Publications by authors named "Jinah Kim"

128 Publications

Deep visual domain adaptation and semi-supervised segmentation for understanding wave elevation using wave flume video images.

Sci Rep 2021 Nov 5;11(1):21776. Epub 2021 Nov 5.

School of Computer Science and Engineering, Kyungpook National University, Daegu, 41566, South Korea.

Accurate water surface elevation estimation is essential for understanding nearshore processes, but it is still challenging due to limitations in measuring water level using in-situ acoustic sensors. This paper presents a vision-based water surface elevation estimation approach using multi-view datasets. Specifically, we propose a visual domain adaptation method to build a water level estimator in spite of a situation in which ocean wave height cannot be measured directly. We also implemented a semi-supervised approach to extract wave height information from long-term sequences of wave height observations with minimal supervision. We performed wave flume experiments in a hydraulic laboratory with two cameras with side and top viewpoints to validate the effectiveness of our approach. The performance of the proposed models were evaluated by comparing the estimated time series of water elevation with the ground-truth wave gauge data at three locations along the wave flume. The estimated time series were in good agreement within the averaged correlation coefficient of 0.98 and 0.90 on the measurement and 0.95 and 0.85 on the estimation for regular and irregular waves, respectively.
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http://dx.doi.org/10.1038/s41598-021-01157-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571332PMC
November 2021

Appropriate use criteria for ancillary diagnostic testing in dermatopathology: New recommendations for 11 tests and 220 clinical scenarios from the American Society of Dermatopathology Appropriate Use Criteria Committee.

J Cutan Pathol 2021 Sep 18. Epub 2021 Sep 18.

Department of Pathology, Cleveland Clinic, Cleveland, Ohio, USA.

Background: Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests.

Methods: RAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2.

Results: For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain."

Limitations: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded.

Conclusions: AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.
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http://dx.doi.org/10.1111/cup.14135DOI Listing
September 2021

Sex and Limb Differences in Lower Extremity Alignment and Kinematics during Drop Vertical Jumps.

Int J Environ Res Public Health 2021 04 3;18(7). Epub 2021 Apr 3.

Department of Physical Education, Yonsei University, Seoul 03722, Korea.

Sex and limb differences in lower extremity alignments (LEAs) and dynamic lower extremity kinematics (LEKs) during a drop vertical jump were investigated in participants of Korean ethnicity. One hundred healthy males and females participated in a drop vertical jump, and LEAs and LEKs were determined in dominant and non-dominant limbs. A 2-by-2 mixed model MANOVA was performed to compare LEAs and joint kinematics between sexes and limbs (dominant vs. non-dominant). Compared with males, females possessed a significantly greater pelvic tilt, femoral anteversion, Q-angle, and reduced tibial torsion. Females landed on the ground with significantly increased knee extension and ankle plantarflexion with reduced hip abduction and knee adduction, relatively decreased peak hip adduction, knee internal rotation, and increased knee abduction and ankle eversion. The non-dominant limb showed significantly increased hip flexion, abduction, and external rotation; knee flexion and internal rotation; and ankle inversion at initial contact. Further, the non-dominant limb showed increased peak hip and knee flexion, relatively reduced peak hip adduction, and increased knee abduction and internal rotation. It could be suggested that LEAs and LEKs observed in females and non-dominant limbs might contribute to a greater risk of anterior cruciate ligament injuries.
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http://dx.doi.org/10.3390/ijerph18073748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038346PMC
April 2021

Adaptive Homeostatic Strategies of Resilient Intrinsic Self-Regulation in Extremes (RISE): A Randomized Controlled Trial of a Novel Behavioral Treatment for Chronic Pain.

Front Psychol 2021 12;12:613341. Epub 2021 Apr 12.

Department of Psychology, Midwestern University, Glendale, AZ, United States.

Current treatments for chronic pain have limited benefit. We describe a resilience intervention for individuals with chronic pain which is based on a model of viewing chronic pain as dysregulated homeostasis and which seeks to restore homeostatic self-regulation using strategies exemplified by survivors of extreme environments. The intervention is expected to have broad effects on well-being and positive emotional health, to improve cognitive functions, and to reduce pain symptoms thus helping to transform the suffering of pain into self-growth. A total of 88 Veterans completed the pre-assessment and were randomly assigned to either the treatment intervention ( = 38) or control ( = 37). Fifty-eight Veterans completed pre- and post-testing (intervention = 31, control = 27). The intervention covered resilience strengths organized into four modules: (1) engagement, (2) social relatedness, (3) transformation of pain and (4) building a good life. A broad set of standardized, well validated measures were used to assess three domains of functioning: health and well-being, symptoms, and cognitive functions. Two-way Analysis of Variance was used to detect group and time differences. Broadly, results indicated significant intervention and time effects across multiple domains: (1) Pain decreased in present severity [ = 5.02, < 0.05, η = 0.08], total pain over six domains [ = 14.52, < 0.01, η = 0.21], and pain interference [ = 6.82, < 0.05, η = 0.11]; (2) Affect improved in pain-related negative affect [ = 7.44, < 0.01, η = 0.12], fear [ = 7.70, < 0.01, η = 0.12], and distress [ = 10.87, < 0.01, η = 0.16]; (3) Well-being increased in pain mobility [ = 5.45, < 0.05, η = 0.09], vitality [ = 4.54, < 0.05, η = 0.07], and emotional well-being [ = 5.53, < 0.05, η = 0.09] Mental health symptoms and the cognitive functioning domain did not reveal significant effects. This resilience intervention based on homeostatic self-regulation and survival strategies of survivors of extreme external environments may provide additional sociopsychobiological tools for treating individuals with chronic pain that may extend beyond treating pain symptoms to improving emotional well-being and self-growth. Registered with ClinicalTrials.gov (NCT04693728).
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http://dx.doi.org/10.3389/fpsyg.2021.613341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074861PMC
April 2021

A rare case of metronidazole induced recurrent pancreatitis.

Pancreatology 2021 Jan 5;21(1):318-319. Epub 2020 Nov 5.

Harrisburg Gastroenterology, LTD., 4760 Union Deposit Road, Harrisburg, PA, 17111, USA. Electronic address:

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http://dx.doi.org/10.1016/j.pan.2020.11.001DOI Listing
January 2021

Chronic stress has lasting effects on improved cued discrimination early in extinction.

Learn Mem 2020 08 15;27(8):319-327. Epub 2020 Jul 15.

Department of Psychology, Arizona State University, Tempe, Arizona 85287-1104, USA.

Chronic stress typically leads to deficits in fear extinction when tested soon after chronic stress ends. Given the importance of extinction in updating fear memories, the current study examined whether fear extinction was impaired in rats that were chronically stressed and then given a break from the end of chronic stress to the start of fear conditioning and extinction. Male rats were chronically stressed by restraint (6 h/d/21 d) and tested soon (termed immediate, STR-IMM), or 3 or 6 wk after a rest period from restraint (termed rest or "R," STR-R3, STR-R6). In Experiment 1, STR-R3 and STR-R6 discriminated between the cue and nonshock context better than STR-IMM or control. Interestingly, STR-IMM showed high freezing to the nonshock context. Consequently, Experiment 2 investigated whether STR-IMM generalized across contexts, which was not supported. Experiment 3 determined whether STR-IMM were susceptible to second-order conditioning to a novel context, but showed that the level of second-order conditioning was similar for all groups. These findings reveal that rats exposed to chronic stress and then given a rest period of 3 or 6 wk, express unique fear extinction profiles compared to control and STR-IMM. Specifically, STR-R demonstrated excellent cue and context discrimination during extinction, and perhaps showed a stress inoculation effect. For STR-IMM, the heightened freezing under these extensive acclimation parameters was not attributed to generalization nor to second-order fear conditioning to "safe" contexts and, instead, may reflect hypervigilance.
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http://dx.doi.org/10.1101/lm.051060.119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365016PMC
August 2020

Opioid antidote induced pulmonary edema and lung injury.

Respir Med Case Rep 2020 29;30:101107. Epub 2020 May 29.

Department of Internal Medicine, UPMC Pinnacle, Harrisburg, PA, USA.

Introduction: Opioid overdose emergencies are increasing every year, naloxone is the antidote for the treatment of opioid overdose. Naloxone is being dispensed to even lay persons through some programs to prevent opioid overdose deaths.

Case: 23 year old patient presented with naloxone treated opioid overdose complained of chest pain, pink frothy sputum production and shortness of breath. Physical exam showed tachycardia, tachypnea and coarse breath sounds. Imaging of the lungs showed diffuse pulmonary edema. Within an hour after the administration of naloxone patient developed pulmonary edema and lung injury. Patient was managed with non-invasive positive pressure ventilation which improved patient's symptoms in less than 6 hours confirmed by radiological improvement in 24-36 hrs.

Discussion: There are no specific observation guidelines post naloxone treatment in opiate overdose patients. We recommend early treatment of naloxone induced pulmonary complications during the observation period with non-invasive positive pressure ventilation to reduce the morbidity.
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http://dx.doi.org/10.1016/j.rmcr.2020.101107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287275PMC
May 2020

Regional variation in states' naloxone accessibility laws in association with opioid overdose death rates-Observational study (STROBE compliant).

Medicine (Baltimore) 2020 May;99(22):e20033

Department of Family Medicine, Chungbuk National University Hospital, Cheongju, Chungbuk.

Though overall death from opioid overdose are increasing in the United States, the death rate in some states and population groups is stabilizing or even decreasing. Several states have enacted a Naloxone Accessibility Laws to increase naloxone availability as an opioid antidote. The extent to which these laws permit layperson distribution and possession varies. The aim of this study is to investigate differences in provisions of Naloxone Accessibility Laws by states mainly in the Northeast and West regions, and the impact of naloxone availability on the rates of drug overdose deaths.This cross-sectional study was based on the National Vital Statistics System multiple cause-of-death mortality files. The average changes in drug overdose death rates between 2013 and 2017 in relevant states of the Northeast and West regions were compared according to availability of naloxone to laypersons.Seven states in the Northeast region and 10 states in the Western region allowed layperson distribution of naloxone. Layperson possession of naloxone was allowed in 3 states each in the Northeast and the Western regions. The average drug overdose death rates increased in many states in the both regions regardless of legalization of layperson naloxone distribution. The average death rates of 3 states that legalized layperson possession in the West region decreased (-0.33 per 100,000 person); however, in states in the West region that did not allow layperson possession and states in the Northeast region regardless of layperson possession increased between 2013 and 2017.The provision to legalize layperson possession of naloxone was associated with decreased average opioid overdose death rates in 3 states of the West region.
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http://dx.doi.org/10.1097/MD.0000000000020033DOI Listing
May 2020

Effects of a 4-Week Short-Foot Exercise Program on Gait Characteristics in Patients With Stage II Posterior Tibial Tendon Dysfunction.

J Sport Rehabil 2020 Mar 31;30(1):120-128. Epub 2020 Mar 31.

Context: Clinically, it has been suggested that increased activation of intrinsic foot muscles may alter the demand of extrinsic muscle activity surrounding the ankle joint in patients with stage II posterior tibial tendon dysfunction. However, there is limited empirical evidence supporting this notion.

Objective: The purpose of this study was to investigate the effects of a 4-week short-foot exercise (SFE) on biomechanical factors in patients with stage II posterior tibial tendon dysfunction.

Design: Single-group pretest-posttest.

Setting: University laboratory.

Participants: Fifteen subjects (8 males and 7 females) with stage II posterior tibial tendon dysfunction who had pain in posterior tibial tendon, pronated foot deformity (foot posture index ≥+6), and flexible foot deformity (navicular drop ≥10 mm) were voluntarily recruited.

Intervention: All subjects completed a 4-week SFE program (15 repetitions × 5 sets/d and 3 d/wk) of 4 stages (standing with feedback, sitting, double-leg, and one-leg standing position).

Main Outcome Measures: Ankle joint kinematics and kinetics and tibialis anterior and fibularis longus muscle activation (% maximum voluntary isometric contraction) during gait were measured before and after SFE program. Cohen d effect size (ES [95% confidence intervals]) was calculated.

Results: During the first rocker, tibialis anterior activation decreased at peak plantarflexion (ES = 0.75 [0.01 to 1.49]) and inversion (ES = 0.77 [0.03 to 1.51]) angle. During the second rocker, peak dorsiflexion angle (ES = 0.77 [0.03 to 1.51]) and tibialis anterior activation at peak eversion (ES = 1.57 [0.76 to 2.39]) reduced. During the third rocker, the peak abduction angle (ES = 0.80 [0.06 to 1.54]) and tibialis anterior and fibularis longus activation at peak plantarflexion (ES = 1.34 [0.54 to 2.13]; ES = 1.99 [1.11 to 2.86]) and abduction (ES = 1.29 [0.50 to 2.08]; ES = 1.67 [0.84 to 2.50]) decreased.

Conclusions: Our 4-week SFE program may have positive effects on changing muscle activation patterns for tibialis anterior and fibularis longus muscles, although it could not influence their structural deformity and ankle joint moment. It could produce a potential benefit of decreased tibialis posterior activation.
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http://dx.doi.org/10.1123/jsr.2019-0211DOI Listing
March 2020

TERT and TERT promoter in melanocytic neoplasms: Current concepts in pathogenesis, diagnosis, and prognosis.

J Cutan Pathol 2020 Aug 3;47(8):710-719. Epub 2020 Apr 3.

Laboratorio Recavarren Emanuel, Clínica Ricardo Palma, Lima, Peru.

Background And Objective: Located on chromosome locus 5p15.33, telomerase reverse transcriptase (TERT or hTERT) encodes the catalytic subunit of telomerase which permits lengthening and preservation of telomeres following mitosis. Mutations in TERT promoter (TERT-p) upregulate expression of TERT, allowing survival of malignant cells and tumor progression in wide variety of malignancies including melanoma. The objective of this review is to examine the roles of TERT and TERT-p in the pathogenesis, diagnosis, and prognostication of cutaneous melanoma.

Methods: All studies of TERT or TERT-p in cutaneous melanocytic neoplasms with the following inclusion criteria were reviewed: publication date between 2010 and 2019, English language, and series of ≥3 cases were reviewed for evidence supporting the role of TERT in pathogenesis, diagnosis, and prognosis. Studies with <3 cases or focused primarily on mucosal or uveal melanocytic tumors were excluded.

Results And Conclusion: TERT-p mutations are frequent in chronic and non-chronic sun damage melanoma and correlate with adverse prognosis, inform pathogenesis, and may provide diagnostic support. While TERT-p mutations are uncommon in acral melanoma, TERT copy number gains and gene amplification predict reduced survival. Among atypical spitzoid neoplasms, TERT-p mutations identify biologically aggressive tumors and support the diagnosis of spitzoid melanoma. TERT-p methylation may have prognostic value in pediatric conventional melanoma and drive tumorigenesis in melanoma arising within congenital nevi. Finally, TERT-p mutations may aid in the differentiation of recurrent nevi from recurrent melanoma.
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http://dx.doi.org/10.1111/cup.13691DOI Listing
August 2020

Ciliation Index Is a Useful Diagnostic Tool in Challenging Spitzoid Melanocytic Neoplasms.

J Invest Dermatol 2020 07 22;140(7):1401-1409.e2. Epub 2020 Jan 22.

Department of Dermatology, University of California, San Francisco, CA, USA; Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.

The loss of primary cilia on melanocytes is a useful biomarker for the distinction of melanoma from conventional melanocytic nevi. It is unknown whether ciliation status is beneficial for diagnosing spitzoid tumors-a subclass of melanomas that present inherently ambiguous histology and are challenging to classify. We evaluated the Ciliation Index (CI) in 68 cases of spitzoid tumors ranging from Spitz nevi and atypical Spitz tumors to spitzoid melanoma. We found a significant decrease in CI within the spitzoid melanoma group when compared with either the Spitz nevi or atypical Spitz tumors groups. In addition, we used a machine-learning-based algorithm to determine the value of CI when considered in combination with other histopathologic and molecular features commonly used for diagnosis. We found that a low CI was consistently ranked as a top predictive feature in the diagnosis of malignancy. Predictive models trained on only the top four predictive features (CI, asymmetry, hyperchromatism, and cytologic atypia) outperformed standard histologic assessment in an independent validation cohort of 56 additional cases. The results provide an alternative approach to evaluate diagnostically challenging melanocytic lesions, and further support the use of CI as an ancillary diagnostic test.
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http://dx.doi.org/10.1016/j.jid.2019.11.028DOI Listing
July 2020

Pityriasis rubra pilaris-like graft-vs-host disease following allogeneic stem cell transplant in two patients.

Clin Case Rep 2019 Dec 14;7(12):2491-2494. Epub 2019 Nov 14.

Department of Dermatology Stanford University Medical Center Stanford California.

Chronic cutaneous graft-vs-host disease (GVHD) has several atypical variants. We describe two cases of GVHD with clinical and histopathologic features of pityriasis rubra pilaris (PRP), which responded to additional immunosuppression. Recognition of this newly described PRP-like clinical presentation of GVHD may prompt early consideration of additional steroid-sparing therapies.
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http://dx.doi.org/10.1002/ccr3.2458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935619PMC
December 2019

High-throughput Sequencing of Subcutaneous Panniculitis-like T-Cell Lymphoma Reveals Candidate Pathogenic Mutations.

Appl Immunohistochem Mol Morphol 2019 Nov/Dec;27(10):740-748

Departments of Pathology.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a malignant primary cutaneous T-cell lymphoma that is challenging to distinguish from other neoplastic and reactive panniculitides. In an attempt to identify somatic variants in SPTCL that may be diagnostically or therapeutically relevant, we performed both exome sequencing on paired tumor-normal samples and targeted sequencing of hematolymphoid-malignancy-associated genes on tumor biopsies. Exome sequencing was performed on skin biopsies from 4 cases of skin-limited SPTCL, 1 case of peripheral T-cell lymphoma, not otherwise specified with secondary involvement of the panniculus, and 2 cases of lupus panniculitis. This approach detected between 1 and 13 high-confidence somatic variants that were predicted to result in a protein alteration per case. Variants of interest identified include 1 missense mutation in ARID1B in 1 case of SPTCL. To detect variants that were present at a lower level, we used a more sensitive targeted panel to sequence 41 hematolymphoid-malignancy-associated genes. The targeted panel was applied to 2 of the biopsies that were evaluated by whole exome sequencing as well as 5 additional biopsies. Potentially pathogenic variants were identified in KMT2D and PLCG1 among others, but no gene was altered in >2 of the 7 cases sequenced. One variant that was notably absent from the cases sequences is RHOA G17V. Further work will be required to further elucidate the genetic abnormalities that lead to this rare lymphoma.
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http://dx.doi.org/10.1097/PAI.0000000000000683DOI Listing
July 2020

Pembrolizumab in Relapsed and Refractory Mycosis Fungoides and Sézary Syndrome: A Multicenter Phase II Study.

J Clin Oncol 2020 01 18;38(1):20-28. Epub 2019 Sep 18.

National Cancer Institute, Bethesda, MD.

Purpose: To assess the efficacy of pembrolizumab in patients with advanced relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS).

Patients And Methods: CITN-10 is a single-arm, multicenter phase II trial of 24 patients with advanced MF or SS. Patients were treated with pembrolizumab 2 mg/kg every 3 weeks for up to 24 months. The primary end point was overall response rate by consensus global response criteria.

Results: Patients had advanced-stage disease (23 of 24 with stage IIB to IV MF/SS) and were heavily pretreated with a median of four prior systemic therapies. The overall response rate was 38% with two complete responses and seven partial responses. Of the nine responding patients, six had 90% or more improvement in skin disease by modified Severity Weighted Assessment Tool, and eight had ongoing responses at last follow-up. The median duration of response was not reached, with a median response follow-up time of 58 weeks. Immune-related adverse events led to treatment discontinuation in four patients. A transient worsening of erythroderma and pruritus occurred in 53% of patients with SS. This cutaneous flare reaction did not result in treatment discontinuation for any patient. The flare reaction correlated with high PD-1 expression on Sézary cells but did not associate with subsequent clinical responses or lack of response. Treatment responses did not correlate with expression of PD-L1, total mutation burden, or an interferon-γ gene expression signature.

Conclusion: Pembrolizumab demonstrated significant antitumor activity with durable responses and a favorable safety profile in patients with advanced MF/SS.
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http://dx.doi.org/10.1200/JCO.19.01056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943974PMC
January 2020

Investigation of the relationship between localized cumulative stress and plantar tissue stiffness in healthy individuals using the in-vivo indentation technique.

J Mech Behav Biomed Mater 2019 10 20;98:157-162. Epub 2019 Jun 20.

Division of Mechanical and Biomedical Engineering, Ewha Womans University, Republic of Korea. Electronic address:

This study was conducted to determine whether prolonged and repetitive exercise stiffens the plantar soft tissue. Healthy female subjects in their early 20s with a similar body mass index but different majors (13 engineers (controls) and 13 ballet dancers) were recruited. Tissue thickness was measured using ultrasound, while peak stress, stress distribution, and center of pressure were obtained Zebris pressure mat. Stiffness was evaluated using a custom-made tissue indentation system. F-test and independent sample T-test were used to determine significant differences between the two groups. No significance was found in the thickness of the second sub-metatarsal head (MTH) and heel between the two groups. In the second sub-MTH, the ballet group showed higher peak stress, loading rate, and stiffness than the control group. Conversely, in the heel region, all the results were higher for the control group. The results of this study quantify the impact of exercise on the stiffness of plantar soft tissue and confirm that even healthy individuals who do prolonged and repetitive exercise have stiffer plantar soft tissue.
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http://dx.doi.org/10.1016/j.jmbbm.2019.06.020DOI Listing
October 2019

Use of the Ciliation Index to Distinguish Invasive Melanoma From Associated Conventional Melanocytic Nevi.

Am J Dermatopathol 2020 Jan;42(1):11-15

Section of Dermatopathology, Department of Pathology, Stanford University Medical Center, Stanford, CA.

Our understanding of melanoma precursors and progression to melanoma has developed as a result of advances in the field of molecular diagnostics. We now better understand the potential for genetic heterogeneity within a single lesion. Combined tumors can pose a diagnostic challenge when deciding the line between benign and malignant, which in turn has direct implications for patient management. Primary cilia (PC) are ubiquitous sensory organelles that have essential functions in cellular proliferation, differentiation, and development. The ciliation index (percentage of ciliated melanocytes) has been shown to reliably differentiate melanoma, which fail to ciliate, from melanocytic nevi, which retain PC. We therefore analyzed the potential for using the ciliation index to differentiate benign and malignant components in combined melanocytic lesions. We collected patient samples (n = 10) of unequivocal combined lesions with both melanoma and associated nevus components. Melanocytes were highlighted with SOX10 and costained with gamma-Tubulin and acetylated alpha-Tubulin to highlight the basal body and cilium, respectively. The number of melanocytes retaining cilia under high-power microscopy was examined. The melanoma component had average of 4% ciliation (SD: 7%), whereas the associated nevus component was significantly higher with 59% ciliation (SD: 17%). These data show that PC may be a reliable means of distinguishing benign from malignant components within a single tumor. The ciliation index may be a helpful tool in distinguishing challenging cases of combined lesions of melanoma in situ with a dermal nevus component from invasive melanoma, thus promoting improved staging and clinical management.
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http://dx.doi.org/10.1097/DAD.0000000000001459DOI Listing
January 2020

Depletion of primary cilium in acral melanoma.

J Cutan Pathol 2019 Sep 14;46(9):665-671. Epub 2019 May 14.

Department of Dermatology, Palo Alto Medical Foundation, Palo Alto, California.

Background: A eukaryotic cell's primary cilium (PC) is critical for cell signaling, migration and homeostasis. Primary cilium dysfunction has been demonstrated in several malignancies, but whether primary cilia loss occurs in acral melanoma has remained unknown. To address this, we examined the ciliation index (% melanocytes containing a PC) of patient-derived, biopsy-proven acral melanoma and compared these to benign acral nevi.

Methods: We generated a pilot initiative study that included six acral melanomas and seven acral nevi derived from the foot. Using fluorescent immunohistochemistry, we calculated ciliation indexes of Sox10+ melanocytes.

Results: Average ciliation index for acral nevi was 74.0% (SE of the mean [SEM] 3.3%) vs 9.3% for acral melanoma (SEM 5.7%), finding a statistically significant difference between the groups (P-value <.001, two tailed t test).

Conclusion: The data show a significant loss of primary cilia in malignant acral melanoma vs benign acral nevi, suggesting that cilia may play an important role during acral melanoma formation. Our data, which should be validated by a larger study with longer follow-up period, suggest that examining ciliation index may be a useful diagnostic test when distinguishing benign acral nevi from melanoma.
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http://dx.doi.org/10.1111/cup.13484DOI Listing
September 2019

Primary cardiac angiosarcoma with right atrial wall rupture: A case report.

Medicine (Baltimore) 2019 Apr;98(14):e15020

Department of Oncology and Hematology, Soonchunhyang University Seoul Hospital, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.

Rationale: Cardiac angiosarcoma is the most common malignant tumor of the heart and a rare disease with rapid disease progression and poor prognosis. Cardiac wall rupture is an extremely rare complication.

Patient Concerns: A 32-year-old woman presented with an acute onset of epigastric pain and chest discomfort at first time when she visited an emergency room.

Diagnoses: A cardiac mass was identified on echocardiography and subsequently performed chest computed tomography and cardiac magnetic resonance imaging revealed the cardiac tumor at right atrium with right atrial wall rupture and hematogenous lung metastasis. Histopathologic diagnosis of metastatic angiosarcoma was done by open lung biopsy.

Interventions: The patient was treated with palliative chemotherapy for the primary cardiac tumor and hematogenous lung metastasis.

Outcomes: The follow-up imaging studies revealed treatment response of the primary cardiac tumor and hematogenous lung metastasis.

Lessons: Clinical and radiologic evaluation of the cardiac angiosarcoma was well performed in our case with various diagnostic imaging modalities including echocardiography, chest computed tomography, cardiac magnetic resonance imaging, and fluorodeoxyglucose-positron emission tomography/computed tomography. This case report well demonstrates typical imaging findings of a rare cardiac tumor and emphasizes importance of early investigation for accurate diagnosis and proper management of the cardiac tumor.
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http://dx.doi.org/10.1097/MD.0000000000015020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456144PMC
April 2019

Role of imaging in low-grade cutaneous B-cell lymphoma presenting in the skin.

J Am Acad Dermatol 2019 Oct 29;81(4):970-976. Epub 2019 Jan 29.

Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: Whole-body imaging is the current standard of care for staging all patients presenting with skin lesions of B-cell lymphomas (BCLs), regardless of skin disease extent; however, supporting data are lacking.

Objective: To determine the clinical utility of imaging in the detection of systemic involvement in low-grade cutaneous BCLs in the skin.

Methods: Retrospective cohort analysis of patients presenting with cutaneous lesions of BCLs at Memorial Sloan Kettering Cancer Center and Stanford University during 1997-2016.

Results: At initial staging, of the 522 patients, extracutaneous disease was noted in 3.6% and 8.8% of patients with marginal zone lymphoma (MZL, n = 306) and follicle center lymphoma (FCL, n = 216) histology, respectively. In patients with systemic involvement, imaging alone identified 81.8% (9/11) of MZL cases and 89.4% of follicular lymphoma cases. In primary cutaneous MZL, 1.7% of patients subsequently had extracutaneous involvement (median follow-up 45 months), and in primary cutaneous FCL. 3.0% subsequently had extracutaneous involvement (median follow-up 47 months).

Limitations: This was a retrospective study.

Conclusion: Imaging is effective at identifying patients with systemic involvement in indolent BCLs present in the skin; however, incidence is low. After negative initial staging, primary cutaneous MZL patients may be followed clinically without routine imaging.
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http://dx.doi.org/10.1016/j.jaad.2019.01.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661219PMC
October 2019

Pilot studies demonstrate the potential benefits of antiinflammatory therapy in human lymphedema.

JCI Insight 2018 10 18;3(20). Epub 2018 Oct 18.

Department of Medicine, VA Palo Alto Health Care System/Stanford University, Palo Alto, California, USA.

Background: Lymphedema is a common condition affecting millions around the world that still lacks approved medical therapy. Because ketoprofen, an NSAID, has been therapeutic in experimental lymphedema, we evaluated its efficacy in humans.

Methods: We first performed an exploratory open-label trial. Patients with either primary or secondary lymphedema received ketoprofen 75 mg by mouth 3 times daily for 4 months. Subjects were evaluated for changes in histopathology, with skin thickness, limb volume, and tissue bioimpedance changes serving as secondary endpoints. Based on our encouraging findings, we next conducted a placebo-controlled trial, with the primary outcome defined as a change in skin thickness, as measured by skin calipers. Secondary endpoints for this second study included histopathology, limb volume, bioimpedance, and systemic inflammatory mediators.

Results: We enrolled 21 lymphedema patients in the open-label trial, from November 2010 to July 2011. Histopathology and skin thickness were significantly improved at 4 months compared with baseline. In the follow-up, double-blind, placebo-controlled trial, we enrolled 34 patients from August 2011 to October 2015, with 16 ketoprofen recipients and 18 placebo-treated subjects. No serious adverse events occurred. The ketoprofen recipients demonstrated reduced skin thickness, as well as improved composite measures of histopathology and decreased plasma granulocyte CSF (G-CSF) expression.

Conclusion: These 2 exploratory studies together support the utility of targeted antiinflammatory therapy with ketoprofen in patients with lymphedema. Our results highlight the promise of such approaches to help restore a failing lymphatic circulation.

Trial Registration: ClinicalTrials.gov NCT02257970.
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http://dx.doi.org/10.1172/jci.insight.123775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237444PMC
October 2018

Utility of CD30, Ki-67, and p53 in assisting with the diagnosis of mycosis fungoides with large cell transformation.

J Cutan Pathol 2019 Jan 14;46(1):33-43. Epub 2018 Nov 14.

Department of Dermatology, Palo Alto Medical Foundation, Palo Alto, California.

Introduction: Mycosis fungoides (MF) with large cell transformation (LCT) is an advanced stage of cutaneous lymphoma with a poor prognosis. Identification of LCT is critical and especially challenging when the number of large abnormal lymphocytes is near but below 25%. We propose that Ki-67 and p53 may be useful in making this diagnosis.

Methods: We identified 17 patients with advanced stage (T3 or T4) MF without LCT and 38 patients with a biopsy-confirmed new diagnosis of MF with LCT treated at our institution's cutaneous lymphoma clinic from 2012 to 2016. Seventeen patients underwent 22 biopsies with advanced stage MF (control), and 38 patients with 46 biopsies of MF with LCT were included in this study.

Results: The MF cohort had an average CD30 expression of 4%, while the MF-LCT cohort had an average CD30 expression of 22% (P < 0.05). The MF cohort had an average Ki-67 staining of 13%, while the MF-LCT group had an average Ki-67 staining of 57% (P < 0.05). Forty-seven percent of the MF-LCT group was positive for p53; on the other hand, none of the MF control group showed increased p53 expression (P < 0.05).

Discussion: While CD30 shows some value in delineating large cell transformation, Ki-67 and p53 appear to be useful immunohistochemical markers in the diagnosis of LCT.
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http://dx.doi.org/10.1111/cup.13375DOI Listing
January 2019

Reply to: "Use of immortal time within survival analysis".

J Am Acad Dermatol 2019 01 8;80(1):e19-e20. Epub 2018 Sep 8.

Department of Dermatology, Stanford University School of Medicine, Redwood City, California. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2018.08.042DOI Listing
January 2019

Mediastinal and retroperitoneal fibrosis as a manifestation of breast cancer metastasis: A case report and literature review.

Medicine (Baltimore) 2018 Aug;97(32):e11842

Department of Radiology Department of Cardiothoracic Surgery Department of Pathology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.

Rationale: Mediastinal and retroperitoneal fibrosis as a manifestation of metastasis from malignancies is rare disease and particularly, cases of mediastinal fibrosis have been rarely reported.

Patient Concerns: A 60-year-old woman presented with dyspnea and bilateral flank pain. The patient had no previous history of malignancy.

Diagnoses: A contrast-enhanced chest computed tomography scan revealed a left breast mass and infiltrative soft tissue masses in the mediastinum and retroperitoneum, which showed high fluorodeoxyglucose uptake on positron emission tomography scan. The left breast mass was proven as a malignancy on biopsy and surgical excisional biopsy of the mediastinal mass revealed metastasis from the breast cancer on histopathologic examination.

Interventions: Our patient was treated with palliative hormone therapy for the primary breast cancer and metastasis with mediastinal and retroperitoneal fibrosis.

Outcomes: Follow-up imaging studies showed improvement of the primary breast cancer and also metastasis.

Lessons: We report this rare case to emphasize that mediastinal and retroperitoneal fibrosis can be a presentation of metastasis from various primary malignancies. We expect that appropriate diagnosis and treatment for metastatic mediastinal and retroperitoneal fibrosis can have a beneficial effect on disease course and prognosis of the patient.
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http://dx.doi.org/10.1097/MD.0000000000011842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133628PMC
August 2018

Evidence behind the use of molecular tests in melanocytic lesions and practice patterns of these tests by dermatopathologists.

J Cutan Pathol 2018 Nov 22;45(11):839-846. Epub 2018 Aug 22.

Departments of Dermatology and Pathology, Stanford University School of Medicine, Stanford, California.

Background: The gold standard for the diagnosis of melanocytic lesions is histologic examination. However, as histologic examination can have its limitations, there are many clinical scenarios in which additional testing may be appropriate in an attempt to render a definitive diagnosis.

Methods: A literature review for three ancillary tests-comparative genomic hybridization (CGH)/single-nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and gene expression profiling by quantitative reverse transcription polymerase chain reaction (qRT-PCR)-was compiled and current use patterns were tabulated. Survey of the practice patterns of these tests by dermatopathologists was also accessed in the attendees of the American Society of Dermatopathology Annual Meeting (Chicago, 2016).

Results: Here we summarize the use of these molecular tests in melanocytic lesions. We found that 54.4% of the respondents surveyed utilize (or expect consultants to utilize) molecular testing of melanocytic lesions in their practice when appropriate.

Conclusions: CGH/SNP arrays, FISH testing, and qRT-PCR applied to melanocytic lesions have allowed for more accurate classification. Just over half of those surveyed use molecular testing for melanocytic lesion with the majority sending their cases out for completion of the molecular test.
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http://dx.doi.org/10.1111/cup.13327DOI Listing
November 2018

PD-L1 Expression and Tumor-Infiltrating Lymphocytes in High-Risk and Metastatic Cutaneous Squamous Cell Carcinoma.

Otolaryngol Head Neck Surg 2019 01 17;160(1):93-99. Epub 2018 Jul 17.

1 Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California, USA.

Objective: To characterize programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) positivity for locally aggressive or regionally metastatic cutaneous head and neck squamous cell carcinoma (cHNSCC).

Study Design: Retrospective chart review, followed by immunohistochemical staining of archived tumor specimens.

Setting: Tertiary academic medical center.

Subjects And Methods: After identification of 101 patients treated surgically for locally advanced or regionally metastatic cHNSCC, archived tissue was stained and graded for PD-L1 expression in addition to TIL presence. Cross-tabulation was performed to examine the association between either of these variables and clinicopathologic features and outcomes.

Results: A total of 101 patients met inclusion criteria, but archived tissue was available only for 83 (31 primaries, 52 metastases). The majority of primary tumors demonstrated grade 1 PD-L1 staining, while grade 2 staining was more likely for metastases. Neither high- nor low-grade PD-L1 expression correlated with any clinicopathologic variable for primary tumors. However, for metastases, high-grade staining was significantly associated with regional recurrence (15 of 19, P = .02). TILs were present for 65% of primary tumors and 90% of regional metastases but did not correlate with any clinicopathologic variables.

Conclusion: Diffuse expression of PD-L1 in this study highlights the possibility of using immunotherapy in the form of programmed death 1/PD-L1 blockade to improve treatment for this devastating disease. However, further studies are needed to clarify the significance of PD-L1 expression and TIL positivity for locally advanced or regionally metastatic cHNSCC.
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http://dx.doi.org/10.1177/0194599818788057DOI Listing
January 2019

Indeterminate Dendritic Cell Tumor: A Report of Two New Cases Lacking the ETV3-NCOA2 Translocation and a Literature Review.

Am J Dermatopathol 2018 Oct;40(10):736-748

Department of Pathology, University of Virginia Medical Center.

Indeterminate dendritic cell tumor (IDCT) is a cutaneous proliferation of histiocytes that share morphologic and immunophenotypic properties with Langerhans cells. IDCT was recently included in the updated WHO classification of tumors of hematopoietic and lymphoid tissues. Recent studies have shown that some cases of IDCT demonstrate an ETV3-NCOA2 translocation, supporting the idea that IDCT is a clonal neoplasm. We report 2 new cases of IDCT at our institution lacking the ETV3-NCOA2 translocation. We also present a comprehensive review of reported cases of IDCT in the medical literature. Eighty-five cases of IDCT were reported in the literature between 1985 and 2016. The median age at diagnosis was 45 years. In contrast to Langerhans cell histiocytosis, IDCT is limited to the skin in the majority of cases (88%) and generally follows an indolent clinical course. Most reported lesions are cured with complete excision. However, the histologic features of IDCT and langerhans cell histiocytosis are similar. Conjoint immunostaining for CD1a and langerin is necessary for optimal classification.
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http://dx.doi.org/10.1097/DAD.0000000000001191DOI Listing
October 2018

Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: A retrospective case-control study.

J Am Acad Dermatol 2018 Dec 29;79(6):1047-1052. Epub 2018 May 29.

Department of Dermatology, Stanford University School of Medicine, Redwood City, California. Electronic address:

Background: Cutaneous adverse events are common with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors. However, the nature of the specific cutaneous adverse event of dermatitis has not been investigated across various PD-1/PD-L1 inhibitors. Oncologic outcomes potentially associated with dermatitis are not well characterized.

Objective: To assess the nature of dermatitis after exposure to a PD-1/PD-L1 inhibitor and oncologic outcomes associated with dermatitis.

Methods: Retrospective, matched, case-control study conducted at a single academic center.

Results: The most common histologic patterns were lichenoid dermatitis (50%) and spongiotic dermatitis (40%). The overall tumor response rate was 65.0% for the case patients and 17.0% for the controls (P = .0007) (odds ratio, 7.3; 95% confidence interval, 2.3-23.1). The progression-free survival and overall survival times were significantly longer for the case patients than for the controls by Kaplan-Meier analysis (P < .0001 and .0203, respectively).

Limitations: The retrospective design and relatively small sample size precluded matching for all cancer types.

Conclusions: Lichenoid and spongiotic dermatitis associated with PD-1/PD-L1 inhibitors could be a sign of robust immune response and improved oncologic outcomes. The value of PD-1/PD-L1-related dermatitis in predicting cancer outcomes awaits investigation through prospective multicenter studies for specific cancer types.
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http://dx.doi.org/10.1016/j.jaad.2018.05.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445549PMC
December 2018

Expression of the transcription factor ZBTB46 distinguishes human histiocytic disorders of classical dendritic cell origin.

Mod Pathol 2018 09 9;31(9):1479-1486. Epub 2018 May 9.

Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Distinguishing classical dendritic cells from other myeloid cell types is complicated by the shared expression of cell surface markers. ZBTB46 is a zinc finger and BTB domain-containing transcription factor, which is expressed by dendritic cells and committed dendritic cell precursors, but not by plasmacytoid dendritic cells, monocytes, macrophages, or other immune cell populations. In this study, we demonstrate that expression of ZBTB46 identifies human dendritic cell neoplasms. We examined ZBTB46 expression in a range of benign and malignant histiocytic disorders and found that ZBTB46 is able to clearly define the dendritic cell identity of many previously unclassified histiocytic disease subtypes. In particular, all examined cases of Langerhans cell histiocytosis and histiocytic sarcoma expressed ZBTB46, while all cases of blastic plasmacytoid dendritic cell neoplasm, chronic myelomonocytic leukemia, juvenile xanthogranuloma, Rosai-Dorfman disease, and Erdheim-Chester disease failed to demonstrate expression of ZBTB46. Moreover, ZBTB46 expression clarified the identity of diagnostically challenging neoplasms, such as cases of indeterminate cell histiocytosis, classifying a fraction of these entities as dendritic cell malignancies. These findings clarify the lineage origins of human histiocytic disorders and distinguish dendritic cell disorders from all other myeloid neoplasms.
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http://dx.doi.org/10.1038/s41379-018-0052-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138663PMC
September 2018

Histopathologic approach to epidermotropic lymphocytic infiltrates.

Semin Cutan Med Surg 2018 Mar;37(1):56-60

Palo Alto Medical Foundation, Palo Alto, California, USA.

Mycosis fungoides is the most common and therefore quintessential cutaneous lymphoma and is typically characterized by an epidermotropic infiltrate of atypical monoclonal CD4+ lymphocytes. Classical histopathologic findings include epidermotropism, lymphocytes with convoluted nuclear contours and surrounding perinuclear "halos," and papillary dermal fibrosis. Atypical lymphocytes may occasionally form Pautrier's microabscesses with tagging of lymphocytes along the basal keratinocytes. Unfortunately, a variety of benign inflammatory infiltrates, as well as other cutaneous lymphomas, may demonstrate some similar histopathologic findings. Herein, we review the wide array of epidermotropic T-cell lymphomas and discuss distinguishing features between these entities. We also offer an algorithmic approach utilizing histopathologic, immunophenotypic, and molecular techniques that can be used for analyzing an epidermotropic T-cell infiltrate in order to render a specific diagnosis.
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http://dx.doi.org/10.12788/j.sder.2018.003DOI Listing
March 2018
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