ABSTRACT
Pancreatic ductal adenocarcinoma represents one of the solid tumors showing the worst prognosis worldwide, with a high recurrence rate after adjuvant or neoadjuvant therapy. Circulating tumor DNA analysis raised as a promising non-invasive tool to characterize tumor genomics and to assess treatment response. In this study, surgical tumor tissue and sequential blood samples were analyzed by next-generation sequencing and were correlated with clinical and pathological characteristics. Thirty resectable/borderline pancreatic ductal adenocarcinoma patients treated at the Hospital Universitario de Navarra were included. Circulating tumoral DNA sequencing identified pathogenic variants in KRAS and TP53, and in other cancer-associated genes. Pathogenic variants at diagnosis were detected in patients with a poorer outcome, and were correlated with response to neoadjuvant therapy in borderline pancreatic ductal adneocarcinoma patients. Higher variant allele frequency at diagnosis was associated with worse prognosis, and thesum of variant allele frequency was greater in samples at progression. Our results build on the potential value of circulating tumor DNA for non-metastatic pancreatic ductal adenocarcinoma patients, by complementing tissue genetic information and as a non-invasive tool for treatment decision. Confirmatory studies are needed to corroborate these findings.
Subject(s)
Carcinoma, Pancreatic Ductal , Circulating Tumor DNA , Pancreatic Neoplasms , Humans , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/blood , Circulating Tumor DNA/genetics , Circulating Tumor DNA/blood , Male , Female , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/blood , Aged , Middle Aged , Prognosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/blood , High-Throughput Nucleotide Sequencing/methods , Gene Frequency , Proto-Oncogene Proteins p21(ras)/genetics , Aged, 80 and over , Tumor Suppressor Protein p53/genetics , MutationABSTRACT
In ecosystems, natural radionuclides are present in the environment and living organisms. The 238U natural decay chain produces multiple radioactive elements, such as 234U, 226Ra, 210Pb, and 210Po. These radionuclides can be found in air, water, rocks, soil, and other biotic and abiotic components, mainly derived from minerals, such as zircon and apatite. In this study, we determined the activity concentration of radionuclides from the 238U decay chain in the sediment of a coastal ecosystem on the southern Mexican coast in the western Caribbean, an ecosystem minimally affected by industrial activities. Methods included high-resolution gamma-ray spectrometry and alpha-particle spectrometry. Results showed that the sediment samples had an activity concentration range of 18.2-36.6 Bq/kg for 238U, 25.0-41.4 Bq/kg for 234U, 10.1-37.3 Bq/kg for 210Pb, and 29.9-46.0 Bq/kg for 210Po. Water samples ranged between 17.9 and 36.3 mBq/L and 27.9-66.0 mBq/L for 238U and 234U, respectively. The activity concentration of these radionuclides in the sediment and water of this area is compared with that of other coral reefs worldwide, providing a radiometric baseline for comparison purposes.
Subject(s)
Coral Reefs , Geologic Sediments , Radiation Monitoring , Water Pollutants, Radioactive , Water Pollutants, Radioactive/analysis , Geologic Sediments/chemistry , Uranium/analysis , Caribbean Region , Ecosystem , Radioisotopes/analysisABSTRACT
Background: The treatment of minimal change disease (MCD) consists of a high dose of steroids for several months, implying significant drug toxicity. Nevertheless, relapses of steroid-sensitive MCD usually respond to lower doses of steroids. Methods: The objective of this study was to analyze whether a low dose of steroids (LDS) is effective for the treatment of MCD relapses. Since 2018, new relapses of steroid-sensitive adult patients with MCD in three Spanish centers have been treated with LDS. The cumulative dose of steroids, the time to remission, and the relapse-free time were compared between relapses treated with LDS and previous relapses of the same patients treated with a standard dose of steroids (SDS). Results: A total of 51 relapses in 31 patients were treated with LDS and compared with 48 historical relapses of the same patients treated with SDS. The mean doses of prednisone adjusted by weight for the initial treatment were 0.45 mg/kg (0.40-0.51 mg/kg) in the relapses treated with LDS and 0.88 mg/kg (0.81-1.00 mg/kg) in those treated with SDS. The mean cumulative doses of prednisone in LDS- and SDS-treated relapses were 1,191 mg (801-1,890 mg) and 3,700 mg (2,755-5,800 mg), respectively. The duration of treatment was 63 days (42-117 days) in the LDS group and was 140 days (65-195 days) in the SDS group. All patients achieved complete remission within 1 month after steroid therapy in both groups. The times to remission of the LDS and SDS groups were 19.10 ± 12.80 and 18.93 ± 12.98 days, respectively (p = 0.95). Conclusion: Among the steroid-sensitive patients with MCD, relapse therapy with LDS (0.5 mg/kg) appears effective and allows minimization of the steroid cumulative dose.
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This paper presents information on the morphological, morphometric, and dental sex differences in the dwarf round ray Urotrygon nana. We recorded 12 morphological traits, sex, the distribution pattern of dermal denticles, the number of tooth rows, and the tooth shape of 466 individuals. The disc width of females ranged from 50 to 172 mm and that of males ranged from 53 to 135 mm. A neuronal classification model and a correspondence analysis showed that female disc width was 21.5% broader, and the distance from the rostrum to the anus was 17.7% longer than that of males, whereas males presented 19.5% greater distance between the nostrils, 9.7% greater preorbital snout length, 6.8% greater cloaca to caudal-fin length, 2.7% greater interorbital distance, and 1.1% greater total length than females. The disc of adult males, including the abdominal cavity area, was densely covered with dermal denticles, which were slightly larger than those observed in females. Females presented homodont dentition with molariform teeth and a smooth lozenge-shaped crown with rounded margins. Males exhibited homodonty but with tooth morphology variations in individuals of different sizes (from molariforms to sharper cusp teeth). There were changes in disc shape (from subcircular to oval), distribution and size of dermal denticles (more abundant and larger), and tooth shape (from molariform to monocuspid teeth) during male development, from neonates to adults. U. nana exhibited sexual dimorphism in size, disc shape, number and shape of teeth, and distribution and size of dermal denticles.
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OBJECTIVE: To evaluate the impact of the different types of neoplasms and lineages on mortality of patients with SLE. METHODS: Retrospective and observational comparison of the neoplasm-related deaths in patients with SLE and the general Spanish population reported in the Spanish Hospital Discharge Database. To determine the impact of SLE on the risk of dying from each neoplasm lineage, a binary logistic regression considering age, female sex, tobacco and alcohol consumption, was performed. RESULTS: During 2016-2019, 139 531 in-hospital deaths from neoplasms were certified in Spain (91 in patients with SLE). Patients with SLE presented a lower mortality rate from solid organ neoplasms, (80.2% vs 91.1%, OR 0.393), linked to their lower risk of colorectal carcinoma (1.1% vs 10.8%, OR 0.110). By contrast, gynaecological neoplasms presented a higher risk (8.8% vs 3%, OR 3.039) in the deceased patients with SLE, associated with the higher frequency of vulvar neoplasms (2% vs 0.2%, OR 14.767) and cervical carcinomas (3.3% vs 0.5%, OR 3.809). Haematological neoplasm-related deaths were also more prevalent in patients with SLE (19.8% vs 8.9%, OR 2.546), mostly attributable to the higher proportion of deaths due to non-Hodgkin's lymphoma (11% vs 2.9%, OR 4.060) of B cell lineage (9.9% vs 2.5%, OR 4.133). CONCLUSIONS: Patients with SLE present a higher risk of death from vulvar neoplasms, cervical carcinomas and B-cell non-Hodgkin's lymphoma in comparison with the general Spanish population. In addition to developing strategies that might help to attenuate their occurrence and impact, such as decreasing the immunosuppressive burden, specific early detection programmes for these conditions should be investigated and considered carefully.
Subject(s)
Carcinoma , Genital Neoplasms, Female , Lupus Erythematosus, Systemic , Lymphoma, Non-Hodgkin , Female , Humans , Carcinoma/complications , Genital Neoplasms, Female/complications , Lupus Erythematosus, Systemic/complications , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/epidemiology , Registries , Retrospective Studies , MaleABSTRACT
Our goal was to assess the coagulation profile in the immediate postoperative time after major liver surgery and its association with the liver function. Our hypothesis is that a decreased synthesis of the coagulation factor levels reflects an impaired liver synthesis following hepatic resection and will be associated with poor outcomes. This is a prospective, observational study recruiting consecutive patients scheduled for major liver resection in a tertiary hospital. Coagulation profile was assessed by conventional assays, viscoelastic assays and coagulation factor levels preoperatively and, on postoperative days 1, 2 and 6. Factor VIII to protein C (FVIII/PC) ratio has been used as a surrogate marker of hemostatic imbalance. Liver function was measured with conventional and indocyanine green (ICG) clearance tests, which were obtained preoperatively and on postoperative days 1 and 2. Sixty patients were recruited and 51 were included in the study. There is a clear increase in FVIII/PC ratio after surgery, which was significantly associated with low liver function, being more pronounced beyond postoperative day 2 and in patients with poorer liver function ( P â<â0.001). High FVIII/PC ratio values were significantly associated with higher postoperative morbidity, prolonged ICU and hospital stay and less survival ( P â<â0.05). High FVIII/PC ratio on postoperative day 2 was found to be predictor of posthepatectomy liver failure (PHLF; area under the ROC curveâ=â0.8129). Early postoperative high FVIII/PC ratio values are associated with low liver function, PHLF and poorer outcomes in patients undergoing major hepatic resection.
Subject(s)
Hepatectomy , Liver Function Tests , Humans , Carcinoma, Hepatocellular/surgery , Factor VIII , Hemostatics , Hepatectomy/adverse effects , Liver Neoplasms/surgery , Postoperative Complications/etiology , Protein C/analysis , Retrospective StudiesABSTRACT
BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.
Subject(s)
Diabetes Mellitus, Type 2 , Glomerulonephritis , Kidney Diseases , Adult , Humans , Middle Aged , Cohort Studies , Kidney Diseases/complications , Glomerulonephritis/drug therapy , Glomerulonephritis/complications , Proteinuria/etiology , Proteinuria/complications , Serum Albumin , Sodium , Glucose , Diabetes Mellitus, Type 2/complicationsABSTRACT
Background: Genetic causes are increasingly recognized in patients with focal segmental glomerulosclerosis (FSGS), but it remains unclear which patients should undergo genetic study. Our objective was to determine the frequency and distribution of genetic variants in steroid-resistant nephrotic syndrome FSGS (SRNS-FSGS) and in FSGS of undetermined cause (FSGS-UC). Methods: We performed targeted exome sequencing of 84 genes associated with glomerulopathy in patients with adult-onset SRNS-FSGS or FSGS-UC after ruling out secondary causes. Results: Seventy-six patients met the study criteria; 24 presented with SRNS-FSGS and 52 with FSGS-UC. We detected FSGS-related disease-causing variants in 27/76 patients (35.5%). There were no differences between genetic and non-genetic causes in age, proteinuria, glomerular filtration rate, serum albumin, body mass index, hypertension, diabetes or family history. Hematuria was more prevalent among patients with genetic causes. We found 19 pathogenic variants in COL4A3-5 genes in 16 (29.3%) patients. NPHS2 mutations were identified in 6 (16.2%) patients. The remaining cases had variants affecting INF2, OCRL, ACTN4 genes or APOL1 high-risk alleles. FSGS-related genetic variants were more common in SRNS-FSGS than in FSGS-UC (41.7% vs 32.7%). Four SRNS-FSGS patients presented with NPHS2 disease-causing variants. COL4A variants were the most prevalent finding in FSGS-UC patients, with 12 patients carrying disease-causing variants in these genes. Conclusions: FSGS-related variants were detected in a substantial number of patients with SRNS-FSGS or FSGS-UC, regardless of age of onset of disease or the patient's family history. In our experience, genetic testing should be performed in routine clinical practice for the diagnosis of this group of patients.
ABSTRACT
Copper nanoparticles (CuNPs) can be synthesized by green methods using plant extracts. These methods are more environmentally friendly and offer improved properties of the synthesized NPs in terms of biocompatibility and functional capabilities. Traditional medicine has a rich history of utilization of herbs for millennia, offering a viable alternative or complementary option to conventional pharmacological medications. Plants of traditional herbal use or those with medicinal properties are candidates to be used to obtain NPs due to their high and complex content of biocompounds with different redox capacities that provide a dynamic reaction environment for NP synthesis. Other synthesis conditions, such as salt precursor concentration, temperature, time synthesis, and pH, have a significant effect on the characteristics of the NPs. This paper will review the properties of some compounds from medicinal plants, plant extract obtention methods alternatives, characteristics of plant extracts, and how they relate to the NP synthesis process. Additionally, the document includes diverse applications associated with CuNPs, starting from antibacterial properties to potential applications in metabolic disease treatment, vegetable tissue culture, therapy, and cardioprotective effect, among others.
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BACKGROUND: Multidrug-resistant Gram-negative bacterial (MRGNB) infections represent a major public health threat. Cancer patients and, among them, hematological patients are most vulnerable to these infections. Gut colonization by MRGNB is a common phenomenon occurring during hospitalization and chemotherapy exposure. In the neutropenic phase that occurs after chemotherapy, MRGNB translocation occurs increasing patient's mortality. Fluoroquinolone prophylaxis with ciprofloxacin or levofloxacin efficacy is now being questioned due to the increase of incidence in MRGNB. METHODS: A phase III randomized, controlled, clinical trial, open-label parallel-group with a 1:1 ratio, aimed to demonstrate the non-inferiority of oral fosfomycin versus oral ciprofloxacin for febrile neutropenia prevention in patients with acute leukemia (AL) or hematopoietic cell transplant (HSC) receptors. Weekly surveillance cultures are planned to detect gut colonization. Changes in fecal microbiome at the beginning and end of prophylaxis will also be analyzed. DISCUSSION: This trial will provide evidence of the efficacy of an alternative drug to ciprofloxacin for febrile neutropenia prevention in high-risk hematological patients. The battery of planned microbiological studies will allow us to evaluate prospectively the microbiological safety of both pharmacological strategies in terms of the selection of MRGNB occurring in each arm. In addition, valuable information on the way in which each drug changes the fecal microbiome of the patients throughout the treatment will be generated. TRIAL REGISTRATION: Clinical trials NCT05311254, Registered on 5 April 2022, https://clinicaltrials.gov/ct2/show/NCT05311254?term=FOVOCIP&cntry=ES&draw=2&rank=1 . PROTOCOL VERSION: 3.0, dated 20 May 2022.
Subject(s)
Febrile Neutropenia , Fosfomycin , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Humans , Ciprofloxacin/adverse effects , Fosfomycin/therapeutic use , Febrile Neutropenia/diagnosis , Febrile Neutropenia/drug therapy , Anti-Bacterial Agents/adverse effectsABSTRACT
Photoproteins, luminescent proteins or optoproteins are a kind of light-response protein responsible for the conversion of light into biochemical energy that is used by some bacteria or fungi to regulate specific biological processes. Within these specific proteins, there are groups such as the photoreceptors that respond to a given light wavelength and generate reactions susceptible to being used for the development of high-novel applications, such as the optocontrol of metabolic pathways. Photoswitchable proteins play important roles during the development of new materials due to their capacity to change their conformational structure by providing/eliminating a specific light stimulus. Additionally, there are bioluminescent proteins that produce light during a heatless chemical reaction and are useful to be employed as biomarkers in several fields such as imaging, cell biology, disease tracking and pollutant detection. The classification of these optoproteins from bacteria and fungi as photoreceptors or photoresponse elements according to the excitation-emission spectrum (UV-Vis-IR), as well as their potential use in novel applications, is addressed in this article by providing a structured scheme for this broad area of knowledge.
Subject(s)
Bacteria , Luminescent Proteins/metabolism , Bacteria/metabolismABSTRACT
Invasive aspergillosis (IA) is a major cause of morbidity and mortality in patients receiving allogeneic haematopoieticcell transplantation. The deep immunosuppression and a variety of potential additional complications developed in these patients result in IA reaching mortality rates of around 50-60%. This mortality is even higher when the patients are infected with azole-resistant isolates, demonstrating that, despite the complexity of management, adequate azole treatment can have a beneficial effect. It is therefore paramount to understand the reasons why antifungal treatment of IA infections caused by azole-susceptible isolates is often unsuccessful. In this respect, there are already various factors known to be important for treatment efficacy, for instance the drug concentrations achieved in the blood, which are thus often monitored. We hypothesize that antifungal persistence may be another important factor to consider. In this study we present two case reports of haematological patients who developed proven IA and suffered treatment failure, despite having been infected with susceptible isolates, receiving correct antifungal treatment and reaching therapeutic levels of the azole. Microbiological analysis of the recovered infective isolates showed that the patients were infected with multiple strains, several of which were persisters to voriconazole and/or isavuconazole. Therefore, we propose that azole persistence may have contributed to therapeutic failure in these patients and that this phenomenon should be considered in future studies.
ABSTRACT
Monoclonal gammopathies (MGs) are a wide range of diseases that may evolve or progress over time. Comorbidity plays a critical role in this setting. The co-occurrence of two MGs is not a rare event. The evidence on the association of systemic light chain (AL) amyloidosis and multiple myeloma (MM) is scarce and controversial. Herein we aim to address this topic in a large series of patients of a referral center. All consecutive AL amyloidosis patients treated at our center from January 2005 to April 2023 were prospectively enrolled in a clinical and epidemiological registry. 141 patients diagnosed with AL amyloidosis were included, of which 7 (5%) had localized whereas 134 presented with systemic disease. The heart was the most frequently affected organ (90.3%). 25 patients (18.7%) fulfilled the IMWG diagnostic criteria of MM (AL/MM). Time-dependent association between AL and MM showed that the synchronous pattern is more frequent than the appearance of a second primary malignancy. The diagnostic delay was six months (m). Patients with AL/MM had a poorer median overall survival (OS) than AL-only patients (35.5 m, CI 95% 0-88.9, vs. 52.6 m, CI 95% 16.7-88.5), but this difference was not statistically significant. The prognosis in AL is dominated by the heart involvement, which is massive in this series. In our Cox regression model, only three prognostic variables remain as independent prognostic factors: age, N-terminal pro-brain natriuretic peptide (≥8500 ng/L), and undergoing an autologous stem cell transplant, whereas left ventricular ejection fraction shows a marginal effect. More and large studies focusing on the AL/MM association are needed to uncover the characteristics and prognostic impact of this association.
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INTRODUCTION: Metabolic syndrome (MetS), prediabetes (PreDM) and Fatty Liver Disease (FLD) share pathophysiological pathways concerning type 2 diabetes mellitus (T2DM) onset. The non-invasive assessment of fatty liver combined with PreDM and MetS features screening might provide further accuracy in predicting hyperglycemic status in the clinical setting with the putative description of singular phenotypes. The objective of the study is to evaluate and describe the links of a widely available FLD surrogate -the non-invasive serological biomarker Hepatic Steatosis Index (HSI)- with previously described T2DM risk predictors, such as preDM and MetS in forecasting T2DM onset. PATIENTS AND METHODS: A retrospective ancillary cohort study was performed on 2799 patients recruited in the Vascular-Metabolic CUN cohort. The main outcome was the incidence of T2DM according to ADA criteria. MetS and PreDM were defined according to ATP III and ADA criteria, respectively. Hepatic steatosis index (HSI) with standardized thresholds was used to discriminate patients with FLD, which was referred as estimated FLD (eFLD). RESULTS: MetS and PreDM were more common in patients with eFLD as compared to those with an HSI < 36 points (35% vs 8% and 34% vs. 18%, respectively). Interestingly, eFLD showed clinical effect modification with MetS and PreDM in the prediction of T2DM [eFLD-MetS interaction HR = 4.48 (3.37-5.97) and eFLD-PreDM interaction HR = 6.34 (4.67-8.62)]. These findings supported the description of 5 different liver status-linked phenotypes with increasing risk of T2DM: Control group (1,5% of T2DM incidence), eFLD patients (4,4% of T2DM incidence), eFLD and MetS patients (10,6% of T2DM incidence), PreDM patients (11,1% of T2DM incidence) and eFLD and PreDM patients (28,2% of T2DM incidence). These phenotypes provided independent capacity of prediction of T2DM incidence after adjustment for age, sex, tobacco and alcohol consumption, obesity and number of SMet features with a c-Harrell=0.84. CONCLUSION: Estimated Fatty Liver Disease using HSI criteria (eFLD) interplay with MetS features and PreDM might help to discriminate patient risk of T2DM in the clinical setting through the description of independent metabolic risk phenotypes. [Correction added on 15 June 2023, after first online publication: The abstract section was updated in this current version.].
Subject(s)
Diabetes Mellitus, Type 2 , Metabolic Syndrome , Non-alcoholic Fatty Liver Disease , Prediabetic State , Humans , Diabetes Mellitus, Type 2/complications , Glucose , Retrospective Studies , Cohort Studies , Metabolic Syndrome/epidemiology , Metabolic Syndrome/complications , Prediabetic State/epidemiology , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/complications , Phenotype , Risk FactorsABSTRACT
Bispecific antibodies are a promising type of therapy for the treatment of cancer due to their ability to simultaneously inhibit different proteins playing a role in cancer progression. The development in lung cancer has been singularly intense because of the increasingly vast knowledge of the underlying molecular routes, in particular, in oncogene-driven tumors. In this review, we present the current landscape of bispecific antibodies for the treatment of lung cancer and discuss potential scenarios where the role of these therapeutics might expand in the near future.
Subject(s)
Antibodies, Bispecific , Lung Neoplasms , Humans , Antibodies, Bispecific/therapeutic use , Lung Neoplasms/pathology , ImmunotherapyABSTRACT
Circulating tumor DNA (ctDNA) has emerged as a promising non-invasive source to characterize genetic alterations related to the tumor. Upper gastrointestinal cancers, including gastroesophageal adenocarcinoma (GEC), biliary tract cancer (BTC) and pancreatic ductal adenocarcinoma (PADC) are poor prognostic malignancies, usually diagnosed at advanced stages when no longer amenable to surgical resection and show a poor prognosis even for resected patients. In this sense, ctDNA has emerged as a promising non-invasive tool with different applications, from early diagnosis to molecular characterization and follow-up of tumor genomic evolution. In this manuscript, novel advances in the field of ctDNA analysis in upper gastrointestinal tumors are presented and discussed. Overall, ctDNA analyses can help in early diagnosis, outperforming current diagnostic approaches. Detection of ctDNA prior to surgery or active treatment is also a prognostic marker that associates with worse survival, while ctDNA detection after surgery is indicative of minimal residual disease, anticipating in some cases the imaging-based detection of progression. In the advanced setting, ctDNA analyses characterize the genetic landscape of the tumor and identify patients for targeted-therapy approaches, and studies show variable concordance levels with tissue-based genetic testing. In this line, several studies also show that ctDNA serves to follow responses to active therapy, especially in targeted approaches, where it can detect multiple resistance mechanisms. Unfortunately, current studies are still limited and observational. Future prospective multi-center and interventional studies, carefully designed to assess the value of ctDNA to help clinical decision-making, will shed light on the real applicability of ctDNA in upper gastrointestinal tumor management. This manuscript presents a review of the evidence available in this field up to date.
ABSTRACT
BACKGROUND: Thrombotic microangiopathy (TMA) is a complication of malignant hypertension (mHTN) attributed to high blood pressure (BP). However, no studies have investigated in patients with mHTN of different aetiologies whether the presence of TMA is associated with specific causes of mHTN. METHODS: We investigated the presence of TMA (microangiopathic haemolytic anaemia and thrombocytopenia) in a large and well-characterized cohort of 199 patients with mHTN of different aetiologies [primary HTN 44%, glomerular diseases 16.6%, primary atypical haemolytic uraemic syndrome (aHUS) 13.1%, renovascular HTN 9.5%, drug-related HTN 7%, systemic diseases 5.5%, endocrine diseases 4.5%]. Outcomes of the study were kidney recovery and kidney failure. RESULTS: Patients with TMA [40 cases (20.1%)] were younger, were more likely female and had lower BP levels and worse kidney function at presentation. Their underlying diseases were primary aHUS (60%), drug-related mHTN (15%), glomerular diseases [all of them immunoglobulin A nephropathy (IgAN); 10%], systemic diseases (10%) and primary HTN (5%). The presence of TMA was 92.3% in primary aHUS, 42.9% in drug-related HTN, 36.4% in systemic diseases, 12.1% in glomerular diseases and 2.3% in primary HTN. No patient with renovascular HTN or mHTN caused by endocrine diseases developed TMA, despite BP levels as high as patients with TMA. A higher proportion of TMA patients developed kidney failure as compared with patients without TMA (56.4% versus 38.9%, respectively). CONCLUSIONS: The presence of TMA in patients with mHTN should guide the diagnosis towards primary aHUS, drug-related mHTN, some systemic diseases and IgAN, while it is exceptional in other causes of mHTN.
Subject(s)
Atypical Hemolytic Uremic Syndrome , Hypertension, Malignant , Hypertension , Kidney Diseases , Purpura, Thrombotic Thrombocytopenic , Renal Insufficiency , Thrombotic Microangiopathies , Humans , Female , Hypertension, Malignant/complications , Thrombotic Microangiopathies/complications , Purpura, Thrombotic Thrombocytopenic/complications , Purpura, Thrombotic Thrombocytopenic/diagnosis , Kidney , Atypical Hemolytic Uremic Syndrome/diagnosis , Kidney Diseases/complications , Renal Insufficiency/complications , Hypertension/complicationsABSTRACT
Metamaterials are broadly defined as artificial, electromagnetically homogeneous structures that exhibit unusual physical properties that are not present in nature. They possess extraordinary capabilities to bend electromagnetic waves. Their size, shape and composition can be engineered to modify their characteristics, such as iridescence, color shift, absorbance at different wavelengths, etc., and harness them as biosensors. Metamaterial construction from biological sources such as carbohydrates, proteins and nucleic acids represents a low-cost alternative, rendering high quantities and yields. In addition, the malleability of these biomaterials makes it possible to fabricate an endless number of structured materials such as composited nanoparticles, biofilms, nanofibers, quantum dots, and many others, with very specific, invaluable and tremendously useful optical characteristics. The intrinsic characteristics observed in biomaterials make them suitable for biomedical applications. This review addresses the optical characteristics of metamaterials obtained from the major macromolecules found in nature: carbohydrates, proteins and DNA, highlighting their biosensor field use, and pointing out their physical properties and production paths.