Multi-Organ Systems Involvement in COVID-19 is Associated With a Worse Prognosis.

Background: Coronavirus disease 2019 (COVID-19) has multiple organ system involvement but the association of organ system involvement with disease prognosis has not been reported. We study the association of organ systems involved with in-hospital mortality and hospital length of stay (LOS) in COVID-19. Methods: Retrospective study of 808 consecutive patients with confirmed-laboratory diagnosis of COVID-19 in a New York hospital from March 1-May 15, 2020. Results: Increased number of organs systems involved was associated with increased odds for in-hospital mortality (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.11-1.66, p < 0.01) and increased LOS (B = 0.02, SE = 0.01, p < 0.05). Increased platelet count was associated with decreased odds for mortality (OR: 0.996, 95% CI: 0.994-0.998, p < 0.001). Increased white blood cell count was associated with increased odds for mortality (OR: 14.00, 95% CI: 3.41-57.38, p < 0.001). Increased creatinine and glucose were each associated with increased LOS (B = 0.11, SE = 0.04, p < 0.01, and B = 0.12, SE = 0.05, p < 0.05, respectively). Increased odds for mortality were also found in high FiO2 oxygen requirement (OR: 11.63, 95% CI: 3.90-34.75, p < 0.001) and invasive mechanical ventilation (OR: 109.93, 95% CI: 29.44-410.45, p < 0.001). Conclusion: Multiple organ systems involvement in COVID-19 is associated with worse prognosis. Clinical/laboratory values corresponding to each organ system may be used as prognostic tools in clinical settings to tailor treatments for COVID-19 patients.

ALK Rearrangement Positive Lung Adenocarcinoma in Pregnancy Treated With Alectinib: A Case Report.

There are few reported cases of ALK gene rearranged (ALK+) non-small cell lung cancer (NSCLC) during pregnancy. There is a lack of information on the safety of ALK inhibitors in pregnant patients. We present a 25-year-old African American woman who was diagnosed with metastatic ALK+ lung adenocarcinoma at 15 weeks of gestation. Treatment with alectinib was initiated at 18 weeks' gestation with resultant radiological treatment response. The patient did not experience any adverse effects from alectinib during her pregnancy. An elective induction of labor at 39 weeks resulted in an uncomplicated vaginal delivery. This case adds to available data and provides insight on the safety of using alectinib in a pregnant, ALK+ NSCLC patient, allowing the patient to continue her pregnancy to term while treating advanced lung adenocarcinoma.

Sepsis-Related Outcomes of Patients with Philadelphia-Negative Myeloproliferative Neoplasms.

We analyzed the National Inpatient Sample (NIS) database to study the sepsis-related outcomes in patients with Philadelphia negative myeloproliferative neoplasms (MPN). A total of 82,087 patients were included, most had essential thrombocytosis (83.7%), followed by polycythemia vera (13.7%), and primary myelofibrosis (2.6%). Sepsis was diagnosed in 15,789 (19.2%) patients and their mortality rate was higher than nonseptic patients (7.5% vs 1.8%; p < .001). Sepsis was the most significant risk factor of mortality (aOR, 3.84; 95% CI, 3.51-4.21), others included liver disease (aOR, 2.42; 95% CI, 2.11-2.78), pulmonary embolism (aOR, 2.26; 95% CI, 1.83-2.80), cerebrovascular disease (aOR, 2.05; 95% CI, 1.81-2.33), and myocardial infarction (aOR, 1.73; 95% CI, 1.52-1.96).

Sepsis-related outcomes of patients with Philadelphia-negative myeloproliferative neoplasms.

We analyzed the National Inpatient Sample (NIS) database to study the sepsis-related outcomes in patients with Philadelphia negative myeloproliferative neoplasms (MPN). A total of 82,087 patients were included, most had essential thrombocytosis (83.7%), followed by polycythemia vera (13.7%), and primary myelofibrosis (2.6%). Sepsis was diagnosed in 15,789 (19.2%) patients and their mortality rate was higher than non-septic patients (7.5% vs 1.8%; P<.001). Sepsis was the most significant risk factor of mortality (aOR, 3.84; 95% CI, 3.51-4.21), others included liver disease (aOR, 2.42; 95% CI, 2.11-2.78), pulmonary embolism (aOR, 2.26; 95% CI, 1.83-2.80), cerebrovascular disease (aOR, 2.05; 95% CI, 1.81-2.33), and myocardial infarction (aOR, 1.73; 95% CI, 1.52-1.96).

Renal Manifestations and their Association with Mortality and Length of Stay in COVID-19 Patients at a Safety-net Hospital.

Background: Renal involvement in COVID-19 leads to severe disease and higher mortality. We study renal parameters in COVID-19 patients and their association with mortality and length of stay in hospital. Methods: A retrospective study (n=340) of confirmed COVID-19 patients with renal involvement determined by the presence of acute kidney injury. Multivariate analyses of logistic regression for mortality and linear regression for length of stay (LOS) adjusted for relevant demographic, comorbidity, disease severity, and treatment covariates. Results: Mortality was 54.4% and mean LOS was 12.9 days. For mortality, creatinine peak (OR:35.27, 95% CI:2.81, 442.06, p<0.01) and persistent renal involvement at discharge (OR:4.47, 95% CI:1.99,10.06, p<0.001) were each significantly associated with increased odds for mortality. Increased blood urea nitrogen peak (OR:0.98, 95%CI:0.97,0.996, p<0.05) was significantly associated with decreased odds for mortality. For LOS, increased blood urea nitrogen peak (B:0.001, SE:<0.001, p<0.01), renal replacement therapy (B:0.19, SE:0.06, p<0.01), and increased days to acute kidney injury (B:0.19, SE:0.05, p<0.001) were each significantly associated with increased length of stay. Conclusion: Our study emphasizes the importance in identifying renal involvement parameters in COVID-19 patients. These parameters are associated with LOS and mortality, and may assist clinicians to prognosticate COVID-19 patients with renal involvement.

Glucose dysregulation and its association with COVID-19 mortality and hospital length of stay.

BACKGROUND AND AIMS: We investigate the impact of blood glucose on mortality and hospital length of stay (HLOS) among COVID-19 patients. METHODS: Retrospective study of 456 patients with confirmed COVID-19 and glycemic dysregulation in the New York City area. RESULTS: We found that impaired glucose adjusted for other organs systems involved (OR:1.87; 95% CI:1.36-2.57, p < 0.001), increased glucose nadir (OR:34.28; 95% CI:3.97-296.05, p < 0.01) and abnormal blood glucose levels at discharge (OR:5.07; 95% CI:2.31-11.14, p < 0.001) were each significantly associated with increased odds for mortality. New or higher from baseline insulin requirement during hospitalization (OR:0.34; 95% CI:0.15-0.78; p < 0.05) was significantly associated with decreased odds for mortality. Increased glucose peak (B = 0.001, SE=<0.001, p < 0.001), new or higher from baseline insulin requirement during hospitalization (B = 0.11, SE = 0.03, p < 0.001), and increased days to dysglycemia (B = 0.15, SE = 0.04, p < 0.001) were each significantly associated with increased HLOS. Increased glucose nadir (B = -0.67, SE = 0.07, p < 0.001), insulin intravenous drip (B = -0.10, SE = 0.05, p < 0.05), and increased proportion days endocrine system involved (B = -0.25, SE = 0.06, p < 0.001) were each significantly associated with decreased HLOS. CONCLUSION: Glucose dysregulation adversely affects mortality and HLOS in COVID-19. These data can help clinicians to guide patient treatment and management in COVID-19 patients.

Landfill leachate treatment using hydrodynamic cavitation: exploratory evaluation.

Hydrodynamic cavitation is a new technology used for the treatment of wastewater. Landfill leachates contain a large variety of organic pollutants and inorganic matter, with recalcitrant and bio-refractory compounds. The present study was designed to evaluate the effect of hydrodynamic cavitation on landfill leachate quality indices. Three experimental designs were proposed. First, the influence of collection climate on leachate quality characteristics was analyzed. Second, the best cavitation time was chosen, which promoted the greatest reduction in the effluent pollutant load. Finally, the hydrogen peroxide (H2O2) concentration was evaluated as an adjuvant in the cavitation process. A model TEKMASH TEK-1SL equipment was used. This cavitation unit operated with a flow rate of 30 m3 h-1, a temperature of 75 °C, and an inlet pressure of 3 bar. The cavitation chamber was of the annular flow type. The statistical analyses were run through ANOVA and Tukey's test, with significance α = 0.05. The response variables for the factors were biochemical oxygen demand (BOD5), chemical oxygen demand (COD), total organic carbon (TOC) and total suspended solids (TSS). An influence of the climatic condition on the leachate quality parameters was found, and the difference was marked in COD. In all cases, both for the cavitation process and for the cavitation-oxidant scheme, there was a reduction of 23%-51% BOD5, 30%-53% COD, 12%-21% TOC and 100% removal in TSS. In a 30-minute treatment, the highest COD removal percentage was reached, corresponding to 53.20%. Furthermore, a 200 ppm concentration of hydrogen peroxide enhanced the reduction of BOD5 and COD with proportions of 51.55% and 38.21%, respectively. Hydrodynamic cavitation offers advantages in the treatment of wastewater and can be used as an independent technique or as a hybrid method.

Hematologic Involvement as a Predictor of Mortality in COVID-19 Patients in a Safety Net Hospital.

INTRODUCTION: COVID-19 affects the hematologic system. This article evaluated the impact of hematologic involvement of different blood cell line parameters of white blood cells including absolute neutrophil count (ANC), hemoglobin, and platelets in COVID-19 patients and their association with hospital mortality and length of stay (LOS). METHODS: This was a retrospective study of 475 patients with confirmed positive COVID-19 infection and hematologic abnormalities in the metropolitan New York City area. RESULTS: Elevated absolute neutrophil count (OR: 1.20; 95% CI: 1.02-1.42; p < 0.05) increased days of hematologic involvement (OR: 4.44; 95% CI: 1.42-13.90; p < 0.05), and persistence of hematologic involvement at discharge (OR: 2.87; 95% CI: 1.20-6.90; p < 0.05) was associated with higher mortality. Higher hemoglobin at admission (OR: 0.77; 95% CI:0.60-0.98; p < 0.001) and platelets peak (OR: 0.995; 95% CI: 0.992-0.997; p < 0.001) were associated with decreased mortality. Patients with higher white blood cell peak (B = 0.46; SE = 0.07; p < 0.001) and higher hemoglobin at admission (B = 0.05; SE = 0.01; p < 0.001) were associated with higher LOS. Those with higher hemoglobin nadir (B = -0.06; SE = 0.01; p < 0.001), higher platelets nadir (B = -0.001; SE = < 0.001; p < 0.001), and hematologic involvement at discharge or death (B = -0.06; SE = 0.03; p < 0.05) were associated with lower LOS. CONCLUSIONS: These findings can be used by clinicians to better risk-stratify patients with hematologic involvement in COVID-19 and tailor therapies potentially to improve patient outcomes.

"CUIDARAS " : A Nominal and Personalized Health Care Model. Effectiveness of a Massive Screening for Colorectal Cancer Detection at Community level.

Health systems provides care only to those people who spontaneous demand for attention; excluding those who dont perceive illness or are not aware enough to consult. Alternative healthcare models based on the nominal-personalized care like "University Center for Integrated Care of Referred Health Care" (CUIDARAS) may have better results. In order to demonstrate benefits of this model, it was performed an experience based in colorectal cancer (CRC) detection and care that focused the entire population of the town. METHODS: It is an intervention study for early detection of CRC. A survey and a physical examination were performed in each adult from "CH" town. Two visits were made. Blood in stool test (BIST) was self-collected, analyzed and results delivered with appointment for a programmed video-colonoscopy (VCC) when test was positive. RESULTS: people enrolled (n546) had 59.9+/-6.4 yrs. Adherence was 93.8% of the target population; 99.2% performed BIST; while 95.3% a positive BIST had access to VCC and treatment. Overall cost of the experience (stool test, VCC, biopsy, local treatment) was 7685 USD, while costs associated to an advanced CRC classic treatment was USD 9577/patient (USD 26098 if treatment included bevacizumab). CONCLUSION: The present study based on preventive actions like blood in stool test, applied as a screening to all inhabitants in town, had 93.8% of adherence and high level of CRC early detection. A health model based on personalized care (CUIDARAS), achieved more effective results in terms health care and disease prevention, with a favorable benefit/cost ratio compared with classical health care provide by current system. Key words: Model of care; colorectal cancer; CUIDARAS; personalized care.

MELD-Na score, Acute Physiologic and Chronic Health Evaluation II score, and SOFA score and their association with mortality in critically ill COVID-19 patients with liver injury: A retrospective single-center study.

Background: The Acute Physiologic and Chronic Health Evaluation II (APACHE-II), Sequential Organ Failure Assessment (SOFA), and Model for End-Stage Liver Disease modified for Sodium concentration (MELD-Na) scores are validated to predict disease mortality. We studied the prognostic utility of these scoring systems in critically ill coronavirus disease 2019 (COVID-19) patients with liver injury. Methods: This was a retrospective study of 291 confirmed COVID-19 and liver injury patients requiring intensive care unit level of care. These patients required supplemental oxygen requirement with fraction of inspired oxygen >55% and/or the use of vasopressor. MELD-Na, SOFA, and APACHE-II scores were adjusted. Outcomes were mortality and length of stay (LOS). Results: SOFA (odds ratio: 0.78, 95% confidence interval: 0.63-0.98, P < 0.05) was associated with decreased odds for mortality. APACHE-II and MELD-Na were not associated with mortality or LOS. Conclusions: We suggest that the novel nature of COVID-19 necessitates new scoring systems to predict outcomes in critically ill COVID-19 patients with liver injury.

Epidermal inclusion cyst in the thyroid gland.

Epidermal inclusion cysts (EIC) are common benign lesions of the skin, ovaries, and testicles. However, their occurrence in thyroid gland is rare. We reported a case in which a 57-year-old male patient with history of nontoxic uninodular goiter presented with dysphonia and dysphagia. The cytology of ultrasound guided fine needle aspiration of the thyroid nodule revealed epidermal cyst. Despite the benign presentation. The patient underwent lobectomy to relieve his clinical symptoms and the surgical pathology exam confirmed the diagnosis of benign thyroid cyst, consistent with EIC of the thyroid.

Clinical and neuroimaging spectrum of hyperglycemia-associated chorea-ballism: systematic review and exploratory analysis of case reports.

Hyperglycemia-associated chorea-ballism (HCB) is an infrequent neurological syndrome occurring predominantly in elderly females and in the setting of non-ketotic hyperglycemia (NKH). A systematic review was conducted in accordance with the PRISMA statement. Studies published between 1980 and 2018 that reported demographic, clinical, laboratory and imaging features from patients with HCB were screened. 136 studies describing 286 patients were included in the analysis. The patients included had a median age of 72 years; those with ketotic hyperglycemia (KH) were older (p<0.001). Women and NKH patients were the most frequently affected (63% and 92%, respectively). The median glucose level at admission was 420 mg/dL (IQR 328-535), and was significantly higher in KH (p=0.009). Moreover, the absence of a clear lesion on imaging studies and the finding of bilateral imaging evidence of lesions were each more frequent in the KH group (p=0.036 and p=0.008, respectively). 48 cases (19.4%) presented with bilateral CT/MRI lesions, having higher values of plasma osmolarity compared with the patients with unilateral lesions (p=0.011). Every patient received hypoglycemic treatment, but only 174 (60.84%) were prescribed neuroleptics. 213 patients (84.86%) showed a total recovery, after a median of 14 days (IQR 3-31). Bilateral chorea-ballism was supported by bilateral imaging evidence of involvement in only 60% of the cases (positive predictive value). Patients not prescribed neuroleptics, with negative lentiform nucleus involvement, and age within the third tertile (≥ 78 years) had an odds ratio of 6.6 (CI 95% 1.18-141.10) for a complete clinical recovery. Significant differences were identified between types of hyperglycemia and regarding the clinical and imaging laterality features. Furthermore, the predictor variables evaluated showed potential utility for assessing the prognosis of HCB patients.

Factores asociados con la presencia de secuelas fibrocavitarias torácicas en pacientes con antecedente de tuberculosis pulmonar del Hospital Universitario de Santander, Bucaramanga, Colombia / Factors associated with the presence of thoracic fibrocavitary sequelae in patients with a history of pulmonary tuberculosis from Hospital Universitario de Santander, Bucaramanga, Colombia

Objetivo: Determinar las variables relacionadas con el desarrollo de secuelas fibrocavitarias torácicas en pacientes con antecedente de tuberculosis pulmonar en Santander. Métodos: Cohorte retrospectiva de 141 pacientes con diagnóstico previo de tuberculosis, captados mediante muestreo no probabilístico de casos consecutivos en consulta de neumología (Hospital Universitario de Santander). Se realizó un análisis descriptivo, bivariado y multivariado a las variables recolectadas de las historias clínicas. Resultados: El 66% de los pacientes pertenecían al sexo masculino, con una edad promedio de 52 ± 16,91 años, evidenciando un tiempo promedio desde el contagio hasta el momento de la captación de 69 meses y un antecedente de tabaquismo del 46%. El 68% referían tos y se realizó fibrobroncoscopia al 41%. El 89% mostraron algún tipo de secuelas, distribuidas así: Torácicas parenquimatosas 88%, Pleurales 30%, Vías respiratorias 45%, Mediastinales 38% y Vasculares 5%. Fueron variables asociadas a la presencia de alguna secuela la edad del paciente; el tiempo mayor a 17 meses desde el diagnóstico de tuberculosis; la edad de diagnóstico de tuberculosis; la confirmación diagnóstica de tuberculosis por fibrobroncoscopia y síntomas como disnea, cianosis y tos. Discusión: El presente estudio estableció la prevalencia de secuelas de tuberculosis en el 88,65% de los sujetos con tuberculosis curada en Bucaramanga, Santander, Colombia. Es el primer estudio en la región en el que se evaluaron factores asociados con el desarrollo de secuelas de tuberculosis, encontrando como factor importante el uso de fibrobroncoscopia como método diagnóstico.

Factors associated with the presence of thoracic fibrocavitary sequelae in patients with a history of pulmonary tuberculosis from Hospital Universitario de Santander, Bucaramanga, Colombia

Objective: To determine the variables associated with the development of thoracic fibrocavitary sequelae in patients with a history of pulmonary tuberculosis in Santander. Methods: A retrospective cohort of 141 patients previously diagnosed with tuberculosis, recruited using non-probability consecutive sampling at pneumology consultations (Hospital Universitario de Santander). A descriptive, bivariate and multivariate analysis was performed with all the variables collected from the medical records. Results: Sixty-six percent of the patients were males, with an average age of 52+/-16.91 years, evidencing an average time span of 69 months from the moment of the infection to the moment they were recruited, and a history of tobacco use of 46%. Sixty-eight percent stated they had cough and a fibrobronchoscopy was performed in 41%. Eighty-nine percent exhibited some type of sequelae, classified as follows: Parenchymal thoracic 88%, pleural 30%, respiratory tract 45%, mediastinal 38% and vascular 5%. The variables associated with the presence of a sequela were the age of the patient; a period of time exceeding 17 months since the moment of the tuberculosis diagnosis; the age of diagnosis; the diagnostic confirmation of tuberculosis by fibrobronchoscopy and symptoms such as dyspnea, cyanosis and cough. Discussion: This study establishes the incidence of tuberculosis sequelae in 88.65% of the subjects with tuberculosis treated in Bucaramanga, Santander, Colombia. It is the first study in the region evaluating the factors associated with the development of tuberculosis sequelae, in which the use of fibrobronchoscopies as a diagnostic method was found to be an important factor.

Disease-associated polyglutamine stretches in monomeric huntingtin adopt a compact structure.

Abnormal polyglutamine (polyQ) tracts are the only common feature in nine proteins that each cause a dominant neurodegenerative disorder. In Huntington's disease, tracts longer than 36 glutamines in the protein huntingtin (htt) cause degeneration. In situ, monoclonal antibody 3B5H10 binds to different htt fragments in neurons in proportion to their toxicity. Here, we determined the structure of 3B5H10 Fab to 1.9 Å resolution by X-ray crystallography. Modeling demonstrates that the paratope forms a groove suitable for binding two ß-rich polyQ strands. Using small-angle X-ray scattering, we confirmed that the polyQ epitope recognized by 3B5H10 is a compact two-stranded hairpin within monomeric htt and is abundant in htt fragments unbound to antibody. Thus, disease-associated polyQ stretches preferentially adopt compact conformations. Since 3B5H10 binding predicts degeneration, this compact polyQ structure may be neurotoxic.

An immunologic model for rapid vaccine assessment -- a clinical trial in a test tube.

While the duration and size of human clinical trials may be difficult to reduce, there are several parameters in pre-clinical vaccine development that may be possible to further optimise. By increasing the accuracy of the models used for pre-clinical vaccine testing, it should be possible to increase the probability that any particular vaccine candidate will be successful in human trials. In addition, an improved model will allow the collection of increasingly more-informative data in pre-clinical tests, thus aiding the rational design and formulation of candidates entered into clinical evaluation. An acceleration and increase in sophistication of pre-clinical vaccine development will thus require the advent of more physiologically-accurate models of the human immune system, coupled with substantial advances in the mechanistic understanding of vaccine efficacy, achieved by using this model. We believe the best viable option available is to use human cells and/or tissues in a functional in vitro model of human physiology. Not only will this more accurately model human diseases, it will also eliminate any ethical, moral and scientific issues involved with use of live humans and animals. An in vitro model, termed "MIMIC" (Modular IMmune In vitro Construct), was designed and developed to reflect the human immune system in a well-based format. The MIMIC System is a laboratory-based methodology that replicates the human immune system response. It is highly automated, and can be used to simulate a clinical trial for a diverse population, without putting human subjects at risk. The MIMIC System uses the circulating immune cells of individual donors to recapitulate each individual human immune response by maintaining the autonomy of the donor. Thus, an in vitro test system has been created that is functionally equivalent to the donor's own immune system and is designed to respond in a similar manner to the in vivo response.

In vitro and in vivo characterization of a novel antibody-like single-chain TCR human IgG1 fusion protein.

We have constructed a protein composed of a soluble single-chain TCR genetically linked to the constant domain of an IgG1 H chain. The Ag recognition portion of the protein binds to an unmutated peptide derived from human p53 (aa 264-272) presented in the context of HLA-A2.1, whereas the IgG1 H chain provides effector functions. The protein is capable of forming dimers, specifically staining tumor cells and promoting target and effector cell conjugation. The protein also has potent antitumor effects in an in vivo tumor model and can mediate cell killing by Ab-dependent cellular cytotoxicity. Therefore, single-chain TCRs linked to IgG1 H chains behave like Abs but possess the ability to recognize Ags derived from intracellular targets. These fusion proteins represent a novel group of immunotherapeutics that have the potential to expand the range of tumors available for targeted therapies beyond those currently addressed by the conventional Ab-based approach.

Sepsis: evaluacion clinica y manejo / Sepsis: clinical evaluation and treatment

Se presenta el sindrome septico como una amenaza mortal, los factores que facilitan su progreso y los mecanismos subyacentes que explican las manifestaciones clinicas. Se revisa la manera racional de tratarlo de acuerdo a la patogenia