Clinical and Histopathologic Profile of Patients with Cutaneous Metastasis in a Tertiary Hospital in the Philippines.

INTRODUCTION: Cutaneous metastases represent 2% of skin tumors, with an overall incidence of 5.3%. Although rare, clinical presentations of cutaneous metastasis vary and can be mistaken for benign and malignant skin conditions. METHODOLOGY: This was a descriptive, retrospective review of all patients diagnosed with cutaneous metastasis seen at the Department of Dermatology from January 2013 to December 2019. Clinical and histopathologic data from the patients were collated from medical records, and slides were retrieved for review. RESULTS: A total of 115 patients were included and 122 slides reviewed. There were more female than males, the mean age was 52.3 ± 14.0 years of age. The most common primary cancer was the breast, and accordingly, the most common location was anterior chest. Among the 122 slides reviewed from 104 patients, the most common histologic type was adenocarcinoma (72.1%), and showed the infiltrative pattern (26.2%). Other histologic types seen were melanoma (13.1%), leukemic infiltrates (11.5%), squamous origin (2.5%), and epithelioid sarcoma (0.8%). Lymphovascular invasion and dermal sclerosis were observed. Immunohistochemical stains were performed in only 13.9% of the cases. There was a high concurrence of the clinical with the histopathologic diagnosis (95.6%). CONCLUSION: Although rare, patients with cutaneous metastasis may present in dermatology clinics. Knowledge of clinical features and low threshold for doing biopsies may prove useful for these patients. Similarly, dermatopathologists should be able to recognize histologic features of cutaneous metastasis morphologically. Histologic features may be subtle and may be reminiscent of benign inflammatory conditions, hence judicious use of immunohistochemical staining is recommended.

How Scientists Perceive CRISPR's Translational Promise and the Implications for Individuals with Genetic Conditions.

CRISPR (clustered regularly interspaced short palindromic repeats) somatic genome editing, an important promissory technology, presents a case study of the movement of basic scientists into translational research. In this paper, we explore how scientists experience the pulls of CRISPR's power and the pushes of economic and societal pressures in adopting new translational roles. Given basic scientists' emerging contact with and influence upon individuals with genetic conditions, we also examine how scientists understand the perspectives of affected populations, both as potential subjects of early experiments and as the patients who could receive future treatments. Finally, we consider the ethical implications of our findings and call for innovative approaches to translational research that help scientists engage with people with genetic conditions in early translational research.

Spot the difference: A case of Hailey-Hailey Disease in a 64-year-old Filipino female

@#Hailey-Hailey disease (HHD) is an uncommon acantholytic disorder of the skin. This is a case of a 64-year-old Filipino female with a chronic history of painful and malodorous intertriginous plaques. Histopathologic evaluation showed overlapping features of pemphigus vulgaris and Hailey-Hailey disease. A negative direct immunofluorescence test clinched the diagnosis of Hailey-Hailey disease. The patient was advised regarding preventive measures and treated with topical antibiotics and corticosteroids with improvement of her lesions.

Decoded: A case report on dedifferentiated Liposarcoma on the Gluteal area

@#Dedifferentiated liposarcoma is a soft tissue sarcoma of adipocytic lineage. Histopathology and immunohistochemistry are essential for diagnosis. A 51-year-old Filipino woman presented with a rapidly enlarging left gluteal tumor. Histopathology revealed a multilobulated tumor having prominent myxoid stroma with numerous stellate-shaped, atypical cells bearing atypical mitotic figures. Other lobules were composed of sheets of pleomorphic cells, with atypical mitotic figures. The tumor stained positively with alcian blue, vimentin, MDM2 and p16 stains. Other immunohistochemical (IHC) studies done (pancytokeratin, CK7, CK 20, CD 34, CEA, desmin, EMA, SMA, S100) showed negative results. After a 2 cm wide excision of the sarcoma, patient was free from local tumor recurrence for 2 months, after which she was lost to follow-up. We report this case and a brief review of the current literature on dedifferentiated liposarcoma.

Informed consent for early-phase clinical trials: therapeutic misestimation, unrealistic optimism and appreciation.

Unrealistic therapeutic beliefs are very common-the majority of patient-subjects (up to 94%) enrol in phase 1 trials seeking and expecting significant medical benefit, even though the likelihood of such benefit has historically proven very low. The high prevalence of therapeutic misestimation and unrealistic optimism in particular has stimulated debate about whether unrealistic therapeutic beliefs in early-phase clinical trials preclude adequate informed consent. We seek here to help resolve this controversy by showing that a crucial determination of when such therapeutic beliefs are ethically problematic turns on whether they are causally linked and instrumental to the motivation to participate in the trial. Thus, in practice, it is ethically incumbent on researchers to determine which understanding and beliefs lead to the participant's primary motivation for enrolling, not to simply assess understanding, beliefs and motivations independently. We further contend that assessing patient-subjects' appreciation as a component of informed consent-it is already an established component of decision-making capacity assessments-can help elucidate the link between understanding-beliefs and motivation; appreciation refers to an individual's understanding of the personal significance of both the medical facts and the experience of trial participation. Therefore, we recommend that: (1) in addition to the usual question, 'Why do you want to participate in this trial?', all potential participants should be asked the question: 'What are you giving up by participating in this trial?' and (2) researchers should consider the settings in which it may be possible and practical to obtain 'two-point consent'.

Efficacy and safety of topical Adenosine for Androgenetic Alopecia in adults: A systematic review

Background@#Androgenetic alopecia (AGA), also known as pattern hair loss, is the most common type of hair loss in men and women. Due to very limited therapeutic options, search for other effective and safe drugs is necessary.@*Objectives@#This review aims to evaluate the efficacy and safety of a potential treatment option, topical adenosine, for AGA in male and female adults.@*Methods@#A search of databases (Cochrane Library, Pubmed Medline, and others) was performed with no time limitations placed. We included human interventional studies published in English involving the use of topical adenosine for AGA in healthy adult males and females. Risk bias assessment was performed using the Cochrane Collaboration criteria.@*Results@#All four trials in this review, with a total of 260 participants, used 0.75% topical adenosine lotion twice a day for a period of 6-12 months. Comparators were placebo, topical niacinamide, and topical minoxidil. Evaluated parameters include improvement in baldness grading as assessed by dermatologists and investigators, improvement and satisfaction as assessed by participants, anagen growth, thick/thin/vellus hair ratio, and hair density. Two trials found significant improvement with thick hair ratio (>60 or >80 μm) with the use of topical adenosine while two trials showed higher overall participant satisfaction with topical adenosine. Few to no adverse effects were reported with its use. @*Conclusion@#This is the first systematic review involving topical adenosine for AGA. Topical adenosine may be effective in increasing thick hair ratio and improving the self-perception of hair growth. With minimal to no adverse effects, it may serve as an adjunct or alternative to present treatment options. However, more studies are needed to strengthen these findings.

Malignant mystique: Porocarcinoma in three adult Filipinos

@#Porocarcinoma is a rare, cutaneous adnexal malignancy usually seen in elderly patients. We present three females with varying lesions located at the head region with a history of a sudden increase in growth. Histologically, all were composed of nests of basaloid cells showing atypia, mitotic figures and eccrine-differentiated ductal elements. One patient underwent excision (0.5 cm margin) and was recurrence-free one-month post-op. This series also brings a brief review of the current literature on porocarcinoma.

Azathiopine for the treatment of extensive forms of alopecia areata: A systematic review

@#<p style="text-align: justify;"><strong>BACKGROUND:</strong> Alopecia areata (AA) is an autoimmune hair disorder, with the clinical variants ophiasis and extensive variants AA totalis and universalis, having poor response to therapy. Oral steroids are used to treat the severe variants, requiring prolonged therapy, which leads to side effects while discontinuation leads to high relapse rate. Azathioprine is a steroid-sparing agent for the severe AA forms.</p><p style="text-align: justify;"><strong>OBJECTIVE:</strong> To review the current evidence on the therapeutic efficacy and adverse effects of azathioprine for severe forms of alopecia areata</p><p style="text-align: justify;"><strong>METHODS:</strong> Published articles utilizing azathioprine for alopecia areata were obtained until July 2018 from PubMed, MEDLINE, Cochrane Library, TRIP database, HERDIN, and Google Scholar.</p><p style="text-align: justify;"><strong>RESULTS:</strong> Seven articles underwent a full-length review. Clinical variants include patchy, diffuse, steroid-resistant, reticulate, totalis, universalis, ophiasis, and sisaipho. Doses ranged from 2 to 2.5 mg/kg/day or weekly 5 mg/kg pulse therapy. Initial response ranged from 6 to 12 weeks, with almost complete resolution by 32 weeks. Response was sustained for 6 months upon discontinuation, with only 14% relapsing at 2.5 months. Adverse effects were gastrointestinal discomfort, elevated liver function tests, and myelosuppression.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> There is emerging evidence on the efficacy and safety of azathioprine for the treatment of extensive forms of alopecia areata. Randomized-controlled trials are needed to evaluate its efficacy.</p>

Stochastic predictors from the DXA scans of human lumbar vertebrae are correlated with the microarchitecture parameters of trabecular bone.

The purpose of this study was to provide a novel stochastic assessment of inhomogeneous distribution of bone mineral density (BMD) from the Dual-energy X-ray Absorptiometry (DXA) scans of human lumbar vertebrae and identify the stochastic predictors that were correlated with the microarchitecture parameters of trabecular bone. Eighteen human lumbar vertebrae with intact posterior elements from 5 cadaveric spines were scanned in the posterior-anterior projection using a Hologic densitometer. The BMD map of human vertebrae was obtained from the raw data of DXA scans by directly operating on the transmission measurements of low- and high-energy X-ray beams. Stochastic predictors were calculated by fitting theoretical models onto the experimental variogram of the BMD map, rather than grayscale images, from DXA scans. In addition, microarchitecture parameters of trabecular bone were measured from the 3D images of human vertebrae acquired using a Micro-CT scanner. Significant correlations were observed between stochastic predictors and microarchitecture parameters. The sill variance, representing the standard deviation of the BMD map to some extent, had significantly positive correlations with bone volume, trabecular thickness, trabecular number and connectivity density. The sill variance was also negatively associated with bone surface to volume ratio and trabecular separation. This study demonstrates that the stochastic assessment of the inhomogeneous distribution of BMD from DXA scans of human lumbar vertebrae can reveal microarchitecture information of trabecular bone. However, future studies are needed to examine the potential of stochastic predictors from routine clinical DXA scans in providing bone fragility information complementary to BMD.

Random field assessment of inhomogeneous bone mineral density from DXA scans can enhance the differentiation between postmenopausal women with and without hip fractures.

Bone mineral density (BMD) measurements from Dual-energy X-ray Absorptiometry (DXA) alone cannot account for all factors associated with the risk of hip fractures. For example, the inhomogeneity of bone mineral density in the hip region also contributes to bone strength. In the stochastic assessment of bone inhomogeneity, the BMD map in the hip region is considered as a random field and stochastic predictors can be calculated by fitting a theoretical model onto the experimental variogram of the BMD map. The objective of this study was to compare the ability of bone mineral density and stochastic assessment of inhomogeneous distribution of bone mineral density in predicting hip fractures for postmenopausal women. DXA scans in the hip region were obtained from postmenopausal women with hip fractures (N=47, Age: 71.3±11.4 years) and without hip fractures (N=45, Age: 66.7±11.4 years). Comparison of BMD measurements and stochastic predictors in assessing bone fragility was based on the area under the receiver operating characteristic curves (AUC) from logistic regression analyses. Although stochastic predictors offered higher accuracy (AUC=0.675) in predicting the risk of hip fractures than BMD measurements (AUC=0.625), this difference was not statistically significant (p=0.548). Nevertheless, the combination of stochastic predictors and BMD measurements had significantly (p=0.039) higher prediction accuracy (AUC=0.748) than BMD measurements alone. This study demonstrates that stochastic assessment of bone mineral distribution from DXA scans can serve as a valuable tool in enhancing the prediction of hip fractures for postmenopausal women in addition to BMD measurements.

Shape transition during nest digging in ants.

Nest building in social insects is among the collective processes that show highly conservative features such as basic modules (chambers and galleries) or homeostatic properties. Although ant nests share common characteristics, they exhibit a high structural variability, of which morphogenesis and underlying mechanisms remain largely unknown. We conducted two-dimensional nest-digging experiments under homogeneous laboratory conditions to investigate the shape diversity that emerges only from digging dynamics and without the influence of any environmental heterogeneity. These experiments revealed that, during the excavation, a morphological transition occurs because the primary circular cavity evolves into a ramified structure through a branching process. Such a transition is observed, whatever the number of ants involved, but occurs more frequently for a larger number of workers. A stochastic model highlights the central role of density effects in shape transition. These results indicate that nest digging shares similar properties with various physical, chemical, and biological systems. Moreover, our model of morphogenesis provides an explanatory framework for shape transitions in decentralized growing structures in group-living animals.