Management of fetal head and neck masses: Evaluation of prenatal factors associated with airway obstruction and decision for definitive airway and ex-utero intrapartum treatment at birth.

OBJECTIVE: Fetal head and neck masses can result in critical airway obstruction. Our study aimed to evaluate prenatal factors associated with the decision for a definitive airway, including ex-utero intrapartum treatment (EXIT), at birth among at-risk fetuses. METHODS: A single-institution retrospective review evaluated all fetal head and neck masses prenatally diagnosed from 2005 to 2023. The primary outcome was the decision for a definitive airway at birth, including intubation, tracheostomy, or EXIT. RESULTS: Thirty four patients were included, with 23 deliveries occurring at our institution. 8/23 (35%) patients received a definitive airway at birth, six underwent an EXIT procedure, and two required intubation only. Patients who received a definitive airway had higher rates of polyhydramnios (50% vs. 7%, p = 0.03), tracheal narrowing on ultrasound (US) (50% vs. 0%, p = 0.01), tracheal displacement on US (63% vs. 0%, p < 0.01), abnormal fetal breathing on US (50% vs. 0%, p = 0.01), tracheal narrowing or displacement on magnetic resonance imaging (MRI) (75% vs. 7%, p < 0.01), and larger mass maximum diameter (7.9 vs. 4.3 cm, p = 0.02). In our series, 100% of patients with polyhydramnios, tracheal narrowing or displacement on either US or MRI, and abnormal fetal breathing on US received a definitive airway at birth. CONCLUSION: Prenatal findings of tracheal narrowing or displacement, polyhydramnios, and abnormal fetal breathing are strongly associated with the decision for a definitive airway at birth and warrant mobilization of appropriate resources.

Parametric Solid Models of the At-Term Uterus From Magnetic Resonance Images.

Birthing mechanics are poorly understood, though many injuries during childbirth are mechanical, like fetal and maternal tissue damage. Several biomechanical simulation models of parturition have been proposed to investigate birth, but many do not include the uterus. Additionally, most solid models rely on segmenting anatomical structures from clinical images to generate patient geometry, which can be time-consuming. This work presents two new parametric solid modeling methods for generating patient-specific, at-term uterine three-dimensional geometry. Building from an established method of modeling the sagittal uterine shape, this work improves the uterine coronal shape, especially where the fetal head joins the lower uterine wall. Solid models of the uterus and cervix were built from five at-term patients' magnetic resonance imaging (MRI) sets. Using anatomy measurements from MRI-segmented models, two parametric models were created-one that employs an averaged coronal uterine shape and one with multiple axial measurements of the coronal uterus. Through finite element analysis, the two new parametric methods were compared to the MRI-segmented high-fidelity method and a previously published elliptical low-fidelity method. A clear improvement in the at-term uterine shape was found using the two new parametric methods, and agreement in principal Lagrange strain directions was observed across all modeling methods. These methods provide an effective and efficient way to generate three-dimensional solid models of patient-specific maternal uterine anatomy, advancing possibilities for future research in computational birthing biomechanics.

Pre- and Periviable PPROM after Fetoscopic Laser Surgery: Are Survival Outcomes Better than We Think?

INTRODUCTION: Limited data exist regarding outcomes when pre- and periviable PPROM (PPROM ≤26 weeks of gestation) occurs as a complication of fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS). METHODS: This is a retrospective cohort study of FLS cases performed at a single institution between January 2015 and May 2021. Study inclusion was limited to patients with monochorionic-diamniotic twin pregnancies complicated by TTTS who underwent FLS. Patients were grouped by pPPROM status, and further stratified to those continuing with expectant management, and outcomes were compared between groups. The primary outcome was survival to live birth of at least one twin. RESULTS: During the study period, 171 patients underwent FLS and a total of 96 (56.1%) subjects satisfied inclusion criteria. Among included subjects, 18 (18.8%) experienced pPPROM after FLS and 78 (81.2%) did not. Baseline characteristics were similar between groups. Among patients with pPPROM, 11 (61.1%) pursued expectant management and 7 (38.9%) opted for pregnancy termination. Among expectantly managed subjects, median pPPROM-to-delivery interval was 47.0 days (6.0-66.0 IQR) with a median gestational age at delivery of 29+1 weeks (24 + 4-33 + 6 IQR). Rates of survival to live birth of at least one twin (90.9% vs. 96.2% p = 0.42) were similar between those with pPPROM undergoing expectant management and those without pPPROM. Dual survivorship (45.5% vs. 78.2%, p = 0.03), perinatal survival to live birth (68.2% vs. 87.2%, p = 0.05), and perinatal survival to newborn hospital discharge (59.1% vs. 85.9%, p = <0.01) were all significantly lower among those with pPPROM. Gestational age at delivery was lower among those continuing with pregnancies complicated by pPPROM (29 + 1 vs. 32+5 weeks, p = <0.01). CONCLUSION: Survival of at least one twin to live birth remained high among those pursing expectant management after experiencing post-FLS pPPROM, suggesting that the outlook after this complication is not necessarily poor. However, this complication was associated with lower chances of dual survival and greater prematurity.

Investigation into the genetics of fetal congenital lymphatic anomalies.

OBJECTIVE: Congenital lymphatic anomalies (LAs) arise due to defects in lymphatic development and often present in utero as pleural effusion, chylothorax, nuchal and soft tissue edema, ascites, or hydrops. Many LAs are caused by single nucleotide variants, which are not detected on routine prenatal testing. METHODS: Demographic data were compared between two subcohorts, those with clinically significant fetal edema (CSFE) and isolated fetal edema. A targeted variant analysis of LA genes was performed using American College of Medical Genetics criteria on whole exome sequencing (WES) data generated for 71 fetal edema cases who remained undiagnosed after standard workup. RESULTS: CSFE cases had poor outcomes, including preterm delivery, demise, and maternal preeclampsia. Pathogenic and likely pathogenic variants were identified in 7% (5/71) of cases, including variants in RASopathy genes, RASA1, SOS1, PTPN11, and a novel PIEZO1 variant. Variants of uncertain significance (VOUS) were identified in 45% (32/71) of cases. In CSFEs, VOUS were found in CELSR1, EPHB4, TIE1, PIEZO1, ITGA9, RASopathy genes, SOS1, SOS2, and RAF1. CONCLUSIONS: WES identified pathogenic and likely pathogenic variants and VOUS in LA genes in 51% of fetal edema cases, supporting WES and expanded hydrops panels in cases of idiopathic fetal hydrops and fluid collections.

Sleep-disordered Breathing in Pregnancy and after Delivery: Associations with Cardiometabolic Health.

Rationale: Knowledge gaps exist regarding health implications of sleep-disordered breathing (SDB) identified in pregnancy and/or after delivery. Objectives: To determine whether SDB in pregnancy and/or after delivery is associated with hypertension (HTN) and metabolic syndrome (MS). Methods: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be Heart Health Study) (N = 4,508) followed participants initially recruited during their first pregnancy. Participants returned for a visit 2-7 years after pregnancy. This study examined a subgroup who underwent SDB assessments during their first pregnancy (n = 1,964) and a repeat SDB assessment after delivery (n = 1,222). Two SDB definitions were considered: 1) apnea-hypopnea index (AHI) ⩾ 5 and 2) oxygen desaturation index (ODI) ⩾ 5. Associations between SDB and incident HTN and MS were evaluated with adjusted risk ratios (aRRs). Measurements and Main Results: The aRR for MS given an AHI ⩾ 5 during pregnancy was 1.44 (95% confidence interval [CI], 1.08-1.93), but no association with HTN was found. ODI ⩾ 5 in pregnancy was associated with both an increased risk for HTN (aRR, 2.02; 95% CI, 1.30-3.14) and MS (aRR, 1.53; 95% CI, 1.19-1.97). Participants with an AHI ⩾ 5 in pregnancy that persisted after delivery were at higher risk for both HTN (aRR, 3.77; 95% CI, 1.84-7.73) and MS (aRR, 2.46; 95% CI, 1.59-3.76). Similar associations were observed for persistent ODI ⩾ 5 after delivery. Conclusions: An AHI ⩾ 5 in pregnancy was associated with an increased risk of MS. An ODI ⩾ 5 in pregnancy was significantly associated with both HTN and MS. Participants with persistent elevations in AHI and ODI during pregnancy and at 2-7 years after delivery were at the highest risk for HTN and MS. Clinical trial registered with www.clinicaltrials.gov (NCT02231398).

Effectiveness and Safety of Lower Dose of Rivaroxaban for Cancer-Related Venous Thromboembolism: A Retrospective Cohort Study.

BACKGROUND: Primary and recurrent venous thromboembolism (VTE) commonly occur in patients with cancer. However, because of the National Health Insurance regulations, available dosage forms, and clinical conditions, the prescribed dose of rivaroxaban may not be consistent with its recommended dose. OBJECTIVE: To evaluate the 6-month recurrence rate of VTE and safety of rivaroxaban for patients with cancer. METHODS: Patients with new cancer diagnosis or recurrence from 2014 to 2018 who initiated rivaroxaban for VTE from January 2015 to January 2019 were included. We set the rivaroxaban initiation date as the index date and followed up the patients for 180 days. We collected information regarding the starting and maintenance dose/frequency and the treatment duration. The efficacy outcome was the recurrence of VTE within 180 days. The safety outcome included the major bleeding rate and clinically relevant nonmajor bleeding (CRNMB) rate. RESULTS: Approximately, 46.2% of the 65 included patients received a standard starting dose, and 45% of patients received a maintenance dose above 15 mg (median: 23.9 and 13.1 mg per day, respectively). Two-thirds of the patients stopped treatment within 180 days. Recurrent VTE occurred in 2 (3.1%) patients within 6 months. The major bleeding rate was 7.7%, and the CRNMB rate was 3.1%. CONCLUSION AND RELEVANCE: The 6-month recurrence rate of VTE and safety profile were similar between the lower and standard dose of rivaroxaban. This result may be applied to the institutions with dosage availability limited by formulary regulation and patients who cannot use full dose because of clinical considerations.

Effect of abdominal weight training with and without cough machine assistance on lung function in the patients with prolonged mechanical ventilation: a randomized trial.

PURPOSE: The patients with prolonged mechanical ventilation (PMV) have the risk of ineffective coughing and infection due to diaphragm weakness. This study aimed to explore the effect of abdominal weight training (AWT) intervention with/without cough machine (CM) assistance on lung function, respiratory muscle strength and cough ability in these patients. METHODS: Forty patients with PMV were randomly assigned to three groups: AWT group (n = 12), AWT + CM group (n = 14) and control group (n = 14). Change of maximum inspiratory pressure (MIP), Maximum expiratory pressure (MEP) and peak cough flow (PCF) between 1 day before and 2 weeks after the intervention were compared among these three groups. RESULTS: MIP before and after intervention in AWT group (30.50 ± 11.73 vs. 36.00 ± 10.79; p < 0.05) and AWT + CM group (29.8 ± 12.14 vs. 36.14 ± 10.42; p < 0.05) compared with control group (28.43 ± 9.74 vs 26.71 ± 10.77; p > 0.05) was significantly improved. MEP before and after intervention in AWT group (30.58 ± 15.19 vs. 41.50 ± 18.33; p < 0.05) and AWT + CM group (27.29 ± 12.76 vs 42.43 ± 16.96; p < 0.05) compared with control group (28.86 ± 10.25 vs. 29.57 ± 14.21; p > 0.05) was significantly improved. PCF before and after intervention in AWT group in AWT group (105.83 ± 16.21 vs. 114.17 ± 15.20; p < 0.05) and AWT + CM group (108.57 ± 18.85 vs. 131.79 ± 38.96; p < 0.05) compared to control group (108.57 ± 19.96 vs. 109.86 ± 17.44; p > 0.05) showed significant improvements. AWT + CM group had significantly greater improvements than control group in MIP and peak cough flow than control group (13.71 ± 11.28 vs 19.64 ± 29.90, p < 0.05). CONCLUSION: AWT can significantly improve lung function, respiratory muscle strength, and cough ability in the PMV patients. AWT + CM can further improve their expiratory muscle strength and cough ability. Trial registration ClinicalTrials.gov registry (registration number: NCT0529538 retrospectively registered on March 3, 2022).

Comparative effects of EMG-driven robot-assisted therapy versus task-oriented training on motor and daily function in patients with stroke: a randomized cross-over trial.

BACKGROUND: Robot-assisted hand training has shown positive effects on promoting neuromuscular control. Since both robot-assisted therapy and task-oriented training are often used in post-stroke rehabilitation, we raised the question of whether two interventions engender differential effects in different domains. METHODS: The study was conducted using a randomized, two-period crossover design. Twenty-four chronic stroke survivors received a 12-session robot-assisted intervention followed by a 12-session task-oriented intervention or vice versa. A 1-month washout period between each intervention was implemented. Outcome measures were evaluated before the intervention, after the first 12-session intervention, and after the second 12-session intervention. Clinical assessments included Fugl-Meyer Assessment for Upper Extremity, Wolf Motor Function Test, Action Research Arm Test and Motor Activity Log. RESULTS: Our findings suggested that EMG-driven robot-assisted therapy was as effective as task-oriented training in terms of improving upper limbs functional performance in activity domain, and robot-assisted therapy was more effective in improving movement duration during functional tasks. Task-oriented training showed better improvement in body function domain and activity and participation domain, especially in improving spontaneous use of affected arm during daily activities. CONCLUSIONS: Both intervention protocol had their own advantages in different domains, and robot-assisted therapy may save manpower and be considered as an alternative intervention to task-oriented training. Combining the two approaches could yield results greater than either alone, which awaits further study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03624153. Registered on 9th August 2018, https://clinicaltrials.gov/ct2/show/NCT03624153 .

Urate-lowering Therapy and Chronic Kidney Disease Development in Patients with Gout.

Objectives: Chronic kidney disease (CKD) has emerged as a global health concern. Many studies have identified an association between hyperuricemia and CKD, and some studies have revealed that urate-lowering therapy (ULT) can attenuate CKD progression. However, only a few studies have explored the role of ULT in the prevention of new onset CKD. Methods: To compare the risk of incident CKD between users and nonusers of ULT in patients with gout, we conducted a 13-year population-based retrospective cohort study. Overall incidence of CKD was compared between 7126 ULT users and 7126 matched ULT nonusers. Results: The CKD incidence rate for both the users and nonusers of ULT was 1.7 per 100 person-years, after adjusting for sex, age, region of residence, comorbidities, and medications used. No significant difference in CKD risk (adjusted hazard ratio [aHR]: 0.97; 95% confidence interval [CI]: 0.88-1.07) was noted between the ULT users and nonusers. In the subgroup of patients with diabetes mellitus (DM) and without hypertension (HT), ULT tended to be associated with lower risk of incident CKD (aHR: 0.52; 0.95% CI: 0.28-0.97). Compared with the risk of new onset CKD in patients receiving xanthine oxidase inhibitors, those receiving uricosuric agents seemed to have a lower risk of developing CKD (aHR: 0.81, 95% CI: 0.67-0.99). Conclusion: This population-based cohort study indicated that ULT is not associated with lower risk of CKD development. However, in the subgroup of patients with DM and without HT, ULT is associated with significantly lower risk of incident CKD.

The role of fetal echocardiogram after detection of extracardiac anomalies in utero (fetal echocardiogram for extracardiac malformations).

OBJECTIVE: We aimed to investigate the utility of comprehensive screening fetal echocardiography (FE) for patients diagnosed with any type of fetal extracardiac malformation (ECM) at a single multidisciplinary fetal center. METHODS: We retrospectively reviewed all patients presenting to our referral center for FE due to a prenatal diagnosis of ECM (January 2013-December 2018). RESULTS: Among 641 patients with ≥1 ECM referred for FE, 78 (12.2%) had CHD diagnosed at 25.6 ± 0.5 weeks. The frequency of CHD by type of ECM ranged from 35.1% for craniofacial to 9.8% for thoracic. Increasing number of fetal ECMs was strongly associated with CHD: odds ratio 2.01 (95% confidence interval: 1.06-3.69) for two ECMs, 9.57 (2.00-49.05) for three ECMs, and 11.68 (3.84-37.15) for more than three ECMs. Of fetuses with ECM and an abnormal genetic finding, 33.3% had CHD as compared to 10.9% of those without (p < 0.0001). Obstetric anatomy sonogram detected 43.6% of CHD. CONCLUSION: CHD was commonly diagnosed among fetuses with any type of ECM at our center but was not always detected on obstetric sonogram. As the presence of CHD may impact decision-making and perinatal care, patients with a diagnosis of any fetal ECM should be considered for FE.

Association between constipation and childhood nocturnal enuresis in Taiwan: a population-based matched case-control study.

BACKGROUND: The relationship between constipation and childhood nocturnal enuresis (NE) has been previously reported; however, this relationship remains controversial. The present study aimed to evaluate the association between constipation and childhood NE. METHODS: Data from the Longitudinal Health Insurance Database 2000 (LHID 2000) of Taiwan National Health Insurance Research Database from 2000 to 2013 were collected. A total of 2286 children were enrolled in this study: a case group of 1143 children aged 5-18 years who were diagnosed with NE (NE group) and an age- and sex-matched control group of 1143 children without NE. Conditional logistic regression and odds ratio (OR) for NE were used to examine the association between constipation and childhood NE. RESULTS: The prevalence of NE in the case group (NE group, aged 5-18 years) was 1.03% from 2000 to 2013. The NE group had a higher percentage of constipation in 1 year before the diagnosis of NE. After stratification for sex, both boys and girls with constipation had higher OR for NE. With stratification for age, children aged 5-12 and 7-12 years had a higher OR for NE. CONCLUSIONS: Constipation is associated with childhood NE in Taiwan, particularly in children aged 5-7 and 7-12 years.

Increased risk of knee osteoarthritis in patients using oral N-acetylcysteine: a nationwide cohort study.

BACKGROUND: Knee osteoarthritis (OA) is known to be a progressive degenerative disorder; however, recent evidence suggests that inflammatory mediators contribute to cartilage degradation. Studies have reported that N-acetylcysteine (NAC) had a promising effect on the reduction of the synthesis of proinflammatory and structural mediators by synovial cells. Given the lack of relevant clinical trials, we conducted this study to determine the relationship between NAC use and risk of knee OA. METHODS: We designed a retrospective cohort study from 2000 to 2013. Patients who received oral NAC over 28 days within 1 year after the first prescription were defined as the case group, whereas those without NAC use were considered as candidates of the control group. We adopted 1:4 propensity-score matching by age, sex, index year, and comorbidities to obtain the control group. The primary outcome was a new diagnosis of knee OA during the follow-up period. RESULTS: Our study sample comprised 12,928 people who used NAC and 51,715 NAC nonusers. NAC users had a significantly higher incidence of osteoarthritis (adjusted hazard ratio: 1.42, P < .001) than did NAC nonusers. Also, in analyses stratified by age group and sex, all subgroups exhibited a significantly higher incidence of knee osteoarthritis (P < .0001) among NAC users than among NAC nonusers. The use of oral NAC was associated with nearly four-fold increased the risk of knee OA in the young age group. CONCLUSIONS: Long-term use of oral NAC is associated with a higher risk of knee OA.

A Single-Center Experience with a Pregnant Immigrant Population and Zika Virus Serologic Screening in New York City.

OBJECTIVE: Our institution is in an area of New York City with a large population of immigrants from Zika virus endemic areas. With the recent Zika virus outbreak, we sought to examine our center's experience with screening for Zika virus and outcomes among patients who tested positive for the disease during pregnancy. STUDY DESIGN: We performed a chart review of all pregnant patients who tested positive (positive serum or urine polymerase chain reaction [PCR]) or presumed positive (immunoglobulin M [IgM] enzyme-linked immunosorbent assay [ELISA] positive or IgM ELISA equivocal with positive plaque reduction neutralization test) for Zika virus. All tests were performed by the Department of Health (DOH) and followed Centers for Disease Control and Prevention guidelines in effect at the time of specimen collection. Testing of cord blood, placenta, and/or neonatal blood were/was performed by the DOH for New York County. Prenatal ultrasounds for fetal head size and surveillance for calcifications were performed by maternal-fetal medicine specialists. Infant head ultrasound results were included when available. RESULTS: Between March 2016 and April 2017, 70 pregnant patients were positive or presumed positive for Zika infection during pregnancy. Of those, 16 women had positive urine or serum PCR and the remaining 54 were presumed positive. Among positive cases, five women tested positive via urine PCR only, nine women tested positive via serum PCR only, and two women had both positive urine and serum PCR. Fifteen of 67 infants (22%) born during the study period were born to mothers with positive urine or serum PCR testing. Sixty-five newborns were clinically normal with normal head measurements. Of the intracranial ultrasound performed, one infant had a grade 1 intraventricular hemorrhage, four had incidental choroid plexus cysts, and one had severe ventriculomegaly that was also noted antenatally. There were 2 positive and 15 equivocal infant serum IgM samples and 1 positive placental PCR from these pregnancies. There were four pregnancy terminations and two cases with fetal anomalies in this population that were split evenly between patients who tested positive and those who tested presumed positive for Zika virus during pregnancy. CONCLUSION: We found no differences in pregnancy or neonatal outcomes between women who tested positive and presumed positive for Zika virus during pregnancy. Testing of infants and placenta tissue after delivery was largely inconclusive. Improvement in testing for Zika virus infection is needed to determine which pregnancies are at risk for congenital anomalies. Further research is still needed to determine which children are at risk for poor neurodevelopmental outcomes related to Zika virus and how to best coordinate care among the immigrant population during a new disease epidemic.

Telehealth Uptake into Prenatal Care and Provider Attitudes during the COVID-19 Pandemic in New York City: A Quantitative and Qualitative Analysis.

OBJECTIVE: This study aimed to (1) determine to what degree prenatal care was able to be transitioned to telehealth at prenatal practices associated with two affiliated hospitals in New York City during the novel coronavirus disease 2019 (COVID-19) pandemic and (2) describe providers' experience with this transition. STUDY DESIGN: Trends in whether prenatal care visits were conducted in-person or via telehealth were analyzed by week for a 5-week period from March 9 to April 12 at Columbia University Irving Medical Center (CUIMC)-affiliated prenatal practices in New York City during the COVID-19 pandemic. Visits were analyzed for maternal-fetal medicine (MFM) and general obstetrical faculty practices, as well as a clinic system serving patients with public insurance. The proportion of visits that were telehealth was analyzed by visit type by week. A survey and semistructured interviews of providers were conducted evaluating resources and obstacles in the uptake of telehealth. RESULTS: During the study period, there were 4,248 visits, of which approximately one-third were performed by telehealth (n = 1,352, 31.8%). By the fifth week, 56.1% of generalist visits, 61.5% of MFM visits, and 41.5% of clinic visits were performed via telehealth. A total of 36 providers completed the survey and 11 were interviewed. Accessing technology and performing visits, documentation, and follow-up using the telehealth electronic medical record were all viewed favorably by providers. In transitioning to telehealth, operational challenges were more significant for health clinics than for MFM and generalist faculty practices with patients receiving public insurance experiencing greater difficulties and barriers to care. Additional resources on the patient and operational level were required to optimize attendance at in-person and video visits for clinic patients. CONCLUSION: Telehealth was rapidly implemented in the setting of the COVID-19 pandemic and was viewed favorably by providers. Limited barriers to care were observed for practices serving patients with commercial insurance. However, to optimize access for patients with Medicaid, additional patient-level and operational supports were required. KEY POINTS: · Telehealth uptake differed based on insurance.. · Medicaid patients may require increased assistance for telehealth.. · Quick adoption of telehealth is feasible..

Application of water quality model to analyze pollution hotspots and the impact on reservoir eutrophication.

Sustainable reservoir watershed management is crucial to maintain a water supply system. The purpose of this study is to assess the pollution sources of the Bao-Shan Reservoir, which is an off-stream reservoir and is the study reservoir herein. Most water source of the Bao-Shan Reservoir is from the Shang-Ping Watershed. This study applies the EPA's Storm Water Management Model (SWMM) and the Vollenweider model (VM) to analyze the pollution hotspots in the reservoir watershed and the impact of the pollutions on the reservoir water quality. The results indicate that non-point source pollution is the main pollution in the Shang-Ping Watershed. The pollution hotspots are located in the sub-watersheds S1, S3, S4, and S5. These sub-watersheds have higher total phosphorus (TP) loads per unit area. In order to protect the water quality of the Bao-Shan Reservoir, this study suggests that the TP load entering the reservoir needs to be reduced by about 16% to 24%. The control of non-point source pollution needs to be preferentially implemented in the Shang-Ping Watershed. The analysis and discussion in this study are a useful reference for reservoir watershed management.

Level of Hepatitis B (HB) Core Antibody Associates With Seroclearance of HBV DNA and HB Surface Antigen in HB e Antigen-Seronegative Patients.

BACKGROUND & AIMS: Although a low level of hepatitis B surface antigen (HBsAg) is a marker of hepatitis B virus (HBV) seroclearance, additional biomarkers are needed for more accurate prediction. We investigated whether quantification of antibody against HBV core protein (anti-HBc) can identify patients with undetectable levels of HBV DNA and HBsAg seroclearance among those who were HBV e antigen (HBeAg)-seronegative. METHODS: We performed a retrospective analysis of data from a community-based cohort of individuals (30-65 years old) in Taiwan who were HBsAg seropositive, anti-HCV negative, and free of cirrhosis and/or liver cancer, recruited from 1991 through 1992, and evaluated every 6-12 months until June 30, 2004. We measured levels of anti-HBc in blood samples from 2500 participants who were seronegative for HBeAg. The first date at which a sample tested negative for HBV DNA or HBsAg, and remained negative in subsequent tests, was designated as the date of spontaneous HBV DNA undetectability or HBsAg seroclearance. We calculated cumulative incidences of HBV DNA undetectability and HBsAg seroclearance; associations between level of anti-HBc and undetectability of HBV DNA or HBsAg seroclearance were estimated by Cox proportional hazard regression. The effects of time on the associations between level of anti-HBc and HBsAg seroclearance was assessed by the area under the receiver operating characteristic curve (AUROC) analysis. RESULTS: After a 12-year follow-up period, higher proportions of subjects with levels of anti-HBc <3 log IU/mL had undetectable levels of HBV DNA (58%) and HBsAg seroclearance (53%) than subjects with higher levels of anti-HBc (29.6% and 19.8%, respectively) (P < .001). For subjects with levels of HBsAg <102 IU/mL and anti-HBc <3 log IU/mL, the adjusted rate ratio of HBV DNA undetectability was 16.45 (95% CI, 11.15-24.28) and of HBsAg seroclearance was 17.95 (95% CI, 12.49-25.81), compared to subjects with higher levels of HBsAg and anti-HBc. A model that included level of anti-HBc as a parameter identified subjects with HBsAg seroclearance within 10 years with an AUROC of 82%; this value was significantly higher than that from models that include only level of HBV DNA and HBsAg (P < .0001). CONCLUSIONS: In a retrospective analysis of a large cohort of patients with chronic HBV infection in Taiwan, we associated levels of anti-HBc <3 log IU/mL with undetectable HBV DNA and HBsAg seroclearance occurred within 10 years; patients who also have levels of HBsAg <102 IU/mL have greater odds. Combining data on levels of HBsAg, HBV DNA, and anti-HBc is able to identify HBeAg-seronegative patients who can achieve HBsAg seroclearance with an AUROC value of 82%.

Association Between High Levels of Hepatitis B Core Antibody and Seroclearance of Hepatitis B e Antigen in Individuals With Chronic Hepatitis B Virus Infection.

For chronic hepatitis B patients, hepatitis B e antigen (HBeAg) seroclearance signals a transition from an immunologically active phase to an inactive carrier state with a reduction in hepatitis B virus (HBV) DNA levels and a reduced risk of hepatocellular carcinoma (HCC).1 Predictors of HBeAg seroclearance include lower HBV DNA levels, viral genotype, the precore mutation, and higher serum alanine aminotransferase (ALT) levels.2.

A novel PCR-based point-of-care method enables rapid, sensitive and reliable diagnosis of Babesia gibsoni infection in dogs.

BACKGROUND: Babesia gibsoni (B. gibsoni) is an intraerythrocytic protozoan parasite of dogs that causes fever and hemolytic illness. A timely diagnosis is essential for the disease management. RESULTS: Here, we report a QubeMDx PCR system which enables a rapid, sensitive and reliable diagnosis of B. gibsoni near the dog patient. Within 30 min, this diagnostic assay was able to detect as low as 0.002% parasitemia of the dog blood. Using clinical samples, this new assay was validated to demonstrate 100% agreement with real-time PCR. CONCLUSIONS: This novel diagnostic method provides a reliable point-of-care test to assist in the identification of B. gibsoni.

Predictors of sleep-disordered breathing in pregnancy.

BACKGROUND: Sleep-disordered breathing (SDB) is common in pregnancy, but there are limited data on predictors. OBJECTIVES: The objective of this study was to develop predictive models of sleep-disordered breathing during pregnancy. STUDY DESIGN: Nulliparous women completed validated questionnaires to assess for symptoms related to snoring, fatigue, excessive daytime sleepiness, insomnia, and restless leg syndrome. The questionnaires included questions regarding the timing of sleep and sleep duration, work schedules (eg, shift work, night work), sleep positions, and previously diagnosed sleep disorders. Frequent snoring was defined as self-reported snoring ≥3 days per week. Participants underwent in-home portable sleep studies for sleep-disordered breathing assessment in early (6-15 weeks gestation) and mid pregnancy (22-31 weeks gestation). Sleep-disordered breathing was characterized by an apnea hypopnea index that included all apneas, plus hypopneas with ≥3% oxygen desaturation. For primary analyses, an apnea hypopnea index ≥5 events per hour was used to define sleep-disordered breathing. Odds ratios and 95% confidence intervals were calculated for predictor variables. Predictive ability of the logistic models was estimated with area under the receiver-operating-characteristic curves, along with sensitivities, specificities, and positive and negative predictive values and likelihood ratios. RESULTS: Among 3705 women who were enrolled, data were available for 3264 and 2512 women in early and mid pregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%, respectively. At each time point in gestation, frequent snoring, chronic hypertension, greater maternal age, body mass index, neck circumference, and systolic blood pressure were associated most strongly with an increased risk of sleep-disordered breathing. Logistic regression models that included current age, body mass index, and frequent snoring predicted sleep-disordered breathing in early pregnancy, sleep-disordered breathing in mid pregnancy, and new onset sleep-disordered breathing in mid pregnancy with 10-fold cross-validated area under the receiver-operating-characteristic curves of 0.870, 0.838, and 0.809. We provide a supplement with expanded tables, integrated predictiveness, classification curves, and an predicted probability calculator. CONCLUSION: Among nulliparous pregnant women, logistic regression models with just 3 variables (ie, age, body mass index, and frequent snoring) achieved good prediction of prevalent and incident sleep-disordered breathing. These results can help with screening for sleep-disordered breathing in the clinical setting and for future clinical treatment trials.