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Open Access Publications from the University of California

Scholarly Works (14 results)

  • Article
  • Peer Reviewed
Dermatology Online Journal, Volume 24, Issue 2 (2018)

The term, autosomal recessive congenital ichthyosis (ARCI), describes a group of rare genetic skin diseases of cornification involving hyperkeratotic scaling at birth. The defective skin barrier function may lead to dehydration, body temperature instability, and high susceptibility to infections. In most cases of ARCI, neonates are born with a collodion membrane covering the body, often presenting with ectropion and eclabium. We report a premature female neonate presenting with hyperkeratotic scaling at birth without a collodion membrane. She was managed with placement in a humidified isolette, prophylactic antibiotics, dilute bleach baths, petrolatum ointment, and artificial eye drops. By the fourth week of life, there was marked improvement in her skin with the large, brown, plate-like scales on the trunk and extremities becoming lighter in color and finer in appearance. The ichthyosis genetic panel showed mutations in the ABCA12 gene resulting in the lamellar ichthyosis phenotype of ARCI. Our literature review revealed at least 28 patients with ARCI who were not born as collodion babies. Although collodion babies are a hallmark of most ARCI cases, clinicians should be aware of neonates with ARCI born without a collodion membrane and expedite appropriate workup and treatment.

    Cover page: Lamellar ichthyosis in a female neonate without a collodion membraneCreative Commons 'BY-NC-ND' version 4.0 license
    • Article
    • Peer Reviewed
    Dermatology Online Journal, Volume 24, Issue 1 (2018)

    Background: Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are cutaneous hypersensitivityreactions that develop in response to specific triggers such as medications and certain infections. Vaccines, which undergo rigorous safety testing prior to use in humans, are a rare cause of SJS/TEN and little is known about the frequency of such events and corresponding pathogenesis.

    Objective: Herein, we discuss a case of suspected TEN in a 19-year-old woman who received the meningococcal B vaccine (the first report of such an association) and conduct a systematic review of the associated literature. We also discuss management of this patient with a single dose of etanercept.

    Methods: Relevant literature was searched using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method.Results: A total of 29 articles reporting EM, SJS, or TEN following vaccination were included from >5 countries. Of the 29, 22 articles reported EM, 6/29 reported SJS, and 4/29 reported TEN (3 articlesreported cases of both EM and SJS/TEN).

    Conclusions: We suggest consideration of vaccines as an etiology for cases of SJS or TEN that begin with an EM-like presentation, and provide further evidence for the use of etanercept as a viable treatment for TEN.

      Cover page: Vaccine-induced toxic epidermal necrolysis: A case and systematic reviewCreative Commons 'BY-NC-ND' version 4.0 license
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2016)
      Despite significant advances in early detection and treatment, breast cancer still remains a major cause of morbidity and mortality for women. Our understanding of the molecular heterogeneity of the disease has significantly expanded over the past decade and the role of cell cycle signaling in both breast cancer oncogenesis and anti-estrogen resistance has gained increasing attention. The mammalian cell cycle is driven by a complex interplay between cyclins and their associated cyclin-dependent kinase (CDK) partners, and dysregulation of this process is one of the hallmarks of cancer. Despite this, initial results with broadly acting CDK inhibitors were largely disappointing. However, recent preclinical and phase I/II clinical studies using a novel, oral, reversible CDK4/6 inhibitor, palbociclib (PD-0332991), have validated the role of CDK4/6 as a potential target in estrogen receptor-positive (ER+) breast cancers. This review highlights our current understanding of CDK signaling in both normal and malignant breast tissues, with special attention placed on recent clinical advances in inhibition of CDK4/6 in ER+ disease.
        Cover page: Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2011)

        Background

        In humans, inorganic arsenic (iAs) is metabolized to methylated arsenical species in a multistep process mainly mediated by arsenic (+3 oxidation state) methyltransferase (AS3MT). Among these metabolites is monomethylarsonous acid (MMAIII), the most toxic arsenic species. A recent study in As3mt-knockout mice suggests that unidentified methyltransferases could be involved in alternative iAs methylation pathways. We found that yeast deletion mutants lacking MTQ2 were highly resistant to iAs exposure. The human ortholog of the yeast MTQ2 is N-6 adenine-specific DNA methyltransferase 1 (N6AMT1), encoding a putative methyltransferase.

        Objective

        We investigated the potential role of N6AMT1 in arsenic-induced toxicity.

        Methods

        We measured and compared the cytotoxicity induced by arsenicals and their metabolic profiles using inductively coupled plasma-mass spectrometry in UROtsa human urothelial cells with enhanced N6AMT1 expression and UROtsa vector control cells treated with different concentrations of either iAsIII or MMAIII.

        Results

        N6AMT1 was able to convert MMAIII to the less toxic dimethylarsonic acid (DMA) when overexpressed in UROtsa cells. The enhanced expression of N6AMT1 in UROtsa cells decreased cytotoxicity of both iAsIII and MMAIII. Moreover, N6AMT1 is expressed in many human tissues at variable levels, although at levels lower than those of AS3MT, supporting a potential participation in arsenic metabolism in vivo.

        Conclusions

        Considering that MMAIII is the most toxic arsenical, our data suggest that N6AMT1 has a significant role in determining susceptibility to arsenic toxicity and carcinogenicity because of its specific activity in methylating MMAIII to DMA and other unknown mechanisms.
          Cover page: Involvement of N-6 Adenine-Specific DNA Methyltransferase 1 (N6AMT1) in Arsenic Biomethylation and Its Role in Arsenic-Induced Toxicity
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2023)
          BACKGROUND: In-hospital dermatological care has shifted from dedicated dermatology wards to consultation services, and some consulted patients may require postdischarge follow-up in outpatient dermatology. Safe and timely care transitions from inpatient-to-outpatient specialty care are critical for patient health, but communication around these transitions can be disjointed, and workflows can be complex. OBJECTIVE: In this 3-phase quality improvement effort, we developed and evaluated an intervention that leveraged an electronic health record (EHR) feature, known as SmartPhrase, to enable a new workflow to improve transitions from inpatient care to outpatient dermatology. METHODS: Phase 1 (February-March 2021) included interviews with patients and process mapping with key stakeholders to identify gaps and inform an intervention: a SmartPhrase table and associated workflow to promote collection of patient information needed for scheduling follow-up and closed-loop communication between dermatology and scheduling teams. In phase 2 (April-May 2021), semistructured interviews-with dermatologists (n=5), dermatology residents (n=5), and schedulers (n=6)-identified pain points and refinements. In phase 3, the intervention was evaluated by triangulating data from these interviews with measured changes in scheduling efficiency, visit completion, and messaging volume preimplementation (January-February 2021) and postimplementation (April-May 2021). RESULTS: Preintervention pain points included unclear workflow for care transitions, limited patient input in follow-up planning, multiple messaging channels (eg, EHR based, email, and phone messages), and time-inefficient patient tracking. The intervention addressed most pain points; interviewees reported the intervention was easy to adopt and improved scheduling efficiency, workload, and patient involvement. More visits were completed within the desired timeframe of 14 days after discharge during the postimplementation period (21/47, 45%) than the preimplementation period (28/41, 68%; P=.03). The messaging workload also decreased from 88 scheduling-related messages sent for 25 patients before implementation to 30 messages for 8 patients after implementation. CONCLUSIONS: Inpatient-to-outpatient specialty care transitions are complex and involve multiple stakeholders, thus requiring multifaceted solutions. With deliberate evaluation, broad stakeholder input, and iteration, we designed and implemented a successful solution using a standard EHR feature, SmartPhrase, integrated into a standardized workflow to improve the timeliness of posthospital specialty care and reduce workload.
            Cover page: Evolution of a Project to Improve Inpatient-to-Outpatient Dermatology Care Transitions: Mixed Methods Evaluation.
            • Article
            • Peer Reviewed
            LBL Publications (2024)
            Ditopic bis-pyrazolylpyridine ligands usually react with divalent metal ions (M2+) to produce dinuclear triple-stranded helicates [M2L3]4+ or, via π⋯π interactions, dimers of monoatomic complexes ([ML3]2)4+. The introduction of an additional benzene ring at each end of ligand L increases the number of aromatic contacts within the supramolecular aggregate by 40%, driving the self-recognition process in an irreversible manner. Consequently, the mixing of new bis-pyrazolylquinoline L2 with FeX2 salts leads to crystallization of the tripartite high-spin assemblies (X@[Fe(L2)3]2)3+ (X = Cl, Br or I). The aggregates exhibit exceptional stability, as confirmed by a combination of paramagnetic 1H NMR techniques, demonstrating their persistence in solution. Our investigations further reveal that the guests Br- and I- are retained inside the associate in solution but Cl- is immediately released, resulting in the formation of the empty supramolecular dimer ([Fe(L2)3]2)4+.
              Cover page: Engineered π⋯π interactions favour supramolecular dimers X@[FeL 3 ] 2 (X = Cl, Br, I): solid state and solution structure
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2024)
              We sought to investigate the feasibility of longitudinal monitoring of disease activity from home in people with hidradenitis suppurativa (HS). Over 6 months, our novel digital tool collected 421 photos of HS-affected skin from 27 participants and captured trends in pain and quality of life scores. We found that participants with mild disease were more likely to share their progress than those with more severe disease, which is favourable as it may suggest a role for remote monitoring in tracking disease progression. This pilot provides proof of concept that will support future studies.
                Cover page: Longitudinal remote monitoring of hidradenitis suppurativa: a pilot study.
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2022)

                Purpose

                Circulating tumor DNA (ctDNA) analyses allow for postoperative risk stratification in patients with curatively treated colon and breast cancers. Use of ctDNA in esophagogastric cancers (EGC) is less characterized and could identify high-risk patients who have been treated with curative intent.

                Methods

                In this retrospective analysis of real-world data, ctDNA levels were analyzed in the preoperative, postoperative, and surveillance settings in patients with EGC using a personalized multiplex polymerase chain reaction-based next-generation sequencing assay. Plasma samples (n = 943) from 295 patients at > 70 institutions were collected before surgery, postoperatively, and/or serially during routine clinical follow-up from September 19, 2019, to February 21, 2022. ctDNA detection was annotated to clinicopathologic features and recurrence-free survival.

                Results

                A total of 295 patients with EGC were analyzed, and 212 patients with stages I-III disease were further explored. Pretreatment ctDNA was detected in 96% (23/24) of patients with preoperative time points. Postoperative ctDNA was detected in 23.5% (16/68) of patients with stage I-III EGC within 16 weeks (molecular residual disease window) after surgery without receiving systemic therapy. ctDNA detection at any time point after surgery (hazard ratio [HR], 23.6; 95% CI, 10.2 to 66.0; P < .0001), within the molecular residual disease window (HR, 10.7; 95% CI, 4.3 to 29.3; P < .0001), and during the surveillance period (HR, 17.7; 95% CI, 7.3 to 50.7; P < .0001) was associated with shorter recurrence-free survival. In multivariable analysis, ctDNA status and clinical stage of disease were independently associated with outcomes.

                Conclusion

                Using real-world data, we demonstrate that postoperative tumor-informed ctDNA detection in EGC is feasible and allows for enhanced patient risk stratification and prognostication during curative-intent therapy.
                  Cover page: Analysis of Circulating Tumor DNA to Predict Risk of Recurrence in Patients With Esophageal and Gastric Cancers
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2021)
                  We investigated whether serial measurements of circulating tumor DNA (ctDNA) and functional tumor volume (FTV) by magnetic resonance imaging (MRI) can be combined to improve prediction of pathologic complete response (pCR) and estimation of recurrence risk in early breast cancer patients treated with neoadjuvant chemotherapy (NAC). We examined correlations between ctDNA and FTV, evaluated the additive value of ctDNA to FTV-based predictors of pCR using area under the curve (AUC) analysis, and analyzed the impact of FTV and ctDNA on distant recurrence-free survival (DRFS) using Cox regressions. The levels of ctDNA (mean tumor molecules/mL plasma) were significantly correlated with FTV at all time points (p < 0.05). Median FTV in ctDNA-positive patients was significantly higher compared to those who were ctDNA-negative (p < 0.05). FTV and ctDNA trajectories in individual patients showed a general decrease during NAC. Exploratory analysis showed that adding ctDNA information early during treatment to FTV-based predictors resulted in numerical but not statistically significant improvements in performance for pCR prediction (e.g., AUC 0.59 vs. 0.69, p = 0.25). In contrast, ctDNA-positivity after NAC provided significant additive value to FTV in identifying patients with increased risk of metastatic recurrence and death (p = 0.004). In this pilot study, we demonstrate that ctDNA and FTV were correlated measures of tumor burden. Our preliminary findings based on a limited cohort suggest that ctDNA at surgery improves FTV as a predictor of metastatic recurrence and death. Validation in larger studies is warranted.
                    Cover page: Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2021)

                    Background

                    Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is strongly associated with favorable outcome. We examined the utility of serial circulating tumor DNA (ctDNA) testing for predicting pCR and risk of metastatic recurrence.

                    Patients and methods

                    Cell-free DNA (cfDNA) was isolated from 291 plasma samples of 84 high-risk early breast cancer patients treated in the neoadjuvant I-SPY 2 TRIAL with standard NAC alone or combined with MK-2206 (AKT inhibitor) treatment. Blood was collected at pretreatment (T0), 3 weeks after initiation of paclitaxel (T1), between paclitaxel and anthracycline regimens (T2), or prior to surgery (T3). A personalized ctDNA test was designed to detect up to 16 patient-specific mutations (from whole-exome sequencing of pretreatment tumor) in cfDNA by ultra-deep sequencing. The median follow-up time for survival analysis was 4.8 years.

                    Results

                    At T0, 61 of 84 (73%) patients were ctDNA positive, which decreased over time (T1: 35%; T2: 14%; and T3: 9%). Patients who remained ctDNA positive at T1 were significantly more likely to have residual disease after NAC (83% non-pCR) compared with those who cleared ctDNA (52% non-pCR; odds ratio 4.33, P = 0.012). After NAC, all patients who achieved pCR were ctDNA negative (n = 17, 100%). For those who did not achieve pCR (n = 43), ctDNA-positive patients (14%) had a significantly increased risk of metastatic recurrence [hazard ratio (HR) 10.4; 95% confidence interval (CI) 2.3-46.6]; interestingly, patients who did not achieve pCR but were ctDNA negative (86%) had excellent outcome, similar to those who achieved pCR (HR 1.4; 95% CI 0.15-13.5).

                    Conclusions

                    Lack of ctDNA clearance was a significant predictor of poor response and metastatic recurrence, while clearance was associated with improved survival even in patients who did not achieve pCR. Personalized monitoring of ctDNA during NAC of high-risk early breast cancer may aid in real-time assessment of treatment response and help fine-tune pCR as a surrogate endpoint of survival.
                      Cover page: Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival.
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