Pharmacological induction of diabetes mellitus in pregnant female mice: a comparison of two doses and routes of administration.

OBJECTIVE: This study aimed to compare two routes of administration and different dosages of streptozotocin (STZ) for the pharmacological induction of gestational diabetes mellitus (GDM) in pregnant CD1 females. MATERIALS AND METHODS: 35 female CD1 mice were divided into 5 groups (n = 7). Diabetes mellitus (DM) was induced with STZ by two routes and two doses: 1) Control Group without administration of STZ (CL), 2) Intraperitoneal Group with 200 mg of STZ/Kg of weight (IP200), 3) Intraperitoneal Group with 230 mg of STZ/Kg of weight (IP230), 4) Subcutaneous Group with 200 mg of STZ/Kg of weight (SC200) and 5) Subcutaneous Group with 230 mg of STZ/Kg of weight (SC230). Body weight, food and water intake, glycemia, Homeostatic Model Assessment of Insulin Resistance Index (HOMA-IR), survival, and birth rate were identified. RESULTS: The SC230 group turned out to be the most effective dose and route for the induction of GDM in pregnant females. This scheme managed to reproduce sustained hyperglycemia with high HOMA-IR, the presence of polyphagia, polydipsia, and weight loss. In addition, the birth rate and survival were high compared to the other doses and routes of administration. CONCLUSIONS: The administration of a single dose of 230 mg/kg of weight by subcutaneous route supposes advantages compared to previously used models since it decreases the physiological stress due to manipulation and the costs since it does not require repeated doses or adjuvants such as high lipid diets to potentiate the diabetogenic effect of STZ. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-abstract-12.jpg.

Prospective Study on Individualized Dose Adjustment of Tolvaptan Based on Urinary Osmolality in Patients With ADPKD.

Introduction: Tolvaptan has been shown to reduce renal volume and delay disease progression in autosomal-dominant polycystic kidney disease (ADPKD). However, no biomarkers are currently available to guide dose adjustment. We aimed to explore the possibility of individualized tolvaptan dose adjustments based on cut-off values for urinary osmolality (OsmU). Methods: This prospective cohort study included patients with ADPKD, with rapid disease progression. Tolvaptan treatment was initiated at a dose of 45/15 mg and increased based on OsmU, with a limit set at 200 mOsm/kg. Primary renal events (25% decrease in estimated glomerular filtration rate [eGFR] during treatment), within-patient eGFR slope, and side effects were monitored during the 3-year follow-up. Results: Forty patients participated in the study. OsmU remained below 200 mOsm/kg throughout the study period, and most patients required the minimum tolvaptan dose (mean dose, 64 [±10] mg), with a low discontinuation rate (5%). The mean annual decline in eGFR was -3.05 (±2.41) ml/min per 1.73 m2 during tolvaptan treatment, compared to the period preceding treatment, corresponding to a reduction in eGFR decline of more than 50%. Primary renal events occurred in 20% of patients (mean time to onset, 31 months; 95% confidence interval [CI] = 28-34). Conclusion: Individualized tolvaptan dose adjustment based on OsmU in patients with ADPKD and rapid disease progression provided benefits in terms of reducing eGFR decline, compared with reference studies, and displayed lower dropout rates and fewer side effects. Further studies are required to confirm optimal strategies for the use of OsmU for tolvaptan dose adjustment in patients with ADPKD.

Solitary fibrous tumor of the pleura with air cystic component.

We present an uncommon case of a solitary fibrous tumor of the pleura with the appearance of an air-containing cystic mass. We discuss the differential diagnosis through the imaging findings, the hypothetical origins of the air component, and the possible relationship between the air component and the aggressivity of the tumor.

[Translated article] A systematic review of the literature: The use of metaphyseal sleeves in revision total knee arthroplasty.

BACKGROUND AND OBJECTIVES: The purpose of this study is to analyse the indications, complications, survivorship and clinical/functional outcome of metaphyseal sleeves as a treatment option in revision total knee arthroplasty. MATERIAL AND METHOD: A systematic review was made following the PRISMA recommendations on the use of metaphyseal sleeves for revision total knee arthroplasty. We included prospective and retrospective studies published in the last 10 years looking at implant survivorship, clinical and functional outcome with a minimum follow-up of 2 years. RESULTS: The included studies showed good both functional and clinical outcomes. The overall reoperation rate was 16.2%, with an overall survival rate of 92.2% and aseptic survivorship of 98.2%. CONCLUSIONS: Metaphyseal sleeves are a good treatment option for this surgery, especially in AORI II or III type bone defects, achieving good intraoperative and primary stability of the implant, with good and rapid osseointegration.

Mathematical modeling for operative improvement of the decoloration of Acid Red 27 by a novel microbial consortium of Trametes versicolor and Pseudomonas putida: A multivariate sensitivity analysis.

In this work, it is presented a first approach of a mathematical and kinetic analysis for improving the decoloration and further degradation process of an azo dye named acid red 27 (AR27), by means of a novel microbial consortium formed by the fungus Trametes versicolor and the bacterium Pseudomonas putida. A multivariate analysis was carried out by simulating scenarios with different operating conditions and developing a specific mathematical model based on kinetic equations describing all stages of the biological process, from microbial growth and substrate consuming to decoloration and degradation of intermediate compounds. Additionally, a sensitivity analysis was performed by using a factorial design and the Response Surface Method (RSM), for determining individual and interactive effects of variables like, initial glucose concentration, initial dye concentration and the moment in time for bacterial inoculation, on response variables assessed in terms of the minimum time for: full decoloration of AR27 (R1 = 2.375 days); maximum production of aromatic metabolites (R2 = 1.575 days); and full depletion of aromatic metabolites (R3 = 12.9 days). Using RSM the following conditions improved the biological process, being: an initial glucose concentration of 20 g l-1, an initial AR27 concentration of 0.2 g l-1 and an inoculation moment in time of P. putida at day 1. The mathematical model is a feasible tool for describing AR27 decoloration and its further degradation by the microbial consortium of T. versicolor and P. putida, this model will also work as a mathematical basis for designing novel bio-reaction systems than can operate with the same principle of the described consortium.

Multicentre, prospective, randomized control non-inferiority trial of bladder catheter management in colon surgery.

AIM: Perioperative bladder catheterization is a controversial issue. Most current recommendations are based on data from open surgery extrapolated to enhanced recovery after surgery or fast-track programmes ranging between 24 and 48 h. The aim of this study is to provide a rationale for reducing catheterization time while at the same time avoiding acute urine retention (AUR), in patients undergoing scheduled laparoscopic colon surgery. METHOD: This is a multicentre, prospective, controlled, randomized non-inferiority study of bladder catheter management in patients undergoing scheduled laparoscopic colon surgery, randomized into two groups: experimental (with catheter removal immediately after surgery) and control (with catheter removal 24 h post-surgery). The main outcome will be the development of AUR, and secondary outcomes the development of urinary infection within the first 30 days and hospital stay. Demographic, surgical and pathological variables will also be evaluated, especially the development of adverse effects assessed according to the Clavien scale and the Comprehensive Complication Index. Following the literature, we assume an incidence of AUR of 11% and a margin of non-inferiority (delta) of 8% and estimate that a sample size of 208 patients per group will be required (with an estimated 10% of losses per group). CONCLUSIONS: In this study we try to demonstrate that the bladder catheter can be removed immediately after scheduled laparoscopic colon surgery, without increasing acute urine retention. This measure would offers the benefits of earlier mobilization and reduces catheter-related morbidity.

A systematic review of the literature: The use of metaphyseal sleeves in revision total knee arthroplasty. / Una revisión sistemática de la literatura: el uso de vainas metafisarias en cirugía de revisión de artroplastia de rodilla.

BACKGROUND AND OBJECTIVES: The purpose of this study is to analyze the indications, complications, survivorship and clinical/functional outcome of metaphyseal sleeves as a treatment option in revision total knee arthroplasty. MATERIAL AND METHOD: A systematic review was made following the PRISMA recommendations on the use of metaphyseal sleeves for revision total knee arthroplasty. We included prospective and retrospective studies published in the last 10 years looking at implant survivorship, clinical and functional outcome with a minimum follow-up of 2 years. RESULTS: The included studies showed good both functional and clinical outcomes. The overall reoperation rate was 16.2%, with an overall survival rate of 92.2% and aseptic survivorship of 98.2%. CONCLUSIONS: Metaphyseal sleeves are a good treatment option for this surgery, especially in AORI II or III type bone defects, achieving good intraoperative and primary stability of the implant, with good and rapid osseointegration.

[Hypertension as a common element of renal transplantation with pressor kidney and posterior reversible encephalopathy syndrome]. / Hipertensión como elemento común de trasplante renal con riñón presor y del síndrome de encefalopatía posterior reversible.

Secondary arterial hypertension accounts for only 5-10% of cases of arterial hypertension, hence the importance of its clinical suspicion for diagnosis. One of the most common causes of secondary hypertension is renovascular hypertension, caused by renal hypoperfusion and activation of the renin-angiotensin-aldosterone system. In addition to arterial hypertension being one of the most prevalent cardiovascular risk factors in the population, its poor control can cause acute neurological disorders such as Posterior Reversible Leukoencephalopathy syndrome (PRES), being characteristic the appearance of visuals alterations. Next, we present the case of a kidney transplant patient with well-controlled arterial hypertension with worsening secondary to renal artery stenosis and development of PRES.

Improvement of photocatalytic activity in the degradation of 4-chlorophenol and phenol in aqueous medium using tin-modified TiO2 photocatalysts.

In this work, we present the synthesis of TiO2 photocatalysts modified with different % mol of tin using the sol-gel method. The materials were characterized using different analytical techniques. The Rietveld refinement, XPS, Raman and UV-Vis techniques confirm the substitution of tin in the TiO2 structural lattice due to changes in crystal lattice parameters, the low-energy shift of the Sn 3d5/2 orbital, generation of oxygen vacancies and the decreased band gap and increased BET surface area. The material with 1 mol% tin shows superior catalytic activity compared to the references for the degradation of 40 ppm 4-chlorophenol (3 hours of reaction) and 50 ppm phenol (6 hours of reaction). Reactions fit pseudo first order kinetics in both instances. The increase in photodegradation efficiency was attributed to the generation of energy levels below the TiO2 conduction band caused by the incorporation of 1% mol of tin, oxygen vacancies, and the heterojunction formed between the brookite-anatase-rutile, causing inhibition of the recombination of the electron (e-) and hole (h+) photogenerated species. The easy synthesis, low cost and increased photodegradation efficiency of the photocatalyst with 1 mol% tin have the potential to favor the remediation of recalcitrant compounds in water.

The carbon footprint of cataract surgery in Spain.

BACKGROUND AND PURPOSE: Climate change is one of the most important threats to human health nowadays. The healthcare industry produces a significant part of greenhouse gases (GHG) emissions. The aim of this study is to assess direct and indirect GHG emissions due to cataract surgery in Spain to identify opportunities for improving. METHODS: This observational case series study estimates and analyses the carbon footprint of a single cataract surgery using phacoemulsification in Ávila Hospital. ISO standard 14064 was applied. RESULTS: The carbon footprint of a single cataract surgery in Ávila Hospital was 86.62kg CO2eq. Medical and pharmaceutical equipment were responsible for 85% of GHG emissions. CONCLUSIONS: Collaboration between pharmaceuticals and ophthalmologists is important to improve the environmental impact of cataract surgery. Future research is needed to introduce changes that do not compromise patient and surgeon safety. Green surgery models could play an encouraging role in the new global health scene.

Association between a Frailty Index from Common Laboratory Values and Vital Signs (FI-LAB) and Hospital and Post-Hospital Outcomes in Veterans with COVID-19 Infection.

OBJECTIVES: Determine the association of higher FI-LAB scores, derived from common laboratory values and vital signs, with hospital and post-hospital outcomes in Veterans hospitalized with COVID-19 infection. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, multicenter, cohort study of 7 Veterans Health Administration (VHA) medical centers in Florida and Puerto Rico. Patients aged 18 years and older hospitalized with COVID-19 and followed for up to 1 year post discharge or until death. Clinical Frailty Measure: FI-LAB. MAIN OUTCOMES AND MEASURES: Hospital and post-hospital outcomes. RESULTS: Of the 671 eligible patients, 615 (91.5%) patients were included (mean [SD] age, 66.1 [14.8] years; 577 men [93.8%]; median stay, 8 days [IQR:3-15]. There were sixty-one in-hospital deaths. Veterans in the moderate and high FI-LAB groups had a higher proportion of inpatient mortality (13.3% and 20.6%, respectively) than the low group (4.1%), p <0.001. Moderate and high FI-LAB scores were associated with greater inpatient mortality when compared to the low group, OR:3.22 (95%CI:1.59-6.54), p=.001 and 6.05 (95%CI:2.48-14.74), p<0.001, respectively. Compared with low FI-LAB scores, moderate and high scores were also associated with prolonged length of stay, intensive care unit (ICU) admission, and transfer. CONCLUSIONS AND RELEVANCE: In this study of patients admitted to 7 VHA Hospitals during the first surge of the pandemic, higher FI-LAB scores were associated with higher in-hospital mortality and other in-hospital outcomes; FI-LAB can serve as a validated, rapid, feasible, and objective frailty tool in hospitalized adults with COVID-19 that can aid clinical care.

Oncological monitoring after transanal total mesorectal excision (TaTME) for rectal neoplasia.

BACKGROUND: The surgical treatment of choice for rectal neoplasia is total mesorectal excision (TME). The transanal approach enables a better approach in male and obese patients and/or those with a narrow pelvis and in patients with small tumors. Short-term results are comparable with those for laparoscopy or the open approach, but the medium- and long-term oncological data are sparse. The aim of the present study was to evaluate our early experience with transanal TME (TaTME). METHODS: This was a retrospective study conducted on patients who underwent TaTME at our center between August 2013 and April 2017 with a follow-up ≥ 3 years. Histopathology, complications, mortality, neoplastic recurrence and disease-free survival were analyzed. RESULTS: One hundred patients (68 men and 32 women,, median age 66.8 years [range 29.6-91.2 years]) were included. There were 67 T3 cases (67%) with 74 N0 cases (74%), the mesorectal quality was graded optimal for 87.6% and only 2 cases of radial margin involvement were detected (2%). The median follow-up period was 47.6 months (range 11.8-78.9 months). Eighteen cases of recurrence were diagnosed, of which 3 (3%) recurred locally with an average disease-free period of 43.1 months. Overall survival was 80% and mortality due to progression of disease was 13%. CONCLUSIONS: TaTME is a safe surgical procedure with surgical, anatomopathological and oncological results at 3 years (medium-term) comparable with those for the laparoscopic and open approaches. Better monitoring is required with studies of the long-term functional and quality of life outcomes, i.e., at 5 or 10 years.

Novel Genetic Determinants of Dental Maturation in Children.

Dental occlusion requires harmonious development of teeth, jaws, and other elements of the craniofacial complex, which are regulated by environmental and genetic factors. We performed the first genome-wide association study (GWAS) on dental development (DD) using the Demirjian radiographic method. Radiographic assessments from participants of the Generation R Study (primary study population, N1 = 2,793; mean age of 9.8 y) were correlated with ~30 million genetic variants while adjusting for age, sex, and genomic principal components (proxy for population stratification). Variants associated with DD at genome-wide significant level (P < 5 × 10-8) mapped to 16q12.2 (IRX5) (lead variant rs3922616, B = 0.16; P = 2.2 × 10-8). We used Fisher's combined probability tests weighted by sample size to perform a meta-analysis (N = 14,805) combining radiographic DD at a mean age of 9.8 y from Generation R with data from a previous GWAS (N2 = 12,012) on number of teeth (NT) in infants used as proxy of DD at a mean age of 9.8 y (including the ALSPAC and NFBC1966). This GWAS meta-analysis revealed 3 novel loci mapping to 7p15.3 (IGF2BP3: P = 3.2 × 10-8), 14q13.3 (PAX9: P = 1.9 × 10-8), and 16q12.2 (IRX5: P = 1.2 × 10-9) and validated 8 previously reported NT loci. A polygenic allele score constructed from these 11 loci was associated with radiographic DD in an independent Generation R set of children (N = 703; B = 0.05, P = 0.004). Furthermore, profiling of the identified genes across an atlas of murine and human stem cells observed expression in the cells involved in the formation of bone and/or dental tissues (>0.3 frequency per kilobase of transcript per million mapped reads), likely reflecting functional specialization. Our findings provide biological insight into the polygenic architecture of the pediatric dental maturation process.

COGNITION: a prospective precision oncology trial for patients with early breast cancer at high risk following neoadjuvant chemotherapy.

BACKGROUND: COGNITION (Comprehensive assessment of clinical features, genomics and further molecular markers to identify patients with early breast cancer for enrolment on marker driven trials) is a diagnostic registry trial that employs genomic and transcriptomic profiling to identify biomarkers in patients with early breast cancer with a high risk for relapse after standard neoadjuvant chemotherapy (NACT) to guide genomics-driven targeted post-neoadjuvant therapy. PATIENTS AND METHODS: At National Center for Tumor Diseases Heidelberg patients were biopsied before starting NACT, and for patients with residual tumors after NACT additional biopsy material was collected. Whole-genome/exome and transcriptome sequencing were applied on tumor and corresponding blood samples. RESULTS: In the pilot phase 255 patients were enrolled, among which 213 were assessable: thereof 48.8% were identified to be at a high risk for relapse following NACT; 86.4% of 81 patients discussed in the molecular tumor board were eligible for a targeted therapy within the interventional multiarm phase II trial COGNITION-GUIDE (Genomics-guided targeted post neoadjuvant therapy in patients with early breast cancer) starting enrolment in Q4/2022. An in-depth longitudinal analysis at baseline and in residual tumor tissue of 16 patients revealed some cases with clonal evolution but largely stable genetic alterations, suggesting restricted selective pressure of broad-acting cytotoxic neoadjuvant chemotherapies. CONCLUSIONS: While most precision oncology initiatives focus on metastatic disease, the presented concept offers the opportunity to empower novel therapy options for patients with high-risk early breast cancer in the post-neoadjuvant setting within a biomarker-driven trial and provides the basis to test the value of precision oncology in a curative setting with the overarching goal to increase cure rates.

EXPRESSION OF CHEMOKINE (C-C MOTIF) RECEPTOR 7 IN PROSTATE CANCER TISSUE OF YOUNG PATIENTS AND IN METASTATIC CANCER CELLS.

BACKGROUND: Chemokine (C-C motif) receptor 7 (CCR7) is a chemokine receptor involved in the carcinogenesis of several types of tumors due to its promoting action in epithelial-mesenchymal transition events, invasion, angiogenesis and metastasis. However, its role in prostate cancer (PCa) remains unclear. AIM: To evaluate CCR7 expression by immunohistochemistry in prostate tumors from young patients and to determine the possible relationship with the clinicopathological characteristics. MATERIALS AND METHODS: We analyzed retrospectively paraffin-embedded tissue sections from 23 young PCa (≤ 55 years old) patients and evaluated the transcriptomic expression in the TCGA database. RESULTS: Expression of CCR7 was observed in 15 cases (65%). The tissue samples from younger patients (≤ 50 years) were mostly positive in 72.7% (8/11) of cases. High grade GS (≥ 3) tumors were CCR7-positive in 71% cases. The malignant cells present in lymph nodes were CCR7 positive in 100% cases. The bioinformatic analysis showed a high CCR7 expression associated with the presence of metastasis (FC = 2.6, p = 0.03) in the Cancer Genome Atlas (TCGA) PCa cohort (PRAD). CONCLUSION: We showed that CCR7 expression in tumors from young patients is associated with the early onset of the disease and could also be related to lymph node metastasis.

Embolic stroke of undetermined source: beyond atrial fibrillation.

INTRODUCTION: Embolic stroke of undetermined source (ESUS) accounts for 25% of all cerebral infarcts; only 30% are associated with paroxysmal atrial fibrillation (AF). Various biochemical, electrocardiographic, and echocardiographic findings may suggest left atrial damage and increased risk of embolism in the absence of clinically documented AF or atrial flutter. In this review, we analyse the available evidence on atrial cardiopathy or atrial disease, its involvement in ESUS, and its identification through electrocardiographic, echocardiographic, and serum markers and its possible therapeutic implications. DEVELOPMENT: A systematic search was conducted on MEDLINE (PubMed) using the following MeSH terms: MeSH [ESUS]+[atrial cardiopathy]+[atrial fibrillation]+[interatrial block]+[treatment]. We selected what we considered to be the most useful original prospective or retrospective studies and systematic reviews. We then read the full texts of the articles and checked the references cited in each article. We analyse epidemiological and demographic variables of patients with ESUS, as well as recent evidence related to presentation and prognosis and factors associated with recurrence and mortality. We review the contribution of atrial cardiopathy diagnosis prior to the detection of AF and the clinical, electrocardiographic, and echocardiographic variables and the biochemical markers associated with its development and its potential contribution to cerebral embolism. CONCLUSIONS: The systematic search of biochemical and electrocardiographic, and echocardiographic alterations can be useful to identify ESUS patients at higher risk of recurrence.

Identifying Dementia Risk in Older Veterans Using A Mailing Survey.

Evidence suggests that dementia can be prevented. Patients with frailty may be particularly at risk for cognitive impairment (CI). The aim of this study was to determine dementia risk in older Veterans and whether the risk varies according to frailty status. We also evaluated the feasibility of mailed dementia risk screening. Participants were mailed a questionnaire and the Self-Administered Gerocognitive Examination (SAGE). High dementia risk was defined as having mild cognitive impairment (MCI) on SAGE or a CAIDE score ≥6. Out of 5,432 mailed surveys, we obtained a response rate of 19.75%. Most responders completed the questionnaire items. We identified a total of 689 (75.9%) subjects to be at high risk for dementia. Individuals with frailty were at a greater risk for dementia when compared to robust individuals OR:1.921 (95%CI:1.259-2.930), p=.002. The mailed screening represents a convenient, alternative and scalable approach to screen for dementia risk.