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Mimi Kim

Publications and source records attributed to Mimi Kim.

17 recordsLinked to original sources
PubMed2026

Characterization of the genotypic and phenotypic spectrum of TCF7L2-related neurodevelopmental disorder (TRND).

PURPOSE: TCF7L2 (OMIM 602228; HGNC:11641) is a transcription factor and a critical effector of the Wnt/ β-Catenin pathway. In 2021, 11 pediatric patients with monoallelic predicted loss-of-function (pLOF) TCF7L2 variants and syndromic features were observed. Characterization of patients with pLOF TCF7L2 variants and neurodevelopmental features-herein referred to as TCF7L2-related neurodevelopmental disorder-is urgently needed. METHODS: We leveraged multiple methods (eg, GeneMatcher, DECIPHER, literature review, and public/private repositories) to identify an international cohort of 76 patients with pLOF TCF7L2 variants and neurodevelopmental features and phenotypically characterized them. We also retrospectively searched for an independent cohort of adults with pLOF TCF7L2 variants (n = 11) from more than 60,000 PennMedicine BioBank patients. RESULTS: Among 76 patients with pLOF TCF7L2 variants, speech delay (95.3%), craniofacial dysmorphisms (73.3%), ophthalmologic conditions (65.5%), autism (62.1%), and orthopedic abnormalities (52.6%) were the most commonly observed. Phenotypic differences did not cluster by variant type or genomic locus. Among PennMedicine BioBank patients, an association of nominal significance with type 2 diabetes with renal manifestations (odds ratio = 5.8; P = .03) was detected, warranting further investigation. CONCLUSION: This study represents the most comprehensive characterization of TCF7L2-related neurodevelopmental disorder to date, a novel neurodevelopmental disorder, defining its genotypic and phenotypic spectra. We opened a Simons Searchlight natural history study that is now available for patient enrollment to enhance the understanding of this condition.

Neurodevelopmental syndrome↗
PubMed2006

Gas6/Axl signaling activates the phosphatidylinositol 3-kinase/Akt1 survival pathway to protect oligodendrocytes from tumor necrosis factor alpha-induced apoptosis.

Growth arrest-specific protein 6 (gas6) activity is mediated through the receptor tyrosine kinase family members Axl, Rse, and Mer, all of which are expressed in human oligodendrocytes. In this study, we examined whether recombinant human (rh) gas6 protects oligodendrocytes from growth factor (insulin) withdrawal or tumor necrosis factor-alpha (TNFalpha) cytotoxicity. In addition, we examined whether the effect was caspase-dependent, which receptor mediated the protective effect, and whether survival required Akt1 activation. Oligodendrocyte viability was assessed by O4 staining and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling. Addition of rhgas6 to insulin-depleted cultures resulted in a significant increase in oligodendrocyte viability. Rhgas6 and caspase inhibitors also reduced active caspase-3 immunoreactivity relative to TNFalpha-only-treated cultures. In cultures treated with TNFalpha (100 ng/ml), the oligodendrocyte survival rate was 18% compared with cultures treated with TNFalpha and rhgas6 (64%) or the caspase inhibitors IETD-fmk [z-Ile-Glu(OMe)-Thr-Asp(OMe)-fluoromethyl ketone] (65%) and zVAD-fmk (N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone) (63%). Increased phosphoAkt (Ser473) immunoreactivity was detected 15 min after administration of gas6 and TNFalpha to oligodendrocyte cultures but not in TNFalpha-treated cultures. The gas6 protective effect was abrogated by the Axl decoy receptor Axl-Fc, by the phosphatidylinositol 3 (PI3) kinase inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one], and in Akt1(-/-) oligodendrocytes. Oligodendrocyte cultures established from wild-type and Rse(-/-) mice, but not from Axl(-/-) mice, were also protected from TNFalpha-induced cell death when maintained in rhgas6. We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death.

Apoptosis↗
PubMed2006

ErbB3-dependent motility and intravasation in breast cancer metastasis.

A better understanding of how epidermal growth factor receptor family members (ErbBs) contribute to metastasis is important for evaluating ErbB-directed therapies. Activation of ErbB3/ErbB2 heterodimers can affect both proliferation and motility. We find that increasing ErbB3-dependent signaling in orthotopic injection models of breast cancer can enhance intravasation and lung metastasis with no effect on primary tumor growth or microvessel density. Enhanced metastatic ability due to increased expression of ErbB2 or ErbB3 correlated with stronger chemotaxis and invasion responses to heregulin beta1. Suppression of ErbB3 expression reduced both intravasation and metastasis. A human breast cancer tumor tissue microarray showed a significant association between ErbB3 and ErbB2 expression and metastasis independent of tumor size. These results indicate that ErbB3-dependent signaling through ErbB3/ErbB2 heterodimers can contribute to metastasis through enhancing tumor cell invasion and intravasation in vivo and that ErbB-directed therapies may be useful for the inhibition of invasion independent of effects on tumor growth.

Animals↗
PubMed2006

The effect of moderate-dose corticosteroids in preventing severe flares in patients with serologically active, but clinically stable, systemic lupus erythematosus: findings of a prospective, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Serial measurements of anti-double-stranded DNA (anti-dsDNA) and complement are routine in the management of systemic lupus erythematosus (SLE), but their utility as biomarkers in preemptive treatment to prevent flares remains a subject of controversy. We hypothesized that concomitant elevation of anti-dsDNA and C3a can predict SLE activity in patients with stable or inactive disease and that short-term treatment with corticosteroids can avert flares. METHODS: In this prospective, randomized, double-blind, placebo-controlled trial, 154 patients were evaluated monthly for up to 18 months, with measurements of C3a, C3, C4, CH50, and anti-dsDNA levels. Patients who remained clinically stable but showed serologic evidence of an SLE flare (elevation of both the anti-dsDNA level by 25% and the C3a level by 50% over the previous 1-2 monthly visits) were randomized to receive either prednisone or placebo therapy at a dosage of 30 mg/day for 2 weeks, 20 mg/day for 1 week, and 10 mg/day for 1 week. RESULTS: Forty-one patients (21 randomized to prednisone and 20 randomized to placebo) experienced a serologic flare. Analysis of severe flares occurring 40 mg/day and/or the addition of an immunosuppressive agent. Furthermore, improvement in scores on the Systemic Lupus Erythematosus Disease Activity Index, decreased levels of anti-dsDNA antibodies, and increased levels of C4 occurred 1 month after initiation of prednisone treatment. CONCLUSION: These preliminary data support our hypothesis that in a subset of clinically stable SLE patients with a combination of elevated C3a and anti-dsDNA levels, short-term corticosteroid therapy may avert a severe flare.

Acute Disease↗
PubMed2006

Clinicians' attitudes regarding barriers to the implementation of psychiatric advance directives.

OBJECTIVE: Psychiatric advance directives (PADs) may include documenting advance instructions (AIs) and/or designating health care agents (HCAs). Laws authorizing PADs have proliferated in the past decade, but there has been little research regarding perceptions of barriers to the implementation of PADs among groups of mental health professionals. METHODS: A total of N=591 mental health professionals (psychiatrists, psychologists, and social workers) completed a survey regarding their perceptions of potential barriers to the effective implementation of PADs. RESULTS: Across the three professional groups barriers related to operational features of the work environment (e.g., lack of communication between staff, lack of access to the document) were reported at a higher rate than clinical barriers (e.g., inappropriate treatment requests, consumers' desire to change their mind about treatment during crises). However, psychiatrists were more likely to report clinical barriers to implementation than both psychologists and social workers. In multivariable analyses, legal defensiveness, employment in public sector mental health services, and a belief that treatment refusals will outweigh the benefits of PADs were associated with more perceived barriers, whereas age and endorsing positive perceptions of PADs were associated with fewer perceived barriers. CONCLUSION: Psychiatrists, psychologists and social workers tend to perceive significant potential barriers to PADs, related to operational aspects of these professionals' work environment as well as certain clinical features of PADs for persons with severe mental illness. Additionally, legal defensiveness and general endorsement of PADs appear to shape perceptions of barriers to the effective implementation of PADs.

Adult↗
PubMed2006

Facilitated psychiatric advance directives: a randomized trial of an intervention to foster advance treatment planning among persons with severe mental illness.

OBJECTIVE: Studies show a high potential demand for psychiatric advance directives but low completion rates. The authors conducted a randomized study of a structured, manualized intervention to facilitate completion of psychiatric advance directives. METHOD: A total of 469 patients with severe mental illness were randomly assigned to a facilitated psychiatric advance directive session or a control group that received written information about psychiatric advance directives and referral to resources in the public mental health system. Completion of an advance directive, its structure and content, and its short-term effects on working alliance and treatment satisfaction were recorded. RESULTS: Sixty-one percent of participants in the facilitated session completed an advance directive or authorized a proxy decision maker, compared with only 3% of control group participants. Psychiatrists rated the advance directives as highly consistent with standards of community practice. Most participants used the advance directive to refuse some medications and to express preferences for admission to specific hospitals and not others, although none used an advance directive to refuse all treatment. At 1-month follow-up, participants in the facilitated session had a greater working alliance with their clinicians and were more likely than those in the control group to report receiving the mental health services they believed they needed. CONCLUSIONS: The facilitation session is an effective method of helping patients complete psychiatric advance directives and ensuring that the documents contain useful information about patients' treatment preferences. Achieving the promise of psychiatric advance directives may require system-level policies to embed facilitation of these instruments in usual-care care settings.

Adult↗
PubMed2006

Use of outpatient commitment or related civil court treatment orders in five U.S. communities.

OBJECTIVE: Outpatient commitment and a number of related civil court mechanisms are used to attempt to improve adherence to mental health treatment in the community. This study examined lifetime use rates and correlates of outpatient commitment or related civil court-ordered outpatient treatment in five U.S. communities. METHODS: A total of 1,011 outpatients were recruited and interviewed from five sites: Chicago; Durham, North Carolina; San Francisco; Tampa; and Worcester, Massachusetts. RESULTS: Between 12 and 20 percent of consumers reported outpatient commitment or related civil court-ordered treatment. A history of outpatient commitment or related court orders was significantly more common among participants who lived in staffed residential settings, received assistance with outpatient treatment, and reported poor social support as well as among those who had co-occurring substance use problems, poor psychosocial functioning, a recent history of violent behavior, higher rates of lifetime hospitalization and of involuntary hospitalization, and recent police encounters during mental health crises. Nearly three-quarters of persons who reported outpatient commitment or related civil court orders also reported experiencing other forms of leveraged treatment, and these multiple leveraged-treatment experiences were strongly associated with high perceived coercion and poor satisfaction with treatment. CONCLUSIONS: A history of civil court-ordered outpatient treatment was most common among persons with mental illness who came into contact with multiple mental health, social welfare, and criminal justice agencies, many of which applied their own forms of leveraged treatment in attempts to improve adherence. Further research is needed to guide policy makers in implementing coordinated and effective responses to treatment nonadherence.

Adult↗
PubMed2006

Clinical decision making and views about psychiatric advance directives.

OBJECTIVES: Psychiatric advance directives allow competent persons to document advance instructions or designate a health care agent to communicate their preferences for future mental health treatment in the event of an incapacitating crisis. Although laws authorizing psychiatric advance directives have proliferated, little is known about clinicians' understanding and perceptions of these legal tools. METHODS: A total of 597 mental health professionals (psychiatrists, psychologists, and social workers) completed a survey about their attitudes toward psychiatric advance directives and decision making about following such directives. RESULTS: Approximately half the sample (47 percent) agreed that advance instructions would be helpful to consumers with severe mental illnesses, and a majority (57 percent) endorsed health care agents as beneficial. Regardless of profession, clinicians had more positive attitudes about psychiatric advance directives when they correctly recognized that they were not required by state law to follow directives that note the patient' s refusal of appropriate medical treatment. In multivariate analyses, the decision to abide by a patient' s advance refusal of treatment in a hypothetical scenario was predicted by knowing the laws associated with these directives, valuing family opinions about treatment, and respecting patient autonomy. CONCLUSIONS: Clinicians correctly apprised of the state law were more likely to endorse psychiatric advance directives. Thus clinicians may be more willing to use directives if they are educated about the legal parameters of their implementation. The clinicians' profession had only an indirect influence on whether clinicians would follow an advance instruction that noted the patient's refusal of appropriate treatment; rather, clinicians' values and legal knowledge had the greatest effect, highlighting the potentially complex ethical dilemmas faced by mental health professionals who encounter these directives.

Adult↗
PubMed2004

Extreme heterogeneity in the molecular events leading to the establishment of chiasmata during meiosis i in human oocytes.

In humans, ~50% of conceptuses are chromosomally aneuploid as a consequence of errors in meiosis, and most of these aneuploid conceptuses result in spontaneous miscarriage. Of these aneuploidy events, 70% originate during maternal meiosis, with the majority proposed to arise as a direct result of defective crossing over during meiotic recombination in prophase I. By contrast, <1%-2% of mouse germ cells exhibit prophase I-related nondisjunction events. This disparity among mammalian species is surprising, given the conservation of genes and events that regulate meiotic progression. To understand the mechanisms that might be responsible for the high error rates seen in human females, we sought to further elucidate the regulation of meiotic prophase I at the molecular cytogenetic level. Given that these events occur during embryonic development in females, samples were obtained during a defined period of gestation (17-24 weeks). Here, we demonstrate that human oocytes enter meiotic prophase I and progress through early recombination events in a similar temporal framework to mice. However, at pachynema, when chromosomes are fully paired, we find significant heterogeneity in the localization of the MutL homologs, MLH1 and MLH3, among human oocyte populations. MLH1 and MLH3 have been shown to mark late-meiotic nodules that correlate well with--and are thought to give rise to--the sites of reciprocal recombination between homologous chromosomes, which suggests a possible 10-fold variation in the processing of nascent recombination events. If such variability persists through development and into adulthood, these data would suggest that as many as 30% of human oocytes are predisposed to aneuploidy as a result of prophase I defects in MutL homolog-related events.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Dominant effects of an Msh6 missense mutation on DNA repair and cancer susceptibility.

Mutations in DNA mismatch repair (MMR) genes cause hereditary nonpolyposis colorectal cancer (HNPCC), and MMR defects are associated with a significant proportion of sporadic cancers. MMR maintains genome stability and suppresses tumor formation by preventing the accumulation of mutations and by mediating an apoptotic response to DNA damage. We describe the analysis of a dominant MSH6 missense mutation in yeast and mice that causes loss of DNA repair function while having no effect on the apoptotic response to DNA damaging agents. Our results demonstrate that MSH6 missense mutations can effectively separate the two functions, and that increased mutation rates associated with the loss of DNA repair are sufficient to drive tumorigenesis in MMR-defective tumors.

Animals↗
PubMed2004

Flavopiridol inhibits the growth of GL261 gliomas in vivo: implications for malignant glioma therapy.

The mechanism of action of many chemotherapeutic agents targets the cell cycle. Recently, we demonstrated cytotoxic and other anti-tumor effects of flavopiridol, the first synthetic cyclin dependent kinase (CDK) inhibitor to enter clinical trials, on the murine GL261 glioma cell line in vitro (Newcomb et al., Cell Cycle 2003; 2:243). Given that flavopiridol has demonstrated anti-tumor activity in several human xenograft models, we wanted to evaluate it for anti-glioma activity in vivo in our established subcutaneous and intracranial GL261 experimental tumor models. In particular, the intracranial animal model recapitulates many of the histopathological and biological features of human high-grade glioma including both necrosis with pseudopalisading and invasion of the brain adjacent to tumor. Here we tested the activity of flavopiridol against tumors formed by GL261 cells, first as subcutaneous implants, and then in the intracranial model. We demonstrate efficacy of flavopiridol as a single modality treatment in delaying tumor growth in both animal models. We hypothesize that flavopiridol treatment induced tumor growth delay by two possible mechanisms involving growth arrest combined with recruitment of tumor cells to S-phase. Based on our findings, flavopiridol should be considered as a treatment approach for patients with high-grade glioma.

Animals↗
PubMed2003

Intraperitoneal therapy as consolidation for patients with ovarian cancer and negative reassessment after platinum-based chemotherapy.

Although three large phase III trials have documented the benefit of IP chemotherapy, this therapy as consolidation has been studied in only a few pilot studies. These small studies have included patients with a variety of baseline prognostic characteristics, and only one series had a comparator group of surgically documented pathologic complete response to uniform systemic chemotherapy. No randomized trials have been done to assess the impact of IP consolidation on progression-free survival or survival in either positively or negatively reassessed patients. It is hoped that the current experience will trigger further consideration of future phase III trials to assess the value of IP consolidation after initial induction with chemotherapy (ie, chemical debulking).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Phase I study of amifostine as a cytoprotector of the gemcitabine/cisplatin combination in patients with advanced solid malignancies.

Our objective was to evaluate the role of amifostine as a cytoprotector in patients with solid tumors receiving the myelosuppressive regimen of gemcitabine/cisplatin combination. Patients with advanced solid tumors were randomized to gemcitabine-amifostine-cisplatin (GAP) or gemcitabine-cisplatin (GP) in Cycle 1 (C1) and then were crossed over to the other treatment in Cycle 2 (C2). Amifostine at 740 mg/m2, followed by gemcitabine and cisplatin, were given for 2 consecutive weeks, every 4 weeks. Two GP combinations were studied: G 1000 mg/m2 and P 40 mg/m2 days 1, 8 (high dose), and G 800 mg/m2 and P 30 mg/m2 days 1, 8 (low dose). Forty patients were enrolled. Of the 19 patients treated with high-dose GP, 11 (nine patients GP in C1 and GAP in C2, two patients GAP in C1 and GP in C2) completed 2 cycles of therapy. Of the eight non-evaluable patients, five patients dropped out due to toxicity or refusal after treatment with amifostine in C1. Of the 21 patients treated with low-dose GP, 15 (eight patients GP in C1 and GAP in C2, seven patients GAP in C1 and GP in C2) were likewise evaluable. The incidence of grade 3 or 4 hematologic toxicities was similar for GP and GAP during the first 2 cycles of treatment, and there were no statistically significant differences in mean absolute neutrophil count, hemoglobin level and platelet levels between the cycles in each arm. We conclude that amifostine, at 740 mg/m2, does not lead to less myelosuppression when combined with gemcitabine/cisplatin chemotherapy regimens and may possibly contribute to subjective intolerance.

Adult↗
PubMed2002

Identification of glutathione S-transferase (GST) polymorphisms in brain tumors and association with susceptibility to pediatric astrocytomas.

Polymorphisms in the glutathione S-transferase (GST) genes, a superfamily that plays a key role in carcinogen metabolism, have been associated with an increased susceptibility to several types of cancer. We wished to evaluate whether variant allelic forms of GST isoenzymes were associated with an increased susceptibility for brain tumors and age of tumor onset. Here, we examined 394 brain tumors (221 adult and 173 pediatric cases consisting of 197 astrocytic and 197 non-astrocytic tumors) to determine the frequency of polymorphisms in the GSTM1, GSTT1, and GSTP1 genes compared to a healthy control population. Our data shows that the frequency of GST polymorphisms varies not only between adult and pediatric patients with brain tumors and healthy controls, but also between different histological subtypes of brain tumors occurring in pediatric patients. We found (i) a statistically significant increase in the frequency of the functional GSTM1 allele in high-grade pediatric astrocytomas (p < 0.002), (ii) a significant increase in the frequency of the rare GSTP1 variant Val114/Val114 in pediatric astrocytomas (p < 0.002), and (iii) a significant increase in the frequency of the rare GSTP1 Val114/Val114 genotype among pediatric tumors showing microsatellite instability (MSI) due to defects in mismatch repair (MMR) proteins (p = 0.003). Our results suggest that GSTM1 and GSTP1 polymorphisms may play a role in brain tumor susceptibility by histological subtype, particularly high-grade pediatric astrocytomas. Moreover, the presence of the genetic modifier GSTP1 Val114/Val14 genotype may begin to define a high-risk genotype for cancer susceptibility in the pediatric population.

Adolescent↗
PubMed2002

Behavioral risk factor and preventive health care practice survey of immigrants in the emergency department.

OBJECTIVE: To compare the demographic profiles, behavioral risk factors, and preventive health care practices of adult immigrant and non-immigrant patients while considering the effects of various socioeconomic variables. METHODS: This was a prospective survey administered at a large urban emergency department in New York City. Study subjects were adult immigrant patients presenting in an eight-week period in 1998. One non-immigrant control patient was recruited concurrently with every two immigrant patients. Differences between immigrants and non-immigrants were evaluated using the chi-square test. Multivariate logistic regression models were used to adjust for confounding variables. RESULTS: Eight hundred sixty-nine immigrant patients from 80 countries and 354 non-immigrant patients completed surveys. Immigrants were more likely not to have reached high school (28.9% vs 8.5%; p < 0.001), to have annual family incomes less than $20,000 (73.8% vs 64.5%; p < 0.01), and to have no health coverage (51.7% vs 30.8%; p < 0.001). Immigrant women were more likely never to have had a Papanicolaou test (16.1% vs 1.4%; OR 11.24, 95% CI = 2.70 to 46.8) and never to have performed a self-breast examination (20.8% vs 7.5%; OR 2.03, 95% CI = 1.29 to 3.20). Immigrants were more likely not to use condoms (63.4% vs 42.8%; OR 1.61, 95% CI = 1.20 to 2.15) and never to have visited a dentist (21.2% vs 7.8; OR 2.54, 95% CI = 1.60 to 4.04). Immigrants were more likely never to have received a purified protein derivative (PPD) skin test (30.3% vs 9.1%; OR 3.85, 95% CI = 2.56 to 5.80) and never to have received a tetanus immunization (48.1% vs 13.5%; OR 3.09, 95% CI = 2.17 to 4.42). These differences were independent of age, gender, marital status, employment, education, income, and health insurance status. When analyzing the immigrant group alone, region of origin, length of time in the United States, and English ability were significant independent predictors of higher-risk behavioral profiles and poor preventive health care practices. CONCLUSIONS: Differences exist between the socioeconomic profiles, behavioral risk profiles, and preventive health care practices of immigrant and non-immigrant patients presenting to a large inner-city municipal emergency department. Different populations within a heterogeneous group of immigrants have distinct health risks and public health needs.

Adult↗
PubMedDate not supplied

The fetal Doppler mechanical PR interval: a validation study.

OBJECTIVE: To evaluate the accuracy of pulsed Doppler-derived fetal PR interval measurements obtained by physicians participating in a multicenter prospective fetal echocardiographic study. METHODS: Echocardiograms on healthy fetuses were performed and evaluated by 15 pediatric cardiologists/perinatologists across the United States who are participating in a larger clinical trial involving fetuses at risk for autoantibody-associated congenital heart block. Prior to enrolling women in the main trial, each physician was provided with a teaching tape to demonstrate how the pulsed Doppler-derived PR interval is measured. The procedure involves placing a gated pulsed Doppler sample volume in the left ventricle at the junction of the anterior leaflet of the mitral valve and the left ventricular outflow tract in an apical 5-chamber view, and simultaneously obtaining left ventricular filling and emptying. Time intervals are measured from the onset of the mitral A wave (atrial systole) to the onset of the aortic pulsed Doppler tracing (ventricular systole). This represents the mechanical PR interval. Each physician measured the pulsed Doppler-derived fetal PR interval on 5 different subjects recruited from the physician's specific site. To validate each physician's technique, the tapes were sent to a central facility and the same intervals were remeasured by an experienced central reader (D.M.F.). A physician was determined to have adequate ability to measure the fetal PR interval if all 5 measurements were within +/- 30 ms of the central reader's measurements, where 30 ms corresponds to 25% of the mean observed in normative PR interval data. This difference was deemed to be the minimum clinically important difference in Doppler PR interval. RESULTS: Fourteen of the 15 physicians were considered to have adequate ability to measure the fetal PR interval according to our established criterion. The overall mean difference between the physicians and the central reader's measurements was -0.26 +/- 11.04 ms (p = 0.84). In addition, 95% of the observed differences were included in the interval (-22.23 to 21.81), which is well within our clinically acceptable range of +/- 30 ms. CONCLUSIONS: The pulsed Doppler assessment of the mechanical PR interval in the fetus can be accurately performed after minimal training. This technique may be a valuable tool for identification of early and potentially reversible conduction abnormalities in fetuses at risk for more advanced and permanent forms of heart block associated with maternal antibodies to SSA/Ro-SSB/La.

Arrhythmias, Cardiac↗