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The COVID-19 pandemic has posed significant therapeutic challenges in addressing acute respiratory distress syndrome (ARDS). This serious illness has caused numerous fatalities worldwide and has had profound health and economic impacts. Previous studies have shown that mesenchymal stem cells (MSCs) can suppress ARDS. In this case series, we report on the treatment of nine patients with a single intravenous dose of 100 million hypoxic cultured umbilical cord-derived MSCs (UC-MSCs). Following the intravenous administration of UC-MSCs, obtained from the lining of the umbilical cord, longitudinal laboratory analysis revealed a sustained decrease in inflammatory markers and stabilized pulmonary function in eight out of nine patients. UC-MSCs possess immunomodulatory and anti-inflammatory properties, enabling them to attenuate the cytokine storm and potentially aid in lung repair. Importantly, no adverse events associated with the treatment were observed. These findings collectively suggest that a cell-based approach significantly enhances the survival rate of ARDS induced by SARS-CoV-2 and offers a promising treatment option in both preclinical and clinical settings.

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[This corrects the article DOI: 10.7759/cureus.29921.].

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Background KLS-1 is zinc (Zn) aspartate enriched with isotope 64Zn to 99.2% mass fraction of total zinc. KLS-1 is intended as a novel therapeutic approach for patients with a variety of diseases including but not limited to different forms of cancer and neurodegenerative diseases. The purpose of this first-in-human study was to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics (PK) in patients with medical disorders. Methods The study was designed as consisting of two consecutive parts: the dose escalation part and the dose expansion part. Adult patients with refractory glioblastoma, primary progressive aphasia/dementia, amyotrophic lateral sclerosis, Parkinson's disease (PD), and type 1 diabetes were included. KLS-1 formulated as a 10 mL water solution containing 26.42 mg/mL of 64zinc aspartate (that is equivalent to 5.184 mg/mL of 64Zn) was administered twice weekly in two-week cycles via two-hour intravenous (IV) infusion at various dose levels during the dose escalation part and twice weekly during five subsequent weeks in the dose expansion part. The study was conducted at Pan American Cancer Treatment Center (Tijuana, Mexico) in 2020 and had a duration of 10 months. Results A total of eight patients (all white/Caucasian) were enrolled in both parts of the study. A total of four patients who participated in the dose escalation part were dosed twice weekly at 1, 2, and 4 mg/kg in two-week cycles for each dose level with the dose increased to the next higher level in the subsequent cycle. Dose-limiting toxicities (DLTs) were defined at dose level 4 mg/kg due to treatment-emergent reversible adverse events that required medications for symptomatic relief. The most common drug-related toxicities that occurred in two or more patients (≥25%) were weakness (five patients), fatigue (four patients), dizziness (three patients), nausea (two patients), poor sleep (two patients), and abdominal discomfort (two patients). In the dose expansion part, a dose of 2 mg/kg administered twice weekly was investigated for five continuous weeks in four patients and was established as recommended phase 1b/2 dose. Systemic exposure to KLS-1 (area under the curve (AUC) and maximum serum concentration (Cmax)) increased from 1 to 4 mg/kg and showed a linear relationship. Conclusions Multiple doses of KLS-1 ranging from 1 to 2 mg/kg administered twice a week via intravenous infusion for up to five continuous weeks were safe and well tolerated in patients with different types of therapeutic conditions including but not limited to a few forms of cancer and Parkinson's disease, and the evaluated pharmacokinetic parameters exhibited favorable profile.

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BACKGROUND: Post-intubation tracheoesophageal fistula is a severe complication in long-term mechanical ventilation patients with possible fatal consequences. OBJECTIVE: To describe a case of post-intubation tracheoesophageal fistula and its surgical management. In addition, a brief literature review was effectuated. CASE REPORT: 45-year-old female, suffers ischemic stroke with progressive neurological damage that requires long-term mechanical ventilation. During endoscopic gastrostomy tracheoesophageal fistula is shown. RESULTS: Undergoes surgery for esophageal repair and tracheal resection, through cervicosternotomy. Unfortunately died in the immediate postoperative period. CONCLUSIONS: This complex pathology requires structured protocols for its prevention in patients in whom long-term mechanical ventilation is expected.

ANTECEDENTES: La fístula traqueoesofágica es una complicación en pacientes con ventilación mecánica prolongada. La contaminación pulmonar permanente puede ser grave, con evolución fatal. OBJETIVO: Describir un caso de fístula traqueoesofágica posintubación y hacer una breve revisión de la literatura. CASO CLÍNICO: Mujer de 45 años que sufre un evento cerebrovascular isquémico que condiciona deterioro neurológico progresivo, ameritando ventilación mecánica prolongada. Durante la gastrostomía endoscópica se evidencia una fístula. RESULTADOS: Intervenida quirúrgicamente para reparación esofágica y resección traqueal mediante cervicoesternotomía, lamentablemente fallece en el posoperatorio inmediato. CONCLUSIONES: Esta patología es compleja. Deben implementarse protocolos enfocados en su prevención en pacientes en quienes se espera una ventilación mecánica prolongada.

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The present study aimed to analyze the methylation pattern of the MIR200 family in the colorectal tissues and peripheral blood of colorectal cancer (CRC) patients. Previous informed consent, 102 samples of colorectal tissues (tumor and adjacent normal tissues) and 40 peripheral blood samples were collected from CRC patients. Additionally, we included a reference group of 40 blood samples. DNA extraction was done for colorectal tissues and peripheral blood. For methylation-specific PCR, we used bisulfite-treated DNA and controls for methylated and unmethylated DNA were included to each assay. PCR fragments were separated by 6% polyacrylamide gel electrophoresis. Methylation-positive and methylation-negative results were confirmed by bisulfite genomic sequencing technique. We analyzed 102 colorectal tissues and 40 blood samples from 51 CRC patients. MIR200B/MIR200A/MIR429 methylation analysis discloses no differences among tissues (p>0.05). However, MIR200C/MIR141 methylation showed differences between colorectal tissues and peripheral blood of CRC patients (p<0.0001) and mainly methylated alleles were observed in peripheral blood. These findings suggest a tissue-specific methylation pattern for the MIR200C/MIR141 promoter.

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Despite the worldwide increasing incidence and prevalence of Inflammatory Bowel Disease (IBD), our knowledge about it in Mexico is still limited. The aim of this study is to describe the incidence and prevalence of IBD as well as its clinical and socio-demographical characteristics in Mexico from a nation-wide perspective.Multicenter nation-wide cohort study that included 42 IBD clinics from all over the country that participated with electronically register of the new cases over 17 years as well as all known existing cases together with their clinical and socio-demographical characteristics from patients with IBD (ulcerative colitis [UC], Crohn disease [CD], and inflammatory bowel disease unclassified [IBDU]). The data collection was conducted between January and October 2017. Incidence, prevalence, and mean incidence over 2 decades were then calculated. Data base was analyzed using SPSS v24 program SPSS (version 24, IBM Corp., Armonk, NY, USA).A total of 2645 patients with IBD were registered. The crude incidence rates of IBD, UC, and CD, respectively, were 0.21, 0.16, and 0.04 cases per 100,000-person year. The highest incidence was registered in the year 2015, compared with to the previous years. The mean incidence of IBD has increased steadily from 0.05 to 0.21 per 100,000 person-years over the past 15 years (P = .06). The incidence of IBD new cases have increased significantly throughout the last 16 years, 5.9-fold for IBD, 5.3-fold for UC, and 9.5-fold for CD. The prevalence rates of IBD, UC, and CD, respectively, were 1.83, 1.45, and 0.34 cases per 100,000-person-year.This is the first study from a nation-wide perspective that demonstrated a significant increase of prevalence and incidence of IBD in Mexico in the last 15 years.

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BACKGROUND: The effectiveness of Early Intervention in Psychosis (EIP) services for individuals with a first episode of psychosis (FEP) could be thwarted by high rates of early disengagement.AimsTo investigate which factors predict disengagement with EIP services. METHOD: Using data from a naturalistic cohort of 786 EIP clients in East Anglia (UK), we investigated the association between sociodemographic and clinical predictors and disengagement using univariable and multivariable Cox proportional hazards models. RESULTS: Over half (54.3%) of our sample were discharged before receiving 3 years of EIP care, with 92 (11.7%) participants discharged due to disengagement. Milder negative symptoms, more severe hallucinations, not receiving an FEP diagnosis, polysubstance use and being employed were associated with greater disengagement. CONCLUSIONS: Our findings highlight heterogeneous reasons for disengagement with EIP services. For some patients, early disengagement may hinder efforts to sustain positive long-term EIP outcomes. Efforts to identify true FEP cases and target patients with substance use problems and more severe positive symptoms may increase engagement.Declaration of interestNone.

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The mechanisms underlying discrimination between "self" and "non-self", a central immunological principle, require careful consideration in immune oncology therapeutics where eliciting anti-cancer immunity must be weighed against the risk of autoimmunity due to the self origin of tumors. Whole cell vaccines are one promising immunotherapeutic avenue whereby a myriad of tumor antigens are introduced in an immunogenic context with the aim of eliciting tumor rejection. Despite the possibility collateral damage to healthy tissues, cancer immunotherapy can be designed such that off target autoimmunity remains limited in scope and severity or completely non-existent. Here we provide an immunological basis for reconciling the safety of cancer vaccines, focusing on tumor endothelial cell vaccines, by discussing the following topics: (a) Antigenic differences between neoplastic and healthy tissues that can be leveraged in cancer vaccine design; (b) The layers of tolerance that control T cell responses directed against antigens expressed in healthy tissues and tumors; and, (c) The hierarchy of antigenic epitope selection and display in response to whole cell vaccines, and how antigen processing and presentation can afford a degree of selectivity against tumors. We conclude with an example of early clinical data utilizing ValloVax™, an immunogenic placental endothelial cell vaccine that is being advanced to target the tumor endothelium of diverse cancers, and we report on the safety and efficacy of ValloVax™ for inducing immunity against tumor endothelial antigens.

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Angiogenesis is essential for the growth and metastasis of solid tumors. The tumor endothelium exists in a state of chronic activation and proliferation, fueled by the tumor milieu where angiogenic mediators are aberrantly over-expressed. Uncontrolled tumor growth, immune evasion, and therapeutic resistance are all driven by the dysregulated and constitutive angiogenesis occurring in the vasculature. Accordingly, great efforts have been dedicated toward identifying molecular signatures of this pathological angiogenesis in order to devise selective tumor endothelium targeting therapies while minimizing potential autoimmunity against physiologically normal endothelium. Vaccination with angiogenic antigens to generate cellular and/or humoral immunity against the tumor endothelium has proven to be a promising strategy for inhibiting or normalizing tumor angiogenesis and reducing cancer growth. Here we review tumor endothelium vaccines developed to date including active immunization strategies using specific tumor endothelium-associated antigens and whole endothelial cell-based vaccines designed to elicit immune responses against diverse target antigens. Among the novel therapeutic options, we describe a placenta-derived endothelial cell vaccine, ValloVax™, a polyvalent vaccine that is antigenically similar to proliferating tumor endothelium and is supported by pre-clinical studies to be safe and efficacious against several tumor types.

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La conidiobolomicosis es una micosis subcutánea que se localiza generalmente en la línea media facial; es causada por un hongo saprófito de suelos y vegetales secos, propio de regiones intertropicales, que afecta principalmente a hombres adultos. El agente etiológico C onidiobolus coronatus pertenece a la clase de los Zigomicetos, orden Entomoftorales; se caracteriza por hifas cortas y gruesas, generalmente aseptadas, que crece entre 30°C y 37°C y produce granulomas nasales. Se informan a continuación los hallazgos histológicos de un caso de conidiobolomicosis en un paciente de 31 años de raza negra, natural y procedente de la región de Urabá, quien presentaba deformidad mediofacial con edema de nariz, labio superior e imágenes polipoides en senos maxilares con destrucción del tabique nasal. La biopsia demostró inflamación granulomatosa necrosante difusa en la dermis profunda e hipodermis asociada con eosinófilos y fenómeno de Splendore-Hoeppli, en cuya zona central se ubicaban espacios aparentemente vacíos que contenían el hongo que no se tiñó con HE, pero que sí lo hizo con las coloraciones de PAS y Grocott lo cual permitió la observación de hifas de paredes gruesas y rígidas, con torsión central y extremos cónicos

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Conidiobolomycosis is a subcutaneous mycosis of the facial midline affecting primarily adult males. It is caused by the saprophytic fungus, Conodiobolus coronatus, present in soils and dried vegetables, characteristic of intertropical regions. C. coronatus belongs to the class Zygomycetes, order Entomophthorales; it is a fungus composed of thick, short hyphae that grows at temperatures between 30 degrees C and 37 degrees C and causes nasal granulomas. The histologic findings are described of a case of conidiobolomycosis in a 31-year-old male, born and resident in the Urabá region of Colombia. He presented with a mid-facial deformity of the nose and upper lip edema, and polypoid images in the maxillary sinuses with destruction of the nasal septum. The biopsy revealed a diffuse inflammatory lesion located in the deep dermis and in the hypodermis corresponding to a necrotizing granuloma. Associated eosinophils and the presence of the Splendore-Hoeppli phenomenon were noted in the vacant central zone which apparently corresponded to location of the fungal hyphae. They did not stain with HE stain, but reacted to the PAS and Grocott staining techniques and appeared as rigid, thick-walled hyphae, centrally twisted and with cone-shaped endings.

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