Effect of a multimodal intervention in breast Cancer patients undergoing neoadjuvant therapy: A study protocol of the multimodal project.

BACKGROUND AND AIMS: To determine the effect of a multimodal intervention (nutritional behavior change and physical exercise) on quality of life, chemotherapy response rate and tolerance, histopathological level of the tumor, body composition, and biochemical parameters, in patients diagnosed with breast cancer during neoadjuvant chemotherapy treatment, and to compare them with the control group. METHODS: Anticipated 80 patients diagnosed with breast cancer aged 18-70 years will be recruited for this randomized, unblinded clinical trial based on a nutritional behavior change and physical exercise in patients during the approximately 6 months in which the patient receives neoadjuvant treatment. Participants will be randomly allocated (1:1) to one of two groups (intervention or control). Primary and secondary outcomes will be assessed before the beginning and after the neoadjuvant treatment (before surgery). The primary outcome is quality of life, whereas secondary outcomes include chemotherapy response rate and tolerance, histopathological level of the tumor and body composition (i.e., visceral adipose tissue activity, bone, lean and fat masses). We will analyze blood parameters (i.e., biochemical, inflammatory, and tumor markers) as exploratory outcomes. CONCLUSION: This study will address the influence of a practical and viable multimodal intervention (i.e., nutritional behavior change and physical exercise) on breast cancer patients undergoing neoadjuvant chemotherapy. Given the practical viability of the intervention in real-world settings, our study holds promise for significant scientific and clinical implications.

Adults with metabolically healthy overweight or obesity present more brown adipose tissue and higher thermogenesis than their metabolically unhealthy counterparts.

BACKGROUND: There is a subset of individuals with overweight/obesity characterized by a lower risk of cardiometabolic complications, the so-called metabolically healthy overweight/obesity (MHOO) phenotype. Despite the relatively higher levels of subcutaneous adipose tissue and lower visceral adipose tissue observed in individuals with MHOO than individuals with metabolically unhealthy overweight/obesity (MUOO), little is known about the differences in brown adipose tissue (BAT). METHODS: This study included 53 young adults (28 women) with a body mass index (BMI) ≥25 kg/m2 which were classified as MHOO (n = 34) or MUOO (n = 19). BAT was assessed through a static 18F-FDG positron emission tomography/computed tomography scan after a 2-h personalized cooling protocol. Energy expenditure, skin temperature, and thermal perception were assessed during a standardized mixed meal test (3.5 h) and a 1-h personalized cold exposure. Body composition was assessed by dual-energy x-ray absorptiometry, energy intake was determined during an ad libitum meal test and dietary recalls, and physical activity levels were determined by a wrist-worn accelerometer. FINDINGS: Participants with MHOO presented higher BAT volume (+124%, P = 0.008), SUVmean (+63%, P = 0.001), and SUVpeak (+133%, P = 0.003) than MUOO, despite having similar BAT mean radiodensity (P = 0.354). In addition, individuals with MHOO exhibited marginally higher meal-induced thermogenesis (P = 0.096) and cold-induced thermogenesis (+158%, P = 0.050). Moreover, MHOO participants showed higher supraclavicular skin temperature than MUOO during the first hour of the postprandial period and during the cold exposure, while no statistically significant differences were observed in other skin temperature parameters. We observed no statistically significant differences between MHOO and MUOO in thermal perception, body composition, outdoor ambient temperature exposure, resting metabolic rate, energy intake, or physical activity levels. INTERPRETATION: Adults with MHOO present higher BAT volume and activity than MUOO. The higher meal- and cold-induced thermogenesis and cold-induced supraclavicular skin temperature are compatible with a higher BAT activity. Overall, these results suggest that BAT presence and activity might be linked to a healthier phenotype in young adults with overweight or obesity. FUNDING: See acknowledgments section.

Diagnostic relevance of 2-[18 F]-FDG PET/CT in patients recently diagnosed with monoclonal gammopathy of undetermined significance.

2-[18 F]-FDG PET/CT is a useful diagnostic technique to assess bone and soft tissue disease in multiple myeloma (MM) but is not recommended by the International Myeloma Working Group for the evaluation of monoclonal gammopathy of undetermined significance (MGUS). The objective of this study was to evaluate the role of 2-[18 F]-FDG PET/CT in the management of these patients. An observational retrospective study was conducted on 338 patients with MGUS who underwent 2-[18 F]-FDG PET/CT. The mean age was 70.80 ± 11.84 years, and 69.2% of patients had cardiovascular risk factors. Patients were classified according to their progression risk (Mayo Clinic). The mean post-diagnosis follow-up was 8.35 ± 14.46 months. Pathological findings were recorded in 49 patients: 30 with myeloma bone lesions (15 in the initial study and 15 in follow-up) and 19 with other neoplastic (n = 13) or pathologically significant findings (n = 6). Body mass index, monoclonal component rate (MCR) > 1 g/dL and ≥1 risk factors for MM were significant in univariate logistic regression analyses. The MCR emerged as the main predictor of a positive 2-[18 F]-FDG PET/CT in adjusted multivariate regression analysis, with an area under the receiver operating characteristic curve of 0.785 and cutoff for optimal sensitivity/specificity of 1.0 ng/mL (71.4% sensitivity, 71.2% specificity). 2-[18 F]-FDG PET/CT results correctly classify patients with MGUS and could improve the detection of bone lesions over existing techniques, with the additional possibility of detecting neoplastic processes. The best parameter to predict a positive 2-[18 F]-FDG PET/CT was the MCR.

Beyond SARS-CoV-2: epidemiological surveillance of respiratory viruses in Jalisco, Mexico.

Introduction: Respiratory viral infections represent a significant global health burden. Historically, influenza, rhinovirus, respiratory syncytial virus, and adenovirus have been the prevalent viruses; however, the landscape shifted with the widespread emergence of SARS-CoV-2. The aim of this study is to present a comprehensive epidemiological analysis of viral respiratory infections in Jalisco, Mexico. Methods: Data encompassing individuals with flu-like symptoms from July 2021 to February 2023 was scrutinized for viral diagnosis through PCR multiplex. The effect of social mobility on the increase in respiratory viral diagnosis infection was considered to estimate its impact. Additionally, sequences of respiratory viruses stored in public databases were retrieved to ascertain the phylogenetic classification of previously reported viruses in Mexico. Results: SARS-CoV-2 was the most detected virus (n = 5,703; 92.2%), followed by influenza (n = 479; 7.78%). These viruses were also found as the most common co-infection (n = 11; 50%), and for those with influenza, a higher incidence of severe disease was reported (n = 122; 90.4%; p < 0.001). Regarding comorbidities and unhealthy habits, smoking was found to be a risk factor for influenza infection but a protective factor for SARS-CoV-2 (OR = 2.62; IC 95%: 1.66-4.13; OR = 0.65; IC 95%: 0.45-0.94), respectively. Furthermore, our findings revealed a direct correlation between mobility and the prevalence of influenza infection (0.214; p < 0.001). Discussion: The study presents evidence of respiratory virus reemergence and prevalence during the social reactivation, facilitating future preventive measures.

An Upgrade on the Surveillance System of SARS-CoV-2: Deployment of New Methods for Genetic Inspection.

SARS-CoV-2 variants surveillance is a worldwide task that has been approached with techniques such as Next Generation Sequencing (NGS); however, this technology is not widely available in developing countries because of the lack of equipment and limited funding in science. An option is to deploy a RT-qPCR screening test which aids in the analysis of a higher number of samples, in a shorter time and at a lower cost. In this study, variants present in samples positive for SARS-CoV-2 were identified with a RT-qPCR mutation screening kit and were later confirmed by NGS. A sample with an abnormal result was found with the screening test, suggesting the simultaneous presence of two viral populations with different mutations. The DRAGEN Lineage analysis identified the Delta variant, but there was no information about the other three mutations previously detected. When the sequenced data was deeply analyzed, there were reads with differential mutation patterns, that could be identified and classified in terms of relative abundance, whereas only the dominant population was reported by DRAGEN software. Since most of the software developed to analyze SARS-CoV-2 sequences was aimed at obtaining the consensus sequence quickly, the information about viral populations within a sample is scarce. Here, we present a faster and deeper SARS-CoV-2 surveillance method, from RT-qPCR screening to NGS analysis.

RT-qPCR Assays for Rapid Detection of the N501Y, 69-70del, K417N, and E484K SARS-CoV-2 Mutations: A Screening Strategy to Identify Variants With Clinical Impact.

Background: Several variants of the SARS-CoV-2 have been documented globally during the current COVID-19 pandemic. The N501Y, 69-70del, K417N, and E484K SARS-CoV-2 mutations have been documented among the most relevant due to their potential pathogenic biological effects. This study aimed to design, validate, and propose a fast real-time RT-qPCR assay to detect SARS-CoV-2 mutations with possible clinical and epidemiological relevance in the Mexican population. Methods: Targeting spike (S) gene mutations of SARS-CoV-2 (N501Y, 69-70del, K417N, and E484K), specific primers, and probes for three specific quantitative reverse transcription PCR (RT-qPCR) assays were designed, and validated using Sanger sequencing. These assays were applied in clinical samples of 1060 COVID-19 patients from Jalisco Mexico. Results: In silico analyzes showed high specificity of the three assays. Amplicons of samples were confirmed through sequencing. The screening of samples of COVID-19 patients allowed the identification of the E484K mutation in nine individuals and the identification of P.2 Brazilian variant in Mexico. Conclusion: This work provides low-cost RT-qPCR assays for rapid screening and molecular surveillance of mutations with potential clinical impact. This strategy allowed the detection of E484K mutation and P.2 variant for the first time in samples from the Mexican population.

Activating brown adipose tissue through exercise (ACTIBATE) in young adults: Rationale, design and methodology.

AIMS: The energy expenditure capacity of brown adipose tissue (BAT) makes it an attractive target as a therapy against obesity and type 2 diabetes. BAT activators namely catecholamines, natriuretic peptides and certain myokines, are secreted in response to exercise. ACTIBATE will determine the effect of exercise on BAT activity and mass measured by positron emission tomography/computed tomography (PET/CT, primary outcome) in young adults. ACTIBATE will also investigate the physiological consequences of activating BAT (secondary outcomes). METHODS: ACTIBATE will recruit 150 sedentary, healthy, young adults (50% women) aged 18-25 years. Eligible participants will be randomly assigned to a non-exercise group (n ≈ 50) or one of two exercise groups (n=50 each). Participants in the exercise groups will perform aerobic and strength training 3-4 days/week at a heart rate equivalent to 60% of heart rate reserve (HRres), and at 50% of 1 repetition maximum (RM) for the moderate-intensity group, and at 80% of HRres and 70% RM for the vigorous-intensity group. Laboratory measures completed at baseline and 6 months include BAT activity and mass, resting energy expenditure, meal and cold-induced thermogenesis, body temperature regulation and shivering threshold, body composition and cardiovascular disease risk factors. We will also obtain biopsies from abdominal subcutaneous white adipose tissue and skeletal muscle to analyse the expression of genes encoding proteins involved in the thermogenic machinery. DISCUSSION: Findings from ACTIBATE will have significant implications for our understanding of exercise and its protective effects against the development of type 2 diabetes, obesity and related metabolic diseases. ClinicalTrials.gov ID: NCT02365129.

[Nosocomial myiasis in Latin America and the Caribbean: an overlooked reality?]. / Miasis nosocomiales en América Latina y el Caribe: ¿una realidad ignorada?

Nosocomial myiasis is an infestation by fly larvae that occurs while a patient is hospitalized. To analyze the available information on nosocomial myiasis in Latin America and the Caribbean, a search was done for cases published in the last 52 years. Nine clinical cases were found for Brazil, Costa Rica, French Guiana, Honduras, and Jamaica. Two other publications mention 139 cases in El Salvador and some 32 in Colombia, respectively. The patients and environments described presented conditions that predispose to this type of infestation. Compulsory notification is not usually required for nosocomial myiasis in Latin America and the Caribbean, meaning that there is probably considerable underreporting. Awareness needs to be raised and registry improved of myiasis in the region to aid in adoption of better prevention measures, which will benefit patient care during hospitalization.

Miasis nosocomiales en América Latina y el Caribe: ¿una realidad ignorada? / Nosocomial myiasis in Latin America and the Caribbean: an overlooked reality?

Las miasis nosocomiales son infestaciones por larvas de mosca que se producen después de la hospitalización del paciente. Para analizar la información disponible sobre miasis nosocomiales en América Latina y el Caribe, se realizó una búsqueda de casos publicados en los últimos 52 años. Se encontraron nueve casos clínicos en Brasil, Costa Rica, Guayana Francesa, Honduras y Jamaica. También existen dos publicaciones con datos agregados que mencionan 139 casos en El Salvador y alrededor de 32 en Colombia. Los pacientes y el entorno descritos en los casos presentaron condiciones que predisponen a este tipo de infestaciones. Las miasis nosocomiales en América Latina y el Caribe no suelen ser de declaración obligatoria, por lo que es probable que exista un importante subregistro. Es necesario crear conciencia y mejorar el registro de estas miasis en la región para tomar las medidas más adecuadas de prevención, que beneficien el cuidado del paciente durante su hospitalización.

Nosocomial myiasis is an infestation by fly larvae that occurs while a patient is hospitalized. To analyze the available information on nosocomial m yiasis in Latin America and the Caribbean, a search was done for cases published in the last 52 years. Nine clinical cases were found for Brazil, Costa Rica, French Guiana, Honduras, and Jamaica. Two other publications mention 139 cases in El Salvador and some 32 in Colombia, respectively. The patients and environments described presented conditions that predispose to this type of infestation. Compulsory notification is not usually required for nosocomial myiasis in Latin America and the Caribbean, meaning that there is probably considerable underreporting. Awareness needs to be raised and registry improved of myiasis in the region to aid in adoption of better prevention measures, which will benefit patient care during hospitalization.

Ability of FDG-PET/CT in the detection of gallbladder cancer.

PURPOSE: To assess the value of FDG-PET/CT in the evaluation of gallbladder carcinomas (GBC). METHODS: A prospective cohort of patients with suspicion of or confirmed GBC was studied with FDG-PET/CT. Diagnostic accuracy parameters were calculated in comparison with pathology and/or the clinical course of patients. Clinical impact of PET/CT imaging was estimated. RESULTS: Forty-nine patients were enrolled (34 malignant tumors, 15 benign lesions; 37 staging, 12 restaging). Overall diagnostic accuracy was 95.9% for the diagnosis of the primary lesion, 85.7% for lymph node involvement and 95.9% for metastatic disease. Mean SUVmax in malignant gallbladder lesions was 7.92 ± 6.25 Analysis of ROC curves showed a SUVmax cut-off value of 3.62 for malignancy (S: 78.1%; Sp: 88.2%). Diagnostic accuracy in the restaging group reached 100%. FDG-PET/CT changed the management of 22.4% of the population. COMMENTS: Diagnosis of malignancy or benignity of suspicious gallbladder lesions is accurately made with FDG PET/CT, allowing a precise staging of GBC due to its ability to identify unsuspected metastatic disease. SUVmax has a complementary role in addition to visual analysis.

The value of metabolic imaging to predict tumour response after chemoradiation in locally advanced rectal cancer.

BACKGROUND: We aim to investigate the possibility of using 18F-positron emission tomography/computer tomography (PET-CT) to predict the histopathologic response in locally advanced rectal cancer (LARC) treated with preoperative chemoradiation (CRT). METHODS: The study included 50 patients with LARC treated with preoperative CRT. All patients were evaluated by PET-CT before and after CRT, and results were compared to histopathologic response quantified by tumour regression grade (patients with TRG 1-2 being defined as responders and patients with grade 3-5 as non-responders). Furthermore, the predictive value of metabolic imaging for pathologic complete response (ypCR) was investigated. RESULTS: Responders and non-responders showed statistically significant differences according to Mandard's criteria for maximum standardized uptake value (SUVmax) before and after CRT with a specificity of 76,6% and a positive predictive value of 66,7%. Furthermore, SUVmax values after CRT were able to differentiate patients with ypCR with a sensitivity of 63% and a specificity of 74,4% (positive predictive value 41,2% and negative predictive value 87,9%); This rather low sensitivity and specificity determined that PET-CT was only able to distinguish 7 cases of ypCR from a total of 11 patients. CONCLUSIONS: We conclude that 18-F PET-CT performed five to seven weeks after the end of CRT can visualise functional tumour response in LARC. In contrast, metabolic imaging with 18-F PET-CT is not able to predict patients with ypCR accurately.

[Diagnostic efficacy and discriminatory capacity of positron emission tomography combined with axial tomography of adrenal lesions]. / Efectividad diagnóstica de la tomografía por emisión de positrones con (18)fluorodeoxiglucosa asociada a tomografía axial en la discriminación de benignidad o malignidad de las lesiones suprarrenales.

INTRODUCTION: The usefulness of 18fluorodeoxyglucose positron emission tomography combined with axial tomography (PET-CT) in diagnosing whether adrenal tumours are benign or malignant is assessed. MATERIAL AND METHODS: A retrospective study conducted between June 2005 and May 2009 on a consecutive series of patients on whom a PET-CT scan was performed to study suspected malignant adrenal disease. Focal uptakes were assessed, along with the maximum standard uptake value (SUV), and the ratio of the maximum adrenal/hepatic value. The sensitivity, specificity, positive and negative predictive value of the test, the maximum adrenal uptake values and the ratio for those where the diagnostic yield was maximum. RESULTS: Fifteen patients were included. The final diagnosis showed malignancy in eight and seven were benign. Ten patients had adrenal uptake: three in benign lesions and seven in neoplasias, with a mean uptake value of 6.3 (3.2 in benign lesions and 9.0 in malignant lesions). The mean adrenal/hepatic ratio was 1.8 (0.9 in benign and 2.6 in malignant lesions). When the presence of adrenal uptake is associated with a final diagnosis of malignancy, we obtained a sensitivity of 87.5%, a specificity of 57.1%, and a positive and negative predictive value of 70% and 80%, respectively. An SUV cut-off value of 6, or an adrenal/hepatic uptake ratio of 2, gave a sensitivity of 75%, a specificity of 100%, and a positive and negative predictive value of 100% and 77.7%, respectively. CONCLUSIONS: PET-CT has a high ability to discriminate between benign and malignant lesions in the adrenal disease studied.