Combining Oxidative Stress Markers and Expression of Surfactant Protein A in Lungs in the Diagnosis of Seawater Drowning.

BACKGROUND AND OBJECTIVES: The diagnosis of seawater drowning (SWD) remains one of the most complex and contentious. It is one of the leading causes of unintentional death around the world. In most cases, the forensic pathologist must reach an accurate diagnosis from the autopsy findings and a series of complementary tests such as histopathological, biological, and chemical studies. Despite the lung being the most affected organ in death by submersion, there are few studies on this type of death's impact on this organ. The aim was to investigate human lung cadavers of forensic cases due to different causes of death, the concentration of the oxidative stress markers malondialdehyde (MDA) and γ-glutamyl-l-cysteinyl glycine (GSH), and the relationship with the expression of surfactant protein A (SP-A) to try to discriminate SWD from other types of causes of death. MATERIALS AND METHODS: A total of 93 forensic autopsy cases were analyzed. Deaths were classified into three major groups based on the scene, cause of death, and autopsy findings (external foam, frothy fluid in airways, overlapping medial edges of the lungs): (a) drowning in seawater (n = 35), (b) other asphyxia (n = 33), such as hangings (n = 23), suffocations (n = 6), and strangulation (n = 4), and (c) other causes (n = 25), such as multiple suffocations. Oxidative stress markers (MDA and GSH) and the immunohistochemical expression of SP-A were determined in both lungs. RESULTS: MDA levels were statistically higher in both lungs in cases of SWD than in other causes of death (p = 0.023). Similarly, significantly higher levels of GSH were observed in SWD compared to the rest of the deaths (p = 0.002), which was more significant in the right lung. Higher immunohistochemical expression of SP-A was obtained in the cases of SWD than in the other causes of death, with higher levels in both lungs. The correlation analysis between the levels of oxidative stress (MDA and GSH) in the lung tissue and the expression level of SP-A showed positive and significant results in SWD, both in the alveolar membrane and the alveolar space. CONCLUSIONS: Determining the levels of MDA and GSH in lung tissue and the expression level of SP-A can be of great importance in diagnosing SWD and the circumstances of death. A better understanding of the physiology of submersion is essential for its possible repercussions in adopting measures in the approach to patients who have survived a submersion process. It is also necessary for forensic pathology to correctly interpret the events that lead to submersion.

Do Antiangiogenics Promote Clot Instability? Data from the TESEO Prospective Registry and Caravaggio Clinical Trial.

BACKGROUND: Venous thromboembolism (VTE) is a common complication in cancer patients. Much of its morbidity stems from the development of fatal pulmonary embolisms (PE). Little is known about the factors involved in clot stability, with angiogenesis possibly being implicated. METHODS: The database is from the TESEO prospective registry that recruits cancer patients with VTE from 41 Spanish hospitals. Independent validation was conducted in a cohort from the Caravaggio trial. The objective is to evaluate the association between exposure to antiangiogenic therapies and the PE/VTE proportion in oncological patients. RESULTS: In total, 1,536 subjects were evaluated; 58.4% (n = 894) had a PE and 7% (n = 108) received antiangiogenic therapy (bevacizumab in 75%). The PE/VTE proportion among antiangiogenic-treated individuals was 77/108 (71.3%) versus 817/1,428 (57.2%) among those receiving other alternative therapies (p = 0.004). The effect of the antiangiogenics on the PE/VTE proportion held up across all subgroups except for active smokers or those with chronic obstructive pulmonary disease. Exposure to antiangiogenics was associated with increased PEs, odds ratio (OR) 2.27 (95% CI, 1.42-3.63). In the Caravaggio trial, PE was present in 67% of the individuals treated with antiangiogenics, 50% of those who received chemotherapy without antiangiogenic treatment, and 60% without active therapy (p = 0.0016). CONCLUSION: Antiangiogenics are associated with increased proportion of PE in oncological patients with VTE. If an effect on clot stability is confirmed, the concept of thrombotic risk in cancer patients should be reconsidered in qualitative terms.

Measures to Maintain a SARS-CoV-2 Negative Inpatient Hematological Unit in the Midst of the COVID-19 Pandemic.

The University Hospital of Salamanca, in Spain, had its first COVID-19 case on March 1st and as of May 11th, we had 1,100 positive cases. Based on the vulnerability of patients with blood cancers, on March 9th, the Hematology Department developed a protocol, amended as the new information was available, to maintain the Hematology Unit as a "free COVID-19 island." The protocol included symptom-based surveys and screening tests to patients, caregivers, and healthcare personnel to identify early potential positive cases and prevent its spread. Between March 9 and April 28, 32 asymptomatic patients and caregivers were tested and 68 rT-PCR diagnostic assays have been performed with two positive results. A 106 healthcare workers have been tested (208 rT-PCR) and seven of them were positive. In summary, the implementation of preemptive measures after the first case appeared allowed us to be able to provide treatment to our patients.

Caracterización epidemiológica de pacientes con malaria, notificados por un asegurador en salud en Colombia, 2016-2017 / Epidemiological characterization of patients with malaria notified by a health insurer in Colombia, 2016-2017

Introducción: La malaria es un problema de salud pública para Colombia, con comportamiento endémico/epidémico y variación entre las diferentes áreas de transmisión. Objetivo: Describir las características epidemiológicas de pacientes con malaria, notificados por un asegurador en salud en Colombia durante los años 2016 y 2017. Métodos: Estudio descriptivo, en el que se revisó de forma retrospectiva la base de datos de todos los casos de malaria notificados por un asegurador en salud en Colombia durante los años 2016 y 2017. Se realizó un análisis descriptivo, teniendo en cuenta la naturaleza de las variables. Las variables cualitativas se analizaron a partir de las frecuencias absolutas y relativas. Se usó el test de chi cuadrado para comparar las diferencias entre proporciones, en todos los casos se estableció un valor p< 0,05 como significativo. Los datos se analizaron en el programa SPSS versión 19. Resultados: Durante el período de observación se notificaron 26 017 casos de malaria; el 50 por ciento (13 014) eran hombres y el 50 por ciento (13 003) mujeres. Los grupos etarios más afectados fueron los adultos jóvenes (26,37 por ciento), escolares (15,04 por ciento), preescolares (12,75 por ciento) y adolescentes iniciales (12,18 por ciento). La mayoría de los pacientes estudiados eran indígenas y mulatos; trabajadores no calificados, que residían y fueron notificados en el departamento del Chocó. En cuanto a las características clínicas y paraclínicas se encontró que el 95,9 por ciento de los pacientes eran sintomático, las especies parasitaria más frecuentemente fueron P. falciparum (58,86 por ciento) y P. vivax (35,95 por ciento) y en menor frecuencia P. malariae (0,06 por ciento). Se registró complicaciones en 410 pacientes, estas eran principalmente de tipo hematológicas (56,3 por ciento); sin embargo, también se registraron complicaciones cerebrales, renales, hepáticas y pulmonares. Durante los dos años se observó brotes epidémicos entre las semanas 6 a la 31, y posteriormente se observó un descenso en la notificación de casos. Conclusiones: Este estudio encontró una marcada diferencia en la incidencia de casos de malaria notificados por el asegurador objeto de estudio entre los años 2016 y 2017; la mayoría de estos casos eran por P. falciparum y se registraron en el departamento de Chocó(AU)

Introduction: Malaria is a health problem in Colombia. Its behavior is endemic / epidemic and variation is observed between the different transmission areas. Objective: Describe the epidemiological characteristics of patients with malaria notified by a health insurer in Colombia during the years 2016 and 2017. Methods: A descriptive study was conducted in which a retrospective review was performed of the database of all the malaria cases notified by a health insurer in Colombia during the years 2016 and 2017. A descriptive analysis was done taking into account the nature of the variables. Qualitative variables were analyzed in terms of absolute and relative frequencies. The chi-square test was used to compare the differences between proportions. A value of p< 0.05 was set as significant in all cases. The software SPPS version 19 was used for data analysis. Results: During the observation period a total 26 017 malaria cases were notified, of whom 50 percent were men (13 014) and 50 percent were women (13 003). The most affected age groups were young adults (26.37 percent), schoolchildren (15.04 percent), pre-schoolers (12.75 percent) and preadolescents (12.18 percent). Most of the patients studied were indigenous and mulatto, unskilled workers, and lived or were notified in the department of Chocó. With respect to clinical and paraclinical characteristics, it was found that 95.9 percent of the patients were symptomatic. The most common parasite species were P. falciparum (58.86 percent) and P. vivax (35.95 percent) and to a lesser degree P. malariae (0.06 percent). Complications were recorded in 410 patients. These were mainly hematological (56.3 percent), but brain, kidney, liver and lung complications were also found. During the two study years, epidemic outbreaks were observed between weeks 6 and 31, followed by a decrease in the number of case notifications. Conclusions: The study found a marked difference in the incidence of malaria cases notified by the study insurer between the years 2016 and 2017. Most of these cases were due to P. falciparum and were recorded in the department of Chocó(AU)

Ruxolitinib in refractory acute and chronic graft-versus-host disease: a multicenter survey study.

Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1-5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23-67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63-89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients.

Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study).

BACKGROUND AND OBJECTIVES: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. METHOD: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. RESULTS: Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. CONCLUSIONS: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients.

Acute graft-versus-host disease and bronchiolitis obliterans after autologous stem cell transplantation in a patient with multiple myeloma.

Sixty-seven-year-old patient, diagnosed with multiple myeloma who had received autologous stem cell transplantation, following bortezomib, dexamethasone and thalidomide conventional regimen, achieving complete response, developed rash, diarrhea, and severe respiratory failure, 80 days after the transplantation procedure. He was diagnosed with graft-versus-host disease and bronchiolitis obliterans syndrome.

Accuracy for optical diagnosis of colorectal polyps in clinical practice.

BACKGROUND: Optical diagnostic involves predicting polyp histopathology from its endoscopic characteristics. It is only recommended for diminutive polyps ( < or = 5 mm) and for predictions made with high confidence. OBJECTIVES: To evaluate the accuracy of optical imaging in clinical practice and to assess if optical diagnosis is useful for predicting future colonoscopy surveillance intervals without waiting for histopathological analysis. METHODS: consecutive > 18 years patients were enrolled in this prospective study. Colonoscopies were performed by five expert endoscopists who previously participated in an ex-vivo training. Colonoscopes CF-H180AL and CF-Q180AL were used together with Exera II (Olympus Medical System, Tokyo, Japan) processors. Each polyp was characterized in real time using white light and Narrow Band Imaging. Accuracy of optical diagnosis (S, E, NPV, PPV) and correlation between surveillance interval based on optical diagnosis and histopathological analysis were calculated. RESULTS: 311 colon polyps < 10 mm (216 diminutive) in 195 patients were analyzed. Accuracy of optical diagnostics for predictions made with high confidence: Diminutive polyps(sensitivity 0.59, specificity 0.92, NPV 0.48); polyps < 10 mm (sensitivity 0.73, specificity 0.88, NPV 0.50). An optical diagnosis based surveillance recommendation was given to 90 patients. Concordance with histopathology based recommendation was 92.2% according to the European guideline and 93.3% according to the ESGE guideline. CONCLUSIONS: Optical diagnostics can be used to predict future surveillance intervals immediately after colonoscopy. However, in this study, based on clinical practice, the accuracy of optical imaging is below the recommended standards.

Relationship between tobacco, cagA and vacA i1 virulence factors and bacterial load in patients infected by Helicobacter pylori.

BACKGROUND AND AIM: Several biological and epidemiological studies support a relationship between smoking and Helicobacter pylori (H. pylori) to increase the risk of pathology. However, there have been few studies on the potential synergistic association between specific cagA and vacA virulence factors and smoking in patients infected by Helicobacter pylori. We studied the relationship between smoking and cagA, vacA i1 virulence factors and bacterial load in H. pylori infected patients. METHODS: Biopsies of the gastric corpus and antrum from 155 consecutive patients in whom there was clinical suspicion of infection by H. pylori were processed. In 106 patients H. pylori infection was detected. Molecular methods were used to quantify the number of microorganisms and presence of cagA and vacA i1 genes. A standardized questionnaire was used to obtain patients' clinical data and lifestyle variables, including tobacco and alcohol consumption. Adjusted Odds Ratios (ORadjusted) were estimated by unconditional logistic regression. RESULTS: cagA was significantly associated with active-smoking at endoscope: ORadjusted 4.52. Evidence of association was found for vacA i1 (ORadjusted 3.15). Bacterial load was higher in active-smokers, although these differences did not yield statistical significance (median of 262.2 versus 79.4 copies of H. pylori per cell). CONCLUSIONS: The association between smoking and a higher risk of being infected by a virulent bacterial population and with higher bacterial load, support a complex interaction between H. pylori infection and environmental factors.

Factors related to the effectiveness of variable stiffness colonoscope: results of a multivariate analysis.

BACKGROUND: Various studies and two meta-analysis have shown that a variable stiffness colonoscope improves cecal intubation rate. However, there are few studies on how this colonoscope should be used. OBJECTIVE: The aim of this study was to identify factors related to the advancement of the colonoscope when the variable stiffness function is activated. METHODS: Prospective study enrolling consecutive patients referred for colonoscopy. The variable stiffness colonoscope (Olympus CF-H180DI/L®) was used. We performed univariate and multivariate analyses of factors associated with the success of the variable stiffness function. RESULTS: After the data inclusion period, 260 patients were analyzed. The variable stiffness function was used most in the proximal colon segments (ascending and transverse colon 85%; descending/sigmoid colon 15.2%). The body mass index was lower in patients in whom the endoscope advanced after activating the variable stiffness than those in which it could not be advanced (25.9 + or - 4.8 vs. 28.3 + or - 5.4 kg/m2, p = 0.009). The endoscope advanced less frequently when the stiffness function was activated in the ascending colon versus activation in other segments of the colon (25% vs. 64.5% ascending colon vs. other segments; p < 0.05). In the multivariate analysis, only the colon segment in which the variable stiffness was activated was an independent predictor of advancement of the colonoscope. CONCLUSIONS: The variable stiffness function is effective, allowing the colonoscope advancement especially when applied in the transverse colon, descending colon and sigmoid. However, when used in the ascending colon it has a lower effectiveness.

Myelodysplasia-associated immunophenotypic alterations of bone marrow cells in myeloma: are they present at diagnosis or are they induced by lenalidomide?

Increased risk of acute myeloid leukemia/myelodysplastic syndromes following treatment has been reported in multiple myeloma, but whether dysplastic features are already present at diagnosis remains to be investigated. Using multiparameter flow cytometry, we analyzed the distribution and phenotype of bone marrow hematopoietic cells from 47 multiple myeloma patients (15 symptomatic and 32 high-risk smoldering). From the 32 smoldering myeloma patients, 18 were studied at baseline and 22 after nine cycles of lenalidomide/dexamethasone treatment following the QUIREDEX trial (including 8 from baseline). Phenotypic alterations of bone marrow cells of 7 (47%) symptomatic and 6 (33%) smoldering myeloma patients were detected at baseline; there was no difference in the frequency and extent of phenotypic alterations between symptomatic versus smoldering cases. Likewise, no difference was seen between smoldering myeloma patients studied at baseline versus after lenalidomide/dexamethasone treatment. Our results suggest that phenotypic alterations of bone marrow hematopoietic cells are often present in newly diagnosed symptomatic and smoldering multiple myeloma patients. QUIREDEX trial (NCT00480363).

Does the use of a variable stiffness colonoscope offer advantages during colonoscopy under deep sedation? Results of a randomized trial.

INTRODUCTION: Variable stiffness colonoscope may be useful in performing colonoscopies in nonsedated patients or under endoscopist-controlled sedation. The objective of this study is to evaluate whether this instrument facilitates colonoscopy in patients under deep sedation monitored by an anaesthesiologist. METHODS: Prospective and randomized study enroling consecutive patients referred for colonoscopy under deep sedation monitored by an anaesthesiologist. In group I, a variable stiffness colonoscope was used, whereas in group II, a standard colonoscope was used. The main variable was the need to change the position of the patient during the endoscopy. RESULTS: Fifty-six patients were included in group I (variable stiffness colonoscope) and 54 in group II (standard colonoscope). The caecum was reached in 92.9% of patients in group I and in 90.7% of group II (P=0.7). The time required to reach the caecum was significantly less in group I (6.14±3.5 vs. 7.7±3.8; P=0.035). The variable stiffness colonoscope was effective in 66.7% of cases. Changing the position of the patient was necessary in 12.5% of cases in group I compared with 33.3% of cases in group II (P=0.01). CONCLUSION: The variable stiffness colonoscope avoids the need to change the patient's position and reduces caecal intubation time in patients undergoing colonoscopy under deep sedation controlled by an anaesthesiologist.

Factors associated with non-attendance at outpatient endoscopy.

OBJECTIVE: Non-attendance at endoscopy procedures leads to wasted resources and increased costs. The purpose of this study was to investigate the factors associated with non-attendance. MATERIAL AND METHODS: All patients who attended the outpatient clinic for gastroscopy or colonoscopy examinations were included in the study. Patients who missed their appointment were identified and their data were collected prospectively. Patients who kept their appointment in the same period of time served as controls. RESULTS: Between August 2002 and February 2003, 1051 gastroscopies and 756 colonoscopies were scheduled. A total of 265 patients (14.7%) missed their appointment. No significant differences were found between attendees and non-attendees for mean age, gender, type of examination and day of the week on which the examination was scheduled. The time on the waiting list was longer in patients who did not keep their appointment than in those who did. Fewer appointments were missed in patients with a preferent referral, and among patients referred by their general practitioner a higher percentage failed to keep their appointment compared with those referred by a specialist. In the multivariate analysis, length of time on the waiting list and the source of referral were the only two independent predictive factors for non-attendance. CONCLUSIONS: A longer time on the waiting list and referral by a general practitioner are factors associated with patients failing to keep their endoscopy appointment.