Hospital triage and skin disease: hospital outcomes are differentially associated with cutaneous morphology.

BACKGROUND: Determining the exact dermatologic diagnosis is difficult in the inpatient setting. OBJECTIVE: Determine whether morphologic classification rather than specific diagnosis is associated with hospital outcomes. METHODS: Retrospective single-center study. Information from 1798 inpatient dermatology consults at The Ohio State University Wexner Medical Center from 2012 to 2014 was queried. Dermatologic diseases were categorized into 16 groups based on appearance. Logistic regression was performed comparing mortality rate vs morphology. Linear regression was performed comparing the length of stay (LOS) vs morphology. RESULTS: Morphology was associated with a mortality rate (P = 0.038). The morphologic subgroups acneiform/follicular/occlusion (P = 0.011), blistering disorders (P = 0.009), retiform purpura (P = 0.011), and vasculitis/vascular (P = 0.007) were associated with increased mortality. Morphology was associated with LOS (P = 0.004), and the morbilliform subgroup was associated with increased LOS (P < 0.001). CONCLUSION: This study demonstrated the importance of morphologic diagnosis and its association with mortality rate and LOS. This information may help triage cutaneous disorders in the inpatient setting and determine the relative risk of dermatologic conditions when assessing the need for hospital transfers and more aggressive therapies.

A Case of Minocycline-induced Linear Morphea Reactivation.

Morphea is a localized form of scleroderma that presents with dermal thickening and fibrotic plaques in the absence of internal organ involvement. Like many autoimmune conditions, these plaques have many different phases, starting out as active, red plaques before later burning out, leaving white, fibrotic plaques behind. Many drugs have been shown to induce morphea, including bleomycin and bromocriptine. We present a case of minocycline-induced reactivation of previously burned out morphea plaques. Minocycline is an important drug in dermatology and the reporting of new adverse events is important so as to help clinicians better weigh the risks and benefits of the drug for specific populations.

A Case of Vancomycin-induced Acute Generalized Exanthematous Pustulosis Confirmed by Patch Testing.

Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous drug reaction that presents with the rapid onset of disseminated pustules, erythema, and edema. It is commonly associated with pristinamycin and aminopenicillins, but a few cases of vancomycin induced AGEP have been reported. Here, we describe a patient who presented with AGEP 12 hours following vancomycin administration, and had an atypical clinical course, with the AGEP persisting for weeks. Vancomycin was confirmed to be the etiologic agent with patch testing, a modality with growing evidence for utility in drug-induced reaction cases.

Wee1 Kinase Inhibitor AZD1775 Effectively Sensitizes Esophageal Cancer to Radiotherapy.

PURPOSE: Esophageal cancer is a deadly malignancy with a 5-year survival rate of only 5% to 20%, which has remained unchanged for decades. Esophageal cancer possesses a high frequency of TP53 mutations leading to dysfunctional G1 cell-cycle checkpoint, which likely makes esophageal cancer cells highly reliant upon G2-M checkpoint for adaptation to DNA replication stress and DNA damage after radiation. We aim to explore whether targeting Wee1 kinase to abolish G2-M checkpoint sensitizes esophageal cancer cells to radiotherapy. EXPERIMENTAL DESIGN: Cell viability was assessed by cytotoxicity and colony-forming assays, cell-cycle distribution was analyzed by flow cytometry, and mitotic catastrophe was assessed by immunofluorescence staining. Human esophageal cancer xenografts were generated to explore the radiosensitizing effect of AZD1775 in vivo. RESULTS: The IC50 concentrations of AZD1775 on esophageal cancer cell lines were between 300 and 600 nmol/L. AZD1775 (100 nmol/L) as monotherapy did not alter the viability of esophageal cancer cells, but significantly radiosensitized esophageal cancer cells. AZD1775 significantly abrogated radiation-induced G2-M phase arrest and attenuation of p-CDK1-Y15. Moreover, AZD1775 increased radiation-induced mitotic catastrophe, which was accompanied by increased γH2AX levels, and subsequently reduced survival after radiation. Importantly, AZD1775 in combination with radiotherapy resulted in marked tumor regression of esophageal cancer tumor xenografts. CONCLUSIONS: Abrogation of G2-M checkpoint by targeting Wee1 kinase with AZD1775 sensitizes esophageal cancer cells to radiotherapy in vitro and in mouse xenografts. Our findings suggest that inhibition of Wee1 by AZD1775 is an effective strategy for radiosensitization in esophageal cancer and warrants clinical testing.

Two cases of atypical periorificial dermatitis caused by Candida parapsilosis in patients volunteering in dog shelters.

Candida is a genus of yeasts that can be a part of normal human skin flora, but may cause disease when the skin barrier is compromised. C. albicans is the most common pathogenic species of this genus, but in recent years infection with other species, such as C. parapsilosis has been growing. C. parapsilosis is a species of Candida that has been found in the skin of humans and other mammals, including dogs. In this brief report, the authors describe two cases of atypical periorifical infection with C. parapsilosis in patients who both volunteered in dog shelters. Owing to the atypical presentation of the fungal infections, the isolation of C. parapsilosis as the causative organism and their extensive history of exposure to dogs, these cases may represent the first evidence of possible zoonotic transmission of C. parapsilosis from dogs to humans.

Highlighting a Potential Pitfall: Positive Treponema pallidum Immunohistochemical Stain in a Patient Without Syphilis.

The Treponema pallidum antibody immunohistochemical (IHC) stain has improved our ability to detect the organism histologically. We present a case of a man with genital condyloma acuminatum with a positive T. pallidum IHC stain but negative T. pallidum serologies and no syphilitic symptoms. It has been shown that the T. pallidum antibody IHC can cross-react, staining other spirochetes, including Borrelia burgdorferi and the Brachyspira family of intestinal spirochetes. Because of the proximity of our patient's lesions to the anus, and the persistently negative T. pallidum serologies, we believe nontreponemal spirochetes colonized the condyloma, giving a false-positive T. pallidum IHC. This cross-reactivity is a potential diagnostic pitfall and is important for the dermatopathologist to recognize, thereby avoiding false diagnosis of syphilis.

Distinguishing Stevens-Johnson syndrome/toxic epidermal necrolysis from clinical mimickers during inpatient dermatologic consultation-A retrospective chart review.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions that may present with similar findings to other severe dermatologic diseases. OBJECTIVE: The primary objective of this exploratory study was to explore factors associated with SJS/TEN and develop a model that provides the predicted probability of SJS/TEN for patients for whom the diagnosis of SJS/TEN is considered. METHODS: Retrospective review of consultations for patients with suspected SJS, TEN, or overlap at 4 academic dermatology consultation services. RESULTS: Overall, 208 patients were included; 59 (28.4%) had a final diagnosis of SJS/TEN, and 149 (71.6%) were given a different diagnosis. The most common mimickers were drug hypersensitivity syndrome (n = 21, 10.1%), morbilliform drug eruption (n = 18, 8.7%), erythema multiforme (n = 15, 7.2%), and acute generalized exanthematous pustulosis (n = 13, 6.2%). Nikolsky sign, atypical targets, fever, and lymphopenia were included in a model for predicting the probability of SJS/TEN. LIMITATIONS: All cases were obtained from academic centers, which may limit the generalization of findings to community-based settings. This was an exploratory study with a small number of cases, and external validation of the model performance is needed. CONCLUSION: Early dermatologic evaluation of patients with suspected SJS/TEN is key to separating patients with this condition from those who ultimately receive diagnoses of other serious skin diseases.

MicroRNA molecular profiling identifies potential signaling pathways conferring resistance to chemoradiation in locally-advanced rectal adenocarcinoma.

PURPOSE: There has been growing interest in using chemoradiation (CRT) for non-operative management of rectal cancer, and identifying patients who might benefit most from this approach is crucial. This study identified miRNAs (miRs) associated with clinical outcomes and treatment resistance by evaluating both pre- and post-CRT expression profiles. METHODS: Forty patients, 9 with pathologic complete response (pCR) and 31 with pathologic incomplete response (pIR) were included. MicroRNA was extracted from 40 pre-therapy tumor samples and 31 post-chemoradiation surgical samples with pathologic incomplete response (pIR). A generalized linear model was used to identify miRs associated with pCR. A linear mixed effects model was used to identify miRs differentially expressed before and after treatment. miR expression was dichotomized at the mean and clinical outcomes were evaluated using Cox proportional hazard modeling. RESULTS: Nine miRs were associated with pCR (p<0.05), but none were significant after false discovery rate correction. Among patients with pIR, 68 miRs were differentially expressed between the pre and post-CRT groups (FDR p<0.05). Ingenuity pathway analysis (IPA) demonstrated multiple signaling networks associated with pIR, including p38MAPK, TP53, AKT, IL-6, and RAS. Increased let-7b was correlated with increased distant metastasis (DM), worse relapse-free survival (RFS), and worse overall survival (OS) (p<0.05). CONCLUSIONS: No miRs were significantly correlated with pCR. We identified miRs that were differentially expressed between pre- and post-CRT tumor samples, and these miRs implicated multiple signaling pathways that may confer resistance to CRT. In addition, we identified an association between increased let-7b and worse clinical outcomes (DM, DFS, OS).

Cutaneous Manifestations of Infections in Solid Organ Transplant Recipients.

PURPOSE OF REVIEW: Post-transplant infections present a formidable challenge to the physician due to their varied presentation. Many of these infections begin by inoculation following skin compromise or disseminate to the skin hematogenously, making cutaneous manifestations of infection an important diagnostic clue in the immunocompromised. Quality research in this field is lacking, and this articles seeks to review the literature and present a guide to physicians in order for them to suspect certain infections by their cutaneous presentation. RECENT FINDINGS: The cutaneous presentation of opportunistic infections in transplant patients is extremely varied. However, as more case reports are published, certain patterns specific to individual organisms are emerging. In addition, early recognition is improving outcomes and systemic antibiotic therapy success. Early and correct recognition of disseminated infection in the immunocompromised host can be aided by close attention to cutaneous findings. This allows early and correct antibiotic therapy and improves outcomes.

A case of segmental Darier disease treated with doxycycline monotherapy.

Darier disease is a rare autosomal dominant disorder that results from a mutation in the gene coding for the endoplasmic reticulum membrane calcium pump Ca2+-ATPase type 2 (SERCA2), leading to compromised intercellular adhesion. Patients typically present in the first two decades of life with keratotic, greasy papules in a seborrheic distribution. Segmental Darier disease is a variant with localized disease that follows Blaschko lines. Treatment options include topical and systemic agents including corticosteroids, retinoids, and antibiotics. We present a 67-year-old woman who came to our clinic with segmental Darier disease recalcitrant to topical therapy. Owing to cost and side effect profile, the patient declined treatment with oral retinoids. Doxycycline 100mg daily was started with significant improvement. Tetracyclines both chelate and assist calcium to cross membranes. This mechanism may correct the cellular calcium imbalance present in Darier disease. In addition, tetracyclines have been shown to inhibit metalloproteinase 9, an important part of Darier disease pathogenesis. Owing to its favorable side effect profile, further investigation is warranted to establish doxycycline as a more widely utilized treatment option for Darier disease.

Prognostic value of microRNA expression levels in pancreatic adenocarcinoma: a review of the literature.

BACKGROUND: Clinical and pathologic markers of prognosis and patterns of failure help guide clinicians in selecting patients for adjuvant therapy after surgical resection for pancreatic adenocarcinoma (PDAC). Recent studies have reported the prognostic utility of microRNA profiling in numerous malignancies. Here, we review and summarize the current literature regarding associations between microRNA expression and overall survival in PDAC patients. MATERIALS AND METHODS: We conducted a systematic search in the PubMed database to identify all primary research studies reporting prognostic associations between tumor and/or serum microRNA expression and overall survival in PDAC patients. Eligible articles were reviewed by the authors and relevant findings are summarized below. RESULTS: We found 53 publications that fit our search criteria. In total, 23 up-regulated and 49 down-regulated miRNAs have been associated with worse overall survival. MiR-21 is the most commonly reported miRNA, appearing in 19 publications, all of which report aberrant over-expression and association with shorter survival in PDAC. Other miRNAs that appear in multiple publications include miR-10b, -21, -34a, -155, -196a, -198, -200c, -203, -210, -218, -222, and -328. We summarize the preclinical and clinical data implicating these miRNAs in various molecular signaling pathways and cellular functions. CONCLUSIONS: There is growing evidence that miRNA expression profiles have the potential to provide tumor-specific prognostic information to assist clinicians in more appropriately selecting patients for adjuvant therapy. These molecules are often aberrantly expressed and exhibit oncogenic and/or tumor suppressor functions in PDAC. Additional efforts to develop prognostic and predictive molecular signatures, and further elucidate miRNA mechanisms of action, are warranted.

Molecular profiling of locally-advanced rectal adenocarcinoma using microRNA expression (Review).

Treatment for locally-advanced rectal cancer (LARC) typically consists of neoadjuvant chemoradiation followed by total mesorectal excision. Recently, there has been growing interest in non-operative management for patients who are medically-inoperable or wish to avoid surgical morbidity and permanent colostomy. Approximately 50% of patients who receive pre-operative neoadjuvant chemoradiation develop some degree of pathologic response. Approximately 10-20% of patients are found to have a complete pathologic response, a finding which has frequently been shown to predict better clinical outcomes, including local-regional control, distant metastasis and survival. Many recent studies have evaluated the role of molecular biomarkers in predicting response to neoadjuvant therapy. MicroRNAs (miRNAs) are an emerging class of biomarkers that have the potential to predict which patients are most likely to benefit from pre-operative therapy and from a selective surgical approach. Here, we review the published literature on microRNAs as prognostic and predictive biomarkers in rectal cancer after pre-operative therapy. In the future, the development of prospectively validated miRNA signatures will allow clinical implementation of miRNAs as prognostic and predictive signatures in LARC.