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Cancers Mar 2023Small molecule protein kinase inhibitors (PKIs) have become an effective strategy for cancer patients. However, hepatotoxicity is a major safety concern of these drugs,... (Review)
Review
Small molecule protein kinase inhibitors (PKIs) have become an effective strategy for cancer patients. However, hepatotoxicity is a major safety concern of these drugs, since the majority are reported to increase transaminases, and few of them (Idelalisib, Lapatinib, Pazopanib, Pexidartinib, Ponatinib, Regorafenib, Sunitinib) have a boxed label warning. The exact rate of PKI-induced hepatoxicity is not well defined due to the fact that the majority of data arise from pre-registration or registration trials on fairly selected patients, and the post-marketing data are often based only on the most severe described cases, whereas most real practice studies do not include drug-related hepatotoxicity as an end point. Although these side effects are usually reversible by dose adjustment or therapy suspension, or by switching to an alternative PKI, and fatality is uncommon, all patients undergoing PKIs should be carefully pre-evaluated and monitored. The management of this complication requires an individually tailored reappraisal of the risk/benefit ratio, especially in patients who are responding to therapy. This review reports the currently available data on the risk and management of hepatotoxicity of all the approved PKIs.
PubMed: 36980652
DOI: 10.3390/cancers15061766 -
Cureus Feb 2023To evaluate dermatoscopic features of cutaneous leishmaniasis and to compare its diagnostic accuracy against slit skin smear and skin histopathology.
OBJECTIVE
To evaluate dermatoscopic features of cutaneous leishmaniasis and to compare its diagnostic accuracy against slit skin smear and skin histopathology.
METHODS
This cross-sectional study was conducted at the Department of Dermatology, Pakistan Navy Station (PNS) Shifa Hospital, Karachi, Pakistan, from August 2021 to August 2022. A total of 200 lesions from 70 patients of cutaneous leishmaniasis diagnosed with slit skin smear for Leishmania-Donovan (LD) bodies and skin biopsy were included via non-probability consecutive sampling technique. Dermatoscopic evaluation was performed via a handheld dermatoscope (DELTA 20T; HEINE, Gilching, Germany) on 10x magnification. All dermatoscopic images were analyzed by two different observers who had command of dermatoscopy. Data analysis was done using Statistical Package for the Social Sciences SPSS version 27 (IBM Corp., Armonk, NY, USA).
RESULTS
Common dermatoscopic findings were erythema 200 (100%), hyperkeratosis 140 (70%), crusting 50 (25%), ulceration 42 (21%), milia-like structure 58 (29%), tear drop-like structure 46 (23%), yellow tears 70 (35%), and white starburst pattern 68 (34%). Less common findings were yellow hue 28 (14%), orange areas 26 (13%) and scar seven (3.5%). Vascular structures frequently observed were linear vessels 109 (54.5%), dotted vessels 80 (40%), and hairpin vessels 61 (30.5%); less common findings were comma-shaped vessels 52 (26%), arborizing vessels 20 (10%), crown vessels nine (4.5%). Comparison of dermatoscopic features was done with slit skin smear for LD bodies (p value = 0.003 ) and histopathology (p value = 0.001).
CONCLUSIONS
Dermatoscopy is a non-invasive technique that is helpful in diagnosing cutaneous leishmaniasis, saving time in making rapid diagnosis and saving the need to undergo extensive invasive investigation. Yield of dermatoscopy was comparable to slit smear for LD bodies and histopathology and was found to be effective in making rapid diagnosis with significant accuracy (p value <0.05).
PubMed: 36974240
DOI: 10.7759/cureus.35336 -
Anais Brasileiros de Dermatologia 2023
Topics: Humans; Pemphigus; Conjunctiva; Epidermal Cyst; Herpes Simplex
PubMed: 36949003
DOI: 10.1016/j.abd.2021.09.019 -
JAMA Surgery May 2023Firearm violence is a public health crisis placing significant burden on individuals, communities, and health care systems. After firearm injury, there is increased risk... (Review)
Review
IMPORTANCE
Firearm violence is a public health crisis placing significant burden on individuals, communities, and health care systems. After firearm injury, there is increased risk of poor health, disability, and psychopathology. The newest 2022 guidelines from the American College of Surgeons Committee on Trauma require that all trauma centers screen for risk of psychopathology and provide referral to intervention. Yet, implementing these guidelines in ways that are responsive to the unique needs of communities and specific patient populations, such as after firearm violence, is challenging.
OBSERVATIONS
The current review highlights important considerations and presents a model for trauma centers to provide comprehensive care to survivors of firearm injury. This model highlights the need to enhance standard practice to provide patient-centered, trauma-informed care, as well as integrate inpatient and outpatient psychological services to address psychosocial needs. Further, incorporation of violence prevention programming better addresses firearm injury as a public health concern.
CONCLUSIONS AND RELEVANCE
Using research to guide a framework for trauma centers in comprehensive care after firearm violence, we can prevent complications to physical and psychological recovery for this population. Health systems must acknowledge the socioecological context of firearm violence and provide more comprehensive care in the hospital and after discharge, to improve long-term recovery and serve as a means of tertiary prevention of firearm violence.
Topics: Humans; Firearms; Wounds, Gunshot; Violence; Trauma Centers; Public Health
PubMed: 36947025
DOI: 10.1001/jamasurg.2022.8149 -
Bioinformation 2022CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 (CRISPR-associated system) is used to edit specific genomic sequences with precision and...
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 (CRISPR-associated system) is used to edit specific genomic sequences with precision and efficacy. There are many online platforms/software for the design of gRNAs and related primers. However, there are concerns in design regarding off-site deletions besides knocking out sequences in the target genes. Nonetheless, a well known robust platform for CRISPR/gRNA primers design is CRISPRdirect. We demonstrate the use of this tool in the design of CRISPR/gRNA primers for soluble starch synthases (SSS) II-1, 2, and 3 genes in the Oryza sativa genome followed by the PCR-mediated amplification of SSS genes with corresponding confirmation towards genome editing having improved phenotype features.
PubMed: 36945226
DOI: 10.6026/97320630018471 -
Chronobiology International May 2023The last several decades of shift work tolerance and circadian misalignment research has had mixed results regarding the adverse impact of shift work on work and health...
The last several decades of shift work tolerance and circadian misalignment research has had mixed results regarding the adverse impact of shift work on work and health outcomes. This inconsistency is, in part, due to the circadian typology measure employed and the study methodology. Based on models of shift work and health, the present study examined associations between circadian misalignment, end-of-day strain, and job- and health-related outcomes using the revised Preferences Scale (PS-6). A sample of 129 healthcare workers (76.7% female) from the United States (67%) and Australia (34.1%) aged 22 to 64 responded to a self-report questionnaire on work schedules, work stressors, and well-being. Multiple regression analysis found that the preferences for cognitive activity subscale of the PS-6 moderated the association between shift work and strain ( = -.36, < .001). Those who worked nights experienced more strain if their preferences for cognitive activity were misaligned, whereas no differences in strain were observed among day workers. Moderated-mediation analyses, on the basis 95% confidence intervals, found that shift work had a conditional indirect effect on work-family conflict, job satisfaction, and health-related quality of life, via strain, and the effect was moderated by preferences for cognitive activity. Findings provide additional evidence for the criterion and external validity of the PS-6, and importantly, the present study establishes further support for models of shift work and health. Overall, the analyses highlight the importance of exploring the interactions between shift work and different dimensions of morningness in shift work tolerance research.
Topics: Humans; Female; Male; Sleep; Circadian Rhythm; Work Schedule Tolerance; Quality of Life; Health Personnel; Surveys and Questionnaires; Outcome Assessment, Health Care
PubMed: 36942679
DOI: 10.1080/07420528.2023.2193272 -
Frontiers in Public Health 2023The Innovation for Gender Equality in Academia (IGEA) project is focused on the analysis of the gender composition in academia, on the identification of the health needs...
The Innovation for Gender Equality in Academia (IGEA) project is focused on the analysis of the gender composition in academia, on the identification of the health needs of the academic population and on the assessment of their organizational wellbeing, in order to promote equal working conditions and opportunities. The study, focused on the identification of health needs, involved the construction of an questionnaire in order to collect the socio-demographic characteristics and the perception of working environment of the participants. Differences between males and females were evaluated by the Mann-Whitney test, and Pearson Chi-Square or Fisher exact tests as appropriate, highlighting significant differences between genders regarding the occurrence of anxiety, panic, irritation and annoyance related to work activities. A multivariate logistic regression analysis was performed to identify factors associated with the perception of work-related anxiety/panic, showing a direct association with the difficulty in work performance and the work-related stress during the pandemic period, whereas, an indirect association was found with job satisfaction and the feeling of being appreciated by colleagues. Occupational stress can increase the risk of developing physical and mental conditions, also affecting work performance and absenteeism. It is therefore fundamental to plan targeted interventions, implement policies and specific actions, in order to avoid and reduce any differences related to gender.
Topics: Humans; Male; Female; Gender Equity; Occupational Stress; Job Satisfaction; Working Conditions; Work Performance
PubMed: 36895683
DOI: 10.3389/fpubh.2023.1125496 -
Cureus Jan 2023Squamous cell carcinoma (SCC) is a malignancy that arises from keratinocytes of the epidermis. Cystic variants of several types of cutaneous neoplasms have been rarely...
Squamous cell carcinoma (SCC) is a malignancy that arises from keratinocytes of the epidermis. Cystic variants of several types of cutaneous neoplasms have been rarely described in the literature. We report a case of biopsy-proven, well-differentiated invasive SCC treated with Mohs surgery. On frozen sections, the pathology slides showed benign-appearing cystic structures in the margins that persisted after it had appeared that the original malignancy had been cleared. After taking another Mohs stage due to clinical suspicion, additional SCC was found and was subsequently cleared after two more Mohs stages. To the best of our knowledge, this is the first report to histologically demonstrate biopsy-proven invasive SCC with benign-appearing cystic structures on frozen sections.
PubMed: 36788857
DOI: 10.7759/cureus.33610 -
Journal of Clinical Medicine Feb 2023Epidermolysis bullosa acquisita (EBA) is a rare chronic autoimmune subepidermal blistering disease of the skin and mucous membranes, usually beginning in adulthood. EBA... (Review)
Review
Epidermolysis bullosa acquisita (EBA) is a rare chronic autoimmune subepidermal blistering disease of the skin and mucous membranes, usually beginning in adulthood. EBA is induced by autoantibodies to type VII collagen, a major component of anchoring fibrils in the dermal-epidermal junction (DEJ). The binding of autoantibodies to type-VII collagen subsequently leads to the detachment of the epidermis and the formation of mucocutaneous blisters. EBA has two major clinical subtypes: the mechanobullous and inflammatory variants. The classic mechanobullous variant presentation consists of skin fragility, bullae with minimal clinical or histological inflammation, erosions in acral distribution that heal with scarring, and milia formation. The inflammatory variant is challenging to differentiate from other autoimmune bullous diseases, most commonly bullous pemphigoid (BP) but also mucous membrane pemphigoid (MMP), Brunsting-Perry pemphigoid, and linear IgA dermatosis. Due to its recalcitrance conventional treatment of epidermolysis bullosa acquisita is shown to be demanding. Here we discuss novel therapeutic strategies that have emerged and which could potentially improve the quality of life in patients with EBA.
PubMed: 36769788
DOI: 10.3390/jcm12031139 -
Skin Health and Disease Feb 2023A 65-year-old Japanese woman was referred to our department because of a 5-month history of asymptomatic papules on the face. She was diagnosed with cutaneous...
A 65-year-old Japanese woman was referred to our department because of a 5-month history of asymptomatic papules on the face. She was diagnosed with cutaneous sarcoidosis on the face 20 years ago. All of the lesions had completely disappeared with oral corticosteroids. Twenty years after the diagnosis of sarcoidosis, small papules developed in areas where the cutaneous sarcoidosis had been located. Physical examination revealed four yellow-white papules on the face. Dermoscopy revealed a homogenous, round, and yellow-white lesion. Serum levels of calcium and phosphorus were normal. Histopathology demonstrated calcium deposits in the dermis surrounded by inflammatory infiltrates without sarcoid granulomas. We made a diagnosis of calcinosis cutis. Basal cell carcinoma with calcinosis cutis, milia-like calcinosis cutis, and subcutaneous calcified nodule should be differentiated. Calcinosis cutis can be classified into four subtypes based on pathogenesis: dystrophic, metastatic, idiopathic, and iatrogenic. Dystrophic calcinosis cutis is caused by local tissue damage or abnormalities. Whereas, metastatic calcinosis cutis is often associated with hypercalcaemia, hyperphosphatemia, or hyperparathyroidism. There are reported cases of metastatic calcinosis cutis associated with sarcoidosis because patients with sarcoidosis often present with hypercalcaemia. However, dystrophic calcinosis cutis associated with sarcoidosis has been rarely reported. In the present case, systemic treatment for sarcoidosis may have degraded sarcoid granulomas and yielded necrotic tissue and dermal fibrosis, which might have induced ectopic calcification. Thus, we thought the present case consisted of dystrophic calcinosis cutis that developed in areas with cutaneous sarcoidosis in remission.
PubMed: 36751335
DOI: 10.1002/ski2.174