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La activación de BIM es esencial para la apoptosis desencadenada por el inhibidor de la tirosina quinasa (TKI) del receptor del factor de crecimiento epidérmico (EGFR) en el cáncer de pulmón de células no pequeñas (CPCNP) con mutación de EGFR. Una deleción en el intrón dos del gen BIM da como resultado la generación de isoformas empalmadas alternativamente que alteran su respuesta apoptótica a los TKI, lo que confiere a las células de NSCLC una resistencia intrínseca a estos medicamentos. Los pacientes con ambas alteraciones tienen mala evolución clínica. El estudio actual tuvo como objetivo investigar la eficacia clínica y la tolerabilidad de EGFR-TKI más bevacizumab (Bev) versus EGFR-TKI solos como tratamiento de primera línea en pacientes con NSCLC avanzado con mutaciones de EGFR y deleciones BIM (BIMdel). MATERIALES Y MÉTODOS Se realizó un análisis retrospectivo. BIMdel se detectó mediante análisis de reacción en cadena de la polimerasa y secuenciación directa de ADN. La expresión de la proteína BIM se investigó mediante inmunohistoquímica y los niveles de ARNm de BIM mediante la reacción en cadena de la polimerasa con transcriptasa inversa. Se compararon las características clínicas, la supervivencia general, la supervivencia libre de progresión (PFS), la tasa de respuesta general (ORR) y los eventos adversos relacionados con el tratamiento entre ambos grupos. RESULTADOS Se incluyeron 33 pacientes; 15 recibieron EGFR-TKI y 18 recibieron EGFR-TKI más Bev. La mediana de edad fue de 63 años, con una mayoría de pacientes mujeres reclutadas. Todos los individuos incluidos tenían una puntuación de rendimiento del Grupo Oncológico Cooperativo del Este de 2 o menos. La adición de Bev resultó en un ORR significativamente más alto (94,4 % versus 40 %, P > 0,001). La mediana de SLP fue más larga con el uso de la terapia combinada (11,12 frente a 7,87 meses; P = 0,001). La mediana de supervivencia general tendió a ser más prolongada en los inhibidores de la tirosina quinasa con EGFR más Bev (30,9 frente a 25,4 meses; P = 0,06), pero no alcanzó significación estadística. La respuesta en términos de PFS parcial y completa, así como en general, se vio afectada favorablemente. CONCLUSIÓN Los EGFR-TKI más Bev confirieron una ORR y una SLP significativamente más altas en pacientes con NSCLC avanzado con mutación de EGFR y BIMdel. Se necesitan más estudios prospectivos para validar estos hallazgos. BIM activation is essential for epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)–triggered apoptosis in EGFR-mutant non–small-cell lung cancer (NSCLC). A deletion in the intron two of the BIM gene results in generation of alternatively spliced isoforms that impairs their apoptotic response to TKIs, conferring the NSCLC cells intrinsic resistance to these medications. Patients with both alterations have poor clinical evolution. The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus bevacizumab (Bev) versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletions (BIMdel). MATERIALS AND METHODS A retrospective analysis was conducted. BIMdel was detected using polymerase chain reaction analysis and direct sequencing of DNA. BIM protein expression was investigated by immunohistochemistry, and BIM mRNA levels by reverse transcriptase-polymerase chain reaction. Clinical characteristics, overall survival, progression-free survival (PFS), overall response rate (ORR), and treatment-related adverse events were compared between both groups. RESULTS Thirty-three patients were included; 15 received EGFR-TKIs, and 18 received EGFR-TKIs plus Bev. The median age was 63 years, with a majority of recruited female patients. All included individuals had an Eastern Cooperative Oncology Group performance score of 2 or less. The addition of Bev resulted in a significantly higher ORR (94.4% v 40%, P > .001). Median PFS was longer with the use of the combination therapy (11.12 v 7.87 months; P = .001). Median overall survival tended to be longer in the EGFR-TKIs plus Bev (30.9 v 25.4 months; P = .06) but failed to reach statistical significance. Response in terms of both partial and complete as well as overall favorably affected PFS. CONCLUSION EGFR-TKIs plus Bev conferred a significantly higher ORR and PFS in advanced NSCLC patients with EGFR mutation and BIMdel. Further prospective studies are needed to validate these findings.

Predictive models have played a critical role in local, national, and international response to the COVID-19 pandemic. In the United States, health care systems and governmental agencies have relied on several models, such as the Institute for Health Metrics and Evaluation, Youyang Gu (YYG), Massachusetts Institute of Technology, and Centers for Disease Control and Prevention ensemble, to predict short- and long-term trends in disease activity. The Mayo Clinic Bayesian SIR model, recently made publicly available, has informed Mayo Clinic practice leadership at all sites across the United States and has been shared with Minnesota governmental leadership to help inform critical decisions during the past year. One key to the accuracy of the Mayo Clinic model is its ability to adapt to the constantly changing dynamics of the pandemic and uncertainties of human behavior, such as changes in the rate of contact among the population over time and by geographic location and now new virus variants. The Mayo Clinic model can also be used to forecast COVID-19 trends in different hypothetical worlds in which no vaccine is available, vaccinations are no longer being accepted from this point forward, and 75% of the population is already vaccinated. Surveys indicate that half of American adults are hesitant to receive a COVID-19 vaccine, and lack of understanding of the benefits of vaccination is an important barrier to use. The focus of this paper is to illustrate the stark contrast between these 3 scenarios and to demonstrate, mathematically, the benefit of high vaccine uptake on the future course of the pandemic.

Background Thymomas are a group of rare neoplasms of the anterior mediastinum. The objective of this study was to describe the demographics, clinical characteristics and treatment approaches in Latin America. Methods This was a retrospective multicenter cohort study including patients with histologically proven thymomas diagnosed between 1997 and 2018. Demographics, clinicopathological characteristics and therapeutic outcomes were collected locally and analyzed in a centralized manner. Results A total of 135 patients were included. Median age at diagnosis was 53 years old (19–84), 53.3% (n = 72) of patients were female and 87.4% had an ECOG performance score ranging from 0–1. A total of 47 patients (34.8%) had metastatic disease at diagnosis. Concurrent myasthenia gravis occurred in 21.5% of patients. Surgery was performed in 74 patients (54.8%), comprising 27 (20%) tumorectomies and 47 (34.8%) thymectomies. According to the Masaoka‐Koga system, overall survival (OS) at five‐years was 73.4%, 63.8% and 51%, at stages I–II, III–IVA and IVB, respectively (p = 0.005). Furthermore, patients with low lactate dehydrogenase (LDH) (≤373 IU/L) at baseline and myasthenia gravis concurrence showed significantly better OS (p = 0.001 and p = 0.008, respectively). In multivariate analysis, high LDH levels (HR 2.8 [95% confidence interval [CI]: 1.1–7.8]; p = 0.036) at baseline and not performing a surgical resection (HR 4.1 [95% CI: 1.3–12.7]; p = 0.016) were significantly associated with increased risk of death. Conclusions Our data provides the largest insight into the clinical characteristics and outcomes of patients with thymomas in Latin America. Survival in patients with thymomas continues to be very favorable, especially when subjected to adequate local control., Here, we report the largest analysis of clinical characteristics of thymomas and outcomes in Latin American patients. Out of 135 patients included in the study, 21.5% (n = 29) concurrently presented myasthenia gravis. Relapse‐free survival rates at five‐years were 58.5% for stage I–II, and 35.4% for stage III. Five‐year overall survival rates were 73.4%, 63.8% and 51%, at stages I–II, III–IVA and IVB, respectively.

Introduction and importance Gastrointestinal stromal tumors are the most frequent mesenchymal tumors of the gastrointestinal tract. Complete resection of GISTs is the only chance of cure for patients. When these tumors are located near the esophagogastric junction, the surgical risk can cause deformity or stenosis in the gastric inlet, leading to higher complications and diminishing their quality of life. In such cases, a more sophisticated and tailored approach should be used. Case presentation We present the case of a 42-year-old female; she presented to our office with a 3-year history of nausea, vomiting and abdominal distension. Two GISTs were located near the EGJ, and with a combined approach we achieved complete resection. On follow-ups, the patient is doing well. Clinical Discussion, Conclusion When diagnosis is confirmed, surgical resection must be the first choice for GISTs as complete surgical excision is the only permanent cure. The rise of endoscopic surgery has become a valuable tool and a critical element in surgery. Hybrid techniques that combine laparoscopic and endoscopic approaches can improve the patient's outcomes and provide better results., Highlights • The rise of endoscopic surgery has become a valuable tool and a critical element in surgery. • Early histologic diagnosis and surgical resection is the most reliable way to improve patients' quality of life. • The surgical decision will be what define the future of the patient and, ultimately, his life.

In the past 15 years, B cells have been rediscovered to be not merely bystanders but rather active participants in autoimmune aetiology. This has been fuelled in part by the clinical success of B cell depletion therapies (BCDTs). Originally conceived as a method of eliminating cancerous B cells, BCDTs such as those targeting CD20, CD19 and BAFF are now used to treat autoimmune diseases, including systemic lupus erythematosus and multiple sclerosis. The use of BCDTs in autoimmune disease has led to some surprises. For example, although antibody-secreting plasma cells are thought to have a negative pathogenic role in autoimmune disease, BCDT, even when it controls the disease, has limited impact on these cells and on antibody levels. In this Review, we update our understanding of B cell biology, review the results of clinical trials using BCDT in autoimmune indications, discuss hypotheses for the mechanism of action of BCDT and speculate on evolving strategies for targeting B cells beyond depletion., Examining B cell depletion therapy (BCDT), an approved treatment for B cell malignancies, in autoimmune conditions has provided key insights into basic B cell biology. In this Review, Gommerman and colleagues discuss BCDT in autoimmune conditions, highlighting diseases in which BCDT has been clinically effective and the potential and pitfalls for BCDT in autoimmune conditions in which it has not yet been efficacious.

Old patients with hepatotoxicity have been scarcely studied in idiosyncratic drug-induced liver injury (DILI) cohorts. We sought for the distinctive characteristics of DILI in older patients across age groups. A total of 882 DILI patients included in the Spanish DILI Registry (33% ≥65 years) were categorized according to age: “young” (

Highlights • Complete resection of the gastric GIST in a prompt matter must be done to avoid potentially deadly complications. • If there are the necessary tools to enhance the patient’s recovery, we shouldn’t hesitate to use them. • In emergencies, time is of essence, and surgical services must rise to the challenge., Introduction Upper gastrointestinal bleeding is one of the major manifestations of the stomach's gastrointestinal stromal tumors; when gastric GISTs bleed, they are associated with a poor prognosis and must be treated promptly to avoid dangerous complications. A worrisome side effect of the Covid-19 pandemic is the delay in surgical treatment for seriously ill patients, a rise in surgical complications due to delayed care, lack of access to the healthcare system, and patients' hesitancy to seek care due to fear of the virus. In Ecuador, where limitations were present even in the absence of a pandemic, we are yet to fully know the full extent of the damage this pandemic has caused to ourselves and our patients. Presentation of case We present the case of a 51-year-old female; she presented with upper gastrointestinal bleeding, and a gastric GIST was diagnosed. Due to the size and the symptoms, surgery was planned. Nonetheless, as Ecuador was hit hard by the Covid-19 pandemic to cope with the respiratory patients, surgeries were delayed or canceled. Our patient surgery was delayed for five months until she presented with severe gastrointestinal bleeding that required urgent action and care. Thankfully, she completely recovered. Discussion and conclusions This case is an example of the many complications we expect due to the pandemic; delay in treatment leads to troublesome complications. In these emergencies, time is of the essence, and surgical services must rise to the challenge; in a particular way, this case also proves that if there are the necessary tools to enhance the patient's recovery, we should hesitate to use them. Complete resection of the gastric GIST in a prompt matter must be done to avoid these potentially deadly complications.

Introduction: Triatoma recurva is a Trypanosoma cruzi vector whose distribution and biological development are determined by factors that may influence the transmission of trypanosomiasis to humans. Objective: To identify the potential spatial distribution of Triatoma recurve, as well as social factors determining its presence. Materials and methods: We used the MaxEnt software to construct ecological niche models while bioclimatic variables (WorldClim) were derived from the monthly values of temperature and precipitation to generate biologically significant variables. The resulting cartography was interpreted as suitable areas for T. recurva presence. Results: Our results showed that the precipitation during the driest month (Bio 14), the maximum temperature during the warmest month (Bio 5), and the altitude (Alt) and mean temperature during the driest quarter (Bio 9) determined T. recurva distribution area at a higher percentage evidencing its strong relationship with domestic and surrounding structures. Conclusions. This methodology can be used in other geographical contexts to locate potential sampling sites where these triatomines occur. Resumen Introducción. Triatoma recurva es un vector de Trypanosoma cruzi cuya existencia y desarrollo biológico están determinados por factores que pueden influir en la transmisión de la tripanosomiasis a los seres humanos. Objetivo. Determinar una posible distribución espacial de Triatoma recurva y algunos factores sociales que determinan su presencia. Materiales y métodos. El modelado de nicho ecológico se hizo con el programa MaxEnt empleando las variables bioclimáticas (WorldClim) derivadas de los valores mensuales de temperatura y precipitación para generar variables biológicamente significativas. La cartografía resultante evidenció áreas adecuadas para la presencia de T. recurva. Resultados. Los resultados indicaron que la precipitación del mes más seco (Bio 14), la temperatura máxima del mes más cálido (Bio 5), y la altitud (Alt) y la temperatura media del trimestre más seco (Bio 9), determinaron en mayor porcentaje el área de distribución de T. recurva, observándose que es una especie con una acentuada relación con las estructuras domésticas y circundantes. Conclusión. Esta metodología puede emplearse en otros contextos geográficos para localizar posibles sitios de muestreo de estos triatominos.

Background Situs inversus totalis is a rare genetic condition characterized by the transposition of organs to the opposite side of the body, consequently, clinical syndromes show an atypical clinical picture creating a challenge for the surgery team and predisposing to delays in treatment and diagnosis. Laparoscopic cholecystectomy is the gold standard for acute cholecystitis, and in patients with situs inversus, the laparoscopic technique must be modified to accommodate the patient's anatomy. Case presentation We present the case of a 55-year-old male patient without any past medical history, he presented to the emergency room with abdominal pain in his upper left quadrant. After a thorough examination, acute cholecystitis and situs inversus was diagnosed. He underwent a modified laparoscopic cholecystectomy without complications. In his postoperative period, residual choledocholithiasis was identified and ERCP was done. On follow-ups, the patient is doing well. Conclusions Although rare and technically demanding, laparoscopic cholecystectomy and ERCP in a patient with situs inversus is feasible. The altered anatomy could lead to complex procedures, therefore proper planning and careful execution of intraoperative techniques are required to treat these patients safely and effectively., Highlights • Situs inversus totalis is a rare condition characterized by the transposition of organs to the opposite side of the body. • Laparoscopic cholecystectomy is the gold standard for acute cholecystitis, even in patients situs inversus. • Proper planning and careful execution of intraoperative techniques are required to treat these patients safely.

Purpose To examine the evidence on the cost-effectiveness of implementing pharmacogenomics (PGx) in cardiovascular disease (CVD) care. Methods We conducted a systematic review using multiple databases from inception to 2018. The titles and abstracts of cost-effectiveness studies on PGx-guided treatment in CVD care were screened, and full texts were extracted. Results We screened 909 studies and included 46 to synthesize. Acute coronary syndrome and atrial fibrillation were the predominantly studied conditions (59%). Most studies (78%) examined warfarin–CYP2C9/VKORC1 or clopidogrel–CYP2C19. A payer’s perspective was commonly used (39%) for cost calculations, and most studies (46%) were US-based. The majority (67%) of the studies found PGx testing to be cost-effective in CVD care, but cost-effectiveness varied across drugs and conditions. Two studies examined PGx panel testing, of which one examined pre-emptive testing strategies. Conclusion We found mixed evidence on the cost-effectiveness of PGx in CVD care. Supportive evidence exists for clopidogrel–CYP2C19 and warfarin–CYP2C9/VKORC1, but evidence is limited in other drug–gene combinations. Gaps persist, including unclear explanation of perspective and cost inputs, underreporting of study design elements critical to economic evaluations, and limited examination of PGx panel and pre-emptive testing for their cost-effectiveness. This review identifies the need for further research on economic evaluations of PGx implementation.

Proper health management is essential for productivity in duck farming. However, there is limited information on the effect of management conditions on rates of metabolic problems and parasitic infections in anatids. We evaluated the rates of metabolic syndromes and gastrointestinal parasite involvement in Muscovy ducks up to 12 weeks of age, under 3 management conditions: backyard, organized, and organized with probiotics. Individuals under organized management developed 2 metabolic problems: ascites, which was rare (3.5%), fatal, and affected both males and females, and angel wing syndrome, which was more frequent (10.6%), has low impact on general health, and only affected males. The treatments do not have a significant effect on the development of ascites, but only individuals in controlled conditions presented this syndrome, and due to its low prevalence, further studies with a larger sample size are required. The risk of angel wing syndrome increased significantly with probiotic supplementation. Regarding to parasitic infection, the improvement of sanitary management and the use of probiotics supplementation reduced the occurrence of coccidiosis. Similarly organized management with probiotic supplementation showed a protective effect on helminthiasis by reducing the frequency of Heterakis gallinarum and greatly reducing the helminth egg load. Coccidiosis and helminthiasis infections were not significantly correlated with the final weight of the ducks. Therefore, organized management and the use of probiotics seems to reduce the impact of parasitic infection, although it increases the risk of developing metabolic syndrome.

Mortality in pregnancy due to coronavirus disease 2019 (COVID-19) is a current health priority in developing countries. Identification of clinical and sociodemographic risk factors related to mortality in pregnant women with COVID-19 could guide public policy and encourage such women to accept vaccination. We aimed to evaluate the association of comorbidities and socioeconomic determinants with COVID-19-related mortality and severe disease in pregnant women in Mexico.This is an ongoing nationwide prospective cohort study that includes all pregnant women with a positive reverse-transcription quantitative polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Mexican National Registry of Coronavirus. The primary outcome was maternal death due to COVID-19. The association of comorbidities and socioeconomic characteristics with maternal death was explored using a log-binomial regression model adjusted for possible confounders.There were 176 (1.35%) maternal deaths due to COVID-19 among 13 062 consecutive SARS-CoV-2-positive pregnant women. Maternal age, as a continuous (adjusted relative risk (aRR), 1.08 (95% CI, 1.05-1.10)) or categorical variable, was associated with maternal death due to COVID-19; women aged 35-39 years (aRR, 3.16 (95% CI, 2.34-4.26)) or 40 years or older (aRR, 4.07 (95% CI, 2.65-6.25)) had a higher risk for mortality, as compared with those aged 35 years. Other clinical risk factors associated with maternal mortality were pre-existing diabetes (aRR, 2.66 (95% CI, 1.65-4.27)), chronic hypertension (aRR, 1.75 (95% CI, 1.02-3.00)) and obesity (aRR, 2.15 (95% CI, 1.46-3.17)). Very high social vulnerability (aRR, 1.88 (95% CI, 1.26-2.80)) and high social vulnerability (aRR, 1.49 (95% CI, 1.04-2.13)) were associated with an increased risk of maternal mortality, while very low social vulnerability was associated with a reduced risk (aRR, 0.47 (95% CI, 0.30-0.73)). Being poor or extremely poor were also risk factors for maternal mortality (aRR, 1.53 (95% CI, 1.09-2.15) and aRR, 1.83 (95% CI, 1.32-2.53), respectively).This study, which comprises the largest prospective consecutive cohort of pregnant women with COVID-19 to date, has confirmed that advanced maternal age, pre-existing diabetes, chronic hypertension, obesity, high social vulnerability and low socioeconomic status are risk factors for COVID-19-related maternal mortality. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Appendix-associated hernias are extremely rare. They have been described sporadically in the literature, mostly as inguinal hernias. Appendix-associated incisional hernias are even more unusual. High clinical awareness is needed as complications can arise if misdiagnosis or delay occurs. We present an 80-year-old man with acute appendicitis in an incisional hernia. After successful surgery, the patient made a full recovery.

Helicobacter pylori (H. pylori) eradication using standard triple therapy (STT) with proton pump inhibitors (PPI), amoxicillin and clarithromycin (CLA) has been the standard in Latin America. However, CLA resistance is a rising problem affecting eradication rates. Genetic polymorphisms of CYP2C19, a PPI metabolizer may also affect eradication. The primary aims of this study were to evaluate the effect of clarithromycin resistance on H. pylori eradication in a population from Santiago, and to establish the pooled clarithromycin resistance in Santiago, Chile. Symptomatic adult patients attending a tertiary hospital in Santiago were recruited for this study. CLA resistance and the polymorphisms of CYP2C19 were determined on DNA extracted from gastric biopsies, using PCR. The STT was indicated for 14 days and eradication was determined by a urea breath test 4–6 weeks after therapy. A meta-analysis of CLA resistance studies among adult residents in Santiago was performed. Seventy-three out of 121 consecutive patients had positive rapid urease test (RUT) and received STT. Sixty-nine patients (95%) completed the study. The H. pylori eradication rate was 63% and the prevalence of CLA resistance was 26%. According to the CYP2C19 polymorphisms, 79.5% of the RUT-positive patients were extensive metabolizers. Multivariable analyses showed that only CLA resistance was significantly and inversely associated with failure of eradication (OR: 0.13; 95% confidence interval [95% CI], 0.04–0.49). A meta-analysis of two previous studies and our sample set (combined n = 194) yielded to a pooled prevalence of CLA resistance of 31.3% (95% CI 23.9–38.7). Our study shows that CLA resistance is associated with failure of H. pylori eradication. Given the high pooled prevalence of CLA resistance, consideration of CLA free therapies in Santiago is warranted. We could recommend bismuth quadruple therapy or high-dose dual therapy, according to bismuth availability. Further studies need to evaluate the best therapy.

Experimental autoimmune encephalomyelitis (EAE) is the most common model of multiple sclerosis (MS). This model has been instrumental in understanding the events that lead to the initiation of central nervous system (CNS) autoimmunity. Though EAE has been an effective screening tool for identifying novel therapies for relapsing-remitting MS, it has proven to be less successful in identifying therapies for progressive forms of this disease. Though axon injury occurs in EAE, it is rapid and acute, making it difficult to intervene for the purpose of evaluating neuroprotective therapies. Here, we describe a variant of spontaneous EAE in the 2D2 T cell receptor transgenic mouse (2D2(+) mouse) that presents with hind-limb clasping upon tail suspension and is associated with T cell-mediated inflammation in the posterior spinal cord and spinal nerve roots. Due to the mild nature of clinical signs in this model, we were able to maintain cohorts of mice into middle age. Over 9 mo, these mice exhibited a relapsing-remitting course of hind-limb clasping with the development of progressive motor deficits. Using a combined approach of ex vivo magnetic resonance (MR) imaging and histopathological analysis, we observed neurological progression to associate with spinal cord atrophy, synapse degradation, and neuron loss in the gray matter, as well as ongoing axon injury in the white matter of the spinal cord. These findings suggest that mild EAE coupled with natural aging may be a solution to better modeling the neurodegenerative processes seen in MS.

Convergent beam radiotherapy, or CBRT, currently under development is based on the adaptation of a linear accelerator (linac) to a device which allows to dynamically curve the original trajectory of the electron beam so that it impacts upon a target. This produces a photon beam via Bremsstrahlung which converges on a predetermined focus point (isocenter). Adaptation of the RTHC device is only possible if it is sufficiently compact, as the device must be placed between the linac head exit and the gurney. This requires that new magnetic deflection devices be developed. This paper describes the theoretical and experimental development of controlled-deflection electron beam systems (at energies in MeV ranges) generated in a dual linear accelerator waveguide. A device which follows RTHC geometry is adapted for the system, using new magnetic deflector designs based on permanent neodymium magnets which reach magnetic field intensities in the order of Tesla. The methodology that was developed includes calculations of the radii of curvature with relativistic considerations for mono- and poly-energetic electrons. Deflection angles were calculated based on this theoretical foundation, using a program developed in MatLab® which shows the trajectory of electrons both under ideal conditions (uniform magnetic field) and real conditions (magnetic field defined through intensity distribution). Monte Carlo simulation subroutines were implemented in order to estimate the spectrum of electrons issuing from the linac as well as to directly determine the electron beam trajectory with magnetic deflectors present. Theoretical and simulated results were compared to experiments performed with a clinical linear accelerator, demonstrating correspondence between different methodologies and confirming the ability to achieve electron beam deflection levels necessary for implementation of convergent beam radiotherapy device.

Introduction and aim The MELD score has been established as an efficient and rigorous prioritization system for liver transplant (LT). Our study aimed to evaluate the effectiveness of the MELD score as a system for prioritization for LT, in terms of decreasing the dropout rate in the waiting list and maintaining an adequate survival post-LT in Chile. Materials and methods We analyzed the Chilean Public Health Institute liver transplant registry of candidates listed from October 15th 2011 to December 31st 2014. We included adult candidates (>15 years old) listed for elective cadaveric LT with a MELD score of 15 or higher. Statistical analysis included survival curves (Kaplan–Meier), log-rank statistics and multivariate logistic regression. Results 420 candidates were analyzed. Mean age was 53.6 ± 11.8 years, and 244 were men (58%). Causes of LT included: Liver cirrhosis without exceptions (HC) 177 (66.4%); hepatocellular carcinoma (HCC) 111 (26.4%); cirrhosis with non-HCC exceptions 102 (24.3%) and non-cirrhotic candidates 30 (7.2%). LT rate was 43.2%. The dropout rate was 37.6% at 1-year. Even though the LT rate was higher, the annual dropout rate was significantly higher in cirrhotic candidates (without exceptions) compared with cirrhotics with HCC, and non-HCC exceptions plus non-cirrhotic candidates (47.9%; 37.2% and 24.2%, respectively, with p = 0.004). Post-LT survival was 84% per year, with no significant differences between the three groups (p = 0.95). Conclusion Prioritization for LT using the MELD score system has not decreased the dropout rate in Chile (persistent low donor's rate). Exceptions generate inequities in dropout rate, disadvantaging patients without exceptions.

Importance: This three-part study characterizes the widespread implementation of telehealth during the first year of the COVID-19 pandemic, giving us insight into the role of telehealth as we enter a stage of “new normal” healthcare delivery in the U.S. Objective: The COVID-19 Telehealth Impact Study was designed to describe the natural experiment of telehealth adoption during the pandemic. Using a large claims data stream and surveys of providers and patients, we studied telehealth in all 50 states to inform healthcare leaders. Design, Setting, Participants: In March 2020, the MITRE Corporation and Mayo Clinic founded the COVID-19 Healthcare Coalition (C19HCC), to respond to the pandemic. We report trends using a dataset of over 2 billion healthcare claims covering over 50% of private insurance activity in the U.S. (January 2019-December 2020), along with key elements from our provider survey (July-August 2020) and patient survey (November 2020 - February 2021). Main Outcomes and Measures: There was rapid and widespread adoption of telehealth in Spring 2020 with over 12 million telehealth claims in April 2020, accounting for 49.4% of total health care claims. Providers and patients expressed high levels of satisfaction with telehealth. 75% of providers indicated that telehealth enabled them to provide quality care. 84% of patients agreed that quality of their telehealth visit was good. Results: Peak levels of telehealth use varied widely among states ranging from 74.9% in Massachusetts to 25.4% in Mississippi. Every clinical discipline saw a steep rise with the largest claims volume in behavioral health. Provision of care by out-of-state provider was common at 6.5% (October-December 2020). Providers reported multiple modalities of telehealth care delivery. 74% of patients indicated they will use telehealth services in the future. Conclusions and Relevance: Innovation shown by providers and patients during this period of rapid telehealth expansion constitutes a great natural experiment in care delivery with evidence supporting widespread clinical adoption and satisfaction on the part of both patients and clinicians. The authors encourage continued broad access to telehealth over the next 12 months to allow telehealth best practices to emerge, creating a more effective and resilient system of care delivery.

Background: Amplification of EGFR and its active mutant EGFRvIII are common in glioblastoma (GB). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors (TKIs) or antibodies has shown limited efficacy. To improve the likelihood of effectiveness, we targeted adult patients with recurrent GB enriched for simultaneous EGFR amplification and EGFRvIII mutation, with osimertinib/bevacizumab at doses described for non-small cell lung cancer (NSCLC). Methods: We retrospectively explored whether previously described EGFRvIII mutation in association with EGFR gene amplification could predict response to osimertinib/bevacizumab combination in a subset of 15 patients treated at recurrence. The resistance pattern in a subgroup of subjects is described using a commercial NGS panel in liquid biopsy.Results: There were ten males (66.7%), and the median patient’s age was 56 years (range 38-70 years). After their initial diagnosis, 12 patients underwent partial (26.7%) or total resection (53.3%). Subsequently, all cases received IMRT and concurrent and adjuvant temozolomide (TMZ; the median number of cycles 9, range 6-12). The median follow-up after recurrence was 17.1 months (95% CI 12.3-22.6). All patients received osimertinib/bevacizumab as a second-line intervention with a median progression-free survival (PFS) of 5.1 months (95% CI 2.8-7.3) and overall survival (OS) of 9.0 months (95% CI 3.9-14.0). The PFS6 was 46.7%, and the overall response rate (ORR) was 13.3%. After exposure to the osimertinib/bevacizumab combination, the main secondary alterations were MET amplification, STAT3, IGF1R, PTEN, and PDGFR.Conclusions: While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR amplification plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful benefit. The findings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, findings that contribute to the understanding and targeting in a stepwise rational this pathway.

Resume Introduccion Las ataxias (AT) y paraparesias espasticas hereditarias (PEH) son sindromes neurodegenerativos raros. Nos proponemos conocer la prevalencia de las AT y PEH en Espana en 2019. Pacientes y metodos Estudio transversal, multicentrico, descriptivo y retrospectivo de los pacientes con AT y PEH, desde marzo de 2018 a diciembre de 2019 en toda Espana. Resultados Se obtuvo informacion de 1.809 pacientes procedentes de 11 Comunidades Autonomas, de 47 neurologos o genetistas. Edad media: 53,64 anos ± 20,51 desviacion estandar (DE); 920 varones (50,8%), 889 mujeres (49,2%). En 920 pacientes (47,6%) no se conoce el defecto genetico. Por patologias, 1.371 pacientes (70,9%) diagnosticados de AT, 562 diagnosticados de PEH (29,1%). La prevalencia estimada de AT es 5,48/100.000 habitantes, y la de PEH es 2,24 casos/100.000 habitantes. La AT dominante mas frecuente es la SCA3. La AT recesiva mas frecuente es la ataxia de Friedreich (FRDA). La PEH dominante mas frecuente es la SPG4, y la PEH recesiva mas frecuente es la SPG7. Conclusiones La prevalencia estimada de AT y PEH en nuestra serie es de 7,73 casos/100.000 habitantes. Estas frecuencias son similares a las del resto del mundo. En el 47,6% no se ha conseguido un diagnostico genetico. A pesar de las limitaciones, este estudio puede contribuir a estimar los recursos, visibilizar estas enfermedades, detectar las mutaciones mas frecuentes para hacer los screenings por comunidades, y favorecer los ensayos clinicos.

The implementation in Mexico of the first integrated service in nuclear medicine in the Mexican Peninsula, including Vitalmex's first ABT BG-75 Self-Shielding Cyclotron service in the region, has presented great challenges in all stages of development. The following is a brief but complete summary. The most remarkable challenges, implementing the project are the processes of: project and business planning, construction site planning and licensing, along with the advice of a multidisciplinary professional expert team, this project has achieved the final stage of implementation, and has become fully operational.

Industry 4.0 is facing a fast–development in its technologies, automatizing and restructuring processes in order to make them data–driven. However, its uses are not exclusive for the industry as its name suggests, since it can be extended to health sector. In the next decade, the Digital Twin (a digital replica of a physical asset) is going to face a spread into mainstream market due to its potential applications in the healthcare sector, such as a 24/7 monitoring of the evolution of cancer and its treatment, a heart based on cloud–computing, an even receive medical treatment that adapts to every person. But before seeing this as a reality, there are several obstacles that the researchers need to overcome for the proposed Digital Twins to reach its full–potential.

Hospital San Borja Arriaran, Chile Upon the publication of the LACC study, increasing evidence has emerged regarding the superiority of open versus minimally invasive surgery (MIS) in the treatment of cervical cancer. Introduction to report and compare the surgical results among woman undergoing surgery for cervical cancer with open versus MIS in San Borja Arriaran Hospital. Methods retrospective analysis, involving patients with stage IA1 (lymphovascular invasion), IA2, or IB1 cervical cancer undergoing open or MIS between 2015 to 2019. Data obtained from oncology committee registry. Analysis of demographic, histological and surgical variables. Data analyzed using the Chi2, Student’s t, and Fischer test with a 95% confidence interval and a P value of Results 42 patients analyzed, 20 in the open surgery and 22 MIS group. The mean age (46.2 ± 2.9 v/s 46.9 ± 2.37; P = 0.49). Surgical result, the number of nodes obtained in open surgery was significantly higher than in the MIS technique (27.4 ± 2.6 v/s 20.3 ± 2.04; P = 0.038), with no differences in the number of positive nodes, compromise of surgical margins, parametrial compromise, tumor size or in lymphovascular invasion. There was no significant difference in adjuvance treatment. Due to the short follow-up period in the open surgery group, no recurrence or survival analysis was performed. Conclusion Despite the small sample size, a significant difference in known variables of the oncological result, such as the number of lymph nodes obtained. This provides a first approach regarding oncological outcome. Survival analysis will be evaluated in future analysis.

Saliva is an alternative biofluid to serum for detecting and monitoring IgG to SARS-CoV-2 spike and RBD antigens in COVID-19., While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the antibody response in saliva and its relationship to systemic antibody levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor-binding domain (RBD) in serum and saliva of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3–115 days post-symptom onset (PSO), compared to negative controls. Anti-SARS-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16–30 days PSO. Longitudinal analysis revealed that anti-SARS-CoV-2 IgA and IgM antibodies rapidly decayed, while IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that serum and saliva IgG antibodies to SARS-CoV-2 are maintained in the majority of COVID-19 patients for at least 3 months PSO. IgG responses in saliva may serve as a surrogate measure of systemic immunity to SARS-CoV-2 based on their correlation with serum IgG responses.

The design of a robotic prosthetic hand, based on the control of myoelectric signals is a multidisciplinary task involving areas such as medicine, mechanics and electronics. The implementation of a robotic prosthetic hand could help restore the daily activities of people with amputation, improving their self-esteem and quality of life. This article is mainly focus on the development of a transradial prosthetic hand motion control system. The system uses myoelectric signals processing, for a series of preset gestures that are detected in real-time. Experimental tests of pattern recognition show that the signals have variable amplitudes and frequencies, for instance, the signal strength and the phenomenon of muscle fatigue vary depending on the subject. Hand movement recognition is achieved using EMG feature extraction technique such as Average Amplitude Change, Root Mean Square, Mean Absolute Value, among others. The actual results show that the implemented control system can be effective in performing six gestures or movements on a prototype robotic hand prosthesis.

While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the mucosal immune response and its relationship to systemic antibody levels. Since SARS-CoV-2 initially replicates in the upper airway, the antibody response in the oral cavity is likely an important parameter that influences the course of infection, but how it correlates to the antibody response in serum is not known. Here, we profile by enzyme linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor binding domain (RBD) in serum (n=496) and saliva (n=90) of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3–115 days post-symptom onset (PSO), compared to negative controls. Anti-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16–30 days PSO. Whereas anti-CoV-2 IgA and IgM antibodies rapidly decayed, IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. In a surrogate neutralization ELISA (snELISA), neutralization activity peaks by 31–45 days PSO and slowly declines, though a clear drop is detected at the last blood draw (105–115 days PSO). Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that systemic and mucosal humoral IgG antibodies are maintained in the majority of COVID-19 patients for at least 3 months PSO. Based on their correlation with each other, IgG responses in saliva may serve as a surrogate measure of systemic immunity.One Sentence SummaryIn this manuscript, we report evidence for sustained SARS-CoV-2-specific IgG and transient IgA and IgM responses both at the site of infection (mucosae) and systemically in COVID-19 patients over 3 months and suggest that saliva could be used as an alternative biofluid for monitoring IgG to SARS-CoV-2 spike and RBD antigens.

Surgery in loss of domain hernia can result in high morbidity and mortality. Chronic muscle retraction along with the reduced volume of the peritoneal cavity can lead to potential problems such as abdominal compartment syndrome, ventilatory restriction and an elevated risk of hernia recurrence. This is affected even further by obesity; a high body mass index is strongly associated with poor outcomes after ventral hernia repair. In these individuals, preoperative preparation is vital as it can reduce surgical risks and improve patients’ outcomes. There are many strategies available. Nonetheless, an individualized case approach by a multidisciplinary team is crucial to accurately treat this troublesome pathology. We present the case of a 41-year-old obese patient with a loss of domain ventral hernia. As he had a drug addiction and several psychologic difficulties, a tailored approach was needed to successfully treat the hernia. After preoperative preparation and surgery, the patient underwent full recovery.

Gastric neuroendocrine tumors (NET) are rare tumors with a broad spectrum of symptoms; in recent years, the number of cases has increased due to the growing number of upper endoscopies. Obesity has become a worldwide epidemic and bariatric surgery one of the most effective therapies to control this illness. As more surgeries are performed, the number of histopathological samples will also increase. Incidental discoveries on these histopathological specimens are difficult situations to encounter as medical plans, prognosis and therapy will have to change accordingly. We present the case of a 43-year-old patient who underwent a laparoscopic gastric sleeve. On pathology, a NET was detected, and additional surgery was required. On follow-ups, the patient is doing well.

Highlights • HIV and TB, are a lethal combination in resource-limited countries without adequate follow up. • Intestinal perforation due to TB in an HIV patient is a rare complication and depends on the immune status of the host. • If non-compliance is anticipated when treating TB and HIV, fully supervised therapy should be initiated., Background Coinfection involving Human Immunodeficiency Virus (HIV) and Mycobacterium tuberculosis are particularly problematic in resource-limited countries. When both pathogens are present, they accelerate the deterioration of immunological functions in the patient leading to premature death if left untreated. A close follow-up is essential in these high-risk subjects, as inadequate healthcare usually leads to further complications. Case presentation We present a case of a 26-year-old woman with a past medical history of HIV infection. Nonetheless, she lacked adequate treatment and did not have sufficient medical supervision to control her disease. She presented to the emergency department with an acute abdomen and multiple bowel perforations that demanded intestinal resection. TB/HIV coinfection was detected and a final diagnosis of bowel perforation due to TB was established. Conclusions A high index of suspicion is essential when approaching patients with HIV and acute abdominal pain. A thorough clinical history examination including past medical history, HIV/AIDS (Acquired immunodeficiency syndrome) progression status, and a careful clinical exam are paramount to an early diagnosis and timely medical treatment.

SARS-CoV-2 is a novel respiratory virus that has quickly spread across the globe. The virus uses a protein called Spike and its associated receptor binding domain (RBD) to interact with angiotensin converting enzyme-2 (ACE-2) on the surface of epithelial cells in the respiratory tract. Although a definite correlate of protection against COVID-19 has yet to emerge, many studies have quantified anti-Spike and anti-RBD IgG antibody (Ab) levels, as well as neutralizing Ab in the blood to ascertain immunity. This approach misses out on Ab that are produced in the upper respiratory tract (URT) mucosa – the site of viral encounter. Whether intramuscularly (i.m.) administered COVID-19 vaccines can promote immunity in the mucosa is not well understood. We recently completed a study where we showed that anti-Spike/RBD IgG could be detected in the saliva following i.m. vaccination with either two doses of mRNA vaccines (Pfizer or Moderna) or with a heterologous dosing of Astra Zeneca followed by an mRNA vaccine. Administration of a second dose of mRNA boosted the IgG but not IgA response, with only 30% of participants remaining positive for IgA at this timepoint. At 6 months post-dose 2, these participants had diminished anti-Spike/RBD IgG levels, although secretory component associated anti-Spike Ab were more stable. Examining two prospective cohorts we found that participants who experienced breakthrough infections with SARS-CoV-2 had lower levels of vaccine-induced serum anti-Spike/RBD IgA at 2–4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups. These data suggest that COVID-19 vaccines that elicit a durable IgA response may have utility in preventing infection. We received funding support from CIHR (Fund #15992), a COVID-19 Immunity Task force grant, an “Ontario Together” province of Ontario grant, a CIHR team grant to CoVARR-Net, a Donation from the Royal Bank of Canada (RBC) and a donation from the Krembil Foundation to the Sinai Health System Foundation.

Identifying high-value health care delivery for patients with clinically complex and high-cost conditions is important for future reimbursement models.The objective of this study was to assess the Medicare reimbursement savings of an established palliative care homebound program.This is a retrospective cohort study involving 50 participants enrolled in a palliative care homebound program and 95 propensity-matched control patients at Mayo Clinic in Rochester, Minnesota, between September 1, 2012, and March 31, 2013. Total Medicare reimbursement was compared in the year before enrollment with the year after enrollment for participants and controls.No significant differences were observed in demographic characteristics or prognostic indices between the two groups. Total Medicare reimbursement per program participant the year before program enrollment was $16,429 compared with $14,427 per control patient, resulting in $2004 higher charges per program patient. In 12 months after program enrollment, mean annual payment was $5783 per patient among participants and $22,031 per patient among the matched controls. In the second year, the intervention group had a decrease of $10,646 per patient; the control group had an increase of $7604 per patient. The difference between the participant group and control group was statistically significant (P 0.001) and favored the palliative care homebound program enrollees by $18,251 (95% CI, $11,268-$25,234).The Mayo Clinic Palliative Care Homebound Program reduced annual Medicare expenditures by $18,251 per program participant compared with matched control patients. This supports the role of home-based palliative medicine in delivering high-value care to high-risk older adults.

Conventional radiotherapy is mainly applied by linear accelerators. Although linear accelerators provide dual (electron/photon) radiation beam modalities, both of them are intrinsically produced by a megavoltage electron current. Modern radiotherapy treatment techniques are based on suitable devices inserted or attached to conventional linear accelerators. Thus, precise control of delivered beam becomes a main key issue. This work presents an integral description of electron beam deflection control as required for novel radiotherapy technique based on convergent photon beam production. Theoretical and Monte Carlo approaches were initially used for designing and optimizing device´s components. Then, dedicated instrumentation was developed for experimental verification of electron beam deflection due to the designed magnets. Both Monte Carlo simulations and experimental results support the reliability of electrodynamics models used to predict megavoltage electron beam control.

College students without ADHD may feign symptoms of ADHD to gain access to stimulant medications and academic accommodations. Unfortunately, research has shown that it can be difficult to discriminate malingered from genuine ADHD symptomatology, especially when evaluations are based only on self-report questionnaires. The present study investigated whether nonclinical college students given no additional information could feign ADHD as successfully as those who were coached on symptoms of the disorder. Similar to Jasinski et al. (2011) and other research on feigned ADHD, a battery of neuropsychological, performance validity, and self-report tests was administered. Undergraduates with no history of ADHD or other psychiatric disorders were randomly assigned to 1 of 2 simulator groups: a coached group that was given information about ADHD symptoms, or a noncoached group that was given no such information. Both simulator groups were asked to feign ADHD. Their performance was compared to a genuine ADHD group and a nonclinical group asked to respond honestly. Self-report, neuropsychological, and performance validity test data are discussed in the context of the effect of coaching and its implications for ADHD evaluations. Symptom coaching did not have a significant effect on feigning success. Performance validity tests were moderately effective at detecting feigned ADHD. (PsycINFO Database Record

The present study was a 4-week randomized trial to assess the efficacy and safety of sitagliptin, a dipeptidyl-peptidase-4 inhibitor, in persistent or recurring type 2 diabetes after Roux-en-Y gastric bypass surgery (RYGB). Participants (n = 32) completed a mixed meal test (MMT) and self-monitoring of plasma glucose (SMPG) before and 4 weeks after randomization to either sitagliptin 100 mg daily or placebo daily. Questionnaires were administered to assess gastrointestinal discomfort. Outcome variables were glucose, active glucagon-like peptide-1 and β-cell function during the MMT, and glucose levels during SMPG. Age (56.3 ± 8.2 years), body mass index (34.4 ± 6.7 kg/m2 ), glycated haemoglobin (7.21 ± 0.77%), diabetes duration (12.9 ± 10.0 years), years since RYGB (5.6 ± 3.3 years) and β-cell function did not differ between the placebo and sitagliptin groups at pre-intervention. Sitagliptin was well tolerated, decreased postprandial glucose levels during the MMT (from 8.31 ± 1.92 mmol/L to 7.67 ± 1.59 mmol/L, P = 0.03) and mean SMPG levels, but had no effect on β-cell function. In patients with diabetes and mild hyperglycemia after RYGB, a short course of sitagliptin provided a small but significant glucose-lowering effect, with no identified improvement in β-cell function.

The growth of the surgical industry and the development of surgical techniques have allowed us to achieve better results for patients. Laparoscopic staplers are a crucial tool in laparoscopic surgery, and despite their proven safety and efficiency, they have been associated with technical and mechanical failures on rare occasions. Adequate knowledge of the surgical instruments is critical to accomplishing optimal results and to adequately treating these rare malfunctions and their consequences. We present a case of a surgical stapler malfunction due to a titanium clip during laparoscopic sleeve gastrectomy. This mechanical failure produced a complication that was adequately resolved, and the patient completely recovered. Our brief communication shows that errors during sleeve gastrectomy can occur, and that precise surgical skills along with a close follow-up are crucial to improve the patient outcome when these rare complications arise.

Background Readmissions after aortic dissection (AD) admission are not well described. Using state-based administrative claims data, we sought to define readmission rates after AD and to identify factors associated with them. Methods State Inpatient Databases for Florida (2007-2012) and New York (2008-2012) were queried for AD index admissions. Admissions were stratified by initial treatment strategy: type A open surgery repair (TAOR), type B open surgery repair (TBOR), thoracic endovascular aortic repair (TEVAR), or medical management (MM). All-cause readmission rates were calculated at 30 days, 90 days, and 2 years. Logistic regression was used to identify factors associated with readmission at each time point for all type A admissions (TAOR) or type B admissions (TBOR, TEVAR, MM). Results We identified 4670 patients with an AD index admission. Treatment was with TAOR in 1031 (22%), TBOR in 761 (16%), TEVAR in 412 (9%), and MM in 2466 (53%). Patients were predominantly male (59.4%) and white (61.9%), with a median age of 66 years. Overall mortality during AD index admission was 14.8% (TAOR, 15.8%; TBOR, 17.1%; TEVAR, 9.0%; MM, 14.7%; P = .002 across all groups). All-cause readmission rates were similar across treatment groups at 30 days (9.6%-11%; P = .56), 90 days (15.2%-20%; P = .26), and 2 years (49.2%-54.4%; P = .15). Higher income quartile (vs lowest) was associated with lower odds of early readmission (at 30 days and 90 days) after type B admissions but not after type A admissions. At 2 years, self-pay (vs Medicare) was associated with lower odds of readmission in both type A and type B admissions, whereas higher comorbidity count and black race (vs white) were associated with higher odds of readmission. TEVAR (vs MM) was also associated with higher odds of readmission. Cardiovascular disease was the most common cause for readmission at all time points. Emergency department readmission counts were highest after MM admissions, and ambulatory surgical admissions were highest after TBOR. Both TEVAR and MM initial costs were lower than TAOR and TBOR costs, but at 2 years, costs remained significantly lower only for MM. Conclusions In-state 30-day, 90-day, and 2-year readmission rates after AD were not associated with initial treatment type. Two-year readmissions are common. Strategies to target socioeconomic, race, and geographic factors may reduce variations in readmission patterns after AD admission.

Multiple sclerosis (MS) is characterized by demyelinated and inflammatory lesions in the brain and spinal cord that are highly variable in terms of cellular content. Here, we used imaging mass cytometry (IMC) to enable the simultaneous imaging of 15+ proteins within staged MS lesions. To test the potential for IMC to discriminate between different types of lesions, we selected a case with severe rebound MS disease activity after natalizumab cessation. With post-acquisition analysis pipelines we were able to: (1) Discriminate demyelinating macrophages from the resident microglial pool; (2) Determine which types of lymphocytes reside closest to blood vessels; (3) Identify multiple subsets of T and B cells, and (4) Ascertain dynamics of T cell phenotypes vis-à-vis lesion type and location. We propose that IMC will enable a comprehensive analysis of single-cell phenotypes, their functional states and cell-cell interactions in relation to lesion morphometry and demyelinating activity in MS patients., eLife digest It takes an army of immune cells to defend the body against infection. But sometimes the body’s immune system mistakenly attacks its own cells and chronic inflammatory conditions develop. In multiple sclerosis – also known as “MS” – a horde of immune cells infiltrate the brain and spinal cord, forming lesions which strip nerve cells of their insultation, a protective fatty material called myelin. Nerve cells become damaged, scarred and exposed, and this interferes with messages between the brain and other parts of the body. Advanced imaging techniques have revolutionized the diagnosis of multiple sclerosis by capturing lesions as they develop in the brain and spinal cord. Researchers have also focused their efforts on understanding how immune cells activated in the blood stream invade the central nervous system. To better understand how a mistaken immune response leads to nerve damage in multiple sclerosis, a forensic examination of which immune cells accumulate in brain tissue to form lesions is needed. Standard techniques for analyzing whole tissue samples are however limited by design, capable of detecting only a few cell markers in one section of tissue. Ramaglia et al. have now validated a new imaging technique for looking at an array of cell types in brain tissue in a single sample. The technique – called imaging mass cytometry (or IMC for short) – was used to look at post-mortem brain tissue from a multiple sclerosis patient with an acute form of the illness. The tissue examined had multiple sclerosis lesions present. Different types of immune cells were simultaneously identified and characterized using a panel of antibodies which recognize the signature proteins each immune cell makes when active. The state of the underlying myelin content of the tissue was also characterized. The imaging approach could distinguish between the immune cells of the brain (known as resident microglia) and a type of white blood cell summoned as part of the immune response (infiltrating macrophages). The analysis showed that, in the particular patient examined, microglia are abundant in active lesions in multiple sclerosis; also, different subsets of white blood cells were detected. Measuring how far different immune cells had migrated from nearby blood vessels added insights as to how immune cells move through the brain and which cells may have arrived first. Altogether, Ramaglia et al. have shown that IMC can be used as a discovery tool to gain a deeper understanding of multiple sclerosis lesions and immune cells active in the inflamed brain. Further work will apply this now validated imaging approach to large cohorts of multiple sclerosis patients.

El cáncer de pulmón de células no pequeñas (CPCNP) es responsable del 85% de los casos de cáncer de pulmón (CP). Por lo tanto, se desarrollaron inhibidores de la tirosina quinasa del receptor del factor de crecimiento epitelial (EGFR-TKI) y han mejorado los resultados clínicos de los pacientes con NSCLC con mutación en EGFR. Sin embargo, estos pacientes inevitablemente desarrollan resistencia a esos medicamentos. Algunos de los mecanismos de resistencia son la mutación T790M y la transformación de adenocarcinoma de pulmón a cáncer de pulmón de células pequeñas (CPCP). Por el contrario, solo unos pocos casos de NSCLC con mutación en EGFR informaron una supervivencia a largo plazo de más de 5 años. El presente caso se trata de una mujer de 53 años de edad, nunca fumadora, de origen hispano, que debutó con tos seca sin disnea y dolor intermitente de alta intensidad en hemitórax izquierdo y columna. Fue diagnosticada con CPNM metastásico e inició tratamiento con doble quimioterapia basada en platino. Después de que se identificara una mutación de EGFR, el paciente comenzó la terapia dirigida. A lo largo de los años, el tratamiento se intensificó debido a la resistencia que desarrolló contra los inhibidores de la tirosina quinasa. Se informó la mutación de resistencia T790M y persistió en el tiempo; además años después se constató la aparición de la mutación TP53R213. Se administró tratamiento con osimertinib con éxito durante 10 meses y posteriormente se constató progresión meníngea. Al mismo tiempo, se confirmó la transdiferenciación a SCLC mediante análisis histológico. Posteriormente se administró sin éxito carboplatino/etopósido/osimertinib. El paciente falleció en enero de 2020, tras 12,5 años de supervivencia global (SG) y 10 líneas de tratamiento. Hasta donde sabemos, este artículo presenta una de las supervivencias más largas reportadas de un paciente con LC metastásico con mutación de EGFR. Non-small cell lung cancer (NSCLC) is responsible of 85% of lung cancer (LC) cases. Therefore, epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) were developed and have improved clinical outcomes of EGFR-mutant NSCLC patients. However, these patients inevitably develop resistance to those medications. Some of the resistance mechanisms are T790M mutation and transformation of lung adenocarcinoma to small cell lung cancer (SCLC). Conversely, only a few EGFR-mutant NSCLC cases reported a long-term survival of more than 5 years. The present case concerns a 53-year-old never smoker woman of Hispanic origin, that debuted with dry cough without dyspnea and intermittent high-intensity pain in the left chest and spine. She was diagnosed with metastatic NSCLC and started treatment with platinum-based chemotherapy double. After an EGFR-mutation was identified, the patient started target therapy. Over the years, treatment was escalated because of the resistance she developed against TKIs. T790M resistance mutation was reported and persisted over time; additionally the appearance of TP53R213 mutation was found years later. Treatment with osimertinib was successfully administered for 10 months and after that meningeal progression was found. At the same time, transdifferentiation to SCLC was confirmed by histological analysis. Carboplatin/etoposide/osimertinib was then unsuccessfully administered. The patient died in January 2020, after 12.5 years of overall survival (OS) and 10 lines of treatment. To our knowledge, this article presents one of the longest reported survivals of a metastatic LC patient with EGFR mutation.

BACKGROUND: The aim of the PROMETEO-01 Study was to define the diagnostic accuracy of imaging techniques in colorectal cancer liver metastasis (CRCLM) patients. METHODS: Patients referred to Bologna S. Orsola-Malpighi Hospital performed a computed-tomography scan (CT), magnetic resonance (MR), 18F-FDG-PET/CTscan (PET/CT) and liver contrast-enhanced-ultrasound (CEUS); CEUS was also performed intraoperatively (i-CEUS). Every pathological lesion was compared with imaging data. RESULTS: From December 2007 to August 2010, 84 patients were enrolled. A total of 51 (60.71%) resected patients were eligible for analysis. In the lesion-by-lesion analysis 175 resected lesions were evaluated: 67(38.3%) belonged to upfront resected patients (group-A) and 108 (61.7%) to chemotherapy-pretreated patients (group-B). In all patients the sensitivity of MR proved better than CT (91% vs 82%; P=0.002), CEUS (91 vs 81%; P=0.008) and PET/CT (91% vs 60%; P=0.000), whereas PET/CT showed the lowest sensitivity. In group-A the sensitivity of i-CEUS, MR, CT, CEUS and PET/CT was 98%, 94%, 91%, 84% and 78%, respectively. In group-B the i-CEUS proved equivalent in sensitivity to MR (95% and 90%, respectively, P=0.227) and both were significantly more sensitive than other procedures. The CT sensitivity in group-B was lower than in group-A (77% vs 91%, P=0.024). CONCLUSIONS: A thoraco-abdominal CT provides an adequate baseline evaluation and guides judgment as to the resectability of CRCLM patients. In the subset of candidates for induction chemotherapy to increase the chance of liver resection, the most rational approach is to add MR for the staging and restaging of CRCLM.

Background Tuberculosis (TB) in the gastrointestinal tract or peritoneum is an uncommon condition in clinical practice. Its rarity, combined with its nonspecific presentations, makes this kind of extrapulmonary tuberculosis difficult to diagnose as it can mimic other inflammatory or malignant conditions. Delays in treatment and frequent misdiagnosis can lead to hazardous complications. In countries like Ecuador where the disease is endemic, TB should always be considered in the differential diagnosis of a patients who present with nonspecific abdominal symptoms. In these scenarios, laparoscopy can be an invaluable tool when used with sufficiently high clinical awareness and adequate training. Case presentation We present the case of a 37-year-old female patient from Ecuador with a 1-year history of abdominal pain, nausea, intermittent vomits, night sweats, and weight loss. After clinical evaluation and a laparoscopic intervention, abdominal TB was detected and promptly treated. Antituberculosis chemotherapy was initiated, and the patient successfully recovered. Conclusions High clinical awareness is imperative when approaching abdominal TB due to its wide spectrum of clinical symptoms and its rarity. Early detection and prompt treatment are critical to minimize the possibility of hazardous complications.