The rope sign, a typical and yet infrequent clue.

Cutaneous granulomatous reactions are diverse, both from the clinical and the pathological perspective. Most underlying pathophysiological aspects remain elusive. Interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis have been claimed to be reactions to systemic disorders, such as infectious, inflammatory, or neoplastic conditions. Recently, the overarching term "reactive granulomatous dermatitis" has been coined to unify both entities. We herein report two cases of reactive granulomatous dermatitis presenting with the widely known, albeit infrequent "rope sign" and provide clinicopathological correlation. The two patients included a 53-year-old woman with enlarging erythematous plaques and underlying palpable cords on both sides of trunk near axillae (rope sign), and a 51-year-old woman with personal history of rheumatoid arthritis and a palpable cord on the left aspect of the trunk. Pathological findings were compatible with reactive granulomatous dermatitis in both cases. In conclusion, the rope sign represents a strikingly infrequent but decisive diagnostic clue of reactive granulomatous dermatitis.

Pilomatrixoma of the Forearm in an Elderly Male.

Pilomatrixoma or pilomatricoma is a benign adnexal neoplasm originating from the hair matrix, the inner sheath of the hair follicle, and the hair cortex. Although it is considered rare in adults, numerous cases have been documented in the literature. We present a case of an elderly male who sought consultation due to a newly appearing nodular lesion on his left forearm. Several benign and malignant entities were included in the original differential diagnosis. High-frequency ultrasonographic features suggested a cystic neoplasm with calcification and mild intralesional vascularity. Ultimately, histopathological examination confirmed the diagnosis of pilomatricoma. In this study, our aim is to review the importance of the available diagnostic tools, such as dermoscopy, and the emerging utility of cutaneous high-frequency ultrasonography. Some rarer pathological variants are also discussed, including perforating, anetodermic, bullous and pigmented pilomatricoma. We hope that exposure to these clinical, dermoscopic, ultrasonographic, and histopathological images will encourage clinicians to consider pilomatricoma in their differential diagnosis when approaching nodular lesions, regardless of location and patient's age.

Secondary sclerosing cholangitis induced by systemic chemotherapy.

There are multiple causes of secondary sclerosing cholangitis (SSC), including mechanical obstruction, ischemia, congenital abnormalities, cholangiopathy of the critically ill patient and rarely, chemotherapy (1,2). We present the case of a 52-year-old female with a history of left breast invasive ductal carcinoma treated with neoadjuvant chemotherapy (adriamycin, cyclophosphamide and paclitaxel), surgery and radiotherapy in March 2021. She was admitted in July 2022 due to painless jaundice and pruritus with marked serum cholestasis. Magnetic resonance cholangiopancreatography showed multiple strictures and dilatations involving the intra and extrahepatic bile ducts (Figure 1.A), without any extrinsic stenotic cause. Findings were confirmed by endoscopic retrograde cholangiopancreatography (ERCP) with cholangioscopy (Figure 1.B). Biopsies were negative for malignancy and IgG4 disease. In addition, autoantibodies were negative and serum IgG4 levels were normal. Due to these findings and the history of recent chemotherapy, the patient was diagnosed with paclitaxel-induced sclerosing cholangitis, initiating treatment with ursodeoxycholic acid. Over the following two months, she suffered two episodes of Klebsiella Pneumoniae bacteraemia due to acute cholangitis. Dilatation and placement of plastic stents in both biliary trees were performed and prophylactic antibiotherapy was started. The patient had a poor evolution and was not candidate for liver transplantation on account of a recent neoplasia. She died six months later due to sepsis secondary to multiple hepatic abscesses.

Diagnóstico del proceso de reafirmación profesional, en la carrera de Cultura Física, en Granma

La formación de profesionales, con elevada calidad, es tarea esencial de la Educación Superior, por lo que de manera permanente se demanda de graduados comprometidos con los procesos de desarrollo, donde quedan evidenciados los conocimientos, habilidades y valores en los que se han formado. El diagnóstico tuvo como objetivo caracterizar la situación de la orientación y reafirmación profesional (consolidación de los motivos e intenciones profesionales) en el proceso de estudio de la carrera Licenciatura en Cultura Física, en Granma; a partir de tres dimensiones: pedagógica, psicológica y sociológica. Se aplicaron métodos teóricos y empíricos que mostraron insuficiencias en las acciones planificadas en las estrategias educativas y en el plan de trabajo metodológico de las diferentes disciplinas, un limitado aprovechamiento de las potencialidades del contenido y las actividades extensionistas y bajos niveles de satisfacción por el estudio de la Carrera; lo que se manifestó en la no selección de una esfera de actuación para el futuro desempeño profesional, y en los elevados niveles de deserción de los estudiantes, en los dos primeros años de formación.

A formação de profissionais, com elevada qualidade, é uma tarefa essencial do Ensino Superior, razão pela qual existe uma procura permanente de licenciados comprometidos com processos de desenvolvimento, onde se evidenciam os conhecimentos, competências e valores em que foram formados. O objetivo do diagnóstico foi caracterizar a situação de orientação e reafirmação profissional (consolidação de motivos e intenções profissionais) no processo de estudo do Bacharelado em Cultura Física, no Granma; a partir de três dimensões: pedagógica, psicológica e sociológica. a corrida; o que se manifestou na não seleção de uma esfera de atuação para futura atuação profissional, e nos elevados índices de evasão estudantil, nos dois primeiros anos de formação.

The training of professionals, with high quality, is an essential task of Higher Education, which is why there is a permanent demand for graduates committed to development processes, where the knowledge, skills and values in which they have been trained are evidenced. The objective of the diagnosis was to characterize the situation of professional guidance and reaffirmation (consolidation of professional motives and intentions) in the process of studying the Bachelor's degree in Physical Culture, in Granma; from three dimensions: pedagogical, psychological and sociological. Theoretical and empirical methods were applied that showed insufficiencies in the planned actions in the educational strategies and in the methodological work plan of the different disciplines, a limited use of the potential of the content and extension activities and low levels of satisfaction with the study of the career; which was manifested in the non-selection of a sphere of action for future professional performance, and in the high levels of student dropout, in the first two years of training.

Dynamical changes in the expression of GABAergic and purinergic components occur during the polarization of THP-1 monocytes to proinflammatory macrophages.

The monocytes are key components of innate immunity, as they can differentiate into phagocytic cells or macrophages with proinflammatory or anti-inflammatory phenotypes. The gamma-aminobutyric acid (GABA) and adenosine triphosphate (ATP), two known neurotransmitters, are two environmental signals that contribute to the differentiation of monocytes into macrophages and their subsequent polarization into proinflammatory M1 and anti-inflammatory M2 macrophages. Although monocytes and macrophages express proteins related to GABA and ATP-mediated response (GABAergic and purinergic systems, respectively), it is unknown whether changes in their expression occur during monocyte activation or their differentiation and polarization into macrophages. Therefore, we evaluated the expression levels of GABAergic and purinergic signaling components in the THP-1 monocyte cell line and their changes during monocyte activation, differentiation, and polarization to M1 proinflammatory macrophages. Our results showed that activated monocytes are characterized by increased expression of two GABAergic components, the GABA transporter 2 (GAT-2) and the glutamic acid decarboxylase (GAD)-67, an enzyme involved in GABA synthesis. Also, monocytes showed a pronounced expression of the purinergic receptors P2X4 and P2X7. Interestingly, during differentiation, monocytes increased the expression of the ß2 subunit of GABA A-type receptor (GABA-AR), while the purinergic receptors P2X1 and P2X1del were reduced. In contrast, proinflammatory M1 macrophages showed a reduced expression in the α4 subunit of GABA-AR and GAD67, while P2X4 and P2X7 were overexpressed. These results indicate that dynamical changes in the GABAergic and purinergic components occur during the transition from monocytes to macrophages. Since GABA and ATP are two neurotransmitters, our results suggest that monocytes and macrophages respond to neurotransmitter-induced stimulation and may represent a path of interaction between the nervous and immune systems during peripheral inflammation and neuroinflammation development.

Zinc-Doped Iron Oxide Nanoparticles as a Proton-Activatable Agent for Dose Range Verification in Proton Therapy.

Proton therapy allows the treatment of specific areas and avoids the surrounding tissues. However, this technique has uncertainties in terms of the distal dose fall-off. A promising approach to studying the proton range is the use of nanoparticles as proton-activatable agents that produce detectable signals. For this, we developed an iron oxide nanoparticle doped with Zn (IONP@Zn-cit) with a hydrodynamic size of 10 nm and stability in serum. Cytotoxicity, defined as half of the surveillance, was 100 µg Zn/mL in the U251 cell line. The effect on clonogenic cell death was tested after X-ray irradiation, which suggested a radioprotective effect of these nanoparticles at low concentrations (1-10 µg Zn/mL). To evaluate the production of positron emitters and prompt-gamma signals, IONP@Zn-cit was irradiated with protons, obtaining prompt-gamma signals at the lowest measured concentration (10 mg Zn/mL). Finally, 67Ga-IONP@Zn-cit showed accumulation in the liver and spleen and an accumulation in the tumor tissue of 0.95% ID/g in a mouse model of U251 cells. These results suggest the possibility of using Zn nanoparticles as proton-activatable agents to verify the range by prompt gamma detection and face the challenges of prompt gamma detection in a specific biological situation, opening different avenues to go forward in this field.

Surgical technique for margin widening in the treatment of polypoid nodular malignant back melanoma.

INTRODUCTION AND IMPORTANCE: Nodular melanoma is the second most frequent cutaneous melanoma worldwide and due to its rapid growth rate and non-malignant appearance, is the most aggressive one. In its polypoid form, it is usually found in mucosal areas, but can also be seen on the trunk. This case is presented because it is an unusual manifestation and surgical treatment required wide excision, however, the patient's evolution is favorable. CASE PRESENTATION: 70-year-old female patient shows a progressively growing lesion with irregular border, abnormal color and a heterogeneous appearance. The biopsy yields the histological diagnosis of nodular polypoid melanoma. The surgical technique results in the resection of a 10 × 9 × 67 cm piece with favorable evolution of the patient. CLINICAL DISCUSSION AND CONCLUSIONS: The surgical technique of margin widening is considered a recommended option for polypoid nodular back melanomas. Although the excision is considered vast, the patient's evolution may turn out to be favorable.

Identifying predictive factors for bowel control in patients with spina bifida and spinal cord injuries.

PURPOSE: This study aimed to assess our bowel management program (BMP) and identify predictive factors for bowel control in patients with Spina Bifida (SB) and Spinal Cord Injuries (SCI). Additionally, in patients with SB, we examined the impact of fetal repair (FRG) on bowel control. METHODS: We included all patients with SB and SCI seen in the Multidisciplinary Spinal Defects Clinic at Children's Hospital Colorado from 2020 to 2023. RESULTS: 336 patients included. Fecal incontinence was present in 70% and bowel control in 30%. All patients with urinary control also had bowel control. Fecal incontinence prevalence was higher in patients with ventriculoperitoneal (VP) shunt (84%), urinary incontinence (82%), and wheelchair users (79%) compared to those who did not need a VP shunt (56%), had urinary continence (0%) and non-wheelchair users (52%), respectively (p = < 0.001 in all three scenarios). After completing BMP, 90% remained clean for stool. There was no statistical significance when comparing bowel control in FRG with non-fetal repair group. CONCLUSIONS: Urinary continence predicts bowel control in patients with SB and SCI. Risk factors for fecal incontinence were the need for a VP shunt, urinary incontinence, and wheelchair usage. We did not find any positive impact of fetal repair on bowel and urinary control.

Radiologically supervised bowel management program outcome in patients with chronic idiopathic constipation.

PURPOSE: This study aimed to analyze our radiologically supervised bowel management program (RS-BMP) outcomes in patients with chronic idiopathic constipation (CIC). METHODS: A retrospective study was conducted. We included all patients with CIC who participated in our RS-BMP at Children´s Hospital Colorado from July 2016 to October 2022. RESULTS: Eighty patients were included. The average time with constipation was 5.6 years. Before our RS-BMP, 95% had received non-radiologically supervised treatments, and 71% had attempted two or more treatments. Overall, 90% had tried Polyethylene Glycol and 43% Senna. Nine patients had a history of Botox injections. Five underwent anterograde continence procedure, and one a sigmoidectomy. Behavioral disorders (BD) were found in 23%. At the end of the RS-BMP, 96% of patients had successful outcomes, 73% were on Senna, and 27% were on enemas. Megarectum was detected in 93% of patients with successful outcomes and 100% with unsuccessful outcomes (p = 0.210). Of the patients with BD, 89% had successful outcomes, and 11% had unsuccessful. CONCLUSION: Our RS-BMP has been proven to be effective in treating CIC. The radiologically supervised use of Senna and enemas was the appropriate treatment in 96% of the patients. BD and megarectum were associated with unsuccessful outcomes.

Ectopic variceal bleeding secondary to porto-sinusoidal vascular disease.

Porto-sinusoidal vascular disease (PSVD) is an uncommon cause of portal hypertension (PHT) characterized by typical manifestations of PHT in the absence of an identifiable cause such as cirrhosis or splenoportal thrombosis (1). There are different etiological factors, including oxaliplatin (2). We present the case of a 67-year-old male with a history of locally advanced rectal cancer in 2007 treated with chemotherapy (capecitabine, folinic acid, 5-fluorouracil and oxaliplatin), radiotherapy and surgery with a definitive colostomy. He was admitted for lower gastrointestinal bleeding from the colostomy with no anemia or hemodynamic repercussion. Colonoscopy was performed and no lesions were found. Abdominal computed tomography (CT) showed peristomal varices with porto-systemic collaterals at that level. There was splenomegaly, no evidence of chronic liver disease and the splenoportal axis was permeable. Laboratory tests showed chronic thrombocytopenia. Laboratory results excluded other causes of liver disease, hepatic elastography showed a value of 7.2 kPa and upper gastrointestinal endoscopy ruled out esophagogastric varices. The catheterisation of hepatic veins demonstrated a hepatic venous pressure gradient of 13.5 mmHg and liver biopsy revealed sinusoidal dilatation with sinusoidal and perivenular fibrosis. Because of the clinical context of the patient with a history of treatment with oxaliplatin, he was diagnosed with peristomal ectopic varices secondary to porto-sinusoidal vascular disease. Due to bleeding recurrence, it was finally decided to place a transjugular intrahepatic portosystemic shunt (TIPS).

Managing Low and Moderate Risk Obesity: Insights from a Colombian Reference Center's Experience with Liquid-Filled Intragastric Balloons

Introduction: Liquid-filled intragastric balloons (IGBs) have emerged as a safe and effective option for managing overweight and obesity. However, there is limited information available regarding the implementation of liquid IGBs in individuals with low- and moderate-risk obesity. Objective: The objective of this study was to assess the implementation of liquid IGBs in low- and moderate-risk obese individuals in terms of weight loss, safety, and tolerance at four, six, and twelve months of treatment. Materials and methods: This prospective, descriptive observational study included 109 subjects with low- and moderate-risk obesity (body mass index [BMI] of 30-40 kg/m2), who underwent endoscopic implantation of liquid-filled IGBs. The variables analyzed included sex, age, initial and final weight, percentage of weight loss, and side effects. Results: Out of the 109 subjects, 75.22% were women. The average weight at baseline was 87.22 kg, with an average BMI of 31.59 kg/m2. Three different brands of IGBs were used: Orbera (n=103), Spatz3 (n=3), and Elipse (n=3). The average weight loss showed significant differences when analyzed by months and brands-Ellipse: four months (-4.6 kg), Spatz3: three months (-7 kg), Orbera: six months (15.2 kg), Orbera: twelve months (19.7 kg). The average reduction in BMI achieved was 27.71 kg/m2. The complication rate was 2.75%, with two cases (1.83%) attributed to intolerance (abdominal pain) and one case due to acute appendicitis (0.91%). Conclusions: The findings of this study indicate that liquid-filled IGBs are a safe and effective procedure for managing low- and moderate-risk obesity. A minimum duration of twelve months with an IGB implantation is considered optimal for individuals with low- and moderate-risk obesity.

Introducción: los balones intragástricos (BIG) de llenado líquido han surgido como una opción segura y eficaz para el manejo de sobrepeso y obesidad. En nuestro medio hay poca información acerca de su implementación en obesidad de riesgo bajo y moderado. Objetivo: evaluar la implementación del BIG de contenido líquido en individuos con obesidad de riesgo bajo y moderado en términos de pérdida de peso, seguridad y tolerancia a 4, 6 y 12 meses de tratamiento. Materiales y métodos: estudio observacional prospectivo y descriptivo, se incluyeron a 109 sujetos con obesidad de riesgo bajo y moderado (índice de masa corporal [IMC] de 30 a 40 kg/m2), a quienes se les implantó por vía endoscópica un BIG de llenado líquido. Se analizaron las variables de sexo, edad, peso inicial y final, porcentaje de pérdida de peso y efectos secundarios. Resultados: 109 sujetos, 75,22% correspondieron a mujeres, el peso promedio fue de 87,22 kg, con IMC promedio de 31,59 kg/m2. Se usaron tres marcas (Orbera, n: 103; Spatz, 3, n: 3; y Elipse, n: 3). La pérdida de peso promedio presentó diferencias importantes al analizar por meses y marcas: Elipse: 4 meses (-4,6 kg), Spatz 3: 3 meses (-7 kg), Orbera: 6 meses (15,2 kg), Orbera: 12 meses (19,7 kg). Se logró la reducción del IMC promedio a 27,71 kg/m2. La tasa de complicaciones fue del 2,75%, 2 (1,83%) por intolerancia (dolor abdominal) y una por apendicitis aguda (0,91%). Conclusiones: El BIG de llenado líquido es un procedimiento seguro y eficaz. Un período de implantación del BIG de al menos 12 meses se considera óptimo para obesidad de riesgo bajo y moderado.

The feasibility of debranching aortic arch and visceral arteries with sutureless telescoping anastomoses during open aortic aneurysm repair.

Background: Open repair of aortic aneurysms frequently requires reimplantation of major aortic vessels. Traditional techniques can be time consuming, require meticulous hemostasis, and risk aneurysmal patch degeneration, which can require a challenging reoperation. We describe our experience using a stent graft to create a sutureless anastomosis that obviates these drawbacks. Methods: Between April 2018 and March 2021, all consecutive adult patients who underwent open repair of the aorta with at least one supra-aortic trunk or visceral vessel reimplanted using the sutureless anastomotic technique were included. Anastomoses were constructed by bridging a branch graft and the target artery with a Viabahn self-expanding stent (W.L. Gore & Associates, Flagstaff, AZ). Clinical information and perioperative outcomes for the patients were collected and analyzed. Results: Among 26 patients, 50 individual aortic vessels were debranched using sutureless self-expanding stent anastomoses, including 42 visceral vessels and 8 supra-aortic trunk vessels. Technical success was 100%. The median time to complete the anastomosis was 3 minutes, 12 seconds (range, 2-6 minutes). Perioperative mortality was 15% (n = 4). No stent-related complications, such as occlusion, bleeding, stroke, renal failure requiring hemodialysis, bowel ischemia, or the need for anastomotic reintervention, occurred. Follow-up imaging at 1 year revealed a 100% patency rate and no anastomotic stenosis, misalignment, or kinking. Conclusions: The sutureless anastomosis technique to debranch the aorta during open aortic aneurysm repair is technically feasible and reliably hemostatic and does not require early reintervention. The operative outcomes have been acceptable, and the short-term follow-up imaging findings demonstrated excellent patency without anastomotic kinking. In select cases, sutureless anastomoses are a possible alternative to traditional sutured anastomoses during aortic debranching. Further research is needed to compare the operative times and long-term patency of sutureless anastomosis to those of traditional sutured techniques.

Guía de práctica clínica para el manejo de la pancreatitis aguda en el seguro social del Perú (Essalud)

El presente artículo resume la guía de práctica clínica (GPC) para el manejo de la pancreatitis aguda en el Seguro Social del Perú (EsSalud). Su objetivo es proveer recomendaciones clínicas basadas en evidencia para el manejo de la pancreatitis aguda en EsSalud. Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos. El GEG formuló 7 preguntas clínicas a ser respondidas por la presente GPC. Se realizó búsquedas sistemáticas de revisiones sistemáticas y -cuando fue considerado pertinente- estudios primarios en PubMed durante el 2022. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones, los puntos de buenas prácticas clínicas y flujogramas correspondientes. Finalmente, la GPC fue aprobada con Resolución N° 105-IETSI-ESSALUD-2022. La presente GPC abordó 7 preguntas clínicas sobre fluidoterapia, momento de inicio de nutrición enteral, analgesia, tipo de nutrición, tratamiento antibiótico y quirúrgico. En base a dichas preguntas se formularon 8 recomendaciones (1 fuerte y 7 condicionales), 13 BPC, y 1 flujograma. El presente artículo resume la metodología y las conclusiones basadas en evidencia de la GPC para el manejo de la pancreatitis aguda en EsSalud.

This article summarizes the clinical practice guideline (CPG) for the management of acute pancreatitis in the Social Security of Peru (EsSalud), to provide evidence-based clinical recommendations for the management of acute pancreatitis in EsSalud. A guideline development group (GEG) was formed that included medical specialists and methodologists. The GEG formulated 7 clinical questions to be answered by this CPG. Systematic searches of systematic reviews and -when considered relevant-primary studies were carried out in PubMed during 2022. The evidence was selected to answer each of the clinical questions posed. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the GEG used the GRADE methodology to review the evidence and formulate the recommendations, the points of good clinical practice, and the corresponding ow charts. Finally, the CPG was approved with Resolution No. 105-IETSI-ESSALUD-2022. This CPG addressed 7 clinical questions on buid therapy, start of enteral nutrition, analgesia, type of nutrition, antibiotic, and surgical treatment. Based on these questions, 8 recommendations (1 strong and 7 conditional), 13 BPCs, and 1 flowchart were formulated. This article summarizes the methodology and evidence-based conclusions of the CPG for the management of acute pancreatitis in EsSalud.

Characteristics and Outcomes of Cancer Patients With Venous Thromboembolic Events After Treatment With Immune Checkpoint Inhibitors.

OBJECTIVE: This study aimed to describe the clinical characteristics and outcomes of patients with venous thromboembolism (VTE) after Immune checkpoint inhibitors (ICI), focusing on patients with gastrointestinal (GI) immune-related adverse events (irAE). METHODS: In this retrospective, single-center study, we report the clinical outcomes of adult cancer patients who developed a VTE within 2 years of ICI initiation. Patients were excluded if alternate causes of VTE were present apart from malignancy and cancer therapy. The cohort was classified into those with GI-irAE, non-GI-irAE, and no irAE. A control group with ICI exposure without irAE and VTE was selected for comparative analysis. RESULTS: Of all ICI-treated patients, 1891 (17.2%) were diagnosed with VTE. In all, 501 (4.6%) had no etiology for VTE aside from malignancy and cancer therapy. Of these, 137 patients were included and classified as: 44 GI-irAE, 42 non-GI-irAE, and 51 no irAE. Chemotherapy within 6 months of ICI therapy was associated with increased VTE risk. There was no difference in the clinical course between those exposed to chemotherapy versus ICI therapy alone, time from ICI initiation to VTE, and VTE type, recurrence, or related hospitalization. While there was no difference in VTE-related mortality, the GI-irAE group was associated with lower all-cause mortality and superior overall survival. CONCLUSION: Combined ICI and chemotherapy use increased VTE risk. There is a similar disease course of VTE after ICI exposure, regardless of other irAEs. Co-existing GI-irAE with VTE is associated with superior overall survival. Prospective studies are needed to evaluate the relationship between ICI therapy and VTE and irAE impact on VTE outcomes.

Conjunctival collagen crosslinking for the management of bleb leak.

The purpose of this article is to evaluate the effectiveness of collagen crosslinking of filtering blebs with 0.1% riboflavin stimulated with ultraviolet A radiation in a case of a thin-walled filtering bleb with leakage following an episode of late blebitis. The time to cessation of the bleb leakage was studied, as well as the intraocular pressure, the visual acuity, and the presence of adverse effects during 4 years of follow-up after treatment. A single session of crosslinking was effective in resolving the leakage of the filtering bleb. There were no adverse effects. The intraocular pressure and the visual acuity remained stable after 4 years of follow-up. Collagen crosslinking with 0.1% riboflavin stimulated with ultraviolet A radiation may prove to be a simple, painless, non-invasive, and repeatable treatment of the leaking bleb with the aim of strengthening the collagen fibers of the conjunctiva and avoiding more invasive surgical treatments.

Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03.

BACKGROUND: Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. METHODS: We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. RESULTS: From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors" (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43-22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99-36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. CONCLUSION: Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). GOV IDENTIFIER: NCT01584297.

Atrazine modifies markers of melanocyte maturation and apoptosis in primary skin cultures.

Atrazine (ATZ) is part of a group of herbicides called triazines. ATZ is widely used in agricultural areas of Mexico, commonly used for the selective control of weeds in corn and sorghum crops. The exposure to ATZ can have serious human health effects since its use was associated with the development of cutaneous melanoma in an epidemiological study. The aim of this study was to evaluate the expression of maturation and apoptotic markers in primary skin cultures exposed to ATZ. The primary skin cultures were exposed to 0.1, and 10 µM ATZ with or without ultraviolet (UV) radiation and the expression of maturation and apoptotic markers were evaluated by RT-qPCR. We observed a significant increase in all the melanocyte maturation markers in cells exposed to ATZ with or without UV, with SOX-9 and FAK (melanoblast markers) being the highest. Also, the expression of BCL-2 (anti-apoptotic marker) was the most increased gene in cells exposed to ATZ with or without UV. Low concentrations of ATZ and UV radiation induce genetic changes associated with the development of immature melanocytes and activate mechanisms associated with the inhibition of apoptosis characteristics of malignant cell transformation, which will allow proposing new therapeutic targets and generating new restrictions or care in farmers exposed to pesticides such as the ATZ.

National Burden and Trends for 29 Groups of Cancer in Mexico from 1990 to 2019: A Secondary Analysis of the Global Burden of Disease Study 2019.

The global burden of cancer is on the rise, with varying national patterns. To gain a better understanding and control of cancer, it is essential to provide national estimates. Therefore, we present a comparative description of cancer incidence and mortality rates in Mexico from 1990 to 2019, by age and sex for 29 different cancer groups. Based on public data from the Global Burden of Disease Study 2019, we evaluated the national burden of cancer by analyzing counts and crude and age-standardized rates per 100,000 people with 95% uncertainty intervals for 2019 and trends using the annual percentage change from 1990 to 2019. In 2019, cancer resulted in 222,060 incident cases and 105,591 deaths. In 2019, the highest incidence of cancer was observed in non-melanoma skin cancer, prostate cancer, and breast cancer. Additionally, 53% of deaths were attributed to six cancer groups (lung, colorectal, stomach, prostate, breast, and pancreatic). From 1990 to 2019, there was an increasing trend in incidence and mortality rates, which varied by 10-436% among cancer groups. Furthermore, there were cancer-specific sex differences in crude and age-standardized rates. The results show an increase in the national cancer burden with sex-specific patterns of change. These findings can guide national efforts to reduce health loss due to cancer.