A real-world study of treatment sequences and second-line clinical outcomes in patients with HER2-positive metastatic breast cancer in US community practice.

PURPOSE: Standard-of-care for HER2-positive metastatic breast cancer (HER2 + mBC) patients consists of trastuzumab ± pertuzumab with chemotherapy in first-line (1L), and ado-trastuzumab emtansine (T-DM1) or the more recently approved trastuzumab deruxtecan (T-DXd) in second-line (2L). Contemporary data on treatment sequencing and real-world effectiveness is limited. This study aims to report 2L treatments and outcomes among HER2 + mBC patients in the United States (US). METHODS: HER2 + mBC patients initiating 2L treatment (index date) between January 2014 and February 2021 were identified from the Syapse Learning Health Network (LHN) database. Summary statistics for patient characteristics, treatment received, reasons for 2L discontinuation and time to 2L-clinical outcomes are reported. RESULTS: Of the 312 patients initiating 2L treatment, had a median age of 59 years (interquartile range [IQR], 50-66) at the start of 2L. The majority were white (69%) and had de novo mBC (62%). Top three 2L regimens included T-DM1 ± endocrine therapy (29%), trastuzumab/pertuzumab/taxane (10%) and T-DM1/trastuzumab (8%). Around 88% discontinued 2L and 63% received subsequent treatment. Median time-to-next-treatment was 10.6 months (95% CI, 8.8-13.3) and real-world progression-free-survival was 7.9 months (95% CI, 7.0-9.9). Among 274 patients who discontinued 2L, 47% discontinued due to progression and 17% because of intolerance/toxicity, respectively. CONCLUSION: This real-world US study showed that approximately two-thirds of 2L patients received subsequent therapy and disease progression was the most common reason for 2L discontinuation highlighting the need for timely 2L treatment with the most efficacious drug to allow patients to achieve longer treatment duration and delayed progression.

Use of Telehealth During the COVID-19 Pandemic Among Practicing Maternal-Fetal Medicine Clinicians.

Background: Limited knowledge exists about the drivers of telehealth use among obstetricians during COVID-19 in the United States. We investigated the use of live video visits by Maternal-Fetal Medicine (MFM) clinicians, the factors associated with use and interest in future use. Methods: We drew survey data from 373 clinicians on two outcomes: (1) use of any (vs. no) live video visits during COVID-19 and (2) among users, the extent of live video use. Bivariate and multivariate logistic regressions quantified the association between predisposing (demographic and practice setting characteristics) and enabling factors (prepandemic telehealth use, structural and perceived patient barriers) and each outcome. Results: During the pandemic, 88% reported any use, a jump from 29% prepandemic utilization. Users (vs. nonusers) were younger (p = 0.02); tended to provide comprehensive prenatal care (p = 0.01) and/or inpatient care (p = 0.02), practice in university settings (p = 0.01), engage in various telehealth modalities prepandemic (p ≤ 0.01), and to perceive challenges with technical (p < 0.01), reimbursement (p = 0.05), and patient barriers to internet or data plan access (p ≤ 0.001). After adjusting for covariates, only prepandemic communication through patient portal (adjusted odds ratio [aOR] = 3.85; 95% confidence interval [CI] = 1.33-11.12), perceived patient access barriers (aOR = 5.27; 95% CI = 1.95-14.23), and practice in multiple versus university settings (aOR = 0.18; 95% CI = 0.06-0.56) remained significantly associated with use. Approximately 44% were high users. Prepandemic ultrasound use (aOR = 1.92; 95% CI = 1.17-3.16), perceived patient access barriers (aOR = 1.85; 95% CI = 1.12-3.06) and Midwest versus North practice location (aOR = 0.46; 95% CI = 0.21-0.98) predicted high use. Among high users, 99% wanted to continue offering video visits. Conclusions: We found widespread use of live video obstetric care by MFM clinicians and continued interest in use postpandemic.

Mother-child histocompatibility and risk of rheumatoid arthritis and systemic lupus erythematosus among mothers.

The study objective was to test the hypothesis that having histocompatible children increases the risk of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), possibly by contributing to the persistence of fetal cells acquired during pregnancy. We conducted a case control study using data from the UC San Francisco Mother Child Immunogenetic Study and studies at the Inova Translational Medicine Institute. We imputed human leukocyte antigen (HLA) alleles and minor histocompatibility antigens (mHags). We created a variable of exposure to histocompatible children. We estimated an average sequence similarity matching (SSM) score for each mother based on discordant mother-child alleles as a measure of histocompatibility. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals. A total of 138 RA, 117 SLE, and 913 control mothers were analyzed. Increased risk of RA was associated with having any child compatible at HLA-B (OR 1.9; 1.2-3.1), DPB1 (OR 1.8; 1.2-2.6) or DQB1 (OR 1.8; 1.2-2.7). Compatibility at mHag ZAPHIR was associated with reduced risk of SLE among mothers carrying the HLA-restriction allele B*07:02 (n = 262; OR 0.4; 0.2-0.8). Our findings support the hypothesis that mother-child histocompatibility is associated with risk of RA and SLE.

Increased risk of rheumatoid arthritis among mothers with children who carry DRB1 risk-associated alleles.

OBJECTIVE: To investigate whether a child's genotype affects a mother's risk of rheumatoid arthritis (RA) beyond the risk associated with her genotype and to test whether exposure to fetal alleles inherited from the father increases risk of RA among mothers without risk alleles. METHODS: A case-control study was conducted among 1165 mothers (170 cases/995 controls) and their respective 1482 children. We tested the association between having any child with alleles encoding amino acids (AAs) associated with RA including the 'shared epitope' (SE) and DERAA AA sequences at positions 70-74; AA valine, lysine and alanine at positions 11, 71 and 74 of HLA-DRB1; aspartic acid at position 9 of HLA-B and phenylalanine at position 9 of DPB1. We used logistic regression models to estimate OR and 95% CI for each group of alleles, adjusting for maternal genotype and number of live births. RESULTS: We found increased risk of RA among mothers who had any child with SE (OR 3.0; 95% CI 2.0 to 4.6); DERAA (OR 1.7; 95% CI 1.1 to 2.6); or valine (OR 2.3; 95% CI 1.6 to 3.5), lysine (OR 2.3; 95% CI 1.5 to 3.4) and alanine (OR 2.8; 95% CI 1.2 to 6.4) at DRB1 positions 11, 71 and 74, respectively. Among non-carrier mothers, increased risk of RA was associated with having children who carried DERAA (OR 1.7; 95% CI 1.0 to 2.7) and alleles encoding lysine at DRB1 position 71 (OR 2.3; 95% CI 1.5 to 4.8). CONCLUSION: Findings support the hypothesis that a child's genotype can contribute independently to risk of RA among mothers.

A Child's HLA-DRB1 genotype increases maternal risk of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) disproportionately affects women of reproductive age. During pregnancy, women are exposed to various sources of fetal material possibly constituting a significant immunologic exposure relevant to the development of SLE. The objective of this study was to investigate whether having any children who carry DRB1 alleles associated with SLE increase the risk of maternal SLE. This case-control study is based on the University of California, San Francisco Mother-Child Immunogenetic Study and from studies at the Inova Translational Medicine Institute. Analyses were conducted using data for 1304 mothers (219 cases/1085 controls) and their respective 1664 children. We selected alleles based on their known association with risk of SLE (DRB1*03:01, *15:01, or *08:01) or Epstein-Barr virus (EBV) glycoproteins (*04:01) due to the established EBV association with SLE risk. We used logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for each allele of interest, taking into account maternal genotype and number of live births. We found an increase in risk of maternal SLE associated with exposure to children who inherited DRB1*04:01 from their father (OR 1.9; 95% CI, 1.1-3.2), among *04:01 allele-negative mothers. Increased risk was only present among mothers who were positive for one or more SLE risk-associated alleles (*03:01, *15:01 and/or *08:01). We did not find increased risk of maternal SLE associated with any other tested allele. These findings support the hypothesis that a child's alleles inherited from the father influence a mother's subsequent risk of SLE.

[Factors that influence the interruption of exclusive breastfeeding in nursing mothers]. / Fatores que influenciam na interrupção do aleitamento materno exclusivo em nutrizes.

OBJECTIVE: To identify factors that can influence nursing mothers to interrupt exclusive breastfeeding during the first six months of life of the infant. METHOD: Descriptive, exploratory, qualitative research. Information was collected through semi-structured interviews with 14 nursing mothers who had received prenatal care in the Family Basic Health Units in the city of Campina Grande - PB, from April to May 2013. The data were subjected to the content analysis technique proposed by Bardin. RESULTS: The nursing mothers had little knowledge of the mother-child bond, reduced family spending on child nutrition and the risk of bleeding after delivery. Their beliefs included insufficient milk production, the child´s rejection of the breast, and the possibility of various mammary postpartum complications. CONCLUSIONS: It is necessary to expand the guidance and support of breastfeeding for nursing mothers in the early postpartum period.

First isolate of KPC-2-producing Klebsiella pneumonaie sequence type 23 from the Americas.

KPC-2-producing Klebsiella pneumoniae isolates mainly correspond to clonal complex 258 (CC258); however, we describe KPC-2-producing K. pneumoniae isolates belonging to invasive sequence type 23 (ST23). KPC-2 has scarcely been reported to occur in ST23, and this report describes the first isolation of this pathogen in the Americas. Acquisition of resistant markers in virulent clones could mark an evolutionary step toward the establishment of these clones as major nosocomial pathogens.

A Descriptive Study of Corneal Graft Failure in Retransplant Patients.

OBJECTIVE: To identify the main predictors for corneal graft failure in patients who underwent retransplantation. METHOD: This is a cross-sectional research with a quantitative and analytical approach, conducted based on data from secondary sources of a Human Eye Tissue Bank (HETB) in Northeast Brazil. Data were collected from the medical charts of all patients transplanted between January 2010 and December 2014. Descriptive statistics were used for the univariate analysis by means of absolute and relative frequencies and means. For the inferential analysis, the chi-square (X²) and the Fisher's Exact tests were used. RESULTS: A total of 241 records were reviewed, representing 258 keratoplasties, of which 27 (10.46%) were retransplantations due to corneal graft failure. Of the total, 55.56% of the individuals were female, with a mean age of 58.56 years, 55.56% of the population was brown, and the highest relative frequency of housing found was in the Central Mesoregion. Of the corneal graft failure cases, 88.89% were due to late failure, 30.77% of cases were classified as pseudophakic and 11.57% as aphakic. Through inferential analysis, a statistical association was obtained among the variable "corneal graft failure" and mesoregion of the state, presence of glaucoma, vascularization, and classification of the eye. CONCLUSION: The prognosis of keratoplasty is of multifactorial nature. Factors such as mesoregion of the State (place of residence), glaucoma, corneal vascularization, and aphakic eyes represent predictors for graft failure in the analyzed sample.

Hypothesized role of pregnancy hormones on HER2+ breast tumor development.

Breast cancer incidence rates have declined among older but not younger women; the latter are more likely to be diagnosed with breast cancers carrying a poor prognosis. Epidemiological evidence supports an increase in breast cancer incidence following pregnancy with risk elevated as much as 10 years post-partum. We investigated the association between years since last full-term pregnancy at the time of diagnosis (≤10 or >10 years) and breast tumor subtype in a case series of premenopausal Hispanic women (n = 627). Participants were recruited in the United States, Mexico, and Spain. Cases with known estrogen receptor (ER), progesterone receptor (PR), and HER2 status, with one or more full-term pregnancies ≥1 year prior to diagnosis were eligible for this analysis. Cases were classified into three tumor subtypes according to hormone receptor (HR+ = ER+ and/or PR+; HR- = ER- and PR-) expression and HER2 status: HR+/HER2-, HER2+ (regardless of HR), and triple negative breast cancer. Case-only odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for HER2+ tumors in reference to HR+/HER2- tumors. Participants were pooled in a mixed-effects logistic regression model with years since pregnancy as a fixed effect and study site as a random effect. When compared to HR+/HER2- cases, women with HER2+ tumors were more likely be diagnosed in the post-partum period of ≤10 years (OR = 1.68; 95 % CI, 1.12-2.52). The effect was present across all source populations and independent of the HR status of the HER2+ tumor. Adjusting for age at diagnosis (≤45 or >45 years) did not materially alter our results (OR = 1.78; 95 % CI, 1.08-2.93). These findings support the novel hypothesis that factors associated with the post-partum breast, possibly hormonal, are involved in the development of HER2+ tumors.

Factors that influence mammography use and breast cancer detection among Mexican-American and African-American women.

OBJECTIVE: This study examined factors that influence mammography use and breast cancer detection, including education, health insurance, and acculturation, among Mexican-American (MA) and African-American (AA) women. METHODS: The study included 670 breast cancer cases (388 MAs and 282 AAs), aged 40-86 years at diagnosis. Data on mammography use, detection, and delay in seeking care were collected via questionnaires and medical records. Using a language-based bidimensional acculturation measure, MAs were classified as English-dominant (n = 67), bilingual (n = 173), and Spanish-dominant (n = 148). Mammography prior to diagnosis was assessed by racial/ethnic acculturation subgroup using logistic regression. RESULTS: In age-adjusted models, mammography use was non-significantly lower among English-dominant (OR = 0.84; 95% CI: 0.45-1.59) and bilingual (OR = 0.86; 95% CI: 0.55-1.35) MAs and significantly lower among Spanish-dominant MAs (OR = 0.53; 95% CI: 0.34-0.83) than among AA women. After adjustment for education or insurance, there was no difference in mammography use by race/ethnicity and acculturation subgroup. Despite high self-reported mammography use (75%), a large proportion of cases reported self-detection (59%) and delay in seeking care >90 days (17%). CONCLUSIONS: These findings favor promoting culturally appropriate messaging about the benefits and limitations of mammography, education about breast awareness, and prompt reporting of findings to a health professional.

Screening for High-Risk Human Papillomavirus Using Passive, Self-Collected Menstrual Blood.

OBJECTIVE: To assess concordance and acceptability of a modified menstrual pad compared with a clinician-collected high-risk human papillomavirus (HPV) sample. METHODS: This was a prospective observational study. Women presenting for either cervical cancer screening or with a history of high-risk HPV positivity were eligible. Three samples were requested from participants: 1) clinician-collected cervical specimens; 2) self-collected vaginal swabs; and 3) a modified menstrual pad, which was taken home for use during the next menstruation. All samples were processed using the Cobas HPV test. Menstrual pad dried blood spots were eluted, then similarly processed. RESULTS: Of 153 women enrolled in the study, 106 provided menstrual pad samples and clinician-collected cervical specimens for high-risk HPV analysis. For samples in which the interval between the clinician-collected specimen and the menstrual pad sample was less than 2 months, the concordance was 94% (95% CI 83-98). For women who tested positive for high-risk HPV who presented for general screening and those with more than cervical intraepithelial neoplasia 2, menstrual pad and clinician-collected specimen agreement was 100% (95% CI 32.5-100). Among participants, 22.9% expressed discomfort with the self-collected vaginal swabs and opted out of collection. Overall, 94.0% of participants preferred the menstrual pad over clinician-collected sampling. Twelve patients were found to be positive for HPV on the menstrual pad sample but negative on the clinician-collected specimen. CONCLUSION: Among women who tested positive for HPV, the menstrual pad showed highly concordant results compared with clinician-collected sampling. This collection approach shows promise for integration into cervical cancer prevention programs.

The menstrual cycle phase impacts the detection of plasma cells and the diagnosis of chronic endometritis in endometrial biopsy specimens.

OBJECTIVE: To assess the impact of menstrual cycle phase on the detection of plasma cells. DESIGN: A retrospective cohort study. SETTING: Fertility clinic. PATIENT(S): Biopsies from 157 patients met criteria for inclusion, 91 in the follicular phase and 60 in the luteal phase. Patient groups were similar in body mass index and number of previous live births; however, differed in terms of age, infertility history, and biopsy indication. INTERVENTIONS: Endometrial biopsies from patients at a fertility clinic from 2018-2020 were retrospectively reviewed. Biopsies were excluded if patients had a previous chronic endometritis diagnosis, abnormal uterine cavity or were on hormone therapy. Each case was reviewed by a gynecologic pathologist for plasma cells by hematoxylin and eosin and CD138 staining. Demographic and clinical data were collected. Continuous variables were compared using Welch t test and Wilcoxon's rank sum test, and categorical variables using Pearson's χ2 test. Logistic regression was used to calculate odds ratio and 95% confidence intervals for the association between the presence of plasma cells and cycle phase. Multinomial logistic regression was used to estimate the odds ratios for nominal outcomes. Pathology reports were reviewed. Plasma cell enumeration using hematoxylin and eosin-stained sections and CD138 immunohistochemical stains (performed at the time of biopsy by a gynecologic pathologist) was recorded. MAIN OUTCOME MEASURE(S): Presence and density of plasma cells. RESULT(S): We found a higher likelihood of finding plasma cells in the follicular than in luteal phase (59.3% vs. 19.7%). There was a higher likelihood of finding plasma cells in the early (cycle days 5-8, 29 cases or 76.3% of cases with plasma cells) than in the late follicular phase (cycle days 9-14, 25 cases or 47.2%). There was a higher density of plasma cells in the follicular phase group than in the luteal phase group (25.3% vs. 1.5% scattered and 13.2% vs. 0 clusters). CONCLUSION(S): Plasma cells are more likely to be present during the follicular phase compared with the luteal phase and in the early compared with the late follicular phase. Further studies are needed to identify the optimal timing of biopsy to standardize the diagnosis.

An exploratory analysis of leukocyte telomere length among pregnant and non-pregnant people.

Background: Leukocyte telomere length (LTL) is a biomarker that is affected by older age, psychosocial stress, and medical comorbidities. Despite the relevance of these factors to obstetric practice, little is known about LTL in pregnancy. Our study explored longitudinal LTL dynamics in pregnant and non-pregnant people. Objective: This pilot study compares changes in LTL between pregnant and non-pregnant people over time, explores potential correlations between LTL and mental health measures, and investigates associations between short first-trimester LTL and adverse pregnancy outcomes. Study design: This was a prospective pilot cohort study of nulliparous pregnant and non-pregnant people between ages 18 and 50 who presented for care at a single institution from January to November 2020. Pregnant people were enrolled between 10 and 14 weeks gestation. Participants had two blood samples drawn for LTL; the first on the day of enrollment and the second on postpartum day 1 (pregnant cohort) or 7 months later (non-pregnant cohort). LTL was measured using quantitative PCR. The primary outcome was the difference between pregnant and non-pregnant people in LTL change between the two timepoints (basepair difference per 30-day period). Secondary outcomes included differences in responses to the Patient Health Questionnaire-9 (PHQ-9) and a survey about stress related to COVID-19. Differences in LTL were tested using t-tests and linear regression models, both crude and adjusted for age. A subgroup analysis was conducted within the pregnant cohort to examine whether shorter first-trimester LTL was associated with adverse pregnancy outcomes. We conducted t-tests to compare LTL between people with and without each categorical outcome and computed Pearson correlation coefficients between LTL and continuous outcomes such as gestational age at delivery. Results: 46 pregnant and 30 non-pregnant people were enrolled; 44 pregnant and 18 non-pregnant people completed all LTL assessments. There were no between-group differences in LTL change (-4.2 ± 22.2 bp per 30 days pregnant versus -6.4 ± 11.2 bp per 30 days non-pregnant, adjusted beta 2.1, 95% CI -9.0-13.2, p = 0.60). The prevalence of depression and pandemic-related stress were both low overall. The two groups did not differ in PHQ-9 scores, and no correlations were significant between LTL and PHQ-9 scores. Among the 44 pregnant people, shorter first-trimester LTL was significantly correlated with earlier gestational age at delivery (r = 0.35, p = 0.02). Conclusion: In this exploratory pilot cohort of reproductive-aged people with low levels of psychological stress, we described baseline changes in LTL over time in pregnant and non-pregnant participants. We found a correlation between shorter first-trimester LTL and earlier gestational age at delivery, which warrants further investigation in a larger cohort.

HMOX1 Genetic Polymorphisms Display Ancestral Diversity and May Be Linked to Hypertensive Disorders in Pregnancy.

Racial disparity exists for hypertensive disorders in pregnancy (HDP), which leads to disparate morbidity and mortality worldwide. The enzyme heme oxygenase-1 (HO-1) is encoded by HMOX1, which has genetic polymorphisms in its regulatory region that impact its expression and activity and have been associated with various diseases. However, studies of these genetic variants in HDP have been limited. The objective of this study was to examine HMOX1 as a potential genetic contributor of ancestral disparity seen in HDP. First, the 1000 Genomes Project (1 KG) phase 3 was utilized to compare the frequencies of alleles, genotypes, and estimated haplotypes of guanidine thymidine repeats (GTn; containing rs3074372) and A/T SNP (rs2071746) among females from five ancestral populations (Africa, the Americas, Europe, East Asia, and South Asia, N = 1271). Then, using genomic DNA from women with a history of HDP, we explored the possibility of HMOX1 variants predisposing women to HDP (N = 178) compared with an equivalent ancestral group from 1 KG (N = 263). Both HMOX1 variants were distributed differently across ancestries, with African women having a distinct distribution and an overall higher prevalence of the variants previously associated with lower HO-1 expression. The two HMOX1 variants display linkage disequilibrium in all but the African group, and within EUR cohort, LL and AA individuals have a higher prevalence in HDP. HMOX1 variants demonstrate ancestral differences that may contribute to racial disparity in HDP. Understanding maternal genetic contribution to HDP will help improve prediction and facilitate personalized approaches to care for HDP.

Donation Process and Evaluation of Corneal Tissue in a Slit Lamp.

BACKGROUND: The process of capturing and classifying the viability of corneal tissue for corneal transplantation is complex. The biomicroscopic examination is one of the techniques used to evaluate the quality of corneal tissues. The aim of this study was to analyze the relationship between the evaluation criteria used in biomicroscopic examination using a slit lamp and the classification of the quality of corneal tissue. METHODS: This is a longitudinal, retrospective cohort study, performed at the Human Ocular Tissue Bank in the state of Rio Grande do Norte, Brazil. The sample consisted of 419 corneas donated between 2005 to 2016. RESULTS: After the evaluation, the 419 corneas were classified as excellent (8 -1.91%), good (217 - 51.79%), regular (85 - 20.29%), and bad (109 - 26.01%). The classification of corneal quality attributed by ophthalmologists considered 13 criteria: senile arch, scars, epithelial defect, epithelial exposure, stromal infiltrate, subepithelial opacity, pterygium, Descemet's folds, stromal edema, stromal streak, cornea guttata, specular reflex, and cell loss endothelial. The quality of the cornea classified as excellent and good showed a statistically significant association (P value < .05) with senile arch, scar, epithelial defect, epithelial exposure, Descemet's folds, stromal edema, stromal streak, cornea guttata, specular reflex, and losses of endothelial cells; they had evaluated criteria that were absent or slightly present. CONCLUSIONS: The evaluation of the corneal quality for corneal transplantation should involve the implementation of reliable techniques and trained, qualified professionals. There is a need to create evaluation instruments that consider the criteria according to their degree of interference in the quality of corneal tissue.

Heparin versus 0.9% sodium chloride intermittent flushing for preventing occlusion in newborns with peripherally inserted central catheters: A systematic review protocol.

BACKGROUND: Mechanical factors are primary complications that justify early removal of a peripherally inserted central catheter, and thrombotic catheter occlusion is the most critical mechanical complication associated with loss of device functionality. Studies have investigated these factors in adult patients, but findings are not directly applicable to newborns. Therefore, systematic reviews focusing on this population are necessary for consolidated evidence to aid clinical practice. AIMS: This study aims to evaluate the efficacy of intermittent heparin washing versus 0.9% sodium chloride solution for preventing occlusion in newborns with peripherally inserted central catheters. METHODS: We will use the PubMed, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, CINAHL, and Clinical Trial Databases for article search, without language or publication periods restrictions. Randomized clinical trials evaluating the use of intermittent heparin washing versus 0.9% sodium chloride solution in newborns with peripherally inserted central venous catheters will be included. The primary outcome will be peripherally inserted central catheter occlusion. Two reviewers will independently screen the studies, based on the inclusion criteria, extract the data for each included study and assess the risk of bias using the Cochrane risk of bias tool. The data will be synthesized using the Review Manager software (RevMan 5.4.1). To classify the strength of the evidence of results, we will use the Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE). The review was registered with PROSPERO (registration number CRD42021281509). EXPECTED RESULTS: We expect that this study would reveal the best method for preventing catheter occlusion in newborns with peripherally inserted central catheters.

Addressing postpartum contraception practices utilizing a multidisciplinary Pregnancy Heart Team approach.

BACKGROUND: Cardiovascular disease has emerged as the leading cause of maternal morbidity and mortality, making planned pregnancy, and thereby reliable contraception among people with cardiovascular disease, vital. OBJECTIVE: This study aimed to compare postpartum contraceptive practices among people with cardiovascular disease (cardiac cohort) cared for by a Pregnancy Heart Team to people with other chronic comorbidities (high-risk cohort), and people without comorbidities (low-risk cohort). We hypothesized that the Pregnancy Heart Team influenced baseline contraception counseling and practices among those with cardiovascular disease. STUDY DESIGN: This was a retrospective cohort study comparing postpartum contraceptive practices between a cardiac cohort who received care by a multidisciplinary team between 2012 and 2020 and high-risk and low-risk cohorts delivering at a single academic center between 2016 and 2019. We investigated presence of a contraceptive plan (at birthing admission, discharge, and postpartum visit) and uptake of reliable contraception by 8 weeks postpartum. RESULTS: We included 1464 people: 189 with cardiovascular disease, 197 with other chronic comorbidities, and 1078 low-risk people. At birth hospitalization admission, reliable contraception was planned among 42% of the cardiac cohort, 40% of the high-risk cohort, and 31% of the low-risk cohort, with similar distributions at the time of discharge and at 8 weeks postpartum. Compared with the cardiac cohort, by 8 weeks postpartum, the high-risk cohort had similar odds of using highly reliable forms of contraception (39% vs 36%; adjusted odds ratio, 0.78; 95% confidence interval, 0.50-1.21) and similar odds of having a plan to use the most reliable forms of contraception (intrauterine device, implant, bilateral tubal ligation) at the time of birthing admission (42% vs 40%; adjusted odds ratio, 0.78; 95% confidence interval, 0.50-1.22), discharge (47% vs 45%; adjusted odds ratio, 0.95; 95% confidence interval, 0.61-1.48), and postpartum visit (35% vs 29%; adjusted odds ratio, 0.76; 95% confidence interval, 0.49-1.17). The low-risk cohort had lower odds of using a reliable form of contraception (39% vs 27%; adjusted odds ratio, 0.53; 95% confidence interval, 0.37-0.75) and was less likely to have a plan for reliable contraception at the time of birthing admission (42% vs 31%; adjusted odds ratio, 0.54; 95% confidence interval, 0.38-0.76), discharge (47% vs 33%; adjusted odds ratio, 0.58; 95% confidence interval, 0.4-0.82), and postpartum visit (35% vs 21%; adjusted odds ratio, 0.50; 95% confidence interval, 0.35-0.71). CONCLUSION: People with cardiovascular disease cared for by a Pregnancy Heart Team had higher odds of reliable postpartum contraception planning and uptake compared with a low-risk cohort and similar odds compared with a high-risk cohort. Pregnancy could serve as a critical period for contraception counseling and family planning among people with cardiovascular disease. A multidisciplinary team should be used to address postpartum contraception as a modifiable risk factor to reduce maternal morbidity and mortality among those with cardiovascular disease.

Glutathione-related genetic polymorphisms are associated with mercury retention and nephrotoxicity in gold-mining settings of a Colombian population.

Mercury (Hg) vapor can produce kidney injury, where the proximal tubule region of the nephron is the main target of the Hg-induced oxidative stress. Hg is eliminated from the body as a glutathione conjugate. Thus, single nucleotide polymorphisms (SNPs) in glutathione-related genes might modulate the negative impact of this metal on the kidneys. Glutathione-related SNPs were tested for association with levels of Hg and renal function biomarkers between occupationally exposed (n = 160) and non-exposed subjects (n = 121). SNPs were genotyped by TaqMan assays in genomic DNA samples. Total mercury concentration was measured in blood, urine and hair samples. Regression analyses were performed to estimate the effects of SNPs on quantitative traits. Alleles GCLM rs41303970-T and GSTP1 rs4147581-C were significantly overrepresented in the exposed compared with the non-exposed group (P < 0.01). We found significant associations for GCLM rs41303970-T with higher urinary clearance rate of Hg (ß = 0.062, P = 0.047), whereas GCLC rs1555903-C was associated with lower levels of estimated glomerular filtration rate in the non-exposed group (eGFR, ß = - 3.22, P = 0.008) and beta-2-microglobulin in the exposed group (ß-2MCG, ß = - 19.32, P = 0.02). A SNP-SNP interaction analysis showed significant epistasis between GSTA1 rs3957356-C and GSS rs3761144-G with higher urinary levels of Hg in the exposed (ß = 0.13, P = 0.04) but not in the non-exposed group. Our results suggest that SNPs in glutathione-related genes could modulate the pathogenesis of Hg nephrotoxicity in our study population by modulating glutathione concentrations in individuals occupationally exposed to this heavy metal.

Cornea donation process and tissue quality for transplantation.

INTRODUCTION: The quality of the corneal tissue can be influenced by several factors inherent to the recipient, donor, and to the donation and transplantation process. The donated corneal tissue can be classified by its quality as excellent, good, regular, bad, or unacceptable for transplantation, evaluating it in a slit lamp. OBJECTIVE: To analyze the relationship between the clinical and sociodemographic variables of the donors and the donation process and the classification of the quality of the corneal tissue collected for transplantation. METHODS: This is an epidemiologic study, retrospective cohort type, which addressed the process of cornea donation by the Human Eye Tissue Bank in a reference service in Northeast Brazil. The sample consisted of corneas processed by the Human Eye Tissue Bank of Rio Grande do Norte (n = 419). For descriptive and inferential analysis, the study used the Statistical Package for the Social Sciences (SPSS) software, version 25.0, and considered a significance level of 0.05. Logistic regression analysis was used for the adjustment of the final model. RESULTS: It was verified that the epidemiological profile showed a prevalence of individuals with a mean age of 42.54 years old, male (73.99%), and living in the metropolitan region of the state capital (75.66%). When analyzing the relationship between the clinical and sociodemographic variables of the donors, it was identified that those aged 45 years old or less had better quality corneas (excellent and good), while the chronological variables were predictive factors for corneas of regular and bad qualities. CONCLUSION: The identification of the factors inherent to the donation process and predictors of corneal tissue quality contribute to minimizing the risk of transplantation and to a better ocular prognosis.

Genetic Polymorphisms in Multispecific Transporters Mitigate Mercury Nephrotoxicity in an Artisanal and Small-Scale Gold Mining Community in Colombia.

In artisanal and small-scale gold mining, occupational exposure to mercury (Hg) vapor is related to harmful effects on several organs, including the kidneys. We previously reported significantly increased levels of Hg in blood and urine despite normal kidney function in individuals from Colombia occupationally exposed to Hg compared with those nonexposed. We evaluated the contribution of 4 genetic variants in key genes encoding the transporters solute carrier (SLC; rs4149170 and rs4149182) and ATP-binding cassette(ABC; rs1202169 and rs1885301) in the pathogenesis of nephrotoxicity due to Hg exposure in these groups. Regression analysis was performed to determine the association between the blood- and urine-Hg concentration with SLC and ABC polymorphisms in 281 Colombian individuals (160 exposed and 121 nonexposed to Hg). We found an enrichment of ABCB1 rs1202169-T allele in the exposed group (p = .011; OR= 2.05; 95% CI = 1.18-3.58) compared with the nonexposure group. We also found that carriers of SLC22A8 rs4149182-G and ABCB1 rs1202169-T alleles had a higher urinary clearance rate of Hg than noncarriers (ß = 0.13, p = .04), whereas carriers of SLC22A6 rs4149170-A and ABCB1 rs1202169-C alleles showed abnormal levels of estimated glomerular filtration rate (ß = -84.96, p = .040) and beta-2-microglobulin (ß = 743.38, p < .001). Our results suggest that ABCB1 rs1202169 and its interaction with SLC22A8 rs4149182 and SLC22A6 rs4149170 could mitigate Hg nephrotoxicity by controlling the renal proximal tubule cell accumulation of inorganic Hg. This will be useful to estimate the risk of kidney toxicity associated to Hg and the genetic selection to aid adaptation to Hg-rich environments.