BACKGROUND:Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system. Calcium-sensing receptor (CaSR) inhibits both actions. The latter has been well documented in vitro but not in vivo. The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo. AIM:To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin (CTX) in mice. METHODS:CTX was given orally to C57BL/6 mice to induce diarrhea. Calcium and calcimimetic R568 were used to activate CaSR. To maximize their local intestinal actions, calcium was administered luminally via oral rehydration solution (ORS), whereas R568 was applied serosally using an intraperitoneal route. To verify that their actions resulted from the intestine, effects were also examined on Cre-lox intestine-specific CaSR knockouts. Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl- or clinically by assessing stool consistency and weight loss. RESULTS:CTX induced secretory diarrhea, as evidenced by increases in fecal Cl-, stool consistency, and weight loss following CTX exposure, but did not alter CaSR, neither in content nor in function. Accordingly, calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines. Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts (villinCre/Casrflox/flox) and neuronal CaSR knockouts (nestinCre/Casrflox/flox). CONCLUSION:Treatment of acute secretory diarrheas remains a global challenge. Despite advances in diarrhea research, few have been made in the realm of diarrhea therapeutics. ORS therapy has remained the standard of care, although it does not halt the losses of intestinal fluid and ions caused by pathogens. There is no cost-effective therapeutic for diarrhea. This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.

BACKGROUND:ChatGPT is a free artificial intelligence (AI)-based natural language processing tool that generates complex responses to inputs from users. OBJECTIVES:To determine whether ChatGPT is able to generate high-quality responses to patient-submitted questions in the patient portal. METHODS:Patient-submitted questions and the corresponding responses from their dermatology physician were extracted from the electronic medical record for analysis. The questions were input into ChatGPT (version 3.5) and the outputs extracted for analysis, with manual removal of verbiage pertaining to ChatGPT's inability to provide medical advice. Ten blinded reviewers (seven physicians and three nonphysicians) rated and selected their preference in terms of 'overall quality', 'readability', 'accuracy', 'thoroughness' and 'level of empathy' of the physician- and ChatGPT-generated responses. RESULTS:Thirty-one messages and responses were analysed. Physician-generated responses were vastly preferred over the ChatGPT -responses by the physician and nonphysician reviewers and received significantly higher ratings for 'readability' and 'level of empathy'. CONCLUSIONS:The results of this study suggest that physician-generated responses to patients' portal messages are still preferred over ChatGPT, but generative AI tools may be helpful in generating the first drafts of responses and providing information on education resources for patients.

Pityriasis rosea is an acute, self-limited exanthem that typically occurs in adolescence and young adulthood, classically featuring ovoid erythematous and scaly lesions on the trunk and proximal extremities. While its cause is not definitively known, the classic form of pityriasis rosea may result from the reactivation of latent human herpesvirus (HHV) infections (HHV-6 and HHV-7). Interestingly, drug eruptions that clinically and/or histopathologically resemble pityriasis rosea have also been reported. These pityriasis rosea-like drug eruptions tend to occur at an older age and have a shorter duration than the classic type. As there are different management paradigms, the distinction between classic pityriasis rosea and the mimicking drug eruption is important to recognize. Herein, we report a case of a pityriasis rosea-like drug eruption that occurred in association with imatinib mesylate treatment for chronic myeloid leukemia. We also review the clinicopathologic features of reported cases of pityriasis rosea-like drug eruption, including those due to imatinib. While the clinical morphology of the cutaneous drug-related eruption mimics the lesions seen in classic pityriasis rosea, the presence of unique histopathologic findings, including necrotic keratinocytes, interface dermatitis, and eosinophils, may aid in distinction.

Diarrhea like cholera remains a leading cause of mortality and morbidity globally. Oral rehydration solution (ORS) that developed in 1970s significantly decreases diarrhea mortality; yet, it does not reduce diarrhea morbidity and its usage has reduced persistently. Patients with diarrhea lose not only monovalent ions Na + , K + , Cl − and HCO 3 , which are replaced via ORS, but also divalent ions Zn 2+ and Ca 2+ , which are not routinely replaced, particularly for Ca 2+ . Using several in vitro technologies performed in isolated tissues, we have previously shown that Ca 2+ , a primary ligand that activates the Ca 2+ -sensing receptor, can act on intestinal epithelium and enteric nervous system and reverse cholera toxin-induced fluid secretion. In the present study, using the cholera toxin-pretreated C57BL/6 mice as a model, we show that the anti-diarrheal effect of Ca 2+ can also occur in vivo . Our results raise a question of whether this divalent ion also needs to be replaced in diarrhea management. Perhaps, an ideal rehydration therapy would be solutions that contain both monovalent ions, which reduce diarrhea mortality, and divalent minerals, which reduce diarrhea morbidity.

1. Kimyai-Asadi A, Goldberg LH. Island pedicle flap. Dermatol Clin 2005;23:113–27. 2. Papadopoulos DJ, Pharis DB, Munavalli GS, Trinei F, et al. Nasalis myocutaneous island pedicle flap with bilevel undermining for repair of lateral nasal defects.Dermatol Surg 2002;28: 190–4. 3. Kim YJ, Cho HH, Kim SO, Lee JB, et al. Reconstruction algorithm for nasal basal cell carcinoma with skin involvement only: analysis of 221 cases repaired by minor surgery. Clin Exp Dermatol 2015; 40:728–34. 4. Guo L, Pribaz JR, Pribaz JJ. Nasal reconstruction with local flaps: a simple algorithm formanagement of small defects.Plast Reconstr Surg 2008;122:130–9. Casey Logan, MD* Rhett A. Kent, MD† Eric Finzi, MD, PhD‡§ *Georgetown University School of Medicine Washington, DC †Forefront Dermatology Arlington, VA ‡George Washington School of Medicine Washington, DC §Dermatology and Cosmetic Surgery Associates Greenbelt, Maryland

Harrell, Jane BS*; Nielson, Colton MD†; Rudnick, Eric MD†; Longo-Imedio, Maria I. MD, PhD† Author Information

Leukemia cutis (LC) is rare and can have varying clinical and histopathologic presentations.1,2 In acute lymphoblastic leukemia (ALL), LC has been reported in 1% to 3% of cases and usually after diagnosis, although it can present simultaneously, or even precede, the diagnosis of leukemia.3-5 The clinical appearance of the leukemic infiltrate in the skin typically includes papules, plaques, and nodules and infrequently has mimicked inflammatory disorders.1,3,6,7 Uncommonly, LC also mimics inflammatory disorders histopathologically, with a sparse perivascular or interstitial infiltrate instead of more dense nodular infiltrates.

Background: Unilateral motor impairment is a key symptom used in the diagnosis of transient ischemic attack (TIA). Diffusion-weighted imaging (DWI) is a promising diagnostic tool for detecting ischemic lesions. While both motor impairments and DWI abnormalities are linked to the diagnosis of TIA, the association between these prognostic factors is not well understood. Objective: To examine the association between unilateral motor impairments and the odds of a positive DWI in TIA. Further, to determine whether the time between symptom onset and neuroimaging (delay to scan) influences the odds of a positive DWI. Methods: We used PRISMA guidelines to conduct a systematic search from 1989 to 2018. We included studies that reported number of individuals with/without unilateral motor symptoms and a positive/negative DWI. Results: Twenty-four studies from North America, Australia, Asia, and Europe were submitted to a meta-analysis. A pooled odds ratio of 1.80 (95% CI, 1.45-2.24, p = 0.00; I-2 = 57.38) suggested that the odds of a positive DWI are greater in TIA individuals who experience motor symptoms as compared with those who experience no motor symptoms. Further, increasing the time delay to scan from the symptom onset (>2 days) did not influence the odds of a positive DWI as compared with an earlier scan (<= 2 days). Conclusions: The current meta-analysis provides cumulative evidence from 6710 individuals with TIA that the presence of motor symptoms increases the odds of a positive DWI by two-folds. These findings transform the clinical perception into evidence-based knowledge that motor impairments elevate the risk for brain tissue damage. Unilateral motor impairments in a cerebrovascular event should increase a physician's suspicion of detecting brain infarctions. These findings may influence the clinical management of TIA by generating faster response to motor impairments in TIA and accelerating referral to specialized stroke clinic.

A 30-year-old woman presented with a spreading papular eruption on the vulva, inguinal, and perianal skin of 9 years' duration. A prior course of prednisone provided temporary resolution. Treatment of recent flares with desonide, mupirocin, and topical tacrolimus were ineffective. Medical history was relevant for herpes simplex labialis treated with acyclovir. A similar eruption was observed in her father and paternal grandmother. Physical examination found agminated papules forming plaques on the labia majora and multiple 2- to 5-mm skin-colored exophytic papules on the inner thighs (Fig 1) and perianal skin. A shave biopsy was obtained from the inner thigh (Figs 2 and 3).Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig 3View Large Image Figure ViewerDownload Hi-res image Download (PPT) Question 1: Based on the clinical presentation and histology, what is the most likely diagnosis?A.Transient acantholytic dermatosis (Grover disease)B.Segmental follicular dyskeratosis (Darier disease)C.Segmental Hailey-Hailey diseaseD.Papular acantholytic dyskeratosis (PAD) (of the genitocrural folds)E.Familial dyskeratotic comedones Answers:A.Transient acantholytic dermatosis (Grover disease) – Incorrect. Grover disease is a self-limited pruritic papulovesicular condition with predilection for the trunk, neck, and proximal extremities, sparing the genitocrural region. Histology may resemble pemphigus, Darier disease, or Hailey-Hailey disease or be spongiotic.1Al-Muriesh M. Abdul-Fattah B. Wang X. Zhao M. Chen S. Huang C. Papular acantholytic dyskeratosis of the anogenital and genitocrural area: case series and review of the literature.J Cutan Pathol. 2016; 43: 749-758Crossref PubMed Scopus (10) Google ScholarB.Segmental follicular dyskeratosis (Darier disease) – Incorrect. Darier disease presents in adolescence as greasy, scaly brown papules that may form large verrucous plaques. Histology displays acantholysis with hyperkeratosis and dyskeratotic cells; verrucous epidermal hyperplasia and prominent folliculocentricity are typical. Seborrheic regions are affected with distribution on the trunk, scalp, face and neck in addition to the groin. Nail abnormalities are common.1Al-Muriesh M. Abdul-Fattah B. Wang X. Zhao M. Chen S. Huang C. Papular acantholytic dyskeratosis of the anogenital and genitocrural area: case series and review of the literature.J Cutan Pathol. 2016; 43: 749-758Crossref PubMed Scopus (10) Google Scholar A segmental distribution indicates this form of Darier follows the lines of Blaschko, which is inconsistent with the genitocrural distribution found in this patient.C.Segmental Hailey-Hailey disease – Incorrect. Histopathology shows dyskeratosis and suprabasilar acantholysis with loss of intercellular bridges, classically described as a dilapidated brick wall. The clinical morphology is dissimilar, with painful flaccid vesicles and crusted erosions on intertriginous skin such as the neck, axilla, and groin in a blaschkoid distribution.1Al-Muriesh M. Abdul-Fattah B. Wang X. Zhao M. Chen S. Huang C. Papular acantholytic dyskeratosis of the anogenital and genitocrural area: case series and review of the literature.J Cutan Pathol. 2016; 43: 749-758Crossref PubMed Scopus (10) Google ScholarD.PAD (of the genitocrural folds) – Correct. Discrete white to skin-colored smooth or verrucous papules that coalesce into plaques on the vulva and perineum reflect the morphology of PAD. PAD is a rare chronic acantholytic dermatosis that presents in young women with asymptomatic but persistent lesions limited to the genital, inguinal, and perineal skin. PAD occurs less frequently in men and can involve the penis, scrotum, perineum, or thighs. Histology shows overlapping features of Hailey-Hailey and Darier disease, including suprabasilar acantholysis, parakeratosis, and dyskeratosis. Verrucous epidermal hyperplasia is also typical.1Al-Muriesh M. Abdul-Fattah B. Wang X. Zhao M. Chen S. Huang C. Papular acantholytic dyskeratosis of the anogenital and genitocrural area: case series and review of the literature.J Cutan Pathol. 2016; 43: 749-758Crossref PubMed Scopus (10) Google ScholarE.Familial dyskeratotic comedones – Incorrect. Although the clinical morphology includes discrete asymptomatic hyperkeratotic papules, comedones are the principal lesions. The trunk, extremities, face, and groin are involved. Histology shows dilated infundibula filled with keratin and dyskeratosis; acantholysis is occasionally observed.2Maddala R.R. Ghorpade A. Polavarpu M. Adulkar S.A. Das M. Familial dyskeratotic comedones: a rare entity.Indian Dermatol Online J. 2016; 7: 46-48Crossref PubMed Google Scholar Question 2: If the patient does not improve with topical medications, a reasonable option would be:A.AcitretinB.MethotrexateC.Chronic high potency topical steroidsD.Combination oral magnesium, low-dose naltrexone, and isotretinoinE.Systemic corticosteroids Answers:A.Acitretin – Incorrect. Acitretin is not recommended in a woman of childbearing age unless disease is severe and unresponsive to other therapies.B.Methotrexate – Incorrect. Methotrexate has been reported to be used successfully at doses of 7.5-15 mg weekly but would not be considered first-line treatment in a woman of childbearing age unless disease is severe and unresponsive to other therapies.3Arora H. Bray F.N. Cervantes J. Falto Aizpurua L.A. Management of familial benign chronic pemphigus.Clin Cosmet Investig Dermatol. 2016; 9: 281-290Crossref PubMed Scopus (26) Google ScholarC.Chronic high-potency topical steroids – Incorrect. Short-term use of high-potency topical steroids in these anatomic sites is acceptable, but prolonged use should be avoided to avoid atrophy and striae.D.Combination oral magnesium, low-dose naltrexone, and isotretinoin – Correct. There is no standard treatment for papular acantholytic dyskeratosis that has not responded to topical therapy; however, oral retinoids have successfully induced remission in extensive disease.1Al-Muriesh M. Abdul-Fattah B. Wang X. Zhao M. Chen S. Huang C. Papular acantholytic dyskeratosis of the anogenital and genitocrural area: case series and review of the literature.J Cutan Pathol. 2016; 43: 749-758Crossref PubMed Scopus (10) Google Scholar Oral magnesium may be a useful adjunct, as disease resolution has been observed in Hailey-Hailey disease.4Borghi A. Rimessi A. Minghetti S. Corazza M. Pinton P. Virgili A. Efficacy of magnesium chloride in the treatment of Hailey-Hailey disease: from serendipity to evidence of its effect on intracellular Ca(2+) homeostasis.Int J Dermatol. 2015; 54: 543-548Crossref PubMed Scopus (13) Google Scholar Low-dose naltrexone can be added in patients with refractory disease; however, treatment response to naltrexone alone is variable, and relapses may occur.5Riquelme-Mc Loughlin C. Riera-Monroig J. Morgado-Carrasco D. et al.Low-dose naltrexone therapy in benign chronic pemphigus (Hailey-Hailey disease): a case series.J Am Acad Dermatol. 2019; 81: 644-646Abstract Full Text Full Text PDF PubMed Scopus (9) Google ScholarE.Systemic corticosteroids – Incorrect. Oral corticosteroids have been used to treat severe flares or as maintenance therapy at low doses. However, adverse effects and worsening disease upon discontinuation limit their use.3Arora H. Bray F.N. Cervantes J. Falto Aizpurua L.A. Management of familial benign chronic pemphigus.Clin Cosmet Investig Dermatol. 2016; 9: 281-290Crossref PubMed Scopus (26) Google Scholar Question 3: Which genetic mutation has been implicated in the pathogenesis of this disease?A.ATP7AB.ATP2AC.ATP2C1D.Postzygotic somatic mutationE.Loss of heterozygosity mutation Answers:A.ATP7A – Incorrect. ATP7A or Menkes protein is a copper-transporting ATPase that is mutated in Menkes disease. Progressive neurodegeneration and connective tissue dysfunction are seen, including the characteristic finding of depigmented “kinky” hair.6Tümer Z. Møller L.B. Menkes disease.Eur J Hum Genet. 2010; 18: 511-518Crossref PubMed Scopus (214) Google ScholarB.ATP2A2 – Incorrect. ATP2A2 encodes sarcoplasmic/endoplasmic reticulum ATPase type 2 that is mutated in segmental follicular dyskeratosis (Darier disease).7Guerra L. Pedicelli C. Proto V. Condorelli A.G. Mazzanti C. Castiglia D. A postzygotic ATP2A2 novel mutation identified by next-generation sequencing in mosaic Darier disease.Acta Derm Venereol. 2019; 99: 115-116PubMed Google ScholarC.ATP2C1 – Correct. Historically, PAD was considered to be a separate entity from Hailey-Hailey disease, occurring sporadically in patients without family history. However, evidence of mutations in the ATP2C1 gene suggests a relation to Hailey-Hailey disease.1Al-Muriesh M. Abdul-Fattah B. Wang X. Zhao M. Chen S. Huang C. Papular acantholytic dyskeratosis of the anogenital and genitocrural area: case series and review of the literature.J Cutan Pathol. 2016; 43: 749-758Crossref PubMed Scopus (10) Google Scholar ATP2C1 encodes a calcium-dependent Golgi apparatus ATPase involved in desmosome protein function.D.Postzygotic somatic mutation – Incorrect. Segmental forms of Darier disease and Hailey-Hailey disease can be caused by postzygotic spontaneous somatic mutations.7Guerra L. Pedicelli C. Proto V. Condorelli A.G. Mazzanti C. Castiglia D. A postzygotic ATP2A2 novel mutation identified by next-generation sequencing in mosaic Darier disease.Acta Derm Venereol. 2019; 99: 115-116PubMed Google ScholarE.Loss of heterozygosity mutation – Incorrect. Loss of heterozygosity has been posited as a cause of segmental Darier disease type 2.7Guerra L. Pedicelli C. Proto V. Condorelli A.G. Mazzanti C. Castiglia D. A postzygotic ATP2A2 novel mutation identified by next-generation sequencing in mosaic Darier disease.Acta Derm Venereol. 2019; 99: 115-116PubMed Google Scholar

Autoimmune bullous dermatoses are defined by autoantibodies directed against adhesion proteins in the epidermis or basement membrane zone, resulting in blister formation on the skin and mucosa. Diagnosis depends on lesional biopsy for histopathology and perilesional biopsy for direct immunofluorescence. Additional diagnostic methods include indirect immunofluorescence, enzyme-linked immunosorbent assay, and immunoblot (Western blot), which may be selected in specific clinical scenarios due to improved sensitivity and/or specificity. This contribution reviews the available evidence supporting the use of each method to provide a practical reference for clinicians when diagnosing autoimmune bullous disorders. Techniques and cost are reviewed, and newer diagnostic techniques with potential for clinical application are

Diarrheal disease is a worldwide problem that still causes significant morbidity and mortality among children. Currently, oral rehydration solution (ORS) is the standard of care for acute diarrhea in pediatric patients. Although effective in reducing mortality, ORS does not alleviate diarrheal symptoms, thus reducing caregiver compliance and therapeutic efficacy. This article will briefly review the current problem of pediatric diarrhea and the shortcomings of current therapies; however, the focus of this review is to examine the intestinal calcium-sensing receptor (CaSR). The author summarizes the evidence suggesting that targeting the CaSR will enable clinicians to address all four major pathophysiological mechanisms of diarrheal disease, and substantiates the need for future research regarding this therapy.

Background and purpose Transient ischemic attack (TIA) increases the risk for a subsequent stroke. Typical symptoms include motor weakness, gait disturbance, and loss of coordination. The association between the presence of motor impairments during a TIA and the chances of a subsequent stroke has not been examined. In the current meta-analysis, we examine whether the odds of a stroke are greater in TIA individuals who experience motor impairments as compared with those who do not experience motor impairments. Methods We conducted a systematic search of electronic databases as well as manual searches of the reference lists of retrieved articles. The meta-analysis included studies that reported an odds ratio relating motor impairments to a subsequent stroke, or the number of individuals with or without motor impairments who experienced a subsequent stroke. We examined these studies using rigorous meta-analysis techniques including random effects model, forest and funnel plots, I2, publication bias, and fail-safe analysis. Results Twenty-four studies with 15,129 participants from North America, Australia, Asia, and Europe qualified for inclusion. An odds ratio of 2.11 (95% CI, 1.67–2.65, p = 0.000) suggested that the chances of a subsequent stroke are increased by twofolds in individuals who experience motor impairments during a TIA compared with those individuals who have no motor impairments. Conclusion The presence of motor impairments during TIA is a significantly high-risk clinical characteristic for a subsequent stroke. The current evidence for motor impairments following TIA relies exclusively on the clinical reports of unilateral motor weakness. A comprehensive examination of motor impairments in TIA will enhance TIA prognosis and restoration of residual motor impairments.

PURPOSE: Transient ischemic attack (TIA) increases the risk for a subsequent stroke. Typical symptoms include motor weakness, difficulty with speech, and loss of coordination. The association between the presence of motor impairments during a TIA and the chances of a subsequent stroke has not been systematically examined. In the current study, we examine whether the odds of a recurrent stroke are greater in TIA individuals who experience motor impairments as compared to those who don’t experience motor impairments. METHODS: We conducted systematic search of electronic databases as well as manual searches of the reference lists of retrieved articles. The meta-analysis included studies that reported an odds ratio relating motor impairments to a subsequent stroke, or the number of individuals with or without motor impairments who experienced a subsequent stroke. We examined these studies using rigorous meta-analysis techniques including random effects model, forest and funnel plots, I2, publication bias, and fail-safe analysis. RESULTS: Twenty-two studies with 11,084 participants from North America, Australia, Asia, and Europe qualified for inclusion. An odds ratio of 2.14 (95% CI, 1.66 - 2.77, p = 0.000) suggested that the chances of a subsequent stroke are increased by two-folds in individuals who experience motor impairments during a TIA. CONCLUSIONS: The presence of motor impairments during TIA is a significantly high-risk clinical characteristic for a subsequent stroke, requiring specialist follow-up care and stringent secondary measures to prevent a further stroke. Thus, TIA prognosis warrants more robust quantification of motor impairments beyond clinically determined motor weakness.