Grading Cytologic Epithelial Atypia in Pancreatic Mucinous Cysts Predicts Patient Survival: Correlation With Histologic, Molecular, and Clinical Follow-Up.

Cytologic examination of epithelial cells in cyst fluids from pancreatic mucinous cysts is the optimal method for identifying high-grade atypia (HGA), which may represent histologic high-grade dysplasia (HGD) or invasive carcinoma and thereby classify the cyst as high risk, warranting surgical resection. Cytologic features of HGA were previously described at our institution in 2013 and implemented thereafter, but performance of grading with these criteria has not yet been reported. In total, 1322 pancreatic cyst fluid specimens (2014-2021) were identified; all pathology reports and relevant clinical data were reviewed in detail; and 230 unique cysts (217 patients) contained neoplastic mucinous epithelium. Of the 230 cysts, 178 had low-grade atypia (LGA), and 52 had HGA. Ninety-seven cysts had histologic follow-up: 77 (79%) were resections and 20 (21%) were diagnostic surgical biopsies only. Moreover, 92 (95%) were confirmed neoplastic mucinous cysts, 3 were adenocarcinomas, and 2 were benign entities. Among histologically confirmed neoplastic mucinous cysts, 58 had low-grade dysplasia (LGD); 34 had HGD, of which 14 also had invasive carcinoma. A significantly higher proportion of cysts with HGA (63%) demonstrated at least HGD on follow-up compared to those with LGA (26%, P < .001). The sensitivity and specificity of HGA for accurately classifying a high-risk cyst were 54% and 81%, respectively. Of the 230 cysts, 146 (64%) cysts had corresponding next-generation sequencing results; 31% of HGA cysts harbored a high-risk mutation (TP53, CDKN2A, and/or SMAD4) vs 7% of LGA cysts (P < .001). Among cysts without histologic confirmation, 25% of HGA cysts had high-risk mutation vs 7% of LGA cysts. The grade of cytologic atypia was predictive of overall survival and recurrence-free survival (P < .001 and P = .020, respectively). Implementation of cytologic criteria for HGA in pancreatic mucinous cysts has relatively low sensitivity but modest specificity for classifying a high-risk cyst. Although high-risk mutations were more commonly found in cysts with HGA, their frequency is overall low. Thus, evaluating the degree of cytologic atypia, which is predictive of patient survival, provides significant value and informs patient outcomes.

Neighborhood risk and prenatal care utilization in Rhode Island, 2005-2014.

BACKGROUND: The importance of prenatal care is undeniable, as pregnant persons who receive on-time, adequate prenatal care have better maternal and infant health outcomes compared with those receiving late, less than adequate prenatal care. Previous studies assessing the relationship between neighborhood factors and maternal health outcomes have typically looked at singular neighborhood variables and their relationship with maternal health outcomes. In order to examine a greater number of place-based risk factors simultaneously, our analysis used a unique neighborhood risk index to assess the association between cumulative risk and prenatal care utilization, which no other studies have done. METHODS: Data from Rhode Island Vital Statistics for births between 2005 and 2014 were used to assess the relationship between neighborhood risk and prenatal care utilization using two established indices. We assessed neighborhood risk with an index composed of eight socioeconomic block-group variables. A multivariate logistic regression model was used to examine the association between adequate use and neighborhood risk. RESULTS: Individuals living in a high-risk neighborhood were less likely to have adequate or better prenatal care utilization according to both the APNCU Index (adjusted odds ratio [aOR] 0.91, 95% confidence interval [CI] 0.87-0.95) and the R-GINDEX (aOR 0.88, 95% CI 0.85-0.91) compared with those in low-risk neighborhoods. CONCLUSION: Understanding the impact of neighborhood-level factors on prenatal care use is a critical first step in ensuring that underserved neighborhoods are prioritized in interventions aimed at making access to prenatal care more equitable.

"Evolving Trends in Pancreatic Cystic Tumors: A 3-Decade Single-Center Experience With 1290 Resections".

OBJECTIVE: The aim of this study was to describe our institutional experience with resected cystic tumors of the pancreas with emphasis on changes in clinical presentation and accuracy of preoperative diagnosis. SUMMARY BACKGROUND DATA: Incidental discovery of pancreatic cystic lesions has increased and has led to a rise in pancreatic resections. It is important to analyze surgical outcomes from these procedures, and the prevalence of malignancy, pre-malignancy and resections for purely benign lesions, some of which may be unintended. METHODS: Retrospective review of a prospective database spanning 3 decades. Presence of symptoms, incidental discovery, diagnostic studies, type of surgery, postoperative outcomes, and concordance between presumptive diagnosis and final histopathology were recorded. RESULTS: A total of 1290 patients were identified, 62% female with mean age of 60 years. Fifty-seven percent of tumors were incidentally discovered. Ninety-day operative mortality was 0.9% and major morbidity 14.4%. There were 23 different diagnosis, but IPMN, MCN, and serous cystadenoma comprised 80% of cases. Concordance between preoperative and final histopathological diagnosis increased by decade from 45%, to 68%, and is presently 80%, rising in parallel with the use of endoscopic ultrasound, cytology, and molecular analysis. The addition of molecular analysis improved accuracy to 91%. Of misdiagnosed cases, half were purely benign and taken to surgery with the presumption of malignancy or premalignancy. The majority of these were serous cystadenomas. CONCLUSIONS: Indications and diagnostic work-up of cystic tumors of the pancreas have changed over time. Surgical resection can be performed with very low mortality and acceptable morbidity and diagnostic accuracy is presently 80%. About 10% of patients are still undergoing surgery for purely benign lesions that were presumed to be malignant or premalignant. Further refinements in diagnostic tests are required to improve accuracy.

A Randomized Trial of a Multifactorial Strategy to Prevent Serious Fall Injuries.

BACKGROUND: Injuries from falls are major contributors to complications and death in older adults. Despite evidence from efficacy trials that many falls can be prevented, rates of falls resulting in injury have not declined. METHODS: We conducted a pragmatic, cluster-randomized trial to evaluate the effectiveness of a multifactorial intervention that included risk assessment and individualized plans, administered by specially trained nurses, to prevent fall injuries. A total of 86 primary care practices across 10 health care systems were randomly assigned to the intervention or to enhanced usual care (the control) (43 practices each). The participants were community-dwelling adults, 70 years of age or older, who were at increased risk for fall injuries. The primary outcome, assessed in a time-to-event analysis, was the first serious fall injury, adjudicated with the use of participant report, electronic health records, and claims data. We hypothesized that the event rate would be lower by 20% in the intervention group than in the control group. RESULTS: The demographic and baseline characteristics of the participants were similar in the intervention group (2802 participants) and the control group (2649 participants); the mean age was 80 years, and 62.0% of the participants were women. The rate of a first adjudicated serious fall injury did not differ significantly between the groups, as assessed in a time-to-first-event analysis (events per 100 person-years of follow-up, 4.9 in the intervention group and 5.3 in the control group; hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P = 0.25). The rate of a first participant-reported fall injury was 25.6 events per 100 person-years of follow-up in the intervention group and 28.6 events per 100 person-years of follow-up in the control group (hazard ratio, 0.90; 95% CI, 0.83 to 0.99; P = 0.004). The rates of hospitalization or death were similar in the two groups. CONCLUSIONS: A multifactorial intervention, administered by nurses, did not result in a significantly lower rate of a first adjudicated serious fall injury than enhanced usual care. (Funded by the Patient-Centered Outcomes Research Institute and others; STRIDE ClinicalTrials.gov number, NCT02475850.).

Systematic review of challenging issues in pathology of intraductal papillary mucinous neoplasms.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are a cystic precursor to pancreatic cancer. IPMNs deemed clinically to be at high-risk for malignant progression are frequently treated with surgical resection, and pathological examination of the pancreatectomy specimen is a key component of the clinical care of IPMN patients. METHODS: Systematic literature reviews were conducted around eight topics of clinical relevance in the examination of pathological specimens in patients undergoing resection of IPMN. RESULTS: This review provides updated perspectives on morphological subtyping of IPMNs, classification of intraductal oncocytic papillary neoplasms, nomenclature for high-grade dysplasia, assessment of T stage, distinction of carcinoma associated or concomitant with IPMN, role of molecular assessment of IPMN tissue, role of intraoperative assessment by frozen section, and preoperative evaluation of cyst fluid cytology. CONCLUSIONS: This analysis provides the foundation for data-driven approaches to several challenging issues in the pathology of IPMNs.

Breast cancer stem cells: mechanobiology reveals highly invasive cancer cell subpopulations.

Cancer stem-like cells (CSCs) are a typically small subpopulation of highly tumorigenic cells that can self-renew, differentiate, drive tumor progression, and may mediate drug resistance and metastasis. Metastasis driving CSCs are expected to be highly invasive. To determine the relative invasiveness of CSCs, we isolate distinct subpopulations in the metastatic, MDA-MB-231 breast-cancer cell line, identified by the stem-cell markers aldehyde dehydrogenase (ALDH) and CD44. We determine CSC-subpopulation invasiveness levels using our rapid (2 h) mechanobiology-based assay. Specifically, invasive cells forcefully push and indent the surface of physiological-stiffness synthetic gels to cell-scale depths, where the percentage of indenting cells and their attained depths have previously provided clinically relevant predictions of the metastatic risk in different cancer types. We observe that the small (3.2%) CD44+ALDH+ cell-subpopulation indents more and attains significantly deeper depths (65% indenting to 6 ± 0.3 µm) relative to CD44+ALDH-, CD44-ALDH-, CD44-ALDH+ cells, and the whole-sample control (with 18-44% indenting cells reaching average depths of 4.4-5 µm). The CD44+ALDH+ similarly demonstrates twofold higher migratory capacity in Boyden chambers. The higher invasiveness of CD44+ALDH+ cells reveals their likely role in facilitating disease progression, providing prognostic markers for increased risk of recurrence and metastasis.

The Association of Antenatal Depression and Cesarean Delivery among First-Time Parturients: A Population-Based Study.

OBJECTIVE: Antenatal depression (AD) has been considered a risk factor for cesarean delivery (CD); however, the supporting data are inconsistent. We used a large, nationally representative dataset to evaluate whether there is an association between AD and CD among women delivering for the first time. STUDY DESIGN: We utilized the 2016 to 2019 Multistate Pregnancy Risk Assessment Monitoring System (PRAMS) from the Centers for Disease Control. First-time parturients who reported depression in the 3 months prior to or at any point during their recent pregnancy were compared with those who did not. The mode of delivery was obtained through the birth certificate. Maternal demographics, pregnancy characteristics, and delivery characteristics were compared by the report of AD using bivariable analyses. Population-weighted multivariable regression was performed, adjusting for maternal age, race/ethnicity, insurance, pregnancy complications, preterm birth, and body mass index (BMI). RESULTS: Of the 61,605 people who met the inclusion criteria, 18.3% (n = 11,896) reported AD and 29.8% (n = 19,892) underwent CD. Parturients with AD were younger, more likely to be non-Hispanic white, publicly insured, use tobacco in pregnancy, deliver earlier, have lower levels of education, higher BMIs, and more medical comorbidities (hypertension and diabetes). After adjustment for these differences, there was no difference in risk of CD between those with AD compared with those without (adjusted odds ratio: 1.04; 95% confidence interval: 0.97-1.13). CONCLUSION: In a large, population-weighted, nationally representative sample of first-time parturients, there was no association between AD and CD. KEY POINTS: · Antenatal depression is increasingly common and has multiple known morbidities.. · Prior data on antenatal depression and cesarean delivery are mixed.. · We found no association between depression and cesarean delivery..

Human Gastrointestinal Organoid Models for Studying Microbial Disease and Cancer.

One of the major discoveries in stem cell research in the past decade embraces the development of "organs in a dish," also known as "organoids." Organoids are three-dimensional cellular structures derived from primary stem cells of different organ-specific cell types which are capable of self-renewal and maintenance of the parental lineages. Researchers have developed in vitro organoid models to mimic in vivo host-microbial interactions and disease. In this review, we focus on the use of gastrointestinal organoids as models of microbial disease and cancer.

Barriers to Quality Perioperative Care Delivery in Low- and Middle-Income Countries: A Qualitative Rapid Appraisal Study.

BACKGROUND: Provision of timely, safe, and affordable surgical care is an essential component of any high-quality health system. Increasingly, it is recognized that poor quality of care in the perioperative period (before, during, and after surgery) may contribute to significant excess mortality and morbidity. Therefore, improving access to surgical procedures alone will not address the disparities in surgical outcomes globally until the quality of perioperative care is addressed. We aimed to identify key barriers to quality perioperative care delivery for 3 "Bellwether" procedures (cesarean delivery, emergency laparotomy, and long-bone fracture fixation) in 5 low- and middle-income countries (LMICs). METHODS: Ten hospitals representing secondary and tertiary facilities from 5 LMICs were purposefully selected: 2 upper-middle income (Colombia and South Africa); 2 lower-middle income (Sri Lanka and Tanzania); and 1 lower income (Uganda). We used a rapid appraisal design (pathway mapping, ethnography, and interviews) to map out and explore the complexities of the perioperative pathway and care delivery for the Bellwether procedures. The framework approach was used for data analysis, with triangulation across different data sources to identify barriers in the country and pattern matching to identify common barriers across the 5 LMICs. RESULTS: We developed 25 pathway maps, undertook >30 periods of observation, and held >40 interviews with patients and clinical staff. Although the extent and impact of the barriers varied across the LMIC settings, 4 key common barriers to safe and effective perioperative care were identified: (1) the fragmented nature of the care pathways, (2) the limited human and structural resources available for the provision of care, (3) the direct and indirect costs of care for patients (even in health systems for which care is ostensibly free of charge), and (4) patients' low expectations of care. CONCLUSIONS: We identified key barriers to effective perioperative care in LMICs. Addressing these barriers is important if LMIC health systems are to provide safe, timely, and affordable provision of the Bellwether procedures.

FDA Supplemental Approval Summary: Lenvatinib for the Treatment of Unresectable Hepatocellular Carcinoma.

On August 16, 2018, the U.S. Food and Drug Administration approved lenvatinib (Lenvima, Eisai Inc.) for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Approval was based on an international, multicenter, randomized, open-label, noninferiority trial (REFLECT; NCT01761266) conducted in 954 patients with previously untreated metastatic or unresectable HCC. Patients were randomized (1:1) to receive lenvatinib (12 mg orally once daily for patients with a baseline body weight ≥60 kg and 8 mg orally once daily for patients with a baseline body weight <60 kg) or sorafenib (400 mg orally twice daily) until radiological disease progression or unacceptable toxicity. REFLECT demonstrated that lenvatinib was noninferior but not statistically superior to sorafenib for overall survival (OS; hazard ratio, [HR] 0.92; 95% confidence intervals [CI], 0.79-1.06), with median OS of 13.6 and 12.3 months in the lenvatinib and sorafenib arms, respectively. REFLECT also demonstrated statistically significant improvements in investigator-assessed progression-free survival (PFS; HR, 0.66; 95% CI, 0.57-0.77]; p < 0.001), corresponding to median PFS of 7.4 and 3.7 months and overall response rate of 24.1% vs 9.2% per modified RECIST for HCC (mRECIST) in the lenvatinib and sorafenib arms, respectively. Consistent results were observed by an independent review facility per RECISTv1.1 and per mRECIST. The most common adverse reactions observed in the lenvatinib-treated patients (≥20%) in decreasing frequency were hypertension, fatigue, diarrhea, decreased appetite, arthralgia/myalgia, decreased weight, abdominal pain, palmar-plantar erythrodysesthesia syndrome, proteinuria, dysphonia, hemorrhagic events, hypothyroidism, and nausea. IMPLICATIONS FOR PRACTICE: This article describes the U.S. Food and Drug Administration's review of data from a single trial, REFLECT, that supported the approval of lenvatinib, as a single agent, for the first-line treatment of unresectable hepatocellular carcinoma (HCC). REFLECT was an open-label, noninferiority trial that randomized 954 patients with HCC who were ineligible for liver-directed therapy with no prior systemic therapy for HCC to lenvatinib or sorafenib. REFLECT demonstrated that lenvatinib-treated patients had similar survival, more responses, and longer time to progression than those receiving sorafenib. Serious side effects were more common among lenvatinib-treated patients. Lenvatinib is an effective treatment for patients with previously untreated HCC.

A mesocosm study on bacteria-kelp interactions: Importance of nitrogen availability and kelp genetics.

Macroalgal holobiont studies involve understanding interactions between the host, its microbiota, and the environment. We analyzed the effect of bacteria-kelp interactions on phenotypic responses of two genetically distinct populations of giant kelp, Macrocystis pyrifera (north and south), exposed to different nitrogen (N) concentrations. In co-culture experiments with different N concentration treatments, we evaluated kelp growth responses and changes in three specific molecular markers associated with the N cycle, both in epiphytic bacteria (relative abundance of nrfA-gene: cytochrome c nitrite reductase) and macroalgae (expression of NR-gene: nitrate reductase; GluSyn-gene: glutamate synthase). Both kelp populations responded differently to N limitation, with M. pyrifera-south sporophytes having a lower specific growth rate (SGR) under N-limiting conditions than the northern population; M. pyrifera-north sporophytes showed no significant differences in SGR when exposed to low-N and high-N concentrations. This corresponded to a higher GluSyn-gene expression in the M. pyrifera-north sporophytes and the co-occurrence of specific nrfA bacterial taxa. These bacteria may increase ammonium availability under low-N concentrations, allowing M. pyrifera-north to optimize nutrient assimilation by increasing the expression of GluSyn. We conclude that bacteria-kelp interactions are important in enhancing kelp growth rates under low N availability, although this effect may be regulated by the genetic background of kelp populations.

Validation of semiquantitative FFQ administered to adults: a systematic review.

OBJECTIVE: To conduct a systematic review of studies for the validation of semiquantitative FFQ (SFFQ) that assess food intake in adults. DESIGN: The authors conducted a systematic search in PubMed for articles published as late as January 2020 in Spanish, English, French and Portuguese. Individual searches (twelve in total) paired three hyphenated and non-hyphenated variations of 'semiquantitative food frequency questionnaire' with both 'validity' and 'validation' using the 'all fields' and the 'title/abstract' retrieval categories. Independent extraction of articles was performed by four authors using predefined data fields. SETTING: We searched for original SFFQ validation studies that analysed general diet composition (nutrients with or without food groups or energy analysis) in healthy adults, in any setting, and that also reported correlation coefficients. PARTICIPANTS: Healthy adults. RESULTS: Sixty articles were included. The preferred comparison standard for validation was food records (n 37). The main correlation coefficients used were Pearson's (n 41), and validity coefficients varied from -0·45 to 1. Most correlation coefficients were adjusted by energy (twelve studies presented only crude values). The elements mentioned most frequently were energy, macronutrients, cholesterol, SFA, PUFA, fibre, vitamin C, Ca and Fe. CONCLUSIONS: Although all these SFFQ are reported as validated, coefficients may vary across groups of foods and nutrients. Based on our findings, we suggest researchers to consult our revision before choosing a SFFQ and to review important issues about them, such as their validation, number of items, number of participants, etc. Systematic Review Registration: PROSPERO number CRD42017064716. Available at: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42017064716.

Reframing the early childhood obesity prevention narrative through an equitable nurturing approach.

High-quality mother-child interactions during the first 2,000 days, from conception to age 5 years, are considered crucial for preventing obesity development during early life stages. However, mother-child dyads interact within and are influenced by broader socio-ecological contexts involved in shaping child development outcomes, including nutrition. Hence, the coexistence of both undernutrition and obesity has been noted in inequitable social conditions, with drivers of undernutrition and overnutrition in children sharing common elements, such as poverty and food insecurity. To date, a holistic life-course approach to childhood obesity prevention that includes an equitable developmental perspective has not emerged. The World Health Organization (WHO) Nurturing Care Framework provides the foundation for reframing the narrative to understand childhood obesity through the lens of an equitable nurturing care approach to child development from a life-course perspective. In this perspective, we outline our rationale for reframing the childhood narrative by integrating an equitable nurturing care approach to childhood obesity prevention. Four key elements of reframing the narrative include: (a) extending the focus from the current 1,000 to 2,000 days (conception to 5 years); (b) highlighting the importance of nurturing mutually responsive child-caregiver connections to age 5; (c) recognition of racism and related stressors, not solely race/ethnicity, as part of adverse child experiences and social determinants of obesity; and (d) addressing equity by codesigning interventions with socially marginalized families and communities. An equitable, asset-based engagement of families and communities could drive the transformation of policies, systems and social conditions to prevent childhood obesity.

Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions.

BACKGROUND & AIMS: Although pancreatic cystic lesions (PCLs) are frequently and incidentally detected, it is a challenge to determine their risk of malignancy. In immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analyses of tissue and cyst fluid from pancreatic intraductal papillary mucinous neoplasms, the monoclonal antibody Das-1 identifies those at risk for malignancy with high levels of specificity and sensitivity. We aimed to validate the ability of Das-1 to identify high-risk PCLs in comparison to clinical guidelines and clinical features, using samples from a multicenter cohort. METHODS: We obtained cyst fluid samples of 169 PCLs (90 intraductal papillary mucinous neoplasms, 43 mucinous cystic neoplasms, and 36 non-mucinous cysts) from patients undergoing surgery at 4 tertiary referral centers (January 2010 through June 2017). Histology findings from surgical samples, analyzed independently and centrally re-reviewed in a blinded manner, were used as the reference standard. High-risk PCLs were those with invasive carcinomas, high-grade dysplasia, or intestinal-type intraductal papillary mucinous neoplasms with intermediate-grade dysplasia. An ELISA with Das-1 was performed in parallel using banked cyst fluid samples. We evaluated the biomarker's performance, generated area under the curve values, and conducted multivariate logistic regression using clinical and pathology features. RESULTS: The ELISA for Das-1 identified high-risk PCLs with 88% sensitivity, 99% specificity, and 95% accuracy, at a cutoff optical density value of 0.104. In 10-fold cross-validation analysis with 100 replications, Das-1 identified high-risk PCLs with 88% sensitivity and 98% specificity. The Sendai, Fukuoka, and American Gastroenterological Association guideline criteria identified high-risk PCLs with 46%, 52%, and 74% accuracy (P for comparison to Das-1 ELISA <.001). When we controlled for Das-1 in multivariate regression, main pancreatic duct dilation >5 mm (odds ratio, 14.98; 95% confidence interval, 2.63-108; P < .0012), main pancreatic duct dilation ≥1 cm (odds ratio, 47.9; 95% confidence interval, 6.39-490; P < .0001), and jaundice (odds ratio, 6.16; 95% confidence interval, 1.08-36.7; P = .0397) were significantly associated with high-risk PCLs. CONCLUSIONS: We validated the ability of an ELISA with the monoclonal antibody Das-1 to detect PCLs at risk for malignancy with high levels of sensitivity and specificity. This biomarker might be used in conjunction with clinical guidelines to identify patients at risk for malignancy.

Artificial Intelligence and Pathobiology Join Forces in The American Journal of Pathology.

This Editorial describes the extension in scope of The American Journal of Pathology.

Proteomic analysis of the inhibitory effect of the butanolic fraction of Jacquinia macrocarpa on Fusarium verticillioides.

Jacquinia macrocarpa, a plant native to northwestern Mexico, has an inhibitory effect against phytopathogenic fungi. Previous studies have shown that the butanolic extract of J. macrocarpa causes retardation and atrophy in mycelial growth of Fusarium verticillioides. However, the action mechanism of this extract is unknown. We used a proteomics approach to understand the inhibitory effect of J. macrocarpa butanolic extract, based on differential protein accumulation in F. verticillioides. Proteins were extracted from F. verticillioides cultured in Czapek broth with and without 202.12 µg/mL (IC50) of butanolic extract of J. macrocarpa. Thirty-eight protein spots showing statistically significant changes (ANOVA, p < 0.01) and at least a 2-fold change in abundance between experimental conditions were analyzed by mass spectrometry. Identified proteins were grouped into different biological processes according to Gene Ontology, among them were amino acid metabolism, protein folding and stabilization, protein degradation, protein transport, carbohydrate metabolism, oxidative stress response, and miscellaneous. This work is the first report of changes in the proteomic profile of F. verticillioides exposed to the J. macrocarpa extract. This information provides new insights into the inhibitory mechanism of the extract and represents a starting point for dissection of the fungal response against the J. macrocarpa extract components.

Coping with the Unexpected: Patient Trust in Physicians following Delivery.

OBJECTIVE: Patient's trust in physicians is a significant predictor of continuity, adherence, and satisfaction with care. However, it is unclear what influences a woman's trust in her physician. This study sought to determine if women's trust in their clinicians was affected by unexpected outcomes at the time of delivery. STUDY DESIGN: This is a secondary analysis of a prospective cohort of 300 postpartum women with gestational diabetes mellitus. Participants completed the validated Trust in Physician Scale during their postpartum hospitalization. Participants' scores were compared based on their exposure to an unexpected pregnancy outcome. RESULTS: Of the 300 women consented to participate in this study, 294 completed the Trust in Physician Scale. The mean overall trust score was 80/100 with a range of 42 to 100. Unexpected pregnancy outcomes occurred in 41% (120) of women in this cohort. There was no significant difference in the trust score between women who did and did not have at least one unexpected outcome (0.79 vs. 0.79, p = 0.93). Additionally, there was no significant association between the trust score and any individual unexpected pregnancy outcome. CONCLUSION: Unexpected pregnancy outcomes are not associated with changes in women's trust in their obstetric clinicians. These results emphasize the antepartum period as the essential time for patient-physician relationship building which has important implications for postpartum follow-up and long-term psychiatric sequelae from unexpected outcomes.

Chronic administration of Cl-amidine, a pan-peptidylarginine deiminase inhibitor, does not reverse bone loss in two different murine models of osteoporosis.

Recent in vitro studies have shown a role for the peptidyl-arginine deiminases (PADs) in bone resorption. However, it is unknown whether these enzymes are involved in bone loss in vivo. Thus, we evaluated the antiresorptive effect of a pan-PAD inhibitor in two murine models of osteoporosis: (a) primary osteoporosis induced by ovariectomy (OVX); and (b) secondary osteoporosis associated to Type-1 diabetes induced by streptozotocin (STZ, 50 mg/kg, i.p., five daily administrations). Five weeks after OVX and 15 weeks after injections of STZ, mice received daily administrations of Cl-amidine (3 or 10 mg/kg, i.p.) or vehicle for 30 consecutive days. At the end of the treatment, femur and vertebra were harvested for microCT analysis. Blood samples were collected for determination of antibodies against cyclic citrullinated peptides (anti-CCP) by enzyme-linked immunosorbent assay. Serum levels of anti-CCP antibodies from diabetic mice were not significantly different compared to control mice. However, a significant loss of both trabecular bone at the femoral neck and cortical bone at the femoral diaphysis was found in diabetic mice, and Cl-amidine did not reverse the diabetes-induced bone loss. Mice with OVX had significantly lower serum levels of anti-CCP compared to mice with sham surgery. OVX resulted in significant loss of both trabecular bone at the L5 vertebra and distal femoral metaphysis. Cl-amidine did not block the OVX-induced bone loss. Our results suggest that chronic treatment with Cl-amidine at the doses and period of time administered is not long enough to inhibit bone loss in two different murine models of osteoporosis.

High resolution HLA analysis reveals independent class I haplotypes and amino-acid motifs protective for multiple sclerosis.

We investigated association between HLA class I and class II alleles and haplotypes, and KIR loci and their HLA class I ligands, with multiple sclerosis (MS) in 412 European American MS patients and 419 ethnically matched controls, using next-generation sequencing. The DRB1*15:01~DQB1*06:02 haplotype was highly predisposing (odds ratio (OR) = 3.98; 95% confidence interval (CI) = 3-5.31; p-value (p) = 2.22E-16), as was DRB1*03:01~DQB1*02:01 (OR = 1.63; CI = 1.19-2.24; p = 1.41E-03). Hardy-Weinberg (HW) analysis in MS patients revealed a significant DRB1*03:01~DQB1*02:01 homozyote excess (15 observed; 8.6 expected; p = 0.016). The OR for this genotype (5.27; CI = 1.47-28.52; p = 0.0036) suggests a recessive MS risk model. Controls displayed no HW deviations. The C*03:04~B*40:01 haplotype (OR = 0.27; CI = 0.14-0.51; p = 6.76E-06) was highly protective for MS, especially in haplotypes with A*02:01 (OR = 0.15; CI = 0.04-0.45; p = 6.51E-05). By itself, A*02:01 is moderately protective, (OR = 0.69; CI = 0.54-0.87; p = 1.46E-03), and haplotypes of A*02:01 with the HLA-B Thr80 Bw4 variant (Bw4T) more so (OR = 0.53; CI = 0.35-0.78; p = 7.55E-04). Protective associations with the Bw4 KIR ligand resulted from linkage disequilibrium (LD) with DRB1*15:01, but the Bw4T variant was protective (OR = 0.64; CI = 0.49-0.82; p = 3.37-04) independent of LD with DRB1*15:01. The Bw4I variant was not associated with MS. Overall, we find specific class I HLA polymorphisms to be protective for MS, independent of the strong predisposition conferred by DRB1*15:01.

Correction: High resolution HLA analysis reveals independent class I haplotypes and amino-acid motifs protective for multiple sclerosis.

Since the publication of this article, the authors have found that the numbers of patients and controls were reversed. This study included 412 MS patients and 419 controls. This correction applies to the Abstract, the final paragraph of the Introduction, and the first paragraph of the Materials and Methods. This was entirely a reporting error and does not impact the Results or Conclusions.