Mexican consensus about surgical treatment in early-stage cervicouterine cancer.

Introduction: Cervical cancer is a public health problem in our country and worldwide. Less than 25% of cases are diagnosed in the early stages, where survival is more remarkable than 90% at five years. Here, we review surgical treatment in the early stages of cervical cancer. Methodology: A literature review was carried out in the MEDLINE database. The search was mainly limited to the English language, with priority given to systematic reviews with or without meta-analysis and randomized studies. However, only retrospective or observational evidence was found for some topics. Results: The standard treatment for early-stage cervical cancer is hysterectomy, and its radical nature will depend on the tumor size, lymphovascular permeation, and tumor-specific prognostic factors. Furthermore, the type of surgery (hysterectomy or trachelectomy) will rely on the patient's desire to preserve fertility. Nodal evaluation is indicated as part of the treatment from stage IAI with PLV. However, the sentinel lymph node is more relevant in the treatment. The incidental finding of cervical cancer after a hysterectomy requires a multidisciplinary evaluation to determine the therapeutic approach. Less radical surgery has been described as oncologically safe in low-risk groups. Conclusion: Surgical treatment in its early stages has evolved in recent decades, making it more individualized and seeking less morbidity in patients without compromising their survival.

Total Gestational Weight Gain Is Explained by Leptin and Body Fat, Regardless of Pre-Pregnancy Body Mass Index and Other Adipokines, in Mexican Adolescents.

Pre-pregnancy body mass index (pBMI) is a predictor of gestational weight gain (GWG). However, other factors, such as adipokines and inflammation markers, may also be associated with GWG. The aim of the study was to determine the association of leptin, adiponectin, irisin, and C-reactive protein, with GWG in adolescents. A longitudinal study was conducted from 2018 to 2023 in adolescents with a clinically healthy pregnancy. The assessments included sociodemographic and clinical data, pBMI, percent of body fat, serum concentrations of leptin, adiponectin, irisin, and high-sensitivity C-reactive protein (hsCRP), and total GWG adequacy. Cox regression models were performed, the outcome variables were inadequate and excessive GWG. In 198 participants, being overweight/obesity was marginally associated with a protective effect against inadequate GWG (HR = 0.44, 95%CI = 0.18-1.06), regardless of maternal characteristics and adipokines. Leptin (HR = 1.014, 95%CI = 1.008-1.021), and body fat percent (HR = 1.11, 95%CI = 1.05-1.17) were associated with a higher risk of excessive GWG, independent of other maternal variables such as pBMI, while adiponectin was associated with a lower risk. These findings suggest that, in Mexican adolescents, adipose tissue and its adipokines during pregnancy may play a more significant role in the final GWG than body weight.

Modulating the immune system towards a functional chronic wound healing: A biomaterials and Nanomedicine perspective.

Chronic non-healing wounds persist as a substantial burden for healthcare systems, influenced by factors such as aging, diabetes, and obesity. In contrast to the traditionally pro-regenerative emphasis of therapies, the recognition of the immune system integral role in wound healing has significantly grown, instigating an approach shift towards immunological processes. Thus, this review explores the wound healing process, highlighting the engagement of the immune system, and delving into the behaviors of innate and adaptive immune cells in chronic wound scenarios. Moreover, the article investigates biomaterial-based strategies for the modulation of the immune system, elucidating how the adjustment of their physicochemical properties or their synergistic combination with other agents such as drugs, proteins or mesenchymal stromal cells can effectively modulate the behaviors of different immune cells. Finally this review explores various strategies based on synthetic and biological nanostructures, including extracellular vesicles, to finely tune the immune system as natural immunomodulators or therapeutic nanocarriers with promising biophysical properties.

Genetically engineered loaded extracellular vesicles for drug delivery.

The use of extracellular vesicles (EVs) for drug delivery is being widely explored by scientists from several research fields. To fully exploit their therapeutic potential, multiple methods for loading EVs have been developed. Although exogenous methods have been extensively utilized, in recent years the endogenous method has gained significant attention. This approach, based on parental cell genetic engineering, is suitable for loading large therapeutic biomolecules such as proteins and nucleic acids. We review the most commonly used EV loading methods and emphasize the inherent advantages of the endogenous method over the others. We also examine the most recent advances and applications of this innovative approach to inform on the diverse therapeutic opportunities that lie ahead in the field of EV-based therapies.

PLGA-PEI nanoparticle covered with poly(I:C) for personalised cancer immunotherapy.

Melanoma is the main cause of death among skin cancers and its incidence worldwide has been experiencing an appalling increase. However, traditional treatments lack effectiveness in advanced or metastatic patients. Immunotherapy, meanwhile, has been shown to be an effective treatment option, but the rate of cancers responding remains far from ideal. Here we have developed a personalized neoantigen peptide-based cancer vaccine by encapsulating patient derived melanoma neoantigens in polyethylenimine (PEI)-functionalised poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and coating them with polyinosinic:polycytidylic acid (poly(I:C)). We found that PLGA NPs can be effectively modified to be coated with the immunoadjuvant poly(I:C), as well as to encapsulate neoantigens. In addition, we found that both dendritic cells (DCs) and lymphocytes were effectively stimulated. Moreover, the developed NP was found to have a better immune activation profile than NP without poly(I:C) or without antigen. Our results demonstrate that the developed vaccine has a high capacity to activate the immune system, efficiently maturing DCs to present the antigen of choice and promoting the activity of lymphocytes to exert their cytotoxic function. Therefore, the immune response generated is optimal and specific for the elimination of melanoma tumour cells.

Usefulness of Procalcitonin Levels for Predicting the Microbiological Orientation in Patients with Sepsis.

The main objective of the study was to verify whether levels of procalcitonin (PCT) could guide us toward determining the type of bacteria causing the sepsis and to identify the discriminatory cut-off point in the first urgent laboratory test. This study is a single center retrospective analysis that includes 371 patients with a mean age of 71.7 ± 15.6 years who were diagnosed with sepsis or septic shock. The yield of blood cultures in demonstrating the causative microbiological agent was 24.3% (90), and it was 57, 1% (212) when evaluating all types of cultures. Statistically significant positive differences were observed in the mean value of the PCT between the group that obtained positive cultures and the group that did not (p < 0.0001). The AUC-ROC of PCT values as a guide to the causal bacteria type was 0.68 (95%CI: 0.57-0.78, p < 0.0021). The PCT value that showed the best diagnostic characteristics for identifying Gram-negative rods (GNR) as the causative agent in blood cultures was 2.1 ng/mL. The positive predictive value (PPV) was 78, 9% (66.3-88.1%). The AUC-ROC of the PCT values for sepsis diagnosis, with any positive culture that could be assessed, was 0.67 (95%CI: 0.63-0.73, p < 0.0001). The PCT value that showed the best diagnostic characteristic for predicting sepsis was 3.6 ng/mL.

Factors Associated with Parametrial Involvement in Endometrial Carcinoma in Patients Treated with Radical Hysterectomy.

INTRODUCTION: Describe factors associated with parametrial involvement, and how these factors modify the prognosis of patients with endometrial carcinoma treated with radical hysterectomy. METHODS: Observational study in which categorized patients according to those with and without parametrial involvement. A descriptive analysis and comparative analysis were performed for associations between parametrial spread and clinical, surgical, and pathology variables. RESULTS: We analyzed 85 patients, which 18 (21%) had parametrial involvement. Pathology factors associated with parametrial involvement were the endometrioid subtype, grade 3, and variants of poor prognosis (odds ratio (OR) 3.41, 95% CI 1.09-10.64; P = 0.035), myometrial invasion of over 50% (OR 7.76, 95% CI 1.65-36.44; P = 0.009), serosal involvement (OR 17.07, 95% CI 3.87-75.35; P < 0.001), ovarian metastasis (OR 5.15, 95% CI 1.36-19.46; P = 0.016), positive peritoneal cytology (OR 3.9, 95% CI 1.04-14.77; P = 0.044), and lymph node metastasis (OR 3.4; 95% CI 1.16-9.97; P = 0.026). Five-year disease-free survival was 74% (95% CI 57.4-85.4) for the group without parametrial spread and 50.8% (95% CI 22.7-73.4) for the group with parametrial spread (P = 0.001). Similarly, 5-year overall survival was 85.2% (95% CI 67.9-93.6) for the group without parametrial spread and 47.5% (95% CI 8.1-80.2) for the group with parametrial spread (P = 0.002). CONCLUSION: Factors associated with parametrial involvement were histologies of poor prognosis, tumors affecting uterine serosa, cervix, or spread beyond the uterus. Additionally, parametrial involvement directly affects prognosis by reducing overall survival, disease-free survival and increasing odds for recurrence.

miR-130a expression is related to aortic dilation in bicuspid aortic valve children.

BACKGROUND: Bicuspid aortic valve disease (BAV) is present in 0.5-2% of the population and can promote aortic dilation, eventually leading to fatal consequences. Although some biomarkers have been proposed in adults, no studies have tested these candidates in children. We aimed to evaluate four miRNAs previously described to be related to BAV disease and aortic dilation in adults in a paediatric cohort. METHODS: Eighty participants ≤17 years old (4-17; mean 12) were included. From the BAV group, 40% had a dilated aorta (z score >2). RT‒qPCR were performed in plasma samples to quantify miR-122, miR-130a, miR-486, and miR-718 using the delta-delta Ct method. Functional and enrichment analyses of miR-130a were also performed. RESULTS: miR-130a expression in plasma was found to be significantly lower in BAV patients with a dilated aorta versus nondilated patients (p = 0.008) and healthy TAV controls (p = 0.004). Furthermore, miR-130a expression in plasma was inversely correlated with ascending aorta (r = 0.318, p = 0.004) and aortic root z scores (r = 0.322; p = 0.004). Enrichment analysis showed that miR-130a target genes are related to the TGFß signalling pathway. CONCLUSIONS: miR-130a expression in plasma is decreased in aortic-dilated BAV children compared to nondilated BAV children, helping differentiate low- to high-risk patients. IMPACT: miR-130a expression in plasma is related to aortic dilation in bicuspid aortic valve (BAV) children. To our knowledge, this is the first study that analyses miRNA patterns in bicuspid aortic valve children with aortic dilation. miR-130a expression in plasma could be a biomarker in order to help differentiate low-to high-risk BAV children, which is vitally important for advanced care planning.

Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes.

BACKGROUND: The diabetogenic effect of statins has been well established by clinical trials, Mendelian randomisation studies and meta-analyses. According to large clinical trials, PCSK9 inhibitors (PCSK9i) have no deleterious impact on glucose metabolism. However, few real-life studies have yet evaluated the long-term effects of these drugs on glucose homeostasis and their impact on new-onset diabetes (NODM). METHODS: We studied 218 patients treated with either alirocumab or evolocumab (70% with familial hypercholesterolemia) for at least three years (PCSK9iG). We studied the NODM rate in the nondiabetic group at baseline (168) and overall glucose metabolism control in the whole group. Incidental DM was compared with two groups. The first was a propensity score matching (PSM)-selected group (n = 168) from the database of patients attending the Reus lipid unit (Metbank, n = 745) who were not on PCSK9i (PSMG). The second was a subgroup with a similar age range (n = 563) of the Di@bet.es study (Spanish prospective study on diabetes development n = 5072) (D@G). The incidence was reported as the percentage of NODM cases per year. RESULTS: The fasting glucose (FG) level of the subjects with normoglycaemia at baseline increased from 91 (86-95.5) to 93 (87-101) mg/dL (p = 0.014). There were 14 NODM cases in the PCSK9i group (2.6%/y), all among people with prediabetes at baseline. The incidence of NODM in PSMG and D@G was 1.8%/y (p = 0.69 compared with the PCSK9iG). The incidence among the subjects with prediabetes was 5.1%/y in the PCSK9iG, 4.8%/y in the PSMG and 3.9%/y in the D@G (p = 0.922 and p = 0.682, respectively). In the multivariate analysis, only the FG level was associated with the development of NODM in the PCSK9iG (OR 1.1; 95% CI: 1.0-1.3; p = 0.027). Neither FG nor A1c levels changed significantly in patients with DM at baseline. CONCLUSION: A nonsignificant increase in NODM occurred in the PCSK9iG, particularly in patients with prediabetes, compared with the PSMG and D@G groups. Baseline FG levels were the main variable associated with the development of DM. In the subjects who had DM at baseline, glucose control did not change. The impact of PCSK9i on glucose metabolism should not be of concern when prescribing these therapies.

3D-printed Laponite/Alginate hydrogel-based suppositories for versatile drug loading and release.

Traditional approaches to solid rectal therapies have halted progress, leading to a continual decline in the use of conventional suppositories. Additive manufacturing techniques have been recently explored as a suitable innovative tool for suppository fabrication. However, little advancement has been made in composition materials for 3D-printed suppository (3DPS) manufacturing and still, conventional vehicles are often used for construct fabrication, hindering the growth in the field. As a novelty, this study unveils a ground-breaking Laponite-alginate hydrogel-based 3DPS. Interestingly, this study proposes a novel approach for loading drugs into the 3DPS employing for the first time the post-printing loading. Thus, a passive loading strategy of molecular models is developed, demonstrating the versatility and capacity to load molecules of different charges and molecular sizes within the matrix systems. This novel strategy allows adapting the load of a wide range of drugs into a single ink, which simplifies and speeds up the 3DPS technological development process for drugs with different physico-chemical properties. Additionally, in this research, a displacement strategy of the three-dimensional Laponite matrices is developed in order to enhance the drug release capacity through the 3DPS and their disintegration capacity, resulting in a significant improvement of the drug diffusion through the hydrogel matrix and a rapid disintegration of the 3DPS. Finally, our study demonstrates that the obtained 3DPS have a suitable in vivo behavior, being non-obstructive and allowing the normal motility of the rats intestine.

Mexican consensus on cow's milk protein allergy.

BACKGROUND: The aim of this study is to present the current views of a diverse group of experts on the diagnosis and treatment of Cow's Milk Protein Allergy (CMPA) in children under 2 years of age in Mexico. MATERIAL AND METHODS: The study, led by a scientific committee of five experts in CMPA, was divided into six phases, including a modified Delphi process. A total of 20 panelists, all of whom were pediatric specialists, participated in administering a comprehensive 38-item questionnaire. The questionnaire was divided into two blocks: Diagnosis and Treatment (20 items each). RESULTS: Consensus was reached on all the proposed items, with an agreement rate of over 70% for each of them. As a result, a diagnostic and treatment algorithm was developed that emphasized the reduction of unnecessary diagnostic studies and encouraged breastfeeding whenever possible. In cases where breast milk is not available, appropriate use of hypoallergenic formulas was recommended. In addition, recommendations on treatment duration and gradual reintroduction of cow's milk protein were provided. CONCLUSIONS: The recommendations endorsed by 20 Mexican pediatricians through this study are applicable to everyday clinical practice, thereby enhancing the diagnosis and treatment of children under 2 years of age with CMPA. This, in turn, will foster improved health outcomes and optimize the utilization of healthcare resources.

Role of palliative care intervention in patients with vulvar cancer: a retrospective study.

OBJECTIVE: To describe the experience of a Mexican cancer centre in vulvar cancer and the opportunity to incorporate palliative care (PC) during treatment. PATIENTS AND METHODS: A retrospective study of clinical and sociodemographic characteristics of women with vulvar cancer referred to the PC service (PCS) between 2010 and 2021 is reported. Frequencies were estimated, as well as medians and IQRs, accordingly. Referral time and overall survival were estimated using the Kaplan-Meier method. RESULTS: 125 women with vulvar cancer were seen between 2010 and 2021, but only 42% were seen at PCS, mostly polysymptomatic, after several visits to the emergency room. 89% of the patients seen at PCS died at home. CONCLUSIONS: Vulvar cancer is a rare type of cancer, while squamous cell carcinoma is the most frequent type. At the time of referral, almost half of the patients had severe pain, bleeding, malodor, infection and urinary incontinence. Most of these patients lived in poverty, were poorly educated and had multiple surgeries. PC may play an important role in the care of patients with advanced vulvar cancer, relieving the physical and psychological symptoms, avoiding unnecessary hospitalisation and favouring death at home without pain and other symptoms.

Efficacy, safety and pharmacokinetics of apatinib plus etoposide versus apatinib alone for platinum-resistant recurrent ovarian cancer: protocol of a multicenter, open-label, randomized phase 2 trial.

Background: Currently preferred single-agent nonplatinum chemotherapy or its combination with bevacizumab results in a low response rate and modest survival benefit for platinum-resistant recurrent ovarian cancer, and thus more effective regimens are needed. In our previous phase 2 trial, apatinib plus etoposide showed promising efficacy and an acceptable safety profile in platinum-resistant recurrent ovarian cancer patients. Due to the single-arm design, the role of apatinib still needs to be determined. Methods: In this phase 2 trial, 54 adult patients with platinum-resistant current ovarian cancer will be recruited at 17 sites in China. Patients with prior administration of small-molecule tyrosine kinase inhibitors or etoposide will be excluded. Patients will be randomized (1:1) to receive apatinib (375 mg, orally, once daily) alone or in combination with etoposide (50 mg, orally on days 1-14 of each 21-day cycle) until disease progression or intolerable toxicity. Randomization will be performed using a computerized central randomization system, stratified by platinum resistance for the first time (yes or no). Imaging examinations will be conducted every 6 weeks. The primary endpoint is the objective response rate (ORR) according to the Response Evaluation Criteria In Solid Tumors (version 1.1), which will be compared between groups using the Cochran-Mantel-Haenszel test. Discussion: This study will provide prospective data of 2 experimental regimens using a randomized design. It will help determine whether apatinib monotherapy can provide favorable clinical benefits or needs to be combined with chemotherapy to be effective. Trial Registration: ClinicalTrials.gov Identifier: NCT04383977. It was registered on May 12, 2020.

Are Overweight and Obesity Risk Factors for Developing Metabolic Syndrome or Hypertension after a Preeclamptic Event?

OBJECTIVE: To identify the determinants and risks associated with developing hypertension and metabolic syndrome in the first year postpartum in women who experienced preeclampsia. METHODS: A cohort study was conducted, involving women who had experienced preeclampsia (PE) recently. The control group was women with the same characteristics but a healthy pregnancy. The variables analyzed were somatometry, disease history, pre-pregnancy body mass index (Pre-BMI), and Third Adult Treatment Panel updated (ATP III) metabolic syndrome (MS) data (blood pressure, obesity, triglycerides, high-density lipoproteins, and fasting glucose). These variables were measured at 3, 6, and 12 months postpartum. RESULTS: Women with a history of PE exhibited higher systolic and diastolic blood pressure than women without PE. The risk of developing isolated diastolic arterial hypertension at 3 and 12 months of follow-up was two to eight times greater in women with a history of PE. Factors associated with having higher blood pressure levels were preeclampsia, insulin resistance, age, and BMI. Neither the pre-BMI index nor gestational weight gain (GWG) had any effect on blood pressure in any of the three assessments. Women with preeclampsia had a 5- to 8-fold increased risk of developing MS (which could be explained not only by the history of preeclampsia but also by the history of pre-pregnancy obesity). However, PE was not identified as a risk factor at the six-month evaluation and was only explained by pre-pregnancy obesity and overweight. CONCLUSIONS: Obesity and overweight, as well as preeclampsia, were strongly associated with the development of hypertension and metabolic syndrome during the first year following childbirth.

Soy protein/ß-chitin sponge-like scaffolds laden with human mesenchymal stromal cells from hair follicle or adipose tissue promote diabetic chronic wound healing.

Chronic wounds are a worldwide problem that affect >40 million people every year. The constant inflammatory status accompanied by prolonged bacterial infections reduce patient's quality of life and life expectancy drastically. An important cell type involved in the wound healing process are mesenchymal stromal cells (MSCs) due to their long-term demonstrated immunomodulatory and pro-regenerative capacity. Thus, in this work, we leveraged and compared the therapeutic properties of MSCs derived from both adipose tissue and hair follicle, which we combined with sponge-like scaffolds (SLS) made of valorized soy protein and ß-chitin. In this regard, the combination of these cells with biomaterials permitted us to obtain a multifunctional therapy that allowed high cell retention and growing rates while maintaining adequate cell-viability for several days. Furthermore, this combined therapy demonstrated to increase fibroblasts and keratinocytes migration, promote human umbilical vein endothelial cells angiogenesis and protect fibroblasts from highly proteolytic environments. Finally, this combined therapy demonstrated to be highly effective in reducing wound healing time in vivo with only one treatment change during all the experimental procedure, also promoting a more functional and native-like healed skin.

Enterococcus spp. and Streptococcus spp. bloodstream infections: epidemiology and therapeutic approach

Streptococcus spp. and Enterococcus spp. are frequent etiologies of bloodstream infection and endocarditis. In recent years, the incidence of Enterococcus spp. has been increasing, especially with nosocomial involvement, and with a high mortality rate. In this entity, the risk of endocarditis and its relationship with colorectal neoplastic pathology remains to be clarified, in order to establish indications for echocardiography and colonoscopy. In the case of Streptococcus spp., the risk of endocarditis depends on the species and the mortality rates are usually lower. Finally, in recent years, the treatment of endocarditis has been directed towards oral consolidation regimens and new long-term antibiotic treatments. (AU)

Factors associated with emergency room readmission after elective surgery for ovarian carcinoma.

BACKGROUND: Hospital readmission is a quality metric of hospital care and has been studied in ovarian carcinoma, but its evaluation has several limitations. Also, emergency room (ER) readmission is considered an adverse effect because it represents patient costs. Therefore, our objective was to determine the rate of ER readmission, its causes, and associated factors. METHODS: A retrospective study of 592 patients with ovarian carcinoma who underwent upfront surgery, neoadjuvant therapy, or surgery for recurrent disease. An analysis of factors associated with ER readmission, hospital readmission, and surgical complications was performed, including multivariate analysis to assess for case-mix factors. RESULTS: Of 592 patients, the median age was 51 years, and the predominant type of treatment was the neoadjuvant approach (52.9%); 46% underwent upfront surgeries and six surgeries for recurrence. The ratio to ER readmission was 11.8% (70 patients), of whom 12 patients were admitted more than once. The factors associated with ER readmission were prolonged surgery, intraoperative bleeding, extended hospital stay, the time of the day when the surgery was performed, and post-surgical complications. The hospital readmissions were 4.2%, and the overall morbidity was 17.6%. In the multivariate analysis, the only factor associated with ER readmission was the presence of surgical complications (OR = 39.01). The factors independently associated with hospital readmission were the entrance to the intensive care unit (OR = 1.37), the presence of surgical complications (OR = 2.85), and ER readmission (OR = 1.45). CONCLUSION: ER readmission is an adverse event representing the presence of symptoms/complications in patients. Evaluating the ER readmission independently of the readmission to the hospital is critical because it will allow modifying medical care behaviors to prevent patients from unnecessarily returning to the hospital after a hospital discharge to manage preventable medical problems. TRIAL REGISTRATION: researchregistry7882.