Child Health Providers\u27 Precautionary Discussion of Emotions During Communication about Results of Newborn Genetic Screening

Objective To demonstrate a quantitative abstraction method for Communication Quality Assurance projects to assess physicians\u27 communication about hidden emotions after newborn genetic screening. Design Communication quality indicator analysis. Setting Standardized parent encounters performed in practicing physicians\u27 clinics or during educational workshops for residents. Participants Fifty-nine pediatrics residents, 53 pediatricians, and 31 family physicians. Intervention Participants were asked to counsel standardized parents about a screening result; counseling was recorded, transcribed, and parsed into statements (each with 1 subject and 1 predicate). Pairs of abstractors independently compared statements with a data dictionary containing explicit-criteria definitions. Outcome Measures Four groups of precautionary empathy behaviors (assessment of emotion, anticipation/validation of emotion, instruction about emotion, and caution about future emotion), with definitions developed for both definite and partial instances. Results Only 38 of 143 transcripts (26.6%) met definite criteria for at least 1 of the precautionary empathy behaviors. When partial criteria were counted, this number increased to 80 of 143 transcripts (55.9%). The most common type of precautionary empathy was the instruction about emotion behavior (eg, don\u27t be worried ), which may sometimes be leading or premature. Conclusions Precautionary empathy behaviors were rare in this analysis. Further study is needed, but this study should raise concerns about the quality of communication services after newborn screening

Double-Hit Lymphoma Presenting as Primary Renal Lymphoma: A Case Report

B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements, also known as “double hit” lymphomas (DHL), are rare neoplasms characterized by highly aggressive clinical behavior, complex karyotypes, and a spectrum of pathological features overlapping with Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). Primary renal lymphoma (PRL) by definition is a renal lymphoma without evidence of systemic involvement. PRL is extremely rare with less than 100 cases of both Hodgkin disease and non-Hodgkin lymphoma reported in literature. Double hit lymphomas have extremely poor prognosis, and high resistance to intensive chemotherapy, including high-dose chemotherapy. We describe a very rare case of DHL arising in kidney as PRL in whom concurrent IGH-BCL2 and MYC rearrangements were detected. [J Interdiscipl Histopathol 2013; 1(2.000): 93-97

Development of Asymmetric Facial Depigmentation in a Patient Treated with Dasatinib with New-Onset Hypovitaminosis D: Case Report and Review of the Literature

Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) used to treat imatinib-resistant chronic myelogenous leukemia (CML), as well as other Philadelphia chromosome-positive lymphoproliferative disorders. While the most commonly reported cutaneous side effects with this therapy include a morbilliform eruption, skin exfoliation, and skin irritation, pigmentary abnormalities have also been observed, albeit much more rarely. We present the case of a 72-year-old South Asian male with CML who presented with new-onset hypopigmentation of his face and scalp three years after a dose increase of dasatinib therapy, in the setting of newly discovered borderline hypovitaminosis D. Dasatinib and the other TKIs are believed to induce dyschromias via modulation of the c-kit receptor and its associated signaling pathway, which is involved in melanocyte survival, proliferation, and migration

Case Report Development of Asymmetric Facial Depigmentation in a Patient Treated with Dasatinib with New-Onset Hypovitaminosis D: Case Report and Review of the Literature

Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) used to treat imatinib-resistant chronic myelogenous leukemia (CML), as well as other Philadelphia chromosome-positive lymphoproliferative disorders. While the most commonly reported cutaneous side effects with this therapy include a morbilliform eruption, skin exfoliation, and skin irritation, pigmentary abnormalities have also been observed, albeit much more rarely. We present the case of a 72-year-old South Asian male with CML who presented with new-onset hypopigmentation of his face and scalp three years after a dose increase of dasatinib therapy, in the setting of newly discovered borderline hypovitaminosis D. Dasatinib and the other TKIs are believed to induce dyschromias via modulation of the c-kit receptor and its associated signaling pathway, which is involved in melanocyte survival, proliferation, and migration

Heme oxygenase-1 expression protects melanocytes from stress-induced cell death: implications for vitiligo

To study protection of melanocytes from stress-induced cell death by heme oxygenases during depigmentation and repigmentation in vitiligo, expression of isoforms 1 and 2 was studied in cultured control and patient melanocytes and normal skin explants exposed to UV or bleaching agent 4-TBP. Similarly, expression of heme oxygenases was followed in skin from vitiligo patients before and after PUVA treatment. Single and double immunostainings were used in combination with light and confocal microscopic analysis and Western blotting. Melanocyte expression of heme oxygenase 1 is upregulated, whereas heme oxygenase 2 is reduced in response to UV and 4-TBP. Upregulation of inducible heme oxygenase 1 was also observed in UV-treated explant cultures, in skin of successfully PUVA-treated patients and in melanocytes cultured from vitiligo non-lesional skin. Heme oxygenase encoding genes were subsequently cloned to study consequences of either gene product on cell viability, demonstrating that HO-1 but not HO-2 overexpression offers protection from stress-induced cell death in MTT assays. HO-1 expression by melanocytes may contribute to beneficial effects of UV treatment for vitiligo patient

Skin cancer discovery during total body skin examinations

Background: Patients presenting with a site-specific skin complaint may receive a total body skin examination (TBSE) or a more focused examination. A TBSE may be time-consuming but can potentially detect unsuspected or early stage skin cancers. The purpose of this study was to assess the detection of skin cancers associated with dermatologist-initiated TBSE performed immediately after a focused skin examination on the same patients. Methods: The dermatology records of patients with biopsy-proven melanoma, basal cell carcinoma (BCC), or squamous cell carcinoma (SCC) during a 2-year period were reviewed. Generalized linear mixed-effects models were used to estimate the odds of a lesion being identified by a dermatologist (rather than the patient or the patient\u27s primary health care provider). Results: A total 1563 biopsy-proven cutaneous malignancies were found on 1010 patients. Of these, 797 cancers (51%) were first identified by a dermatologist on TBSE and 764 (48.9%) by the patient or the referring provider. Among tumors first identified by dermatologists (n = 797), 553 (69%) were BCCs, 220 (28%) were SCCs, and 24 (3%) were melanomas. The mean Breslow depth was 0.53 mm (standard deviation: 0.31 mm) for melanomas found on TBSE versus 1.04 mm (standard deviation: 1.68 mm) if identified by patients or referring providers. BCCs were more likely to be identified by a dermatologist during a TBSE (n = 553 [56%] vs. n = 434 [44%]; odds ratio: 1.79; p \u3c .001). Tumors ultimately diagnosed as SCCs were more often identified by patients or patients\u27 primary care providers (n = 302 [58%]; odds ratio: 0.56; p \u3c .001). However, 220 otherwise undetected SCCs were found during dermatologist-performed TBSE. Conclusion: Dermatologist-performed TBSEs identified numerous cutaneous malignancies that might otherwise have remained undiagnosed. Early detection of melanoma or nonmelanoma skin cancer by TBSEs may spare patients significant morbidity and mortality

HDAC inhibition prevents transgene expression downregulation and loss-of-function in T-cell-receptor-transduced T cells.

T cells that are gene-modified with tumor-specific T cell receptors are a promising treatment for metastatic melanoma patients. In a clinical trial, we treated seven metastatic melanoma patients with autologous T cells transduced to express a tyrosinase-reactive T cell receptor (TCR) (TIL 1383I) and a truncated CD34 molecule as a selection marker. We followed transgene expression in the TCR-transduced T cells after infusion and observed that both lentiviral- and retroviral-transduced T cells lost transgene expression over time, so that by 4 weeks post-transfer, few T cells expressed either lentiviral or retroviral transgenes. Transgene expression was reactivated by stimulation with anti-CD3/anti-CD28 beads and cytokines. TCR-transduced T cell lentiviral and retroviral transgene expression was also downregulated in vitro when T cells were cultured without cytokines. Transduced T cells cultured with interleukin (IL)-15 maintained transgene expression. Culturing gene-modified T cells in the presence of histone deacetylase (HDAC) inhibitors maintained transgene expression and functional TCR-transduced T cell responses to tumor. These results implicate epigenetic processes in the loss of transgene expression in lentiviral- and retroviral-transduced T cells. Keywords: HDAC inhibitors; TCR-transduced T cells; cancer immunotherapy; cell therapy; functional responses; gene silencing; gene-modified T cells; sodium butyrate; transgene silencing; vorinostat

Gene expression profiling and multiplex immunofluorescence analysis of bullous pemphigoid immune-related adverse event reveal upregulation of toll-like receptor 4/complement-induced innate immune response and increased density of T

Background: Immune checkpoint inhibitor (ICI)-based cancer therapies cause a variety of cutaneous immune-related adverse events (irAEs) including immunobullous skin eruptions like bullous pemphigoid (BP). However, little is known about the underlying immunopathogenic drivers of these reactions, and understanding the unique gene expression profile and immune composition of BP-irAE remains a critical knowledge gap in the field of oncodermatology/oncodermatopathology. Methods: BP-irAE (n = 8) and de novo BP control (n = 8) biopsy samples were subjected to gene expression profiling using the NanoString® Technologies nCounter PanCancer Immune Profiling Panel. Multiplex immunofluorescence (mIF) studies using markers for T-cells (CD3 and CD8), T helper 1 (TH 1) cells (Tbet), TH 2 cells (Gata3), TH 17 cells (RORγT), and regulatory T-cells (Tregs; FoxP3) were further evaluated using InForm® image analysis. Results: Compared with de novo BP controls, BP-irAE samples exhibited upregulation of 30 mRNA transcripts (p \u3c 0.025), including toll-like receptor 4 (TLR4) and genes associated with complement activation, and downregulation of 89 mRNA transcripts (p \u3c 0.025), including genes associated with TH 2, TH 17, and B-cell immune response. BP-irAE demonstrated a greater density of Tbet+ (TH 1) cells in the dermis (p = 0.004) and fewer Tregs in the blister floor (p = 0.028) when compared with that of de novo control BP samples. Conclusions: BP-irAE exhibited activation of the TLR4/complement-driven classical innate immune response pathway, with dermal TH 1 immune cell polarization and decreased Tregs in the blister floor. TLR/complement signaling may underlie the immunopathogenesis of BP-irAE. Keywords: bullous pemphigoid-irAE; gene expression profiling; immune mechanisms; multiplex immunofluorescence