Cancer is not a risk factor for severe COVID-19 in children, except in patients with recent allogeneic hematopoietic stem cell transplantation or comorbidities.

The EPICO (Spanish general registry of COVID-19 in children)-SEHOP (Spanish Society of Pediatric Hematology and Oncology) platform gathers data from children with SARS-CoV-2 in Spain, allowing comparison between children with cancer or allogeneic hematopoietic stem cell transplantation (alloHSCT) and those without. The infection is milder in the cancer/alloHSCT group than in children without comorbidities (7.1% vs. 14.7%), except in children with recent alloHSCT (less than 300 days), of which 35.7% experienced severe COVID-19. These data have been shared with the SEHOP members to support treatment and isolation policies akin to those for children without cancer, except for those with recent alloHSCT or additional comorbidities. This highlights the collaborative registries potential in managing pandemic emergencies.

Out of hospital cardiac arrest, first steps to know and follow in Mexico to have cardioprotected territories. A point of view of a group of experts / Paro cardiaco extrahospitalario, primeros pasos que se deben conocer y hacer en México para tener espacios cardioprotegidos. Punto de vista de un grupo de expertos

Abstract Sudden cardiac death is a common occurrence. Out-of-hospital cardiac arrest is a global public health problem suffered by ≈3.8 million people annually. Progress has been made in the knowledge of this disease, its prevention, and treatment; however, most events occur in people without a previous diagnosis of heart disease. Due to its multifactorial and complex nature, it represents a challenge in public health, so it led us to work in a consensus to achieve the implementation of cardioprotected areas in Mexico as a priority mechanism to treat these events. Public access cardiopulmonary resuscitation (CPR) and early defibrillation require training of non-medical personnel, who are usually the first responders in the chain of survival. They should be able to establish a basic and efficient CPR and use of the automatic external defibrillator (AED) until the emergency services arrive at the scene of the incident. Some of the current problems in Mexico and alternative solutions for them are addressed in the present work.

Resumen La muerte súbita cardíaca (SCD) es un acontecimiento común. El paro cardiaco extrahospitalario (OHCA) es un problema de salud pública mundial que sufren ≈3.8 millones de personas al año. Se ha avanzado en el conocimiento de esta enfermedad, su prevención y tratamiento, sin embargo, la mayoría de los eventos se producen en personas sin diagnóstico previo de cardiopatía. Debido a su carácter multifactorial y complejo, representa un reto en salud pública, lo que obliga a trabajar en un consenso para lograr la implementación de "Espacios Cardio protegidos" en México, como mecanismo prioritario de atención a estos eventos. La reanimación cardiopulmonar básica (RCPB) y la desfibrilación temprana de acceso público requieren de entrenamiento al personal no médico, que suelen ser los primeros respondientes para iniciar la cadena de la supervivencia. Ellos deberían instaurar una RCPB eficiente y el uso del desfibrilador automático externo (AED) hasta que lleguen al lugar del incidente los servicios de emergencias. El presente trabajo menciona algunos de los problemas actuales en México y algunas opciones de solución para los mismos.

Triple Therapy and Clinical Control in B+ COPD Patients: A Pragmatic, Prospective, Randomized Trial.

INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.

Dual vs Single Cardioversion of Atrial Fibrillation in Patients With Obesity: A Randomized Clinical Trial.

Importance: Atrial fibrillation and obesity are common, and both are increasing in prevalence. Obesity is associated with failure of cardioversion of atrial fibrillation using a standard single set of defibrillator pads, even at high output. Objective: To compare the efficacy and safety of dual direct-current cardioversion (DCCV) using 2 sets of pads, with each pair simultaneously delivering 200 J, with traditional single 200-J DCCV using 1 set of pads in patients with obesity and atrial fibrillation. Design, Setting, and Participants: This was a prospective, investigator-initiated, patient-blinded, randomized clinical trial spanning 3 years from August 2020 to 2023. As a multicenter trial, the setting included 3 sites in Louisiana. Eligibility criteria included body mass index (BMI) of 35 or higher (calculated as weight in kilograms divided by height in meters squared), age 18 years or older, and planned nonemergent electrical cardioversion for atrial fibrillation. Patients who met inclusion criteria were randomized 1:1. Exclusions occurred due to spontaneous cardioversion, instability, thrombus, or BMI below threshold. Interventions: Dual DCCV vs single DCCV. Main Outcomes and Measures: Return to sinus rhythm, regardless of duration, immediately after the first cardioversion attempt of atrial fibrillation, adverse cardiovascular events, and chest discomfort after the procedure. Results: Of 2079 sequential patients undergoing cardioversion, 276 met inclusion criteria and were approached for participation. Of these, 210 participants were randomized 1:1. After exclusions, 200 patients (median [IQR] age, 67.6 [60.1-72.4] years; 127 male [63.5%]) completed the study. The mean (SD) BMI was 41.2 (6.5). Cardioversion was successful more often with dual DCCV compared with single DCCV (97 of 99 patients [98%] vs 87 of 101 patients [86%]; P = .002). Dual cardioversion predicted success (odds ratio, 6.7; 95% CI, 3.3-13.6; P = .01). Patients in the single cardioversion cohort whose first attempt failed underwent dual cardioversion with all subsequent attempts (up to 3 total), all of which were successful: 12 of 14 after second cardioversion and 2 of 14 after third cardioversion. There was no difference in the rating of postprocedure chest discomfort (median in both groups = 0 of 10; P = .40). There were no cardiovascular complications. Conclusions and Relevance: In patients with obesity (BMI ≥35) undergoing electrical cardioversion for atrial fibrillation, dual DCCV results in greater cardioversion success compared with single DCCV, without any increase in complications or patient discomfort. Trial Registration: ClinicalTrials.gov Identifier: NCT04539158.

Anticancer Activity of HER2-targeting CPP-PTEN-THP Chimeric Proteins.

BACKGROUND/AIM: Protein phosphatase and tensin homolog (PTEN) is a tumor suppressor protein with potential to be a new biotechnological drug for PTEN-deficient cancer treatment. This study aimed to develop PTEN-based chimeric proteins (CPP-PTEN-THP) for human epidermal growth factor receptor 2 (HER2)-positive breast cancer treatment, addressing current limitations like inadequate delivery, poor tumor penetration, and low selectivity, while assessing their potential HER2-specific anticancer effects. MATERIALS AND METHODS: pCEFL-EGFP vector was used for both TAT-PTEN-LTV and KLA-PTEN-LTV construction. Non-contact co-cultures were employed using HEK-293T cells for protein expression, and HCC-1954 and MCF-7 cell lines for cytotoxicity testing. Protein detection was analyzed by western blotting and a docking prediction analysis was performed to infer the interactions. RESULTS: Endogenous and recombinant PTEN protein expression was confirmed in cell lysates. A 54-kDa signal matching the theoretical size of PTEN was detected, showing a greater level in TAT-PTEN-LTV (215.1±26.45%) and KLA-PTEN-LTV (129.2±1.44%) compared to endogenous PTEN. After the noncontact co-culture method, cytotoxic studies showed HCC-1954 preferential cell inhibition growth, with 25.95±0.9% and 12.25±1.29% inhibition by KLA-PTEN-LTV and TAT-PTEN-LTV respectively, compared to MCF-7 cells. An LTV-HER2 interaction model was proposed, inferring that LTV interactions are mainly due to the Pro, Trp, and Tyr residues that target HER2. CONCLUSION: The developed PTEN-based chimeric proteins have HER2-specific anticancer activity against HCC-1954 cells.

Design and Evaluation of a Humanized Anti-EGFR huscFv Antibody Fragment in Combination With Metformin in A549 Cells In Vitro.

BACKGROUND/AIM: The epidermal growth factor receptor (EGFR) is over-expressed in several types of cancer, and monoclonal antibody therapy has been the strategy that has shown the best results. This study focused on the construction of a humanized single chain antibody (huscFv) directed against EGFR (HER1). MATERIALS AND METHODS: The CDR grafting method was used to incorporate murine complementarity determining regions (CDRs) of cetuximab into human sequences. A dot blot assay was used to examine the affinity of the huscFv secreted by HEK293T for EGFR. The inhibitory effect on the viability of A549 cells was evaluated using the WST-1 assay. RESULTS: The incorporation of murine CDRs of cetuximab into human sequences increased the degree of humanness by 16.4%. The increase in the humanization of scFv did not affect the affinity for EGFR. Metformin had a dose-dependent effect, with an IC50 of 46 mM, and in combination with huscFv, the cell viability decreased by 45% compared to the 15% demonstrated by huscFv alone. CONCLUSION: The CDR grafting technique is efficient for the humanization of scFv, maintaining its affinity for EGFR and demonstrating its inhibitory effect when combined with metformin in A549 cells.

Out of hospital cardiac arrest, first steps to know and follow in Mexico to have cardioprotected territories. A point of view of a group of experts.

Sudden cardiac death is a common occurrence. Out-of-hospital cardiac arrest is a global public health problem suffered by ≈3.8 million people annually. Progress has been made in the knowledge of this disease, its prevention, and treatment; however, most events occur in people without a previous diagnosis of heart disease. Due to its multifactorial and complex nature, it represents a challenge in public health, so it led us to work in a consensus to achieve the implementation of cardioprotected areas in Mexico as a priority mechanism to treat these events. Public access cardiopulmonary resuscitation (CPR) and early defibrillation require training of non-medical personnel, who are usually the first responders in the chain of survival. They should be able to establish a basic and efficient CPR and use of the automatic external defibrillator (AED) until the emergency services arrive at the scene of the incident. Some of the current problems in Mexico and alternative solutions for them are addressed in the present work.

La muerte súbita cardíaca (SCD) es un acontecimiento común. El paro cardiaco extrahospitalario (OHCA) es un problema de salud pública mundial que sufren ≈3.8 millones de personas al año. Se ha avanzado en el conocimiento de esta enfermedad, su prevención y tratamiento, sin embargo, la mayoría de los eventos se producen en personas sin diagnóstico previo de cardiopatía. Debido a su carácter multifactorial y complejo, representa un reto en salud pública, lo que obliga a trabajar en un consenso para lograr la implementación de "Espacios Cardio protegidos" en México, como mecanismo prioritario de atención a estos eventos. La reanimación cardiopulmonar básica (RCPB) y la desfibrilación temprana de acceso público requieren de entrenamiento al personal no médico, que suelen ser los primeros respondientes para iniciar la cadena de la supervivencia. Ellos deberían instaurar una RCPB eficiente y el uso del desfibrilador automático externo (AED) hasta que lleguen al lugar del incidente los servicios de emergencias. El presente trabajo menciona algunos de los problemas actuales en México y algunas opciones de solución para los mismos.

The In Vitro Inhibitory Activity of Pacaya Palm Rachis versus Dipeptidyl Peptidase-IV, Angiotensin-Converting Enzyme, α-Glucosidase and α-Amylase.

The pacaya palm (Chamaedorea tepejilote Liebm) is an important food that is commonly consumed in Mexico and Central America due to its nutritive value. It is also used as a nutraceutical food against some chronic diseases, such as hypertension and hyperglycemia. However, few reports have indicated its possible potential. For this reason, the goal of this research was to evaluate the effects of the enzymatic activity of the pacaya palm inflorescence rachis on both hypertension and hyperglycemia and the effects of thermal treatments on the enzymatic activity. The enzymatic inhibition of ACE (angiotensin-converting enzyme), DPP-IV (dipeptidyl peptidase-IV), α-glucosidase and α-amylase were evaluated, all with powder extracts of pacaya palm inflorescences rachis. The results indicated that thermally treated rachis showed increased enzymatic inhibitory activity against α-amylase and DPP-IV. However, all rachis, both with and without thermal treatment, showed low- or no enzymatic activity against α-glucosidase and ACE. Apparently, the mechanism of action of the antidiabetic effect of rachis is mediated by the inhibition of α-amylase and DPP-IV and does not contribute with a significant effect on enzymes involved in the hypertension mechanism. Finally, the properties of the extract were modified via the extraction method and the temperature tested.

Exposome and basal cell carcinoma: a multicenter case-control study.

BACKGROUND: While ultraviolet radiation (UVR) present in sunlight is recognized as the main etiological agent of skin cancer, the most frequent form of which is basal cell carcinoma (BCC), other exposome factors like pollution, diet, and lifestyle may also contribute. This study aimed to investigate the association of BCC and exposome-related factors in the Spanish population. METHODS: BCC cases (n = 119) and controls (n = 127) with no history of skin cancer were recruited between April 2020 and August 2022 by 13 dermatologists throughout Spain in this prospective multicenter case-control study. RESULTS: The BCC group had a higher proportion of outdoor workers, more years of UVR exposure, and a greater consumption of drugs (statins, ASA, hydrochlorothiazide, ACE inhibitors and omeprazole), P < 0.05. Avoidance of sun exposure was the most used photoprotection measure in both groups. The use of hats or caps was higher in the BCC group (P = 0.01). The solar protection factor (SPF) used 15 years previously was higher in the control group (P = 0.04). The control group had a higher daily screen time (P < 0.001), and practiced more relaxation activities (P = 0.03). Higher linolenic acid intake and lower coffee consumption were the only dietary variables associated with BCC (P < 0.05). Statistical significance for all the aforementioned variables was maintained in the multivariate analysis (P < 0.05). CONCLUSIONS: The study found a significant association between BCC and multiple exposome-related factors in addition to chronic sun exposure in the Spanish population. Primary prevention strategies should target specific populations, such as outdoor workers, promoting sun-safe behaviors and stress-reducing activities, and also adequate skin photoprotection in patients on certain medications associated with increased BCC risk.

Peritumoral administration of immunomodulatory antibodies as a triple combination suppresses skin tumor growth without systemic toxicity.

BACKGROUND: Skin cancers, particularly keratinocyte cancers, are the most commonly diagnosed tumors. Although surgery is often effective in early-stage disease, skin tumors are not always easily accessible, can reoccur and have the ability to metastasize. More recently, immunotherapies, including intravenously administered checkpoint inhibitors, have been shown to control some skin cancers, but with off-target toxicities when used in combination. Our study investigated whether peritumoral administration of an antibody combination targeting PD-1, 4-1BB (CD137) and VISTA might control skin tumors and lead to circulating antitumor immunity without off-target toxicity. METHODS: The efficacy of combination immunotherapy administered peritumorally or intravenously was tested using transplantable tumor models injected into mouse ears (primary tumors) or subcutaneously in flank skin (secondary tumors). Changes to the tumor microenvironment were tracked using flow cytometry while tumor-specific, CD8 T cells were identified through enzyme-linked immunospot (ELISPOT) assays. Off-target toxicity of the combination immunotherapy was assessed via serum alanine aminotransferase ELISA and histological analysis of liver sections. RESULTS: The data showed that local administration of antibody therapy eliminated syngeneic murine tumors transplanted in the ear skin at a lower dose than required intravenously, and without measured hepatic toxicity. Tumor elimination was dependent on CD8 T cells and was associated with an increased percentage of CD8 T cells expressing granzyme B, KLRG1 and Eomes, and a decreased population of CD4 T cells including CD4+FoxP3+ cells in the treated tumor microenvironment. Importantly, untreated, distal tumors regressed following antibody treatment of a primary tumor, and immune memory prevented growth of subcutaneous flank tumors administered 50 days after regression of a primary tumor. CONCLUSIONS: Together, these data suggest that peritumoral immunotherapy for skin tumors offers advantages over conventional intravenous delivery, allowing antibody dose sparing, improved safety and inducing long-term systemic memory. Future clinical trials of immunotherapy for primary skin cancer should focus on peritumoral delivery of combinations of immune checkpoint antibodies.

Benefits of metabolic surgery on macrovascular outcomes in adult patients with type 2 diabetes: a systematic review and meta-analysis.

Type 2 diabetes (T2D) is a chronic metabolic disorder that affects millions of individuals associated with an increased risk of mortality and macrovascular complications. We aimed to synthesize the benefit of metabolic surgery (MS) on macrovascular outcomes in adult patients with T2D.We included both cohort studies and randomized controlled trials (RCTs) that evaluated MS added to medical therapy compared with medical therapy alone in the treatment of adult patients with T2D. Studies must have evaluated the incidence of any macrovascular complication of the disease for a period of at least 6 months. We performed our search using PubMed, Scopus, EMBASE, Web of Science, and COCHRANE Central database which was performed from inception date until March 2022. The trial protocol was previously registered at PROSPERO (CRD42021243739). A total of 6338 references were screened throughout the selection process from which 16 studies involving 179,246 participants fulfilled inclusion criteria. MS reduced the risk of any cardiovascular event by 44% (relative risk .56 [95% CI, .42-.75]; P = < .001), myocardial infarction by 54% (.46 [95% CI, .26-.83]; P = .009), coronary artery disease by 40% (.60 [95% CI, .42-.85]; P = .004) and heart failure by 71% (.29 [95% CI, .14-.61]; P = .001). It also provided a risk reduction of stroke by 29% (.71 [95% CI, .51-.99]; P = .04) and 38% (.62 [95% CI, .46-.85]; P = .001) for cerebrovascular events. On mortality, MS yields a risk reduction of 55% (.45 [95% CI, .36-.57]; P <.001) in overall mortality and 69% in cardiovascular mortality (relative risk .31 [95% CI, .22-.42]; P < .001). Peripheral vascular disease risk was also reduced. MS in adult patients with T2D can reduce the risk of mortality and of any macrovascular outcomes. However, there is a need for the planning of randomized clinical trials to further analyze and confirm the results.

Espacios cardioprotegidos en México: acciones para prevenir la muerte súbita cardiaca. Una postura de profesionales de la salud.

La muerte súbita cardiaca es un problema de salud pública a nivel mundial. Aunque su incidencia no es conocida, se estima que causa hasta 50% de la mortalidad de origen cardíaco y hasta 20% de la mortalidad total en los adultos. En México, estimaciones previas sugieren que causa en promedio 33 000 muertes al año; sin embargo, los datos no son precisos. La  mitad de los eventos por muerte súbita cardiaca se deben a un paro cardiaco súbito extrahospitalario que, de no ser atendido oportunamente, deriva en una muerte súbita cardiaca. Por tanto, la capacidad de responder pronta y adecuadamente a estos eventos con las maniobras y equipos necesarios mejora la sobrevida de las víctimas. Para atender este problema, en algunos estados del país se han creado espacios cardioprotegidos que permiten realizar maniobras de reanimación cardiopulmonar y desfibrilación cardiaca de acceso público oportunamente. Como objetivo, los profesionales de la salud establecen la importancia de implementar espacios cardioprotegidos y crear políticas públicas al respecto en todo el país.

The Influence of the Exposome in the Cutaneous Squamous Cell Carcinoma, a Multicenter Case-Control Study.

INTRODUCTION: The concept of exposome refers to the total of harmful and beneficial environmental exposures that can help predict the organism's biological responses over time. Ultraviolet radiation (UVR) from sun exposure has been recognized as the main etiological agent of skin cancer, and squamous cell carcinoma (SCC) is one most commonly associated with chronic exposure. However, in recent years, evidence suggests that lifestyle, environmental pollution, and contaminants in water and food can have an influence. OBJECTIVES: To study the relationship between SCC and sun exposure, pollution, stress, and lifestyle in a Spanish cohort. MATERIALS AND METHOD: A multicenter case-control study was carried out in which 13 dermatologists from different regions of Spain recruited cases and controls between April 2020 and August 2022. The group of cases were patients diagnosed with SCC and, as a control group, people who attended Dermatology consultations as companions with no history of skin cancer. RESULTS: A total of 62 patients with SCC and 126 controls were included (62.9% males, median age 76.46 (10.1) and 33.3%, median age 55.7 (15), respectively). The SCC group had experienced more outside work than the controls (75% vs. 22.4%, p < 0.001), less recreational exposure (sunbathing, p = 0.05, and outdoor sports, p = 0.01), and a lower annual income (p = 0.01), with an increase in tobacco exposure (p < 0.001), without differences in other carcinogens, such as ionizing radiation or chemical exposure. The control group had a higher daily screentime use (p < 0.001) and practiced more relaxation activities (p = 0.03). A higher linolenic acid intake and lower coffee consumption were the only dietary variables associated with SCC (p < 0.05). Some chronic medications (anxiolytics, antidepressants, beta-blockers, statins, hydrochlorothiazide, ACE inhibitors, metformin, and omeprazole) were also statistically associated with SCC. Statistical significance for all aforementioned variables was maintained in the multivariate analysis (p < 0.05). CONCLUSIONS: The study found a significant association between SCC and multiple exposome-related factors in addition to chronic sun exposure in the Spanish population. Primary prevention strategies should target specific populations, such as outdoor workers promoting sun-safe behaviors and stress-reducing activities, in addition to adequate skin photoprotection in patients under certain medications associated with SCC.

Risk factors and clinical characteristics of acute and chronic cutaneous graft-versus-host disease in pediatric patients undergoing hematopoietic stem cell transplantation.

Acute and chronic cutaneous graft-versus-host disease (GVHD) are common complications following hematopoietic stem cell transplantation (HSCT) in pediatric patients. In this retrospective study, we explored the risk factors and clinical characteristics of acute and chronic cutaneous GVHD in a case series of children undergoing HSCT at a tertiary referral hospital. We found that 36% of acute cutaneous GVHD was severe and these patients were more likely to have an unrelated donor, and that children with acute cutaneous GVHD who progressed to chronic cutaneous GVHD had a higher proportion of malignant diseases, total body irradiation, and bronchiolitis obliterans compared to those who did not progress to chronic cutaneous GVHD. Our study highlights the importance of identifying and monitoring these high-risk patients to improve the clinical management and outcomes of cutaneous GVHD in pediatric HSCT recipients.

Deep spatial-omics analysis of Head & Neck carcinomas provides alternative therapeutic targets and rationale for treatment failure.

Immune checkpoint inhibitor (ICI) therapy has had limited success (<30%) in treating metastatic recurrent Head and Neck Oropharyngeal Squamous Cell Carcinomas (OPSCCs). We postulate that spatial determinants in the tumor play a critical role in cancer therapy outcomes. Here, we describe the case of a male patient diagnosed with p16+ OPSCC and extensive lung metastatic disease who failed Nivolumab and Pembrolizumab/Lenvatinib therapies. Using advanced integrative spatial proteogenomic analysis on the patient's recurrent OPSCC tumors we demonstrate that: (i) unbiased tissue clustering based on spatial transcriptomics (ST) successfully detected tumor cells and enabled the investigation of phenotypic traits such as proliferation or drug-resistance genes in the tumor's leading-edge and core; (ii) spatial proteomic imagining used in conjunction with ST (SpiCi, Spatial Proteomics inferred Cell identification) can resolve the profiling of tumor infiltrating immune cells, (iii) ST data allows for the discovery and ranking of clinically relevant alternative medicines based on their interaction with their matching ligand-receptor. Importantly, when the spatial profiles of ICI pre- and post-failure OPSCC tumors were compared, they exhibited highly similar PD-1/PD-L1low and VEGFAhigh expression, suggesting that these new tumors were not the product of ICI resistance but rather of Lenvatinib dose reduction due to complications. Our work establishes a path for incorporating spatial-omics in clinical settings to facilitate treatment personalization.

Mapping of SARS-CoV-2 in Waldeyer's lymphatic ring and visceral biopsies: the age and the illness duration's impact.

OBJECTIVE: To study the impact of age and the interval between disease diagnosis and death on the organotropism of SARS-CoV-2. METHOD: Patients underwent post-mortem biopsies from lungs, Waldeyer ring, heart, liver, kidneys and bone marrow between 2020‒2021. SARS-CoV-2 organotropism was mapped by using molecular RT-PCR analyses for SARS-CoV2 targeting the Envelope gene (E), the RNA Polymerase Gene (RdRp), and the Nucleocapsid gene (N). Statistical and linear regression analysis was performed to study the impact of age and illness duration in SARS-CoV-2 organotropism. RESULTS: We performed 158 postmortem biopsies in 21 patients, with a mean age of 76 years old. The mean interval between the diagnosis of the infection to the death was 23 days. The RNA of the SARS-CoV-2 was detected in 100% of lung biopsies, 76%‒82% of Waldeyer's ring biopsies, 55% of heart biopsies, 40% of kidney biopsies, 33% of liver and 25% of bone marrow biopsies. Patients who died before the day 9, presented extensive visceral dissemination of SARS-CoV-2 RNA. Most of the patients older than 80 years (90%) presented visceral dissemination of SARS-CoV-2 RNA, while among younger patients, only 3/11 patients presented visceral dissemination of the virus. The relationship between "age" and "illness duration" and multitropism of the virus was statistically significant (p<0.001). CONCLUSION: Disease interval and age were factors that were significantly associated with RT-PCR positive results in multiple organs. Critical COVID-19 patients have multiorganic viral dissemination in early stages. In the critical older patients, multiorganic viral dissemination is the rule.

A multicenter case-control study comparing sun exposure habits and use of photoprotection measures in patients diagnosed with different types of skin cancer.

BACKGROUND: While skin cancer awareness programs have significantly furthered public understanding about the harmful effects of the sun, there is a disparity between photoprotection knowledge and protection practices. OBJECTIVE: To compare sun exposure habits and photoprotection measures in patients diagnosed with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma versus controls. METHODS: Multicentre case-control observational study carried out by 13 Spanish dermatologists between April 2020 and August 2022. Patients diagnosed with BCC, SCC, or melanoma were considered cases. The control group consisted of individuals with no history of skin cancer. RESULTS: Of the 254 cases (56.2% female; mean age, 62.67 ± 15.65), 119 (31.2%) had BCC, 62 (16.27%) SCC, and 73 (19.1%) melanoma. The control group consisted of 127 (33.33%) individuals. Avoiding sun exposure between 12:00 and 16:00 was the most commonly used photoprotection measure (habitually/always: 63.1%), followed by the use of sunscreen (habitually/always: 58.9%). Patients with melanoma were less likely to use clothing and shade to avoid sun exposure (p < .05), whereas those with BCC and SCC reported greater use of head coverings (p = .01). BCC and SCC groups reported greater sun exposure 15 years prior, whereas controls reported greater use of sunscreen. However, at the time of this study all groups reported using SPF ≥ 21, and the majority SPF > 50. No differences were observed in photoprotection measures between people with and without a previous history of skin cancer. CONCLUSIONS: We describe differences in photoprotection measures and sun exposure patterns among patients diagnosed with different skin tumor types. Whether these differences may influence the type of tumor each developed will require further investigation.

Effect of Early Amiodarone Use on Warfarin Sensitivity, Blood Product Use, and Bleeding in Patients With a Left Ventricular Assist Device.

Data are scarce on the effect of amiodarone on warfarin sensitivity and related outcomes after placement of a left ventricular assist device (VAD). This retrospective study compared 30-day outcomes between patients on amiodarone vs no amiodarone after VAD implant. After exclusions, 220 patients received amiodarone and 136 patients did not. Compared to the no amiodarone group, the amiodarone group had a higher warfarin dosing index (0.53 [0.39, 0.79] vs 0.46 [0.34, 0.63]; P = 0.003), incidence of INR ≥ 4 (40.5 vs 23.5%; P = 0.001), incidence of bleeding (24.1 vs 14%; P = 0.021), and use of INR reversal agents (14.5 vs 2.9%, P ≤ 0.001). Amiodarone was associated with bleeding (OR, 1.95; 95% CI, 1.10-3.47; P = 0.022), but not after adjusting for age, estimated glomerular filtration rate, and platelet count (OR, 1.67; 95% CI, 0.92-3.03; P = 0.089). After VAD implant, amiodarone was associated with increased warfarin sensitivity and administration of INR reversal agents.