Leprosy. An Update: Definition, Pathogenesis, Classification, Diagnosis, and Treatment

Abstract Leprosy is a chronic granulomatous disease caused by the bacillus Mycobacterium leprae. It primarily affects the skin and peripheral nerves and is still endemic in various regions of the world. Clinical presentation depends on the patient's immune status at the time of infection and during the course of the disease. Leprosy is associated with disability and marginalization. Diagnosis is clinical and is made when the patient has at least 1 of the following cardinal signs specified by the World Health Organization: hypopigmented or erythematous macules with sensory loss; thickened peripheral nerves; or positive acid-fast skin smear or skin biopsy with loss of adnexa at affected sites. Leprosy is treated with a multidrug combination of rifampicin, clofazimine, and dapsone. Two main regimens are used depending on whether the patient has paucibacillary or multibacillary disease. © 2011 Elsevier España, S.L. and AEDV. All rights reserved. Resumen La lepra es una enfermedad granulomatosa crónica causado por una micobacteria (M. leprae) que presenta predisposición por la piel y nervios periféricos. La lepra continúa siendo endémica en distintas regiones del mundo. La presentación clínica de la enfermedad depende del estado inmunológico del paciente al adquirirla y durante la evolución de la misma. Es una infección que se asocia a discapacidad y marginación. PALABRAS CLAVE El diagnóstico de lepra es clínico y se hace al tener uno o más de los signos cardinales establecidos por la OMS; máculas hipopigmentadas o eritematosas con disminución de la sensibilidad, engrosamiento de los nervios periféricos y la demostración de bacilos ácido alcohol resistente en una baciloscopia o biopsia de piel, con pérdida de anexos en los sitios afectados. Leprosy. An Update: Definition, Pathogenesis, Classification, Diagnosis, and Treatment 555 El tratamiento es con tres drogas; rifampicina, clofazimina y dapsona. Existen principalmente dos modalidades de tratamiento dependiendo de la presentación clínica del paciente como paucibacilar o multibacilar

Decrease of virulence for BALB/c mice produced by continuous subculturing of Nocardia brasiliensis

<p>Abstract</p> <p>Background</p> <p>Subculturing has been extensively used to attenuate human pathogens. In this work we studied the effect of continuous subculturing of <it>Nocardia brasiliensis </it>HUJEG-1 on virulence in a murine model.</p> <p>Methods</p> <p><it>Nocardia brasiliensis </it>HUJEG-1 was subcultured up to 130 times on brain heart infusion over four years. BALB/c mice were inoculated in the right foot pad with the bacteria subcultured 0, 40, 80, 100 and 130 times (T₀, T₄₀, T₈₀T₁₀₀and T₁₃₀). The induction of resistance was tested by using T₁₃₀to inoculate a group of mice followed by challenge with T0 12 weeks later. Biopsies were taken from the newly infected foot-pad and immunostained with antibodies against CD4, CD8 and CD14 in order to analyze the in situ immunological changes.</p> <p>Results</p> <p>When using T₄₀, T₈₀T₁₀₀and T₁₃₀as inoculums we observed lesions in 10, 5, 0 and 0 percent of the animals, respectively, at the end of 12 weeks. In contrast, their controls produced mycetoma in 80, 80, 70 and 60% of the inoculated animals. When studying the protection of T₁₃₀, we observed a partial resistance to the infection. Immunostaining revealed an intense CD4+ lymphocytic and macrophage infiltrate in healing lesions.</p> <p>Conclusions</p> <p>After 130 in vitro passages of <it>N. brasiliensis </it>HUJEG-1 a severe decrease in its virulence was observed. Immunization of BALB/c mice, with these attenuated cells, produced a state of partial resistance to infection with the non-subcultured isolate.</p

Cemiplimab for the treatment of advanced cutaneous squamous cell carcinoma

Introduction: Cutaneous squamous cell carcinoma (CSCC) is the second most frequent malignant skin cancer, with an increasing worldwide incidence. Cemiplimab is a human monoclonal antibody directed against programmed cell death-1 receptor that acts by blocking T-cell inactivation. It is the first drug approved for the treatment of adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiation. Areas covered: The aim of this review is to analyze the mechanism of action, including pharmacokinetic and pharmacodynamic properties, clinical efficacy, safety, and tolerability of cemiplimab for squamous cell carcinoma. Expert opinion: The introduction of immune checkpoint inhibitors has revolutionized the therapeutic scenario of advanced skin cancers. Many challenges regarding the use of cemiplimab for locally advanced and metastatic CSCC still exist. The use of combination treatments, including the association of different immune checkpoint inhibitors, could be a strategy to increase treatment response, reducing the possibility of therapeutic failure. Also, different schemes of treatment or dose adjustments should be considered in order to reduce toxicity, avoiding treatment discontinuation and increasing patient´s quality of life

Looking into a Better Future: Novel Therapies for Metastatic Melanoma

Even though melanoma represents a small percentage of all cutaneous cancers, it is responsible for most deaths from skin neoplasms. In early stages it can be successfully treated with surgery, but as the disease expands the survival rate drops significantly. For many years the mainstay of treatment for metastatic melanoma was chemotherapeutic agents, even though they failed to prove survival prolongation. After the advent of ipilimumab, a survival benefit and better overall response rate could be offered to the patients. Other new therapies, such as immunotherapies, targeted therapies, vaccines, and small molecules, are currently being studied. Also, combination regimens have demonstrated superiority to some monotherapies. Nowadays, ipilimumab should no longer be considered the first-line therapy given its severe toxicity and lower efficacy, while nivolumab remains efficacious and has a good safety profile. T-VEC as monotherapy has been shown to be an elegant alternative even for the elderly or cases of head and neck melanomas. If the BRAF mutation status is positive, the combination of dabrafenib and trametinib could be an option to consider. Despite the success of the novel treatments, their effectiveness is still limited. New studies have opened up new avenues for future research in melanoma treatment, which is expected to lead to better therapeutic outcomes for our patients. The objective of this review is to discuss the novel therapies for metastatic melanoma that have been tested in humans during the last 3 years to obtain a sharper perspective of the available treatment options for specific patient characteristics

Micro needling: A novel therapeutic approach for androgenetic alopecia, A Review of Literature

Androgenetic alopecia (AGA) is an androgen-dependent hereditary trait resulting in hair miniaturization. It is the most common type of alopecia in men and women. During the last years, multiple treatment modalities have been studied, but only topical minoxidil and finasteride have been approved by the US Food and Drug Administration. Microneedling (MN) is a minimally invasive technique that induces collagen formation, as well as growth factors production and neovascularization. Even though not many studies of MN in alopecia have been performed, it remains a favorable treatment modality; however, no standardized protocol for MN in hair loss has been proposed yet. Current evidence is not sufficient to allow a direct comparison with other therapies, but it shows promises to increase hair density, thickness, and quality of hair, especially when combined with other treatments or when used as a drug delivery system. This article aims to summarize the available literature regarding the use of MN alone or associated with other therapies for the treatment of androgenetic alopecia