Evaluation of ctDNA in the Prediction of Response to Neoadjuvant Therapy and Prognosis in Locally Advanced Rectal Cancer Patients: A Prospective Study.

"Watch and wait" is becoming a common treatment option for patients with locally advanced rectal cancer (LARC) submitted to neoadjuvant treatment. However, currently, no clinical modality has an acceptable accuracy for predicting pathological complete response (pCR). The aim of this study was to assess the clinical utility of circulating tumor DNA (ctDNA) in predicting the response and prognosis in these patients. We prospectively enrolled a cohort of three Iberian centers between January 2020 and December 2021 and performed an analysis on the association of ctDNA with the main response outcomes and disease-free survival (DFS). The rate of pCR in the total sample was 15.3%. A total of 24 plasma samples from 18 patients were analyzed by next-generation sequencing. At baseline, mutations were detected in 38.9%, with the most common being TP53 and KRAS. Combination of either positive magnetic resonance imaging (MRI) extramural venous invasion (mrEMVI) and ctDNA increased the risk of poor response (p = 0.021). Also, patients with two mutations vs. those with fewer than two mutations had a worse DFS (p = 0.005). Although these results should be read carefully due to sample size, this study suggests that baseline ctDNA combined with mrEMVI could potentially help to predict the response and baseline ctDNA number of mutations might allow the discrimination of groups with different DFS. Further studies are needed to clarify the role of ctDNA as an independent tool in the selection and management of LARC patients.

CAtalyzed Reporter Deposition Fluorescence In Situ Hybridization (CARD-FISH) for Complex Environmental Samples.

CARD-FISH technique allows us to increase microbial cell detection compared to traditional FISH assays. Specific nonfluorescent oligonucleotide probes targeting 16S rRNA genes are employed and are chemically activated by the binding of tyramide molecules, with the latter able to generate a cascade of fluorescence signals, improving sensitivity and reducing background noise. The technique has been successfully applied for the detection of microorganisms in different environmental matrices and under different growth conditions (including those where cells are characterized by low physiological activity and low ribosome content). This chapter presents a straightforward procedure to execute CARD-FISH analysis, from sample preparation and fixation, to microscopic visualization, along with relevant technical notes.

Congestive cirrhosis in Osler-Weber-Rendu syndrome: A rare case report.

Hereditary hemorrhagic telangiectasia or Osler-Weber-Rendu syndrome is a rare autosomal dominant vascular disorder characterized by epistaxis, mucocutaneous telangiectasias, and arteriovenous malformations affecting various organs and systems. The liver is a commonly involved organ (74% of patients with hereditary hemorrhagic telangiectasia), although symptomatic liver disease is quite infrequent. In symptomatic cases, clinical manifestations relate most commonly to the predominant type of vascular shunting present (arteriovenous, arterioportal, or portovenous). Clinically, liver disease can manifest as a high-output cardiac failure, portal hypertension, or biliary disease. Imaging plays an important role in diagnosis, characterization, and follow-up of liver involvement, with ultrasound, computed tomography, magnetic resonance imaging, and angiography being useful in this context. We present a case of congestive cirrhosis with florid liver findings in a patient with Osler-Weber-Rendu syndrome. Imaging findings that clinched the diagnosis are reviewed. A brief literature review is also provided.

Cystic Echinococcosis: A Case of Extrahepatic Intra-Abdominal Involvement.

Hydatid disease, or echinococcal disease, is a parasitic infestation caused by the larval stage of the Echinococcus tapeworm and it primarily affects the liver and lung but involvement of other organs is also possible secondary to peritoneal seeding or hematogeneous dissemination. We describe a rare case of extensive abdominal disease, with lesions affecting the liver, peritoneum, and lesser omentum, requiring aggressive surgical intervention. Complementary diagnostic exams were crucial to reach the diagnosis and evaluate the extension of the disease.

Pulmonary inflammatory myofibroblastic tumor: report of 2 cases with radiologic-pathologic correlation.

Inflammatory myofibroblastic tumor is a rare benign tumor that affects most commonly children and young adults. In the lung, it comprises less than 1% of all neoplasms. The authors describe the clinical, radiological, and pathologic features of 2 cases of incidentally discovered pulmonary inflammatory myofibroblastic tumors.

Small bowel intussusception in 2 adults caused by inflammatory polyps.

Inflammatory fibroid polyps are rare, benign pseudotumors of the gastrointestinal tract of unknown etiology, which may rarely present as bowel intussusception and obstruction. The authors describe the clinical, radiologic, and pathologic features of 2 patients with ileal inflammatory fibroid polyps presenting as small bowel intussusception.

Enrichment of Dehalococcoides mccartyi spp. from a municipal activated sludge during AQDS-mediated bioelectrochemical dechlorination of 1,2-dichloroethane to ethene.

The application of bioelectrochemical systems (BES) for the treatment of chloroethanes has been so far limited, in spite of the high frequency that these contaminants are detected at contaminated sites. This work studied the biodegradation of 1,2-dichloroethane (1,2-DCA) in a lab-scale BES, inoculated with a municipal activated sludge and operated under a range of conditions, spanning from oxidative to reductive, both in the presence and in the absence of the humic acid analogue anthraquinone-2,6-disulfonate (AQDS) as a redox mediator. The results showed stable dechlorination of 1,2-DCA to ethene (up to 65±5µmol/Ld), when the BES was operated at a set potential of -300mV vs. SHE, in the presence of AQDS. Sustained filled-and-draw operation resulted in the enrichment of Dehalococcoides mccartyi. The results of this work provide new insights into the applicability of BES for groundwater remediation and the potential interaction between biogeochemistry and 1,2-DCA in humics-rich contaminated aquifers.

Bioelectrochemically-assisted reductive dechlorination of 1,2-dichloroethane by a Dehalococcoides-enriched microbial culture.

The aim of this study was to verify the possibility to use a polarized graphite electrode as an electron donor for the reductive dechlorination of 1,2-dichloroethane, an ubiquitous groundwater contaminant. The rate of 1,2-DCA dechlorination almost linearly increased by decreasing the set cathode potential over a broad range of set cathode potentials (i.e., from -300 mV to -900 mV vs. the standard hydrogen electrode). This process was primarily dependent on electrolytic H2 generation. On the other hand, reductive dechlorination proceeded (although quite slowly) with a very high Coulombic efficiency (near 70%) at a set cathode potential of -300 mV, where no H2 production occurred. Under this condition, reductive dechlorination was likely driven by direct electron uptake from the surface of the polarized electrode. Taken as a whole, this study further extends the range of chlorinated contaminants which can be treated with bioelectrochemical systems.

[Diabetic hyperosmolality. Retrospective study of 60 cases]. / Hiperosmolaridade diabética. Análise retrospectiva de 60 casos.

AIMS AND METHODS: Our aims were to determine the frequency of diabetic hyperosmolality (DH) in our Department, its causes, therapeutic implications and evolution. A five-years retrospective study was performed in 60 patients regarding age, sex, type and duration of diabetes mellitus (DM), previous antidiabetic therapy, underlying diseases, biochemical data, precipitating factors, therapeutic management and outcome. RESULTS: The hyperosmolar coma was responsible for 90% of the metabolic comas and for 3% of the diabetic patients. The median age of the cohort was 54.6 +/- 9.4 years, being females 61.7% and males 38.3% In 40% no prior diagnosis of DM was made and in the remaining patients the previous antidiabetic therapy was unknown in 61%. Altered consciousness was found in 90%, being 28% in coma. The metabolic acidosis was detectable in 22.2%, the average glycaemia was 956 +/- 267 mg/dl and the osmolality was 349.4 +/- 34.3 mosm/l. The precipitating factors were: poor metabolic control in all patients (HbA1C 12.5 +/- 2.75%), infections in 76.6%, suspension of antidiabetic therapy in 10% and concomitant hyperglycaemic drugs in 6.6% of patients. The global mortality was 20%. CONCLUSIONS: The majority of the situations could be preventable if an attempted screening and diagnosis of DM was made and precipitating factors avoid or promptly treated.

[Diabetic nephropathy. Study protocol for pre-kidney transplantation]. / Nefropatia diabética. Protocolo de estudo pré-transplantação renal.

Between May 1990 and October 1998, 67 diabetic patients with end-stage renal disease, on dialysis, were submitted to a standardized protocol in order to assess the coexistence and degree of other diabetic and nondiabetic complications that could affect transplantation. Some of the results were analysed. Type 2 diabetic patients had more abnormal results on the lower limbs doppler ultrasound and on the lower limbs arteriography than type 1 (p < 0.05). Type 2 diabetic patients had more cardiovascular complications so the decision to transplant should be taken on a case by case basis.

Detection of Dehalococcoides spp. by peptide nucleic acid fluorescent in situ hybridization.

Chlorinated solvents including tetrachloroethene (perchloroethene and trichloroethene), are widely used industrial solvents. Improper use and disposal of these chemicals has led to a widespread contamination. Anaerobic treatment technologies that utilize Dehalococcoides spp. can be an effective tool to remediate these contaminated sites. Therefore, the aim of this study was to develop, optimize and validate peptide nucleic acid (PNA) probes for the detection of Dehalococcoides spp. in both pure and mixed cultures. PNA probes were designed by adapting previously published DNA probes targeting the region of the point mutations described for discriminating between the Dehalococcoides spp. strain CBDB1 and strain 195 lineages. Different fixation, hybridization and washing procedures were tested. The results indicated that the PNA probes hybridized specifically and with a high sensitivity to their corresponding lineages, and that the PNA probes developed during this work can be used in a duplex assay to distinguish between strain CBDB1 and strain 195 lineages, even in complex mixed cultures. This work demonstrates the effectiveness of using PNA fluorescence in situ hybridization to distinguish between two metabolically and genetically distinct Dehalococcoides strains, and they can have strong implications in the monitoring and differentiation of Dehalococcoides populations in laboratory cultures and at contaminated sites.

Efficacy of pentane, toluene, and benzene to support aerobic cometabolism of ethylene dibromide.

The ability of pentane, benzene, and toluene to support aerobic cometabolism of ethylene dibromide (1,2-dibromoethane, EDB) was evaluated. A pentane enrichment culture cometabolized EDB, with a transformation capacity of 0.35 µmol EDB/mg biomass (66.2 µg EDB/mg biomass) in the absence of growth substrate. It also cometabolized EDB while actively growing on pentane. However, enrichment cultures grown on benzene or toluene could not cometabolize EDB, with or without their respective growth substrates.

[Diabetes in the elderly: our reality]. / A diabetes na quarta idade: a nossa realidade.

AIM: To evaluate the impact of the aging of our population in the growing of diabetes prevalence, among patients treated inward at our department. MATERIAL AND METHODS: The clinical files of 242 diabetics older than eighty years, treated between 1999 and 2002 were studied retrospectively. Demographic (sex, age, year of first contact), clinical (causes of admission, co-morbidities, duration of diabetes, previous hypoglycaemic treatment, duration of hospitalisation and evolution) and biochemical (glycaemia, HbA1c, lipaemia and C-peptide) data were recorded. RESULTS: A progressive rising in the number of aged patients was found during this period (seven in 1999 to 55 in 2002), with a large proportion of women (73%). The more frequent causes of in-hospital treatment were hyperglycaemia (20.6%) and feet ulcers (septic or necrotic) (16.5%). In nearly 42% of the cohort an acute infection was found. Diabetes was unknown in 13% of cases and less than ten years of duration in 38%. In this cohort most of the patients (77%) were treated with oral hypoglycaemic drugs, mostly sulfonylureas. HbA1c mean value was 10.4 +/- 2.2%; C -peptide was measured in a subset of cases (n=79), suggesting deficient insulin secretion in 18% of them. The global mean duration of hospitalisation was eleven days. Nineteen patients (8%) died during the hospitalization. CONCLUSIONS: In this study, we concluded that diabetes in people older than 75 years, is being progressively more often diagnosed. The general metabolic control was bad (HbA1c mean value--10.4 +/- 2.2%), with a significant number of patients presenting a deficient C-peptide secretion, worsened by frequent coexisting infections. So, a strengthened clinical care, directed to a careful diagnosis and treatment, may effectively contribute to a better prognosis and quality of life of aged diabetic patients.

[Anaplastic thyroid tumor: retrospective analysis of 12 cases]. / Carcinoma anaplásico da tiróide: análise retrospectiva de 12 casos.

Anaplastic thyroid tumor is a rare tumor and constitutes 5 to 10% of thyroid carcinomas. Is one of the most aggressive solid tumors and the prognosis is always fatal with a mean survival of 3 to 7 months. The current therapeutics are scarce and inefficacious. A retrospective analysis was performed in 12 clinical cases of anaplastic thyroid tumor observed at the Department of Endocrinology, Diabetes and Metabolism of the University Hospital of Coimbra. We analysed data relative to sex, previous thyroid pathology, clinical signs and symptoms, date of diagnosis, treatment and outcome. In this series, the anaplastic thyroid carcinoma showed to be a highly malignant tumor with a mortality rate of 100% with a survival after the diagnosis between 15 days and 9 months.