Long-Term Survival of Patients With Cancer, Sepsis, and Vasopressor Requirements Based on Lactate Levels.

A prospective cohort study was conducted to evaluate the 1-year survival of cancer patients with sepsis and vasopressor requirements. Eligible patients were admitted a Comprehensive Cancer Center's ICU and were compared based on their admission lactate levels. Of the 132 included patients, 87 (66%) had high lactate (HL; > 2.0 mmol/L), and 45 (34%) had normal lactate (NL; ≤ 2.0 mmol/L). The 1-year survival rates of the two groups were similar (HL 16% vs. NL 18%; p = 0.0921). After adjustment for ICU baseline characteristics, HL was not significantly associated with a 1-year survival (Hazards ratio, 1.39; 95% CI, 0.94-2.05). Critically ill cancer patients with sepsis and vasopressor requirements, regardless of the lactate level, had 1-year survival of less than 20%. Large multicenter cancer registries would enable to confirm our findings and better understand the long-term trajectories of sepsis in this vulnerable population.

Genes and Pathways Involved in the Progression of Malignant Pleural Mesothelioma: A Meta-analysis of Genome-Wide Expression Studies.

Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural tissue that lines the lungs and is mainly associated with long latency from asbestos exposure. This tumor has no effective therapeutic opportunities nowadays and has a very low five-year survival rate. In this sense, identifying molecular events that trigger the development and progression of this tumor is highly important to establish new and potentially effective treatments. We conducted a meta-analysis of genome-wide expression studies publicly available at the Gene Expression Omnibus (GEO) and ArrayExpress databases. The differentially expressed genes (DEGs) were identified, and we performed functional enrichment analysis and protein-protein interaction networks (PPINs) to gain insight into the biological mechanisms underlying these genes. Additionally, we constructed survival prediction models for selected DEGs and predicted the minimum drug inhibition concentration of anticancer drugs for MPM. In total, 115 MPM tumor transcriptomes and 26 pleural tissue controls were analyzed. We identified 1046 upregulated DEGs in the MPM samples. Cellular signaling categories in tumor samples were associated with the TNF, PI3K-Akt, and AMPK pathways. The inflammatory response, regulation of cell migration, and regulation of angiogenesis were overrepresented biological processes. Expression of SOX17 and TACC1 were associated with reduced survival rates. This meta-analysis identified a list of DEGs in MPM tumors, cancer-related signaling pathways, and biological processes that were overrepresented in MPM samples. Some therapeutic targets to treat MPM are suggested, and the prognostic potential of key genes is shown.

Intraocular pressure values during the water drinking test in a Colombian population / Comportamiento de la presión intraocular durante la prueba de sobrecarga hídrica en población colombiana

Background: Intraocular pressure (IOP) peaks are key factors on the onset and progression of glaucoma. The water drinking test (WDT) detects IOP fluctuations and estimates the maximum IOP. Objective: To assess the IOP variations during the WDT in patients diagnosed or suspected of glaucoma treated at an ophthalmology clinic. Methods: This is an observational, descriptive, and retrospective study, using clinical records of patients whom underwent the WDT between January 2017 and August 2019. Results: The study included 300 eyes. The WDT was positive in 23.3% of the eyes. Basal IOP at 15, 30, and 45 min, as well as the maximum pressure, presented a similar mean, median, and mode, as well as a varying coefficient without much variability. The negative test group had a maximum IOP of 18.9 mmHg, compared with 20.3 mmHg in the positive test group. Conclusion: In a Colombian cohort of patients with diagnosed or suspected glaucoma whom underwent a WDT, 23.3% had positive result. 90% of the tests were positive at the 30-min interval. This test is a complementary tool in the follow-up of patients with glaucoma.

Introducción: Los picos de presión intraocular son factores importantes para la aparición y progresión del glaucoma. La prueba de sobrecarga hídrica permite detectar fluctuaciones de presión intraocular y estimar la presión máxima. Objetivo: Evaluar las variaciones en la presión intraocular durante la prueba de sobrecarga hídrica en pacientes de una clínica oftalmológica. Métodos: Estudio observacional, descriptivo, retrospectivo de revisión de historias clínicas de pacientes sometidos a la prueba de sobrecarga hídrica entre enero de 2017 y agosto de 2019. Resultados: Se incluyeron 300 ojos. La prueba de sobrecarga hídrica fue positiva en el 23,3% de los ojos. La presión intraocular basal, a los 15, 30 y 45 min, al igual que la presión máxima, tuvieron una media, mediana y moda similares, con un coeficiente de variación sin mucha variabilidad. El grupo con resultados negativos tuvo una presión intraocular máxima de 18,9 mmHg comparado con 20,3 mmHg del grupo con resultados positivos. Conclusión: En una cohorte colombiana de pacientes con diagnóstico o sospecha de glaucoma quienes se les realizó la prueba de sobrecarga hídrica, el 23,3% tuvo resultados positivos. El 90% de las pruebas fueron positivas en el intervalo de 30 min. Esta prueba es una herramienta complementaria en el seguimiento de pacientes con glaucoma.

Outcomes and Predictors of 28-Day Mortality in Patients With Solid Tumors and Septic Shock Defined by Third International Consensus Definitions for Sepsis and Septic Shock Criteria.

BACKGROUND: Data assessing outcomes of patients with solid tumors demonstrating septic shock using the Third International Consensus Definitions for Sepsis and Septic Shock are scarce. RESEARCH QUESTION: What are the independent predictors of 28-day mortality in critically ill adults with solid tumors and septic shock? STUDY DESIGN AND METHODS: Cohort of solid tumor patients admitted to the ICU with septic shock. Demographic and clinical characteristics were gathered from the electronic health records. We developed a reduced multivariate logistics regression model to identify independent predictors of 28-day mortality and used Kaplan-Meier plots to assess survival. RESULTS: A total of 271 patients were included. The median age was 62 years (range, 19-94 years); 57.2% were men and 53.5% were White. The most common underlying malignancies were lung (19.2%), breast (7.7%), pancreatic (7.7%), and colorectal (7.4%) cancers. Most patients (84.5%) harbored metastatic disease. Twenty-eight days after ICU admission, 188 patients (69.4%) had died. Nonsurvivors showed a higher rate of advanced cancer, longer hospital stays before ICU admission, and higher Sequential Organ Failure Assessment scores at admission and throughout the ICU stay (P < .001 for all). The multivariate analysis identified metastatic disease (OR, 3.17; 95% CI, 1.43-7.03), respiratory failure (OR, 2.34; 95% CI, 1.15-4.74), elevated lactate levels (OR, 3.19; 95% CI, 1.90-5.36), and Eastern Cooperative Oncology Group performance scores of 3 or 4 (OR, 2.72; 95% CI, 1.33-5.57) as independent predictors of 28-day mortality. Only 38 patients (14%) were discharged home without medical assistance. INTERPRETATION: The 28-day mortality rate of patients with solid tumors and septic shock was considerably high. Factors associated with worse survival included advanced oncologic disease, poor performance status, high lactate level, and concomitant acute respiratory failure. Early goals-of-care discussions should be considered for frail patients with septic shock and advanced metastatic disease without denying access to the appropriate level of care.

Outcomes and Predictors of 28-Day Mortality in Patients With Hematologic Malignancies and Septic Shock Defined by Sepsis-3 Criteria.

BACKGROUND: To describe short-term outcomes and independent predictors of 28-dayx mortality in adult patients with hematologic malignancies and septic shock defined by the new Third International Consensus Definitions (Sepsis-3) criteria. METHODS: We performed a retrospective cohort study of patients admitted to the medical ICU with septic shock from April 2016 to March 2019. Demographic and clinical features and short-term outcomes were collected. We used descriptive statistics to summarize patient characteristics, logistic regression to identify predictors of 28-day mortality, and Kaplan-Meier plots to assess survival. RESULTS: Among the 459 hematologic patients with septic shock admitted to the ICU, 109 (23.7%) had received hematopoietic stem cell transplant. The median age was 63 years (range, 18-89 years), and 179 (39%) were women. Nonsurvivors had a higher Charlson comorbidity index (P=.007), longer length of stay before ICU admission (P=.01), and greater illness severity at diagnosis and throughout the hospital course (P<.001). The mortality rate at 28 days was 67.8% and increased with increasing sequential organ failure assessment score on admission (odds ratio [OR], 1.11; 95% CI, 1.03-1.20), respiratory failure (OR, 3.12; 95% CI, 1.49-6.51), and maximum lactate level (OR, 1.16; 95% CI, 1.10-1.22). Aminoglycosides administration (OR, 0.42; 95% CI, 0.26-0.69), serum albumin (OR, 0.51; 95% CI, 0.31-0.86), and granulocyte colony-stimulating factor (G-CSF) (OR, 0.40; 95% CI, 0.24-0.65) were associated with lower 28-day mortality. Life support limitations were present in 81.6% of patients at death. At 90 days, 19.4% of the patients were alive. CONCLUSIONS: Despite efforts to enhance survival, septic shock in patients with hematologic malignancies is still associated with high mortality rates and poor 90-day survival. These results demonstrate the need for an urgent call to action with higher awareness, including the further evaluation of interventions such as earlier ICU admission, aminoglycosides administration, and G-CSF treatment.

Development of an Amplicon-Based Next-Generation Sequencing Protocol to Identify Leishmania Species and Other Trypanosomatids in Leishmaniasis Endemic Areas.

Trypanosomatid infections are an important public health threat affecting many low-income countries across the tropics, particularly in the Americas. Trypanosomatids can infect many vertebrate, invertebrate, and plant species and play an important role as human pathogens. Among these clinically relevant pathogens are species from the genera Leishmania and Trypanosoma. Mixed trypanosomatid infections remain a largely unexplored phenomenon. Herein, we describe the application of an amplicon-based next-generation sequencing (NGS) assay to detect and identify trypanosomatid species in mammalian reservoirs, human patients, and sand fly vectors throughout regions of Leishmania endemicity. Sixty-five samples from different departments of Colombia, including two samples from Venezuela, were analyzed: 49 samples from cutaneous leishmaniasis (CL) patients, 8 from sand flies, 2 from domestic reservoirs (Canis familiaris), and 6 from wild reservoirs (Phyllostomus hastatus). DNA from each sample served to identify the presence of trypanosomatids through conventional PCR using heat shock protein 70 (HSP70) gene as the target. PCR products underwent sequencing by Sanger sequencing and NGS, and trypanosomatid species were identified by using BLASTn against a reference database built from trypanosomatid-derived HSP70 sequences. The alpha and beta diversity indexes of amplicon sequence variants were calculated for each group. The results revealed the presence of mixed infections with more than two Leishmania species in 34% of CL samples analyzed. Trypanosoma cruzi was identified in samples from wild reservoirs, as well as in sand fly vectors. Coinfection events with three different Leishmania species were identified in domestic reservoirs. These findings depose the traditional paradigm of leishmaniasis as being a single-species-driven infection and redraw the choreography of host-pathogen interaction in the context of multiparasitism. Further research is needed to decipher how coinfections may influence disease progression. This knowledge is key to developing an integrated approach for diagnosis and treatment. IMPORTANCE Traditionally, there has been a frequent, yet incorrect assumption that phlebotomine vectors, animal reservoirs, and human hosts are susceptible to Leishmania infection by a single parasite species. However, current evidence supports that these new vector-parasite-reservoir associations lend vectors and reservoirs greater permissiveness to certain Leishmania species, thus promoting the appearance of coinfection events, particularly in disease-endemic regions. The present study describes the application of an amplicon-based next-generation sequencing (NGS) assay to detect and identify trypanosomatid species in mammalian reservoirs, human patients, and sand fly vectors from regions of endemicity for leishmaniasis. This changes our understanding of the clinical course of leishmaniasis in areas of endemicity.

Both subscales of the Keratoconus End-Points Assessment Questionnaire have excellent test-retest reliability.

Purpose: The keratoconus end-points assessment questionnaire (KEPAQ) is a disease-specific scale designed to evaluate the quality of life in keratoconus patients and provides the measurement of both functional and emotional compromise in keratoconus. It was previously developed, tested, and validated and now we want to evaluate the test-retest reliability of the KEPAQ, in an effort to contribute evidence on its internal consistency and capability of measuring clinical state with minimal inference of random chance. Methods: This is a prospective analytical study, designed to evaluate the test-retest reliability of the KEPAQ through the repeated application of the questionnaire to a group of clinically stable individuals. A number of patients with a confirmed diagnosis of keratoconus underwent double application of the KEPAQ, seven days apart. Mean KEPAQ score was obtained through Rasch analysis, while test-retest reliability was evaluated through Spearman rank-order correlation and intraclass correlation coefficient. Rasch analysis was performed in JMetrik version 4.1.1 (Psychomeasurement Systems LLC; Charlottesville, VA, USA) in a MacBook Air computer running macOS Catalina version 10.15.2 (Apple Inc.; Cupertino, CA, USA). Results: A total of 100 patients were included. For KEPAQ-E, Spearman correlation was R = 0.963 while ICC was 0.981 (95% confidence interval 0.972-0.987). For KEPAQ-F, Spearman correlation was R = 0.921 while ICC was 0.952 (95% confidence interval 0.929-0.968). Conclusion: The KEPAQ is a robust, well-developed, extremely reliable scale which can be confidently used for clinical and research endeavors.

Correction to 'Complex ecological interactions across a focus of cutaneous leishmaniasis in Eastern Colombia: novel description of Leishmania species, hosts and phlebotomine fauna'.

[This corrects the article DOI: 10.1098/rsos.200266.].

Complex ecological interactions across a focus of cutaneous leishmaniasis in Eastern Colombia: novel description of Leishmania species, hosts and phlebotomine fauna.

This study aimed to analyse the patterns of diversity, blood sources and Leishmania species of phlebotomines in a focus of cutaneous leishmaniasis in Arboledas, Eastern Colombia. In total, 1729 phlebotomines were captured in two localities (62.3% Siravita and 37.7% Cinera) and five environments of Norte de Santander. We identified 18 species of phlebotomines: Pintomyia ovallesi (29.8%), Psychodopygus davisi (20.3%), Pi. spinicrassa (18.5%) and Lutzomyia gomezi (15.8%) showed the highest abundance. Species diversities were compared between Cinera (15.00) and Siravita (20.00) and among five microenvironments: forest remnants (19.49), coffee plantations (12.5), grassland (12.99), cane plantations (11.66) and citrus plantations (12.22). Leishmania DNA was detected in 5.8% (80/1380) of females, corresponding mainly to Pi. ovallesi (22/80; 27.2%), Lu. gomezi (17/80; 21.3%) and Pi. spinicrassa (11/80; 13.8%). Leishmania species were 63.1% L. braziliensis, 18.5% L. panamensis, 13.2% L. infantum and 6.1% L. amazonensis. The most frequent feeding sources were Homo sapiens (50%), Bos taurus (13.8%) and Canis lupus familiaris (10.3%). This focus of cutaneous leishmaniasis has a high diversity of Leishmania-carrying phlebotomines that feed on domestic animals. The transmission of leishmaniasis to human hosts was mainly associated with Lu. gomezi, Pi. ovallesi and L. braziliensis.