Tailored treatment of female indirect inguinal hernias by using single-port laparoscopic percutaneous internal ring suture: a comparison between children and adults.

PURPOSE: To compare the outcome of indirect inguinal hernias repaired by using single-port laparoscopic percutaneous internal ring suture (SPIRS) between the pediatric and adult females. METHODS: The medical records of females who were clinically assessed to have inguinal hernia from Oct. 2016 to May 2022 were reviewed. Patients who received laparoscopy for the diagnosis of the hernia type and customized treatment according to their hernia type were included, while those who chose other operation methods initially were excluded. The patients were divided into the adult and pediatric groups based on their age. The demographic characteristics, hernia types, operation durations, and outcomes were analyzed between these two groups. RESULTS: A total of 65 adults and 60 children were included in this study. The median age was 38 years. (range: 23-88) for group A and 3 years (range: 0.1-16) for group P. Indirect hernias were present in 85% of adults and 100% of children. All the indirect hernias were repaired by SPIRS uneventfully. Incidence of contralateral patent processus vaginalis was 24% in adults and 50% in children (p = 0.016). The average operation time was 22/46 min (one/two sides) for the adults and 9/15 min (one/two sides) for the pediatrics (p < 0.010 for both). The overall complication rates were 5.4% and 3.3% for the adult and pediatric group respectively (p = 0.106). No recurrence was observed in the pediatric group, but two adults experienced recurrence and another had chronic postoperative inguinal pain, necessitating reoperation. The mean follow-up period was 38.6 ± 15.4 months for adults and 42.8 ± 18.9 months for children (p = 0.198). CONCLUSION: Our results support that the pathogenesis of indirect inguinal hernia for the female adults is due to the non-obliteration of a congenital processus vaginalis. Tailored treatment of the female IIH by using single-port laparoscopic percutaneous internal ring suture may be an alternative for the management of female IHs.

A phase I study to evaluate the safety, pharmacokinetics, and pharmacodynamics of PF-06939999 (PRMT5 inhibitor) in patients with selected advanced or metastatic tumors with high incidence of splicing factor gene mutations.

BACKGROUND: Protein arginine methyltransferase 5 (PRMT5) methylates multiple substrates dysregulated in cancer, including spliceosome machinery components. PF-06939999 is a selective small-molecule PRMT5 inhibitor. PATIENTS AND METHODS: This phase I dose-escalation and -expansion trial (NCT03854227) enrolled patients with selected solid tumors. PF-06939999 was administered orally once or twice a day (q.d./b.i.d.) in 28-day cycles. The objectives were to evaluate PF-06939999 safety and tolerability to identify maximum tolerated dose (MTD) and recommended part 2 dose (RP2D), and assess pharmacokinetics (PK), pharmacodynamics [changes in plasma symmetric dimethylarginine (SDMA) levels], and antitumor activities. RESULTS: In part 1 dose escalation, 28 patients received PF-06939999 (0.5 mg q.d. to 6 mg b.i.d.). Four of 24 (17%) patients reported dose-limiting toxicities: thrombocytopenia (n = 2, 6 mg b.i.d.), anemia (n = 1, 8 mg q.d.), and neutropenia (n = 1, 6 mg q.d.). PF-06939999 exposure increased with dose. Steady-state PK was achieved by day 15. Plasma SDMA was reduced at steady state (58%-88%). Modulation of plasma SDMA was dose dependent. No MTD was determined. In part 2 dose expansion, 26 patients received PF-06939999 6 mg q.d. (RP2D). Overall (part 1 + part 2), the most common grade ≥3 treatment-related adverse events included anemia (28%), thrombocytopenia/platelet count decreased (22%), fatigue (6%), and neutropenia (4%). Three patients (6.8%) had confirmed partial response (head and neck squamous cell carcinoma, n = 1; non-small-cell lung cancer, n = 2), and 19 (43.2%) had stable disease. No predictive biomarkers were identified. CONCLUSIONS: PF-06939999 demonstrated a tolerable safety profile and objective clinical responses in a subset of patients, suggesting that PRMT5 is an interesting cancer target with clinical validation. However, no predictive biomarker was identified. The role of PRMT5 in cancer biology is complex and requires further preclinical, mechanistic investigation to identify predictive biomarkers for patient selection.

Quasi-bound atoms in collective dynamics of liquid Sb.

We report anab initiosimulation and theoretical study of collective dynamics in liquid Sb at 973 K. An application of the GCM (generalized collective modes) theoretical approach to analysis of simulation-derived time correlation functions resulted in two types of propagating eigenmodes. We found that the almost flat dispersion of the high-frequency branch of propagating modes can be explained by out-of-phase oscillations of nearest neighbors which form quasi-bound atomic pairs for at least 30 ps. We discuss the features of collective dynamics in non-simple metallic melts containing quasi-bound pairs.

Psychological impact after treatment in patients with head and neck cancer.

BACKGROUND: Cancer is the second cause of death all over the world and it causes considerable morbidity, disability, and treatment sequela, which often lead to post-treatment pain and disfigurement. This study aims to evaluate such physical sequelae, and their psychological, (cognitive and emotional), impact, in a cohort of patients treated for Head and Neck (HNC) cancer, in search for methods to help such patients deal effectively with the psychological effects of their cancer treatments adverse consequences. MATERIAL AND METHODS: The sample consists of 56 subjects, 47 men and 9 women, ranging from 47 years to 86 years of age, who were treated for head and neck cancers at Spanish Public General Hospital in the Otolaryngology Unit, Surgery Section. Two types of questionnaires were used in the study: the Questionnaire of Sequelae after Treatment of head and neck carcinoma and the State-Trait Anxiety Inventory (STAI-E and R). RESULTS: With respect to anxiety, the study found high levels of state anxiety which was significantly associated with the degree of perception of social stigma but was not associated with the post-treatment sequelae themselves nor with the level of discomfort that such symptomatic sequelae produced. The presence of a post-surgical stoma with cannula, increased patient's stigma (both components: external rejection and self-rejection) and state anxiety ratings, while there was no difference in state anxiety between cannulated and non-cannulated patients. There are few differences between men and women in terms of the presence of anxiety and their responses are similar in terms of the after-effects of surgery. CONCLUSIONS: Our study confirmed that current treatments for Head and Neck carcinoma generate adverse symptomatic sequela that impose significant psychological and physical burden for these patients. We will discuss the various pathways for preventive intervention that these findings open up.

Cerebrovascular risk factors and their time-dependent effects on stroke survival in the EMMA cohort study

To investigate the time-dependent effects of traditional risk factors on functional disability in all-cause mortality post-stroke, we evaluated data from a long-term stroke cohort. Baseline cerebrovascular risk factors (CVRF) and functionality at 1 and 6 months were evaluated in survivors from a prospective stroke cohort using the modified Rankin scale (m-RS), which classifies participants as improvement of disability, unchanged disability (at least moderate), and worsening disability. Cox regression models considering baseline risk factors, medication use, and functionality 6 months after stroke were fitted to identify their time-dependent effects up to 12 years of follow-up. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) are presented. Among 632 survivors (median age 68, 54% male, 71% first-ever episode), age and functional disability (unchanged and worsening) 6 months after ischemic stroke had time-dependent effects on all-cause mortality risk up to 12 years of follow-up. The most impacting risk factors were unchanged (at least moderate) (HR, 2.99; 95%CI: 1.98-4.52) and worsening disability (HR, 2.85; 95%CI: 1.26-6.44), particularly in the first two years after a stroke event (Time 1: ≥6 mo to <2.5 y). Worsening disability also impacted mortality in the period from ≥2.5 to <7.5 years (Time 2) of follow-up (HR, 2.43 (95%CI: 1.03-5.73). Other baseline factors had a fixed high-risk effect on mortality during follow-up. Post-stroke and continuous medication use had a fixed protective effect on mortality. Functional disability was the main contributor with differential risks of mortality up to 12 years of follow-up.

Data-driven decision making for the screening of cognitive impairment in primary care: a machine learning approach using data from the ELSA-Brasil study

The systematic assessment of cognitive performance of older people without cognitive complaints is controversial and unfeasible. Identifying individuals at higher risk of cognitive impairment could optimize resource allocation. We aimed to develop and test machine learning models to predict cognitive impairment using variables obtainable in primary care settings. In this cross-sectional study, we included 8,291 participants of the baseline assessment of the ELSA-Brasil study, who were aged between 50 and 74 years and were free of dementia. Cognitive performance was assessed with a neuropsychological battery and cognitive impairment was defined as global cognitive z-score below 2 standard deviations. Variables used as input to the prediction models included demographics, social determinants, clinical conditions, family history, lifestyle, and laboratory tests. We developed machine learning models using logistic regression, neural networks, and gradient boosted trees. Participants' mean age was 58.3±6.2 years, 55% were female. Cognitive impairment was present in 328 individuals (4%). Machine learning algorithms presented fair to good discrimination (areas under the ROC curve between 0.801 and 0.873). Extreme Gradient Boosting presented the highest discrimination, high specificity (97%), and negative predictive value (97%). Seventy-six percent of the individuals with cognitive impairment were included among the highest ranked individuals by this algorithm. In conclusion, we developed and tested a machine learning model to predict cognitive impairment based on primary care data that presented good discrimination and high specificity. These characteristics could support the detection of patients who would not benefit from cognitive assessment, facilitating the allocation of human and economic resources.

Association of coronary artery calcium with heart rate variability in the Brazilian Longitudinal Study of Adult Health - ELSA-Brasil

Current data shows that the autonomic and vascular systems can influence each other. However, only a few studies have addressed this association in the general population. We aimed to investigate whether heart rate variability (HRV) was associated with coronary artery calcium (CAC) in a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We examined baseline data from 3138 participants (aged 35 to 74 years) without previous cardiovascular disease who underwent CAC score assessment and had validated HRV recordings. Prevalent CAC was defined as a CAC score>0, and HRV analyses were performed over 5-min segments. We detected CAC score>0 in 765 (24.4%) participants. Subgroup analyses in older participants (≥49 years) adjusted for sociodemographic and clinical variables revealed that CAC score>0 was associated with lower values of standard deviation of NN intervals (SDNN) (odds ratio [OR]=1.32; 95%CI: 1.05,1.65), root mean square of successive differences between adjacent NN intervals (RMSSD) (OR=1.28; 95%CI: 1.02,1.61), and low frequency (LF) (OR=1.53, 95%CI: 1.21,1.92). Interaction analysis between HRV indices and sex in age-stratified groups revealed significant effect modification: women showed increased OR for prevalent CAC in the younger group, while for men, the associations were in the older group. In conclusion, participants aged ≥49 years with low SDNN, RMSSD, and LF values were more likely to present prevalent CAC, suggesting a complex interaction between these markers in the pathogenesis of atherosclerosis. Furthermore, our results suggested that the relationship between CAC and HRV might be sex- and age-related.

Eight-year change in carotid intima-media thickness and associated risk factors in adults with and without psoriasis - the ELSA-Brasil cohort study

The longitudinal association between psoriasis and carotid intima-media thickness (CIMT) has not yet been established. This study aimed do compare CIMT and its change (∆CIMT) after an 8-year follow-up according to psoriasis diagnosis and the association with risk factors in the ELSA-Brasil study. Data from 7564 participants were analyzed (median age of 50.0 [44.0-57.0] years, 56.9% women). CIMT was assessed by ultrasound and ∆CIMT was calculated by subtracting baseline values from follow-up values. Psoriasis participants were identified by self-reported medical diagnosis (n=143) and compared with matched participants without disease (n=572) and with the entire sample without psoriasis (n=7421). Baseline CIMT explained the 8-year CIMT increase only in 36.9% among psoriasis participants and in ∼43.0% in participants without disease. CIMT was associated with age (β=0.002, P=0.002) and hypertension (β=0.029, P=0.034) in psoriasis participants. Among participants without psoriasis, CIMT was associated with age, male sex, low educational attainment, past smoking, obesity, diabetes, hypertension, and dyslipidemia (P<0.05). There was an inverse association of CIMT with private health insurance (β=-0.004, P=0.042) and White ethnicity (β=-0.006, P=0.004) in the entire sample without psoriasis but not in matched participants. Psoriasis participants showed an inverse association between ∆CIMT and diabetes (β=-0.214, P=0.011), while the entire sample without psoriasis showed an inverse association between ∆CIMT and age (β=-0.005, P<0.001), past smoking (β=-0.048, P=0.009), and hypertension (β=-0.048, P=0.009). In conclusion, psoriasis was not associated with CIMT after an 8-year follow-up. The inverse association of ∆CIMT with diabetes in psoriasis participants needs further clarification.

Multiomics in the central Arctic Ocean for benchmarking biodiversity change.

Multiomics approaches need to be applied in the central Arctic Ocean to benchmark biodiversity change and to identify novel species and their genes. As part of MOSAiC, EcoOmics will therefore be essential for conservation and sustainable bioprospecting in one of the least explored ecosystems on Earth.

Short duration of upper extremity lymphedema correlates with a favorable cytokine response after lymph node transfer surgery.

Vascularized lymph node transfer surgery (VLNT) can provide benefit to lymphedema patients. Cytokines may play a role in the development of lymphedema and in the regeneration of lymphatic vessels after VLNT. Our primary aim was to investigate whether the VLNT patients have a specific cytokine profile. Our secondary aim was to see whether the preoperative lymphedema or severity affects the postoperative cytokine response. Wound exudate was gathered from 18 patients undergoing VLNT on the first and sixth postoperative day (POD). The concentrations of IL-10, TNF-α, TGF-ß1 and VEGF-C were analyzed using enzymelinked immune-sorbent assays. A general score was generated to assess the benefit of the surgery. The changes in cytokine concentrations (1st POD-6th POD) were correlated with the pre- and postoperative lymphedema related factors. A shorter duration of lymphedema preoperatively correlated with an increase in the concentration of IL-10 and TNF-ß during the first six PODs (IL-10: r=0.495, p=0.051; TNF-α: r=0.737, p=0.006) and a decrease in the concentration of TGF-ß1 (r= -0.613, p=0.020). The increase of the concentration of TNF-α during the first six PODs also correlated with a greater total general score (r=0.775, p=0.005) and hence indicated a better response to the surgery. The patients with a shorter duration of lymphedema preoperatively had a more favorable cytokine response during the first six PODs after VLNT.

Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer.

The majority of high-grade serous ovarian cancers (HGSCs) are deficient in homologous recombination (HR) DNA repair, most commonly due to mutations or hypermethylation of the BRCA1/2 genes. We aimed to discover how BRCA1/2 mutations shape the cellular phenotypes and spatial interactions of the tumor microenvironment. Using a highly multiplex immunofluorescence and image analysis we generate spatial proteomic data for 21 markers in 124,623 single cells from 112 tumor cores originating from 31 tumors with BRCA1/2 mutation (BRCA1/2mut), and from 13 tumors without alterations in HR genes. We identify a phenotypically distinct tumor microenvironment in the BRCA1/2mut tumors with evidence of increased immunosurveillance. Importantly, we report a prognostic role of a proliferative tumor-cell subpopulation, which associates with enhanced spatial tumor-immune interactions by CD8+ and CD4 + T-cells in the BRCA1/2mut tumors. The single-cell spatial landscapes indicate distinct patterns of spatial immunosurveillance with the potential to improve immunotherapeutic strategies and patient stratification in HGSC.

The potential of mRNA expression evaluation in predicting HER2 positivity in gastroesophageal cancer

Gastroesophageal cancer (GEC) is an aggressive disease characterized by a high frequency of metastasis and poor overall survival rates. GEC presents HER2 overexpression in 5 to 25% of tumors eligible for HER2-targeted therapy. HER2 evaluation requires protein levels and copy number alteration analyses by immunohistochemistry (IHC) and in situ hybridization (FISH or SISH), respectively. These are semiquantitative methodologies that need an expert and well-trained pathologist. Therefore, the use of new surrogate methods for HER2 evaluation in cancer, such as gene expression analysis, might improve GEC HER2 classification. We evaluated HER2 positivity in GEC through conventional IHC and SISH analyses and investigated the potential application of HER2 mRNA expression by quantitative PCR to categorize GEC samples as HER2-positive or HER2-negative. Among 270 GEC samples, 10.9% were HER2-positive by IHC and SISH analyses. HER2 mRNA was overexpressed in HER2-positive GEC samples and presented high accuracy in distinguishing those tumors from HER2-negative GEC. Nevertheless, HER2 mRNA analysis was not capable of classifying HER2-equivocal GEC samples into HER2-positive or -negative according to SISH data. Quantitative PCR analysis showed HER2 overexpression in HER2-positive GEC samples. Nevertheless, HER2 mRNA analysis failed to classify HER2-equivocal GEC according to SISH data.

Patient and Public Involvement and Engagement (PPIE): first steps in the process of the engagement in research projects in Brazil

Patient and Public Involvement and Engagement (PPIE) - sometimes called Community Engagement and Involvement (CEI) - comes as a big challenge but one that can be very helpful for health care professionals and stakeholders in planning better health policies for attending to the main needs of the community. PPIE involves three pillars: public involvement, public engagement, and participation. Public involvement occurs when members of the general population are actively involved in developing the research question, designing, and conducting the research. Public engagement tells people about new studies, why they are important, the impact of results, the possible implication of the main findings for the community, and the possible impact of these new findings in society, as well as, in the dissemination of knowledge to the general population. Participation is being a volunteer in the study. Our experience with PPIE, to the best of our knowledge the first initiative in Brazil, is a partnership with the University of Birmingham, the University of Liverpool, and the NIHR Global Health Group on Atrial Fibrillation (AF) Management focusing on the AF care pathway exploring the important aspects of diagnosis and treatment in the primary care system from a low-middle income area in São Paulo. The involvement of patients/public in the research represents a new step in the process of inclusion of all segments of our society based on patient illness and the gaps in knowledge aiming to open new horizons for continuous improvement and better acceptance of research projects.

Gender differences in mortality in patients with ST-segment elevation myocardial infarction / Diferencias de género en la mortalidad en pacientes con infarto de miocardio con elevación del segmento ST

Abstract Objective: Women with ST-segment elevation myocardial infarction (STEMI) have worst outcomes than men. The objective of the study was to determine gender differences in mortality in patients with STEMI. Methods: Cohort study including patients with STEMI. We recorded demographic and clinical data, laboratory tests, and in-hospital mortality in patients who underwent primary angioplasty and pharmacoinvasive strategy. Kaplan-Meier analysis was used to assess mortality differences between both genders. Results: A total of 340 patients were analyzed, 296 males and 44 females. Mean age of the female group was 64.3 ± 12.3 years. About 98% of females were among Killip-Kimball Class I-II. They had higher risk scores compared to man, longer ischemic time and first medical contact with a difference in comparison to man of 47 and 60 min, respectively. Mortality was 9.1% (4) in the female group. Conclusions: Although the proportion of women had higher mortality than man, we did not found any difference with statistical significance probably due to the lack of representation. We need more awareness in the female population about STEMI, since longer first medical contact time and longer total ischemic time might be one possible explanation of a higher mortality.

Resumen Objetivo: Las mujeres con infarto agudo al miocardio con elevación del segmento ST (SICA CEST) tienen peor pronóstico que los hombres. El objetivo fue determinar las diferencias de mortalidad en género en pacientes con SICA CEST. Metodos: Estudio de cohorte de pacientes con SICA CEST. Se recolectaron datos demográficos, clínicos, de laboratorio y mortalidad intrahospitalaria. Se realizó un análisis de Kaplan-Meier para valorar la mortalidad y determinar diferencias de género. Resultados: Se analizaron 340 pacientes, 296 hombres y 44 mujeres. Se observó que las mujeres tuvieron mayores puntajes en los scores de riesgo, mayor tiempo de primer contacto y tiempo total de isquemia encontrando una diferencia con el grupo de hombres de 47 y 60 minutos respectivamente. La mortalidad intrahospitalaria fue de 9.1% (4) sin diferencia estadísticamente significativa en comparación con los hombres. Conclusiones: Aunque la proporción de mujeres tuvo mayor mortalidad no se encontró diferencia estadísticamente significativa en comparación con los hombres probablemente por el tamaño de la muestra debido a baja representación del grupo femenino. Se necesita mayor conciencia en relación al infarto en el grupo de mujeres, ya que mayor tiempo de primer contacto y mayor tiempo total de isquemia pueden ser una posible explicación de una mayor mortalidad.

Metagenome Sequencing to Explore Phylogenomics of Terrestrial Cyanobacteria.

Cyanobacteria are ubiquitous microorganisms with crucial ecosystem functions, yet most knowledge of their biology relates to aquatic taxa. We have constructed metagenomes for 50 taxonomically well-characterized terrestrial cyanobacterial cultures. These data will support phylogenomic studies of evolutionary relationships and gene content among these unique algae and their aquatic relatives.

Hashtag bone: detrimental effects on bone contrast with metabolic benefits one and five years after Roux-en-Y gastric bypass

Bone loss is a potential adverse consequence of rapid and sustained weight loss after bariatric surgery. The aim of the present study was to evaluate the bone mass, body fat distribution, and metabolic parameters in women submitted to Roux-en-Y gastric bypass (RYGB). The study included the following three groups: one group of lean women (control [C] group) and two groups of obese women, one evaluated one year (B1) and the other five years (B5) after RYGB. Dual-energy X-ray absorptiometry and magnetic resonance imaging were used to determine bone mineral density (BMD; lumbar spine, total hip, and femoral neck) and abdominal fat content (subcutaneous [SAT] and visceral [VAT] adipose tissues, and intrahepatic lipids [IHL]). The BMD/body mass index ratio was lower in the B5 compared with the C group at all sites. Serum C-terminal telopeptide of type I collagen (CTX) levels were higher in the B1 and B5 groups compared with the C group. Individuals submitted to RYGB showed greater SAT but similar VAT and IHL values compared with those in the C group. However, the B5 group had higher mean parathyroid hormone levels compared with the other two groups. Individuals submitted to RYGB presented increased levels of CTX and low BMD for body weight than those in the C group, suggesting that bone catabolism is a persistent alteration associated with RYGB. In conclusion, the long-lasting metabolic benefits obtained with RYGB in obesity are counterbalanced by a persistent catabolic effect of the procedure on bone and mineral metabolism.

Association of sleep disturbances with sarcopenia and its defining components: the ELSA-Brasil study

Sarcopenia and sleep problems share common physiopathology. We aimed to investigate the association of sleep disturbances with sarcopenia and its defining components in Brazilian middle-aged and older adults. In this cross-sectional analysis of the second wave of the ELSA-Brasil study, we included data from 7948 participants aged 50 years and older. Muscle mass was evaluated by bioelectrical impedance analysis and muscle strength by hand-grip strength. Sarcopenia was defined according to the Foundation for the National Institutes of Health criteria. Sleep duration and insomnia complaint were self-reported. Short sleep duration was considered as ≤6 h/night and long sleep duration as >8 h/night. High risk of obstructive sleep apnea (OSA) was assessed using the STOP-Bang questionnaire. Possible confounders included socio-demographic characteristics, lifestyle, clinical comorbidities, and use of sedatives and hypnotics. The frequencies of sarcopenia, low muscle mass, and low muscle strength were 1.6, 21.1, and 4.1%, respectively. After adjustment for possible confounders, high risk of OSA was associated with low muscle mass (OR=2.17, 95%CI: 1.92-2.45). Among obese participants, high risk of OSA was associated with low muscle strength (OR=1.68, 95%CI: 1.07-2.64). However, neither short nor long sleep duration or frequent insomnia complaint were associated with sarcopenia or its defining components. In conclusion, high risk of OSA was associated with low muscle mass in the whole sample and with low muscle strength among obese participants. Future studies are needed to clarify the temporal relationship between both conditions.