EUS-FNA diagnosis of pancreatic tophaceous gout: Two rare cases.

We report two patients with pancreatic tophaceous gout diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of presumed cystic mass lesions. The first case involved a patient who had a recent episode of acute pancreatitis 6 months prior, with subsequent imaging concerning for a pseudocyst or mass lesion. The second case involved a patient with epigastric pain associated with a pancreatic head cystic mass and an erroneous original diagnosis of a mucinous pancreatic neoplasm on EUS-FNA. Diff-Quik stained direct smears on fresh material obtained from EUS-FNA of the lesions showed chalky debris with needle shaped negatively birefringent crystals consistent with gout. For the first case, the chalky material was not present on the H&E stained paraffin embedded formalin fixed cellblock slides. The importance of inclusion of cytologic specimen preparations to examine monosodium urate crystals is emphasized.

The details matter: personalized prediction of live birth after in vitro fertilization in women with polycystic ovary syndrome.

OBJECTIVE: To derive and internally validate a clinical prediction model for live birth (LB) in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF). DESIGN: Retrospective cohort study. SETTING: Four academic reproductive endocrinology clinics. PATIENTS: A total of 207 women with PCOS confirmed using Rotterdam criteria undergoing their first fresh IVF cycle. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The primary outcome was cumulative LB per IVF cycle start. This included any LB that resulted from either fresh embryo transfer or any subsequent frozen embryo transfer from embryos obtained at the index oocyte retrieval. A prediction model was derived using multivariable logistic regression. Covariates considered for inclusion in the prediction model included demographic characteristics, medical history, and prior fertility treatment. Predicted probabilities for LB were calculated using the prediction model which included the 90% shrinkage factor for each adjusted odds ratio. RESULTS: The final model, on the basis of maximization of the area under the receiver operating characteristic curve, included age < 35 years, White race, presence of polycystic ovaries on ultrasound (polycystic ovary morphology), normal body mass index (<25 kg/m2), being metabolically healthy (no metabolic risk factors), and being a nonresponder to ovulation induction agents including letrozole and clomiphene citrate. The area under the receiver operating characteristic curve score for the model was 0.68 (95% confidence interval [CI]: 0.60, 0.77). Predicted probabilities of LB ranged from 8.1% (95% CI: 2.8, 21.5) for a woman who had no favorable predictors to 74.2% (95% CI: 59.5, 84.9) for a woman who had all favorable predictors. CONCLUSION: Our study demonstrated that, in addition to anovulation, the underlying pathophysiology and associated comorbidities alter the likelihood of a successful pregnancy in women with PCOS undergoing IVF. Further validation of this model is needed before it can serve as a tool to personalize prediction estimates for the probability of LB in women with PCOS.

A genetically encoded protein tag for control and quantitative imaging of CAR T cell therapy.

Chimeric antigen receptor (CAR) T cell therapy has been successful for hematological malignancies. Still, a lack of efficacy and potential toxicities have slowed its application for other indications. Furthermore, CAR T cells undergo dynamic expansion and contraction in vivo that cannot be easily predicted or controlled. Therefore, the safety and utility of such therapies could be enhanced by engineered mechanisms that engender reversible control and quantitative monitoring. Here, we use a genetic tag based on the enzyme Escherichia coli dihydrofolate reductase (eDHFR), and derivatives of trimethoprim (TMP) to modulate and monitor CAR expression and T cell activity. We fused eDHFR to the CAR C terminus, allowing regulation with TMP-based proteolysis-targeting chimeric small molecules (PROTACs). Fusion of eDHFR to the CAR does not interfere with cell signaling or its cytotoxic function, and the addition of TMP-based PROTACs results in a reversible and dose-dependent inhibition of CAR activity via the proteosome. We show the regulation of CAR expression in vivo and demonstrate imaging of the cells with TMP radiotracers. In vitro immunogenicity assays using primary human immune cells and overlapping peptide fragments of eDHFR showed no memory immune repertoire for eDHFR. Overall, this translationally-orientied approach allows for temporal monitoring and image-guided control of cell-based therapies.

Regulation of eDHFR-tagged proteins with trimethoprim PROTACs.

Temporal control of protein levels in cells and living animals can be used to improve our understanding of protein function. In addition, control of engineered proteins could be used in therapeutic applications. PRoteolysis-TArgeting Chimeras (PROTACs) have emerged as a small-molecule-driven strategy to achieve rapid, post-translational regulation of protein abundance via recruitment of an E3 ligase to the target protein of interest. Here, we develop several PROTAC molecules by covalently linking the antibiotic trimethoprim (TMP) to pomalidomide, a ligand for the E3 ligase, Cereblon. These molecules induce degradation of proteins of interest (POIs) genetically fused to a small protein domain, E. coli dihydrofolate reductase (eDHFR), the molecular target of TMP. We show that various eDHFR-tagged proteins can be robustly degraded to 95% of maximum expression with PROTAC molecule 7c. Moreover, TMP-based PROTACs minimally affect the expression of immunomodulatory imide drug (IMiD)-sensitive neosubstrates using proteomic and biochemical assays. Finally, we show multiplexed regulation with another known degron-PROTAC pair, as well as reversible protein regulation in a rodent model of metastatic cancer, demonstrating the formidable strength of this system. Altogether, TMP PROTACs are a robust approach for selective and reversible degradation of eDHFR-tagged proteins in vitro and in vivo.

Application of a Multiplex Platform to Identify Novel Biomarkers for Pregnancy Location and Viability.

Determining early pregnancy location and viability can be cumbersome, often requiring serial evaluations. This study aimed to identify novel biomarker candidates for pregnancy location and viability using a pseudodiscovery high-throughput technique. This was a case-control study among patients presenting for early pregnancy assessment, including ectopic pregnancies, early pregnancy losses, and viable intrauterine pregnancies. For pregnancy location, ectopic pregnancy was considered "case" and non-ectopic considered "control." For pregnancy viability, viable intrauterine pregnancy was considered "case" and early pregnancy loss + ectopic pregnancy were considered "control." Using Proximity Extension Assay technology from Olink Proteomics, serum levels of 1012 proteins were compared separately for pregnancy location and viability. Receiver operator characteristic curves were generated to determine a biomarker's discriminative abilities. Analysis included 13 ectopic pregnancies, 76 early pregnancy losses, and 27 viable intrauterine pregnancies. For pregnancy location, 18 markers had an area under the curve (AUC) ≥0.80, with three being expressed more in ectopic compared to non-ectopic pregnancies: thyrotropin subunit beta, carbonic anhydrase 3, and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58. For pregnancy viability, two markers had an AUC ≥0.80: lutropin subunit beta and serpin B8. While some of the markers had previously been implicated in early pregnancy physiology, others were from pathways not previously explored. Using a high-throughput platform, a large number of proteins were screened as potential biomarkers for pregnancy location and viability, and twenty candidate biomarkers were identified. Further exploration of these proteins may facilitate validation as diagnostic tools for establishing early pregnancy diagnoses.

Race, ovarian responsiveness, and live birth after in vitro fertilization.

OBJECTIVE: To determine if ovarian responsiveness to gonadotropin stimulation differs by race/ethnicity and whether this predicts live birth rates (LBRs) in non-White patients undergoing in vitro fertilization (IVF). DESIGN: Retrospective cohort study. SETTING: Academic infertility center. PATIENT(S): White, Asian, Black, and Hispanic patients undergoing ovarian stimulation for IVF. INTERVENTION(S): Self-reported race and ethnicity. MAIN OUTCOME MEASURE(S): The primary outcome was ovarian sensitivity index (OSI), defined as (the number of oocytes retrieved ÷ total gonadotropin dose) × 1,000 as a measure of ovarian responsiveness, adjusting for age, body mass index, infertility diagnosis, and cycle number. Secondary outcomes included live birth and clinical pregnancy after first retrievals, adjusting for age, infertility diagnosis, and history of fibroids, as well as miscarriage rate per clinical pregnancy, adjusting for age, body mass index, infertility diagnosis, duration of infertility, history of fibroids, and use of preimplantation genetic testing for aneuploidy. RESULT(S): The primary analysis of OSI included 3,360 (70.2%) retrievals from White patients, 704 (14.7%) retrievals from Asian patients, 553 (11.6%) retrievals from Black patients, and 168 (3.5%) retrievals from Hispanic patients. Black and Hispanic patients had higher OSIs than White patients after accounting for those with multiple retrievals and adjusting for confounders (6.08 in Black and 6.27 in Hispanic, compared with 5.25 in White). There was no difference in OSI between Asian and White patients. The pregnancy outcomes analyses included 2,299 retrievals. Despite greater ovarian responsiveness, Black and Hispanic patients had lower LBRs compared with White patients, although these differences were not statistically significant after adjusting for confounders (adjusted odds ratio, 0.83; 95% confidence interval [CI], 0.63-1.09, for Black; adjusted odds ratio, 0.93; 95% CI, 0.61-1.43, for Hispanic). Ovarian sensitivity index was modestly predictive of live birth in White and Asian patients but not in Black (area under the curve, 0.51; 95% CI, 0.38-0.64) and Hispanic (area under the curve, 0.50; 95% CI, 0.37-0.63) patients. CONCLUSION(S): Black and Hispanic patients have higher ovarian responsiveness to stimulation during IVF but do not experience a consequent increase in LBR. Factors beyond differences in responsiveness to ovarian stimulation need to be explored to address the racial/ethnic disparity established in prior literature.

Mimickers of neuroendocrine tumors on endoscopic ultrasound-guided fine-needle aspirate material: Need for caution.

Cytologic diagnosis of neuroendocrine tumors can be straightforward on cytologic preparations, given the classical neuroendocrine morphology and expression of neuroendocrine markers confirmed by immunohistochemistry. However, overreliance on neuroendocrine markers can lead to misdiagnosis even if individual cell features suggest a neuroendocrine tumor. We present three unusual cases, two of which were initially diagnosed as neuroendocrine tumors and the third one carried preliminary diagnosis of neuroendocrine tumor on endoscopic ultrasound-guided fine-needle aspirates. These cases subsequently turned out to be cholangioblastic cholangiocarcinoma, metastatic melanoma, and gastric glomus tumor, respectively. We suggest approaches that could have pointed us towards the correct diagnosis at the outset and discuss potential pitfalls.

Application of a Multiplex Platform to Identify Novel Biomarkers for Pregnancy Location and Viability.

Determining early pregnancy location and viability can be cumbersome, often requiring serial evaluations. This study aimed to identify novel biomarker candidates for pregnancy location and viability using a pseudodiscovery high through-put technique. This was a case-control study among patients presenting for early pregnancy assessment, including ectopic pregnancies, early pregnancy losses, and viable intrauterine pregnancies. For pregnancy location, ectopic pregnancy was considered "case" and non-ectopic considered "control." For pregnancy viability, viable intrauterine pregnancy was considered "case" and early pregnancy loss + ectopic pregnancy were considered "control." Using Proximity Extension Assay technology from Olink Proteomics, serum levels of 1012 proteins were compared separately for pregnancy location and viability. Receiver operator characteristic curves were generated to determine a biomarker's discriminative abilities. Analysis included 13 ectopic pregnancies, 76 early pregnancy losses, and 27 viable intrauterine pregnancies. For pregnancy location, 18 markers had an area under the curve (AUC) ≥ 0.80, with three being expressed more in ectopic compared to non-ectopic pregnancies: thyrotropin subunit beta, carbonic anhydrase 3, and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58. For pregnancy viability, two markers had an AUC ≥ 0.80: lutropin subunit beta and serpin B8. While some of the markers were previously identified as implicated in early pregnancy physiology, others were from pathways not previously explored. Using a high through-put platform, a large number of proteins were screened as potential biomarkers for pregnancy location and viability, and twenty candidate biomarkers were identified. Further exploration of these proteins may facilitate validation as diagnostic tools for establishing early pregnancy diagnoses.

Genetics in reproductive endocrinology and infertility.

Tremendous advances in genetics have transformed the field of reproductive endocrinology and infertility over the last few decades. One of the most prominent advances is preimplantation genetic testing (PGT), which allows for the screening of embryos obtained during in vitro fertilization before transfer. Moreover, PGT can be performed for aneuploidy screening, detection of monogenic disorders, or exclusion of structural rearrangements. Refinement of biopsy techniques, such as obtaining samples at the blastocyst rather than the cleavage stage, has helped optimize results from PGT, and technological advances, including next-generation sequencing, have made PGT more efficient and accurate. The continued evolution of the approach to PGT has the potential to further enhance the accuracy of results, expand the application to other conditions, and increase access by reducing cost and improving efficiency.

Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [18F]AlF-FAPI-74.

PURPOSE: Despite the success of chimeric antigen receptor (CAR) T-cell therapy against hematologic malignancies, successful targeting of solid tumors with CAR T cells has been limited by a lack of durable responses and reports of toxicities. Our understanding of the limited therapeutic efficacy in solid tumors could be improved with quantitative tools that allow characterization of CAR T-targeted antigens in tumors and accurate monitoring of response. EXPERIMENTAL DESIGN: We used a radiolabeled FAP inhibitor (FAPI) [18F]AlF-FAPI-74 probe to complement ongoing efforts to develop and optimize FAP CAR T cells. The selectivity of the radiotracer for FAP was characterized in vitro, and its ability to monitor changes in FAP expression was evaluated using rodent models of lung cancer. RESULTS: [18F]AlF-FAPI-74 showed selective retention in FAP+ cells in vitro, with effective blocking of the uptake in presence of unlabeled FAPI. In vivo, [18F]AlF-FAPI-74 was able to detect FAP expression on tumor cells as well as FAP+ stromal cells in the tumor microenvironment with a high target-to-background ratio. We further demonstrated the utility of the tracer to monitor changes in FAP expression following FAP CAR T-cell therapy, and the PET imaging findings showed a robust correlation with ex vivo analyses. CONCLUSIONS: This noninvasive imaging approach to interrogate the tumor microenvironment represents an innovative pairing of a diagnostic PET probe with solid tumor CAR T-cell therapy and has the potential to serve as a predictive and pharmacodynamic response biomarker for FAP as well as other stroma-targeted therapies. A PET imaging approach targeting FAP expressed on activated fibroblasts of the tumor stroma has the potential to predict and monitor therapeutic response to FAP-targeted CAR T-cell therapy. See related commentary by Weber et al., p. 5241.

Higher Incidence of Metabolic Syndrome in Black Women With Polycystic Ovary Syndrome: A Longitudinal Study.

CONTEXT: Cross-sectional studies have identified an increased risk of metabolic syndrome (MetSyn) in women with polycystic ovary syndrome (PCOS), but longitudinal data are limited and primarily include White and European cohorts. OBJECTIVE: To compare the longitudinal risk of MetSyn in Black and White women with PCOS and to identify potential factors mediating the risk of MetSyn. METHODS: Longitudinal cohort study with a follow-up of 5.3 years at an academic medical center. OF: 247 adult women with hyperandrogenic PCOS phenotype with 2 or more visits at least 3 years apart. The main outcome measure was incidence of MetSyn in Black and White women with PCOS. RESULTS: Using a mixed-effects model over time, the incidence of MetSyn was higher in Black women (45.9 ±â€…4.74 per 100 person-years) than in White women (31.3 ±â€…3.03 per 100 person-years) (P < .01) after adjusting for age and medication status. This difference persisted among women under age 30. Among Black women who did not have MetSyn at their prior visit, 28.0% had MetSyn at the next visit, compared with 12.1% of White women after adjusting for age and medication status (P < .01). In both races, the model-based estimated rates of MetSyn increased significantly with increase in body mass index and free testosterone. CONCLUSION: We describe a persistent higher incidence of MetSyn in Black than in White women with PCOS. In addition to early cardiometabolic screening at the time of diagnosis, our findings highlight the need for ongoing and frequent screening in this population.

Building the Bridge: Molecular Imaging Biomarkers for 21st Century Cancer Therapies.

Precision medicine, where the molecular underpinnings of the disease are assessed for tailored therapies, has greatly impacted cancer care. In parallel, a new pillar of therapeutics has emerged with profound success, including immunotherapies such as checkpoint inhibitors and cell-based therapies. Nonetheless, it remains essential to develop paradigms to predict and monitor for therapeutic response. Molecular imaging has the potential to add substantially to all phases of cancer patient care: predicative, companion diagnostics can illuminate therapeutic target density within a tumor, and pharmacodynamic imaging biomarkers can complement traditional modalities to judge a favorable treatment response. This "Focus on Molecular Imaging" article discusses the current role of molecular imaging in oncology and highlights an additional step in clinical paradigm termed a "therapeutic biomarker," which serves to assess whether next generation drugs reach their target to elicit a favorable clinical response.

Postpartum weight retention in women with polycystic ovary syndrome.

BACKGROUND: Compared with women without polycystic ovary syndrome, women with polycystic ovary syndrome have a higher prevalence of cardiometabolic risk factors. Postpartum weight retention has been shown to contribute to these risks in the general population, but little is known about postpartum weight retention among women with polycystic ovary syndrome. OBJECTIVE: This study aimed to compare postpartum weight retention and peripartum weight trends between women with polycystic ovary syndrome and controls. STUDY DESIGN: Data on live, full-term singleton deliveries from January 1, 2014, to January 1, 2019, in women with and without polycystic ovary syndrome were abstracted from the electronic medical record. Weights during the pregestational period, pregnancy, and up to 12 months postpartum were collected. The primary outcome was likelihood of high postpartum weight retention of ≥5 kg above pregestational weight at 12 months after delivery. Secondary outcomes included the prevalence of high weight retention at other postpartum time points (6 weeks, 3 months, 6 months), absolute postpartum weight retention, gestational weight gain, and excess weight gain above the Institute of Medicine guidelines for weight gain in pregnancy. RESULTS: A total of 6333 women had the requisite weight information (pregestational, peak pregnancy, and at least 1 postpartum weight), including 429 (6.8%) with polycystic ovary syndrome. After adjusting for age, pregestational body mass index, race, gestational diabetes mellitus, and parity, women with polycystic ovary syndrome were less likely to be high weight retainers at 6 weeks after delivery (adjusted odds ratio, 0.71; P=.02). There was no difference in postpartum weight retention between groups at 3, 6, and 12 months after delivery. Overall, the prevalence of high weight retainers at 12 months after delivery was high in both groups (22.7% in polycystic ovary syndrome vs 29.2% in controls; P=.13), and there was no difference in absolute weight retention (1.69 kg in polycystic ovary syndrome vs 2.05 kg in controls; P=.25). Although women with polycystic ovary syndrome had a higher pregestational body mass index, they had lower gestational weight gain (median, 12.7 kg) than controls (median, 13.5 kg) (P=.01). These findings were driven by the group with obesity. The percentage of women who surpassed the Institute of Medicine guidelines for gestational weight gain based on the body mass index category was similar between groups (43.4% in polycystic ovary syndrome vs 47.3% in controls; P=.12). Overall, 18.5% of women with polycystic ovary syndrome and 23.4% of controls had a higher body mass index category at 12 months after delivery than before pregnancy. CONCLUSION: Women with polycystic ovary syndrome had lower gestational weight gain and lower likelihood of high weight retention at 6 weeks after delivery but similar weight retention at 12 months after delivery compared with controls. Overall, the large proportion of women with high postpartum weight retention highlights the importance of the peripartum time period for weight management, particularly in this high-risk group predisposed to obesity and cardiometabolic disease.

Evaluation of a convolutional neural network for ovarian tumor differentiation based on magnetic resonance imaging.

OBJECTIVES: There currently lacks a noninvasive and accurate method to distinguish benign and malignant ovarian lesion prior to treatment. This study developed a deep learning algorithm that distinguishes benign from malignant ovarian lesion by applying a convolutional neural network on routine MR imaging. METHODS: Five hundred forty-five lesions (379 benign and 166 malignant) from 451 patients from a single institution were divided into training, validation, and testing set in a 7:2:1 ratio. Model performance was compared with four junior and three senior radiologists on the test set. RESULTS: Compared with junior radiologists averaged, the final ensemble model combining MR imaging and clinical variables had a higher test accuracy (0.87 vs 0.64, p < 0.001) and specificity (0.92 vs 0.64, p < 0.001) with comparable sensitivity (0.75 vs 0.63, p = 0.407). Against the senior radiologists averaged, the final ensemble model also had a higher test accuracy (0.87 vs 0.74, p = 0.033) and specificity (0.92 vs 0.70, p < 0.001) with comparable sensitivity (0.75 vs 0.83, p = 0.557). Assisted by the model's probabilities, the junior radiologists achieved a higher average test accuracy (0.77 vs 0.64, Δ = 0.13, p < 0.001) and specificity (0.81 vs 0.64, Δ = 0.17, p < 0.001) with unchanged sensitivity (0.69 vs 0.63, Δ = 0.06, p = 0.302). With the AI probabilities, the junior radiologists had higher specificity (0.81 vs 0.70, Δ = 0.11, p = 0.005) but similar accuracy (0.77 vs 0.74, Δ = 0.03, p = 0.409) and sensitivity (0.69 vs 0.83, Δ = -0.146, p = 0.097) when compared with the senior radiologists. CONCLUSIONS: These results demonstrate that artificial intelligence based on deep learning can assist radiologists in assessing the nature of ovarian lesions and improve their performance. KEY POINTS: • Artificial Intelligence based on deep learning can assess the nature of ovarian lesions on routine MRI with higher accuracy and specificity than radiologists. • Assisted by the deep learning model's probabilities, junior radiologists achieved better performance that matched those of senior radiologists.

Development and validation of lupus nephritis case definitions using United States veterans affairs electronic health records.

OBJECTIVE: International Classification of Diseases (ICD) codes are commonly used to identify patients with rare diseases in electronic health records (EHRs). However, misclassification is common, impacting the validity of study results. In this study, we compared the accuracies of several ICD-based case definitions of lupus nephritis (LN) in identifying United States veterans with LN. METHODS: Using the Department of Veterans Affairs (VA) EHR, we identified all veterans with ≥1 ICD-9 or 10 diagnostic codes for systemic lupus erythematosus (SLE) between October 1, 1999 and September 30, 2017. A cohort was randomly selected for diagnostic validation and 9 ICD-based LN case definitions were applied to this cohort. The diagnostic accuracy of each definition was assessed against gold standard criterion of biopsy-proven LN. RESULTS: 18,420 veterans had ≥1 ICD-9 or 10 diagnostic codes for SLE; 981 were randomly selected for diagnostic validation. 95 veterans (9.7%) had biopsy-proven LN. The case definitions had high specificity and NPV but variable sensitivity and PPV. The definition containing ≥2 ICD -9 codes for SLE and ≥2 nephritis indicators had the highest combination of sensitivity and specificity (87.4% and 94.6% respectively). ICD-10 code for LN had high specificity (99.8%) and PPV (93.9%). CONCLUSION: ICD-based case definitions of LN in the VA population have high specificity and NPV but variable sensitivity and PPV. Our results may help guide the design of future LN studies in VA cohorts. The choice of specific case definitions depends on the relative importance of different accuracy measures to individual studies.

A Chemical Approach for Programmable Protein Outputs Based on Engineered Cell Interactions.

Cell-cell interactions and communication are crucial to the proper function of complex mammalian physiology including neurocognitive and immune system functions. While many tools are available for observing and perturbing intracellular processes, relatively few exist to probe intercellular processes. Current techniques for studying interactions often rely on direct protein contact, and few can manipulate diverse, functional outputs with tunable protein expression. To address these limitations, we have developed a small-molecule approach based on a trimethoprim prodrug-enzyme pair capable of reporting the presence of two different engineered cell populations with programmable protein outputs. The approach relies on bacterial nitroreductase enzyme catalysis, which is orthogonal to normal mammalian biology, and diffusion of trimethoprim from "activator" cells to "receiver" cells. We test this strategy, which can theoretically regulate many different types of proteins, using biochemical and in vitro culture assays with optical and cytokine protein readouts. This describes the first small-molecule approach capable of detecting and controlling engineered cell-cell outputs, and we anticipate future applications that are especially relevant to the field of immuno-oncology.

Ultrasound-guided fine-needle aspiration of a rectal submucosal nodule.

Although endoscopic biopsy of a rectal submucosal nodule may be nondiagnostic, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) can be an important tool to make diagnosis. We report a case of a female patient who had an EUS-FNA of a submucosal nodule after a nondiagnostic rectal biopsy. The original diagnosis was erroneously rendered as concerning for necrotic neoplasm. The correct diagnosis of Solesta-induced foreign body reaction was made on reviewing the slides once the history of remote Solesta injection was made available. This case illustrates the pathognomonic features of Solesta-induced rectal nodule and underscores the importance of detailed history as well as inclusion of iatrogenic diseases in the differential to prevent erroneous diagnosis and management. Potential pitfalls in cytopathological diagnosis are discussed.

Increased odds of disordered eating in polycystic ovary syndrome: a systematic review and meta-analysis.

PURPOSE: We aimed to identify the risk of eating disorders (ED) in women with polycystic ovary syndrome (PCOS) compared to controls. METHODS: We performed a systematic review and meta-analysis of studies that included women with well-defined PCOS and controls and used validated ED screening/diagnostic tools to measure mean ED score, prevalence of abnormal ED scores, and/or prevalence of specific ED diagnoses such as bulimia nervosa and binge eating disorder. RESULTS: Eight studies, including 470 women with PCOS and 390 controls, met inclusion criteria for the systematic review. Meta-analysis of seven of those studies found that the odds of an abnormal ED score (OR 3.05; 95% CI 1.33, 6.99; four studies) and the odds of any ED diagnosis (OR 3.87; 95% CI 1.43, 10.49; four studies) were higher in women with PCOS compared to controls. CONCLUSIONS: Our study suggests that women with PCOS are at increased odds of having abnormal ED scores and specific ED diagnoses. Given the potential implications of an ED on weight management strategies, our findings support routine screening for ED in this population. LEVEL OF EVIDENCE: Level I, systematic review and meta-analysis.