Transfusion of irradiated red blood cell units with a potassium adsorption filter: A randomized controlled trial.

BACKGROUND: The irradiation of red blood cells (RBCs) causes damage of the RBC membrane with increased potassium (K) leak during storage compared with nonirradiated RBC units of similar age. A previous in vitro study showed a mean reduction of K of 94 ± 5% with a potassium adsorption filter (PAF). STUDY DESIGN AND METHODS: A prospective, single-center, nonblinded, randomized controlled trial (RCT) was designed to evaluate the safety and efficacy of transfusing irradiated RBC units with the PAF. Patients 18 years of age or older who received irradiated RBC units due to chemotherapy-induced anemia were randomly assigned to receive irradiated RBC units with the PAF (PAF group) or with the standard blood infusion set (control group). Primary outcome measures were safety and efficacy of the PAF (absolute change in hemoglobin [Hb] and K, respectively, in patient's blood values after transfusing the irradiated RBC units with or without the PAF). RESULTS: A total of 63 irradiated RBC units were transfused to 17 patients in the control group, and a total of 56 irradiated RBC units were transfused to 13 patients in the PAF group. The absolute change of Hb (9.3 ± 6.3 g/L vs. 8.1 ± 5.8 g/L; p = 0.3) and the absolute change of K (-0.01 ± 0.4 mmol/L vs. -0.01 ± 0.3 mmol/L; p = 0.2) were comparable between the two groups of the trial. CONCLUSION: The transfusion of 1 irradiated RBC unit with the PAF was as safe and efficacious as the transfusion of 1 irradiated RBC unit with the standard blood infusion set in patients with chemotherapy-induced anemia.

Outcomes of treatment of pediatric choroidal neovascularization with intravitreal antiangiogenic agents: the results of the KKESH International Collaborative Retina Study Group.

PURPOSE: To evaluate safety and clinical results of intravitreal antiangiogenic agents for choroidal neovascularization in pediatric patients. METHODS: Retrospective, multicenter, interventional case series. A total of 45 eyes of 39 pediatric patients with choroidal neovascularization of various etiologies were treated with intravitreal injection of antiangiogenic agents (1.25 mg per 0.05 mL of bevacizumab or 0.5 mg per 0.05 mL of ranibizumab). RESULTS: There were 24 girls and 15 boys with group median age of 13 years (range, 3-17 years). Mean follow-up period was 12.8 months (range, 3-60 months). Median visual acuity in terms of logarithm of the minimum angle of resolution at presentation and last follow-up was 0.87 and 0.7, respectively (P = 0.0003). Mean and median number of injections received over the follow-up period was 2.2 and 1, respectively. At the last follow-up, 22 eyes (48%) gained more than 3 lines of vision and 27 eyes (60%) had final visual acuity 20/50 or better. Nine eyes (20%) did not improve and had severe vision loss (20/200 or worse). CONCLUSION: Intravitreal antiangiogenic therapy for choroidal neovascularization in pediatric patients seems temporarily safe and effective in majority of affected eyes. Because of the rarity and character of this condition, it is unlikely that any clinical trials will soon take place to study this or other treatment option.

The chemopreventive capacity of quercetin to induce programmed cell death in hepatocarcinogenesis.

In this study of chemoprevention in the rat modified resistant hepatocyte model, preneoplastic cells were diminished by >60% with quercetin pretreatment compared with those rats treated with N-Diethylnitrosamine (DEN) to induce liver cancer. This decrease occurred associated with an abolished DEN-induced lipid peroxidation as well as activation of caspase 9 and increased caspase 3, as determined by increased expression of cleaved caspase 3 and 9, but not cleaved caspase 8 and increased fragmentation of Poly (ADP-ribose) polymerase (PARP) inducing apoptosis of presumed genetically injured cells, when quercetin was administered before the initiation agent.

ICU Admission Risk Factors for Latinx COVID-19 Patients at a U.S.-Mexico Border Hospital.

OBJECTIVE: Few studies have examined the impact of coronavirus disease 2019 (COVID-19) on the primarily Latinx community along the U.S.-Mexico border. This study explores the socioeconomic impacts which contribute to strong predictors of severe COVID-19 complications such as intensive care unit (ICU) hospitalization in a primarily Latinx/Hispanic U.S.-Mexico border hospital. METHODS: A retrospective, observational study of 156 patients (≥ 18 years) Latinx/Hispanic patients who were admitted for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at a U.S.-Mexico border hospital from April 10, 2020, to May 30, 2020. Descriptive statistics of sex, age, body mass index (BMI), and comorbidities (coronary artery disease, hypertension, diabetes, cancer/lymphoma, current use of immunosuppressive drug therapy, chronic kidney disease/dialysis, or chronic respiratory disease). Multivariate regression models were produced from the most significant variables and factors for ICU admission. RESULTS: Of the 156 hospitalized Latinx patients, 63.5% were male, 84.6% had respiratory failure, and 45% were admitted to the ICU. The average age was 67.2 (± 12.2). Those with body mass index (BMI) ≥ 25 had a higher frequency of ICU admission. Males had a 4.4 (95% CI 1.58, 12.308) odds of ICU admission (p = 0.0047). Those who developed acute kidney injury (AKI) and BMI 25-29.9 were strong predictors of ICU admission (p < 0.001 and p = 0.0020, respectively). Those with at least one reported comorbidity had 1.98 increased odds (95% CI 1.313, 2.99) of an ICU admission. CONCLUSION: Findings show that age, AKI, and male sex were the strongest predictors of COVID-19 ICU admissions in the primarily Latinx population at the U.S.-Mexico border. These predictors are also likely driven by socioeconomic inequalities which are most apparent in border hospitals.

Exploring the Impact of Dawn Phenomenon on Glucose-Guided Eating Thresholds in Individuals With Type 2 Diabetes Using Continuous Glucose Monitoring: Observational Study.

BACKGROUND: Glucose-guided eating (GGE) improves metabolic markers of chronic disease risk, including insulin resistance, in adults without diabetes. GGE is a timed eating paradigm that relies on experiencing feelings of hunger and having a preprandial glucose level below a personalized threshold computed from 2 consecutive morning fasting glucose levels. The dawn phenomenon (DP), which results in elevated morning preprandial glucose levels, could cause typically derived GGE thresholds to be unacceptable or ineffective among people with type 2 diabetes (T2DM). OBJECTIVE: The aim of this study is to quantify the incidence and day-to-day variability in the magnitude of DP and examine its effect on morning preprandial glucose levels as a preliminary test of the feasibility of GGE in adults with T2DM. METHODS: Study participants wore a single-blinded Dexcom G6 Pro continuous glucose monitoring (CGM) system for up to 10 days. First and last eating times and any overnight eating were reported using daily surveys over the study duration. DP was expressed as a dichotomous variable at the day level (DP day vs non-DP day) and as a continuous variable reflecting the percent of days DP was experienced on a valid day. A valid day was defined as having no reported overnight eating (between midnight and 6 AM). ∂ Glucose was computed as the difference in nocturnal glucose nadir (between midnight and 6 AM) to morning preprandial glucose levels. ∂ Glucose ≥20 mg/dL constituted a DP day. Using multilevel modeling, we examined the between- and within-person effects of DP on morning preprandial glucose and the effect of evening eating times on DP. RESULTS: In total, 21 adults (59% female; 13/21, 62%) with non-insulin-treated T2DM wore a CGM for an average of 10.5 (SD 1.1) days. Twenty out of 21 participants (95%) experienced DP for at least 1 day, with an average of 51% of days (SD 27.2; range 0%-100%). The mean ∂ glucose was 23.7 (SD 13.2) mg/dL. People who experience DP more frequently had a morning preprandial glucose level that was 54.1 (95% CI 17.0-83.9; P<.001) mg/dL higher than those who experienced DP less frequently. For within-person effect, morning preprandial glucose levels were 12.1 (95% CI 6.3-17.8; P=.008) mg/dL higher on a DP day than on a non-DP day. The association between ∂ glucose and preprandial glucose levels was 0.50 (95% CI 0.37-0.60; P<.001). There was no effect of the last eating time on DP. CONCLUSIONS: DP was experienced by most study participants regardless of last eating times. The magnitude of the within-person effect of DP on morning preprandial glucose levels was meaningful in the context of GGE. Alternative approaches for determining acceptable and effective GGE thresholds for people with T2DM should be explored and evaluated.

Acute macular neuroretinopathy in dengue virus serotype 1.

PURPOSE: To report a case of acute macular neuroretinopathy (AMN) associated with dengue virus serotype 1 infection. OBSERVATION: An 18-year-old Puerto Rican female was evaluated due to painless paracentral scotomas in each eye that developed after being hospitalized for dengue fever a week before. Clinical examination and multimodal imaging revealed bilateral hypopigmented macular lesions, hyperreflectivity at the outer nuclear and photoreceptor layer, and reduced flow signal in the deep capillary plexus. Additionally, hypoautofluorescent parafoveal lesions were found in the left eye. AMN was diagnosed. Two-month follow-up after the initial evaluation showed resolution of symptoms but persistence of some findings on optical coherence tomography. CONCLUSIONS AND IMPORTANCE: Patients with dengue virus serotype 1 may develop paracentral scotomas with classic AMN findings and obtain complete symptomatic recovery without treatment.

Novel Homozygous LRP5 Mutations in Mexican Patients with Osteoporosis-Pseudoglioma Syndrome.

AIMS: Osteoporosis-pseudoglioma syndrome (OPPG) is an uncommon autosomal recessive disorder characterized by the rare association of early-onset osteoporosis and severe ocular abnormalities such as persistent fetal vasculature and microphthalmia. Biallelic mutations in the low-density lipoprotein receptor-related protein-5 gene (LRP5) have been associated with OPPG. We present clinical and genetic data from three Mexican OPPG patients, a pair of sibs, and a sporadic case. MATERIALS AND METHODS: Three patients underwent clinical examination, including a complete ophthalmic evaluation. Based on the clinical diagnosis of OPPG, the entire coding sequence of LRP5 was polymerase chain reaction-amplified and directly Sanger-sequenced. Genetic testing was extended to the parents of the affected patients. RESULTS: Phenotypic variability was observed in the familial case and molecular analysis identified a novel homozygous c.1145C>T, p.(Pro382Leu) variant in both sibs. As expected, their parents were heterozygous carriers. The sporadic patient exhibited a severe osseous phenotype, microphthalmia, and neurological symptoms. In this patient, homozygosity for the c.442C>T, p.(Gln148*) variant was demonstrated, whereas her parents were heterozygous carriers. The p.(Pro382Leu) pathogenic mutation has been previously reported only in a compound heterozygous state in OPPG patients. CONCLUSIONS: Two novel homozygous missense and nonsense variants were demonstrated in three OPPG cases from Mexico. Our results expand the spectrum of disease-causing LRP5 mutations. This is the first report of OPPG in our population and our findings may potentially add to a genotype-phenotype correlation.

[The role of developmental HOX genes in cervical cancer]. / El papel de los genes del desarrollo tipo HOX en el cáncer cervicouterino.

Cervical cancer (CC) is a multifactorial disease associated to genetic, environmental and epigenetic factors, being the infection by human papillomavirus the main etiologic agent. Additionally, the alteration in the expression of transcription factors has been considered of importance for the development of this tumor. HOX genes encode a group of transcription factors involved in cellular proliferation and differentiation processes during the development of embryonic structures in vertebrates; their aberrant expression is associated with tumorigenesis and metastasis. A range of evidence suggests a role for HOX genes in the development of cervical neoplastic cell. Studies in CC cell lines, primary tumors and premalignant lesions have suggested the involvement of HOXA1, HOXC5, C6, C8 and C10, HOXD9 and HOXD13 in the process of cervical carcinogenesis. Also, the de novo expression of genes HOXB2, B4, B13 and HOXC11-C13 appears to be involved in the process of malignant transformation of cervical epithelial cell. These data would allow to open a field in search of new molecular markers in cervical cancer and the development of new therapeutic strategies for this malignancy.

El cáncer cervicouterino (CaCU) es una enfermedad multifactorial que se asocia a factores genéticos, ambientales y epigenéticos, y cuyo principal agente etiológico es la infección por el virus del papiloma humano. Además, la alteración en la expresión de factores de transcripción ha sido considerada de importancia para el desarrollo de esta neoplasia. Los genes HOX codifican un grupo de factores de transcripción que participan en los procesos de proliferación y diferenciación celular durante el desarrollo de las estructuras embrionarias en los vertebrados; y su expresión aberrante ha sido asociada con oncogénesis y metástasis. Una serie de evidencias sugiere un papel importante para los genes HOX en el desarrollo neoplásico de la célula cervical. Estudios realizados en líneas celulares de CaCU, lesiones premalignas y tumores primarios han sugerido el involucramiento de HOXA1, HOXC5, C6, C8 y C10, HOXD9 y HOXD13 en el proceso de carcinogénesis cervical. Asimismo, la expresión de novo de los genes HOXB2, B4, B13 y HOXC11-C13 parece estar involucrada en el proceso de transformación maligna de la célula del epitelio cervical. Estos datos permitirían abrir un campo en la búsqueda de nuevos marcadores moleculares en cáncer cervical y en el desarrollo de nuevas estrategias terapéuticas para atender esta neoplasia.

Delayed-onset, bleb-associated endophthalmitis caused by Lecythophora mutabilis.

PURPOSE: To report delayed-onset, bleb-associated endophthalmitis caused by Lecythophora mutabilis. DESIGN: Interventional case report. METHODS: Description of an otherwise healthy woman who developed delayed-onset fungal endophthalmitis associated with a preexisting filtering bleb. RESULTS: A 57-year-old woman who underwent trabeculectomy with Mitomycin C in her left eye 8 years earlier presented with a 10-day history of pain and decreased vision in her left eye. She underwent anterior chamber and vitreous taps and injection of intraocular antibiotics. Cultures grew the mold Lecythophora mutabilis. The patient underwent treatment with intraocular and systemic antifungal agents, three pars plana vitrectomies, partial iridectomy, and cryopexy to the bleb and angle structures. Four months after her last treatment, her left eye shows no residual infection, and vision corrects to 20/80. CONCLUSION: Bleb-associated endophthalmitis caused by L. mutabilis is resistant to amphotericin B but responsive to intravitreal and systemic voriconazole together with pars plana vitrectomy, iridectomy, and cryopexy to the bleb and angle structures.

Optical coherence tomographic findings in acute exudative polymorphous vitelliform maculopathy.

PURPOSE: To report two cases of acute exudative polymorphous vitelliform maculopathy. DESIGN: Observational case reports. METHODS: Fluorescein angiography, optical coherence tomography, and electrophysiology were performed. RESULTS: Both patients presented with sudden onset of blurred vision and bilaterally symmetric, central, and perimacular vitelliform lesions. Perimacular lesions were faintly hyperfluorescent early in the disease, but there was no abnormal fluorescence in the macular centers. Optical coherence tomography revealed anterior displacement of the photoreceptor layer by a hypereflective subretinal layer overlying a hyporeflective space above the retinal pigment epithelium-choriocapillaris complex under all lesions and no subretinal fluid. The electrooculogram was abnormal. Near complete resolution occurred over 4 to 8 months, with no improvement in the electrooculogram. CONCLUSIONS: Transient multifocal vitelliform lesions suggest a diagnosis of acute exudative polymorphous vitelliform maculopathy. Optical coherence tomography reveals characteristic anterior displacement of the photoreceptor layer by a subretinal hypereflective deposit similar to that seen in adult-onset foveomacular vitelliform dystrophy.

Cellular retinol binding protein 1 could be a tumor suppressor gene in cervical cancer.

AIMS: Cervical Cancer (CC) is one of the most important health problems in women. It frequently presents genetic changes at chromosome region 3q21. This region contains the Cellular Retinol Binding Protein 1 gene (CRBP1) which has been implicated as an important element in the development of other types of cancer. The main goal of the present work was to determine the molecular alterations of CRBP1 and its relationship to CC. METHODS: To determine the molecular alterations of CRBP1 gene in CC; twenty-six CC and twenty-six healthy cervix samples were evaluated for: 1) Copy number gain by real-time PCR analysis, 2) expression levels by an immunohistochemistry assay on tissue microarray, and 3) the methylation status of the CRBP1 promoter region. RESULTS: The increase in CRBP1 copy number was observed in 10 out of the 26 CC samples analyzed, while healthy cervices samples showed no changes in the copy number. In addition, there was a lack of expression of the CRBP1 gene in an important number of the CC samples (17/26), and the CRBP1 gene promoter was methylated in 15/26 of the CC samples. Interestingly, there was a significant association between the lack of expression of the CRBP1 gene and its methylation status. CONCLUSIONS: The data indicates that, both activating and inactivating changes in the CRBP1 gene could be significant events in the development and progression of CC, and the lack of expression of the CRBP1 protein could be related with to the development of CC. We believe that there is enough evidence to consider to CRBP1 gene as a tumor suppressor gene for CC.

Anti-inflammatory, antioxidant and cytotoxicity activities of methanolic extract and prenylated flavanones isolated from leaves of Eysehardtia platycarpa.

From the methanolic extract of Eysenhardtia platycarpa (leaves), were isolated the prenylated flavanones: 5,7-dihydroxy-6-methyl-8-prenylflavanone (1), 5,7-dihydroxy-6-methyl-8-prenyl-4'-methoxy-flavanone (2), 5,7-dihydroxy-6-prenylflavanone (3), 5-dihydroxy-7-methoxy-6-prenylflavanone (4), 5,7-dihydroxy-8-prenyl-4'-methoxy-flavanone (5). Methanolic extract of E. platycarpa (leaves) and flavanones (5), (2) and (3) showed anti-inflammatory activity according to tested quantities. In addition, flavanone (5) revealed the best percentage reduction of free radical DPPH. Finally, after cytotoxic activity study, the methanolic extract from E. platycarpa leaves and flavanone (4) exhibited promising cytotoxic activity on brine shrimp.

Low frequency of human papillomavirus infection in conjunctival squamous cell carcinoma of Mexican patients.

BACKGROUND: The relationship between Human Papillomavirus (HPV) infection and conjunctiva cancer is controversial. HPV detection will provide more information about the role of this infectious agent in the biology of conjunctiva cancer. In the present study, DNA extracted and purified from 36 Conjunctival Squamous Cell Carcinomas (CSCC) was evaluated by PCR for HPV DNA sequences. The results were correlated with the clinical and histopathological variables. RESULTS: The results showed that HPV DNA was present in 8 CSCC samples (22%); HPV16 was the sole type detected. Significant association was found between HPV detection and the limbus tumor subtype (p = 0.03). All the samples were non-metastatic squamous cell carcinoma. CONCLUSIONS: The HPV presence in CSCC from Mexican patients is not a common event.

Co-expression of metalloproteinases 11 and 12 in cervical scrapes cells from cervical precursor lesions.

The metalloproteinases (MMP) 11 and 12 have been shown to be expressed in cervical cancer (CC). In order to extend our previous results, these MMPs were evaluated in cervical precursor lesions. One hundred seventeen cervical scrapes: thirty-six normal, thirty-six low grade squamous lesions (LSIL), thirty-six high grade (HSIL), nine CC; and, also ninety-nine paraffin-embedded cervical lesions: fifteen normal cervices, thirty eight LSIL, sixteen HSIL, and five CC were collected. The samples were analyzed for relative expression by real time RT-PCR or immunohistochemistry assay. We were able to identify a relative increased expression of MMP11 in 75% and 78% from LSIL and HSIL samples, respectively. While MMP12 expression was 64% and 75% in LSIL and HSIL, respectively. Positive samples for MMP11 expression were also positive for MMP12 expression and also increased according to illness progression. In the tissues, MMP11 or MMP12 expression was observed in the cytoplasm of the neoplastic cells, while in the normal epithelium was absent. The reaction was always stronger for MMP12 than MMP11. MMP11 expression was present in 77% and 66% of LSIL and HSIL, while MMP12 expression was 73% and 68%. There was a relationship between MMP11 or MMP12 expression and HPV infection. Our data are showing a relationship between diagnostic of precursor lesions and the MMP11 and 12 expressions, suggesting that their expression could be an early event in the neoplastic lesions of the cervix and could have clinical significance.