twice daily, while Talazoparib represents a category one recommendation in locally advanced and metastatic Her-2/neu negative BC in women with central nervous system metastases.

Diabetes, pregnancy and spina bifida.

Spina bifida is a disorder characterized by failure of the neural tube to form during embryological development. The early signs in the head and spine may be detected on ultrasound from 11 weeks of gestation. Diabetes is a well-known teratogen factor that increases the chances of birth defects, such as neural tube defects. We report a 12 weeks case of spina bifida in type 1 diabetes.

The Dual Blockade in the Neoadjuvant Setting of HER-2 Positive Early-Stage Breast Cancer.

Patients with positive Her-2/neu breast cancer and a high risk of recurrence are known to benefit from the addition of the dual blockade of Her-2/neu with Trastuzumab and Pertuzumab to the neoadjuvant chemotherapy, a combination which has been demonstrated to give a higher rate of a complete pathologic response in the breast and in the axilla. The purpose of this review is to outline the efficacy of the dual blockade with Trastuzumab and Pertuzumab in the neoadjuvant treatment of high-risk Her-2 positive breast cancer. Electronic databases (Pubmed, Medline, and Cochrane Database of Systematic Reviews) were searched for English- and German-language studies, which were published in the last ten years. The search has been focused on neoadjuvant clinical trials as well as on the data presented in the abstracts published at the San Antonio Breast Cancer Symposium as well as at the annual meeting of the American Society of Clinical Oncology. The results reported in the published clinical trials demonstrated a higher pathologic complete response rate in breast and lymph nodes after using targeted therapy with two anti-Her-2/neu agents - Trastuzumab and Pertuzumab in combination with neoadjuvant chemotherapy for early-stage Her-2/neu positive breast cancers. The pathologic complete response rate is the most important prognostic marker in Her-2/neu positive tumors, a higher pathologic complete response rate being demonstrated to be associated with a better survival outcome in terms of higher overall survival and disease-free survival rates.

Fat-forming Solitary Fibrous Tumor of the Kidney - A Case Report and Literature Review.

Fat-forming solitary fibrous tumors arising from the kidney are extremely rare, with only few cases reported so far. We report the case of a 49-year-old patient investigated for lumbar pain and diagnosed preoperatively with a large retroperitoneal tumor destroying the right kidney. The patient was submitted to surgery, the tumor being resected en bloc with right nephrectomy. The histopathological studies demonstrated the presence of a hemangiopericytoma-like tumor with adipocytary component; the immunohistochemical studies demonstrated the presence of cluster of differentiation 34 (CD34), while human melanoma black (HMB45) staining was negative. Therefore, the diagnostic of fat-forming solitary fibrous tumor of the kidney was established. The postoperative outcome was uneventful, the patient being discharged on the sixth postoperative day. In conclusion, although fat-forming solitary fibrous tumor of the kidney is a very rare entity, this diagnosis should be taken into consideration whenever a large retroperitoneal mass with high adipose content and renal invasion is described at the preoperative studies.

Normal Size Ovary Carcinoma Syndrome with Inguinal Ovarian Cancer Lymph Node Metastases - A Case Report and Literature Review.

Inguinal lymph node mass as the first sign in patients with ovarian cancer represents a rare situation, with only few cases being reported so far. We present the case of a 46-year-old patient who presented for the apparition of bilateral inguinal tumoral masses in the absence of any other pathological signs. The biopsy revealed the presence of an adenocarcinoma with probable genital origin; however, neither the gynaecological examination nor the computed tomography demonstrated the presence of any suspect lesion. The patient was submitted to a positron emission computed tomography which revealed a high capitation in both adnexal areas as well as at the level of the inguinal lymph nodes. The patient was submitted to surgery, the frozen section of the adnexas confirming the ovarian origin of the tumor. Complete cytoreduction to no residual disease was successfully performed. At one-year follow-up the patient is free of any recurrent disease.

Association of Diaphragmatic Surgery as Part of Cytoreductive Effort in Advanced Stage Ovarian Cancer.

BACKGROUND/AIM: Diaphragmatic surgery in advanced-stage ovarian cancer has been considered since long time to increase the rates of postoperative complications. However, improvement of surgical techniques and perioperative management of these patients has lead in the last decade to a safe association of such procedures as part of debulking process. The aim of the current paper was to report our experience regarding the role of diaphragmatic resections as part of debulking surgery for advanced stage ovarian cancer. MATERIALS AND METHODS: Between 2014 and 2016 diaphragmatic surgery was performed in 22 cases with advanced stage ovarian cancer. RESULTS: Diaphragmatic surgery consisted of diaphragmatic peritoneal resection in 10 cases, full thickness diaphragmatic resections in four cases and coagulation of peritoneal nodules in eight cases. In all but two cases debulking surgery to no residual disease was achieved. Other upper abdominal resections consisted of splenectomy - in four cases, liver resections - in three cases, glissonian capsule resections - in eight cases, distal pancreatectomy - in one case and partial gastrectomies in two cases. The postoperative outcomes were similar irrespective of type of diaphragmatic surgical procedure. CONCLUSION: Diaphragmatic surgery is a crucial procedure which can be safely associated as part of debulking surgery for advanced stage ovarian cancer.