Obesity in pregnancy: risk of gestational diabetes

Background: Maternal obesity is a risk factor for gestational diabetes and other adverse pregnancy outcomes, but the body fat distribution may be a more important risk factor than body mass index. Pregnancy is an insulin resistant state and more so, in obese women. Metformin could be beneficial in obese pregnant women due to its insulin sensitizing action. The aims of this study are to investigate visceral fat mass as a risk factor for gestational diabetes (VFM study), to develop a mathematical model for the prediction of gestational diabetes in obese women (VFM study) and to examine the effect of metformin on pregnancy outcomes in obese non-diabetic women (MOP Trial). Methods and Results: VFM study: The body composition of 302 obese pregnant women was assessed using bioelectrical impedance. A mathematical model to predict gestational diabetes using machine learning was developed using visceral fat mass which is a novel risk factor in addition to conventional risk factors. 72 of the women developed gestational diabetes (GDM). These women had higher visceral fat mass. Women with a baseline visceral fat mass ≥ 75th percentile, had a 3-fold risk of subsequent gestational diabetes. The mathematical model predicted gestational diabetes with an average overall accuracy of 77.5% and predicted birth centile classes with an average accuracy of 68%. According to the decision tree developed, VFM emerged as the most important variable in determining the risk of GDM and a VFM < 210 was used as the first split in the decision tree. MOP Trial: 133 obese pregnant women were randomised to either metformin or placebo. The pregnancy outcomes were compared in both groups. Insulin resistance was measured in all women. 118 women completed the trial. Metformin did not reduce the neonatal birth weight z-score, which was the primary outcome of the trial or the incidence of large for gestational age babies. However, metformin therapy significantly reduced gestational weight gain, reduced the pregnancy rise in visceral fat mass, and attenuated the expected physiological rise in insulin resistance at 28 weeks gestation. However, this did not result in an overall significant reduction in the incidence of gestational diabetes. There was a trend towards a reduced incidence of gestational diabetes in women with high baseline insulin resistance randomised to metformin. Conclusions: Visceral fat mass is a novel risk factor for gestational diabetes. The mathematical model successfully predicted gestational diabetes. Metformin reduced gestational weight gain and insulin resistance but did not lower the median neonatal birth weight or reduce the incidence of GDM

Visceral fat mass as a novel risk factor for predicting gestational diabetes in obese pregnant women

Objective To develop a model to predict gestational diabetes mellitus incorporating classical and a novel risk factor, visceral fat mass. Methods Three hundred two obese non-diabetic pregnant women underwent body composition analysis at booking by bioimpedance analysis. Of this cohort, 72 (24%) developed gestational diabetes mellitus. Principal component analysis was initially performed to identify possible clustering of the gestational diabetes mellitus and non-GDM groups. A machine learning algorithm was then applied to develop a GDM predictive model utilising random forest and decision tree modelling. Results The predictive model was trained on 227 samples and validated using an independent testing subset of 75 samples where the model achieved a validation prediction accuracy of 77.53%. According to the decision tree developed, visceral fat mass emerged as the most important variable in determining the risk of gestational diabetes mellitus. Conclusions We present a model incorporating visceral fat mass, which is a novel risk factor in predicting gestational diabetes mellitus in obese pregnant wome

Metformin in Pregnancy: Mechanisms and Clinical Applications

Metformin use in pregnancy is increasing worldwide as randomised controlled trial (RCT) evidence is emerging demonstrating its safety and efficacy. The Metformin in Gestational Diabetes (MiG) RCT changed practice in many countries demonstrating that metformin had similar pregnancy outcomes to insulin therapy with less maternal weight gain and a high degree of patient acceptability. A multicentre RCT is currently assessing the addition of metformin to insulin in pregnant women with type 2 diabetes. RCT evidence is also available for the use of metformin in pregnancy for women with Polycystic Ovarian Syndrome and for nondiabetic women with obesity. No evidence of an increase in congenital malformations or miscarriages has been observed even when metformin is started before pregnancy and continued to term. Body composition and metabolic outcomes at two, seven, and nine years have now been reported for the offspring of mothers treated in the MiG study. In this review, we will briefly discuss the action of metformin and then consider the evidence from the key clinical trials

Searching Full-Text Anatomic Pathology Reports Using Business Intelligence Software

Although the laboratory information system has largely solved the problem of storing anatomic pathology reports and disseminating their contents across the healthcare system, the retrospective query of anatomic pathology reports remains an area for improvement across laboratory information system vendors. Our institution desired the ability to query our repository of anatomic pathology reports for clinical, operational, research, and educational purposes. To address this need, we developed a full-text anatomic pathology search tool using the business intelligence software, Tableau. Our search tool allows users to query the 333,685 anatomic pathology reports from our institutional clinical relational database using the business intelligence tool’s built-in regular expression functionality. Users securely access the search tool using any web browser, thereby avoiding the cost of installing or maintaining software on users’ computers. This tool is laboratory information system vendor agnostic and as many institutions already subscribe to business intelligence software, we believe this solution could be easily reproduced at other institutions and in other clinical departments

Expanding COVID-19 Vaccine Availability: Role for Combined Orthogonal Serology Testing (COST)

Background: The persisting Coronavirus disease 2019 (COVID-19) pandemic and limited vaccine supply has led to a shift in global health priorities to expand vaccine coverage. Relying on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular testing alone cannot reveal the infection proportion, which could play a critical role in vaccination prioritization. We evaluated the utility of a combination orthogonal serological testing (COST) algorithm alongside RT-PCR to quantify prevalence with the aim of identifying candidate patient clusters to receive single and/or delayed vaccination. Methods: We utilized 108,505 patients with suspected COVID-19 in a retrospective analysis of SARS-CoV-2 RT-PCR vs. IgG-nucleocapsid (IgGNC) antibody testing coverage in routine practice for the estimation of prevalence. Prospectively, an independent cohort of 21,388 subjects was simultaneously tested by SARS-CoV-2 RT-PCR and IgGNC to determine the prevalence. We used 614 prospective study subjects to assess the utility of COST (IgGNC, IgM-spike (IgMSP), and IgG-spike (IgGSP)) in establishing the infection proportion to identify a single-dose vaccination cohort. Results: Retrospectively, we observed a 6.3% (6871/108,505) positivity for SARS-CoV-2 RT-PCR, and only 2.3% (2533/108,505) of cases had paired IgGNC serology performed. Prospectively, IgGNC serology identified twice the number of COVID-positive cases in relation to RT-PCR alone. COST further increased the number of detected positive cases: IgGNC+ or IgMSP+ (18.0%); IgGNC+ or IgGSP+ (23.5%); IgMSP+ or IgGSP+ (23.8%); and IgGNC+ or IgMSP+ or IgGSP+ (141/584 = 24.1%). Conclusion: COST may be an effective tool for the evaluation of infection proportion and thus could define a cohort for a single dose and/or delayed vaccination

Multi-institutional Evaluation of Upper Urinary Tract Biopsy Using Backloaded Cup Biopsy Forceps, a Nitinol Basket, and Standard Cup Biopsy Forceps

ObjectiveTo compare the performance of 3 contemporary ureteroscopic biopsy devices for the histopathologic diagnosis of upper tract urothelial carcinoma (UTUC).MethodsWe retrospectively reviewed 145 patients who underwent 182 urothelial biopsies using 2.4F backloaded cup biopsy forceps, a nitinol basket, or 3F standard cup biopsy forceps at 3 tertiary academic centers between 2011 and 2016. Experienced genitourinary pathologists provided an assessment of each specimen without knowledge of the device used for biopsy. For patients who underwent nephroureterectomy without neoadjuvant chemotherapy within 3 months of biopsy-proven UTUC diagnosis, the biopsy grade was compared with both the grade and stage of the surgical specimen.ResultsBiopsy utilization varied among the 3 institutions (P &lt;.0001). Significant variabilities in specimen size (P = .001), the presence of intact urothelium (P = .008), and crush artifact (P = .028) were found among the biopsy devices. The quality of specimens from backloaded cup forceps was rated similarly to the nitinol basket (P &gt;.05) and was favored over standard cup forceps specimens. Grade concordance was not affected by specimen size (P &gt;.05), morphology (P &gt;.1), or location (P &gt;.5). No difference existed among the devices in the rate of acquiring a grade concordant biopsy; however, the backloaded cup forceps provided concordant biopsies that could be distinguished as low- and high-grade (P = .02).ConclusionThe backloaded cup forceps and nitinol basket obtained a higher quality urothelial specimen compared with standard cup forceps. Ureteroscopic biopsy device selection did not significantly impact the accuracy of the histologic diagnosis of UTUC

Multi-institutional Evaluation of Upper Urinary Tract Biopsy Using Backloaded Cup Biopsy Forceps, a Nitinol Basket, and Standard Cup Biopsy Forceps.

ObjectiveTo compare the performance of 3 contemporary ureteroscopic biopsy devices for the histopathologic diagnosis of upper tract urothelial carcinoma (UTUC).MethodsWe retrospectively reviewed 145 patients who underwent 182 urothelial biopsies using 2.4F backloaded cup biopsy forceps, a nitinol basket, or 3F standard cup biopsy forceps at 3 tertiary academic centers between 2011 and 2016. Experienced genitourinary pathologists provided an assessment of each specimen without knowledge of the device used for biopsy. For patients who underwent nephroureterectomy without neoadjuvant chemotherapy within 3 months of biopsy-proven UTUC diagnosis, the biopsy grade was compared with both the grade and stage of the surgical specimen.ResultsBiopsy utilization varied among the 3 institutions (P &lt;.0001). Significant variabilities in specimen size (P = .001), the presence of intact urothelium (P = .008), and crush artifact (P = .028) were found among the biopsy devices. The quality of specimens from backloaded cup forceps was rated similarly to the nitinol basket (P &gt;.05) and was favored over standard cup forceps specimens. Grade concordance was not affected by specimen size (P &gt;.05), morphology (P &gt;.1), or location (P &gt;.5). No difference existed among the devices in the rate of acquiring a grade concordant biopsy; however, the backloaded cup forceps provided concordant biopsies that could be distinguished as low- and high-grade (P = .02).ConclusionThe backloaded cup forceps and nitinol basket obtained a higher quality urothelial specimen compared with standard cup forceps. Ureteroscopic biopsy device selection did not significantly impact the accuracy of the histologic diagnosis of UTUC