Pseudomonas aeruginosa bloodstream infections in children and adolescents: risk factors associated with carbapenem resistance and mortality.

BACKGROUND: Pseudomonas aeruginosa bloodstream infections (PA-BSIs) are a serious disease and a therapeutic challenge due to increasing resistance to carbapenems. Our objectives were to describe the prevalence and risk factors associated with carbapenem resistance (CR) and mortality in children with PA-BSI. METHODS: A retrospective, multi-centre study was carried out, including patients aged <20 years with PA-BSI in four tertiary hospitals in Madrid (Spain) during 2010-2020. Risk factors for CR PA-BSIs and 30-day mortality were evaluated in a multi-variable logistic regression model. RESULTS: In total, 151 patients with PA-BSI were included, with a median age of 29 months (interquartile range: 3.5-87.1). Forty-five (29.8%) cases were CR, 9.9% multi-drug resistant and 6.6% extensively drug resistant. The prevalence of CR remained stable throughout the study period, with 26.7% (12/45) of CR mediated by VIM-type carbapenemase. Patients with BSIs produced by CR-PA were more likely to receive inappropriate empiric treatment (53.3% vs 5.7%, P<0.001) and to have been previously colonized by CR-PA (8.9% vs 0%, P=0.002) than BSIs caused by carbapenem-susceptible P. aeruginosa. CR was associated with carbapenem treatment in the previous month (adjusted odds ratio (aOR) 11.15) and solid organ transplantation (aOR 7.64). The 30-day mortality was 23.2%, which was associated with mechanical ventilation (aOR 4.24), sepsis (aOR 5.72), inappropriate empiric antibiotic therapy (aOR 5.86), and source control as a protective factor (aOR 0.16). CONCLUSION: This study shows a concerning prevalence of CR in children with PA-BSIs, leading to high mortality. Inappropriate empiric treatment and sepsis were associated with mortality. The high prevalence of CR with an increased risk of inappropriate empiric treatment should be closely monitored.

Robotic sacrocolpopexy for the treatment of pelvic organ prolapse in elderly women: comparative analysis of safety and efficacy versus younger women.

INTRODUCTION: Pelvic organ prolapse is a condition with high prevalence in elderly women. With increasing life expectancy and a desire for improved quality of life, a rise in the frequency of surgical treatments for these women is anticipated. The aim is to compare complication, success, and satisfaction rates among elderly patients (aged >70 years) in comparison to younger women undergoing robotic sacrocolpopexy, thereby assessing the safety and efficacy of this surgery in this group of patients. METHOD: A prospective observational comparative study of 123 robotic sacrocolpopexies conducted between December 2016 and June 2022. Patients were stratified by age (cutoff point: 70 years). Baseline characteristics, type, and grade of prolapse, intra and postoperative data, complications, functional and anatomical outcomes, and satisfaction levels were collected. RESULTS: Among the 123 patients, 62.6% were under 70 years old, while 37.4% were 70 years or older, exhibiting similar baseline characteristics, prolapse grade, and type. The percentages of intraoperative (6.5%) and postoperative complications (4.4-9%) were comparable in both age groups. Furthermore, success and satisfaction rates exceeded 90%, with no significant differences between women under and over 70 years during a two-year follow-up. CONCLUSION: Robotic sacrocolpopexy is at least as effective and safe in women aged 70 years or older as in younger individuals, with no higher rates of intra and postoperative complications and similar rates of anatomical and subjective success.

Actinotignum schaalii infection: Challenges in diagnosis and treatment.

Actinotignum schaalii affects elderly people and is associated with individuals with urological-related predispositions, but can be found in a variety of locations, such as cutaneous, intraabdominal, genitourinary and surgical infections. Disseminated infections occur less frequently and are by and large related to urinary tract colonisation. This pathogen is often neglected due to growth requirements, especially in urinary tract infections. We present 107 Actinotignum schaalii isolated from genitourinary samples (80.4%), from skin and soft tissue infections (13.1%), from bone and deep tissue infection (4.7%) and from blood cultures (1.9%). The automated system Alfred 60/AST was paramount for the isolation of 77.6% of the UTI. All the isolates tested were susceptible to penicillin, ampicillin, linezolid, vancomycin, teicoplanin, rifampicin and tetracycline. In conclusion, we present a large series of Actinotignum schaalii infections. This pathogen is hard to isolate, and is resistant to commonly used empirical antimicrobials.

Assessment of chitosan-based adsorbents for glyphosate removal.

Exposure to glyphosate produces various toxic effects, due to this, different methods have been evaluated for its elimination. The objective of this work was to formulate chitosan-based adsorbents and evaluate their efficiency in the removal of glyphosate in vitro. Four films were made by varying the weight ratio of silica/chitosan particles, and four sponges were made by varying the chitosan/chitosan ratio in a reticulated manner. Both adsorbents were characterized based on their porosity, water absorption, glyphosate removal, and reusability. It was found that increasing the porosity in both films and sponges resulted in an increase in the adsorption efficiency of glyphosate. The adsorption process exhibited a better fit in both adsorbents to the pseudo-second-order model. The adsorption of glyphosate to the films fit better with the Langmuir model, demonstrating that the process occurs in the form of a monolayer. In the case of sponges, the adsorption of glyphosate fit better with the Freundlich model, indicating that the process takes place in a multilayer form. Finally, when the reusability was evaluated, the adsorbents showed a loss of effectiveness. However, they still proved to be an efficient alternative for the removal of glyphosate in water, providing a cost-effective and environmentally friendly solution.

Identification of Genetic and Genomic Influences on Progressive Ethanol Consumption in Diversity Outbred Mice.

Genetic factors play a significant role in the risk for development of alcohol use disorder (AUD). Using 3-bottle choice intermittent access ethanol (IEA), we have employed the Diversity Outbred (DO) mouse panel as a model of alcohol use disorder in a genetically diverse population. Through use of gene expression network analysis techniques, in combination with expression quantitative trait loci (eQTL) mapping, we have completed an extensive analysis of the influence of genetic background on gene expression changes in the prefrontal cortex (PFC). This approach revealed that, in DO mice, genes whose expression was significantly disrupted by intermittent ethanol in the PFC also tended to be those whose expression correlated to intake. This finding is in contrast to previous studies of both mice and nonhuman primates. Importantly, these analyses identified genes involved in myelination in the PFC as significantly disrupted by IEA, correlated to ethanol intake, and having significant eQTLs. Genes that code for canonical components of the myelin sheath, such as Mbp, also emerged as key drivers of the gene expression response to intermittent ethanol drinking. Several regulators of myelination were also key drivers of gene expression, and had significant QTLs, indicating that genetic background may play an important role in regulation of brain myelination. These findings underscore the importance of disruption of normal myelination in the PFC in response to prolonged ethanol exposure, that genetic variation plays an important role in this response, and that this interaction between genetics and myelin disruption in the presence of ethanol may underlie previously observed behavioral changes under intermittent access ethanol drinking such as escalation of consumption.

Factors from healthcare delivery affecting breast cancer survival in a health area of Northern of Spain.

OBJECTIVE: Clinical breast cancer decision-making significantly affects life expectancy and management of hospital resources. The aims of the present study were to estimate the time of survival for breast cancer patients and to identify independent factors from healthcare delivery associated with survival rates in a specific health area of Northern of Spain. METHODS: Survival analysis was conducted among a cohort of 2545 patients diagnosed with breast cancer between 2006 and 2012 from the population breast cancer registry of Asturias-Spain and followed up till 2019. Adjusted Cox proportional hazard models were used to identify the independent prognostic factors of all-cause from death. RESULTS: The 5-year survival rate was 80%. Advanced age (>80 years) (hazard ratio, HR: 4.35; 95% confidence interval, CI: 3.41-5.54), hospitalization in small hospitals (HR: 1.46; 95% CI: 1.09-1.97), treatment in oncology wards (HR: 3.57; 95% CI: 2.41-5.27), and length of stay >30 days (HR: 2.24; 95% CI: 1.32-3.79) were the main predictors of death. By contrast, breast cancer suspected via screening was associated with a lower risk of death (HR: 0.55; 95% CI: 0.35-0.87). CONCLUSION: There is room for improvement in survival rates after breast cancer in the health area of Asturias (Northern of Spain). Some healthcare delivery factors, and other clinical characteristics of the tumor influence the survival of breast cancer patients. Strengthening population screening programs could be relevant to increasing survival rates.

Consensus on complementary feeding from the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition: COCO 2023.

Complementary feeding (CF) is defined as the feeding of infants that complements breastfeeding, or alternatively, feeding with a breast milk substitute, and is a process that is more than simply a guide as to what and how to introduce foods. The information provided by healthcare professionals must be up-to-date and evidence-based. Most of the recommendations that appear in the different international guidelines and position papers are widely applicable, but some must be regionalized or adapted to fit the conditions and reality of each geographic zone. The Nutrition Working Group of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN) summoned a group of experts from each of the society's member countries, to develop a consensus on CF, incorporating, whenever possible, local information adapted to the reality of the region. The aim of the present document is to show the results of that endeavor. Utilizing the Delphi method, a total of 34 statements on relevant aspects of CF were evaluated, discussed, and voted upon.

Early treatment with JNJ-46356479, a mGluR2 modulator, improves behavioral and neuropathological deficits in a postnatal ketamine mouse model of schizophrenia.

Positive allosteric modulators of the metabotropic glutamate receptor 2 (mGluR2), such as JNJ-46356479 (JNJ), may mitigate the glutamate storm during the early stages of schizophrenia (SZ), which could be especially useful in the treatment of cognitive and negative symptoms. We evaluated the efficacy of early treatment with JNJ or clozapine (CLZ) in reversing behavioral and neuropathological deficits induced in a postnatal ketamine (KET) mouse model of SZ. Mice exposed to KET (30 mg/kg) on postnatal days (PND) 7, 9, and 11 received JNJ or CLZ (10 mg/kg) daily in the adolescent period (PND 35-60). Mice exposed to KET did not show the expected preference for a novel object or for social novelty, but they recovered this preference with JNJ treatment. Similarly, KET group did not show the expected dishabituation in the fifth trial, but mice treated with JNJ or CLZ recovered an interest in the novel animal. Neuronal immunoreactivity also differed between treatment groups with mice exposed to KET showing a reduction in parvalbumin positive cells in the prefrontal cortex and decreased c-Fos expression in the hippocampus, which was normalized with the pharmacological treatment. JNJ-46356479 treatment in early stages may help improve the cognitive and negative symptoms, as well as certain neuropathological deficits, and may even obtain a better response than CLZ treatment. This may have relevant clinical translational applications since early treatment with mGluR2 modulators that inhibit glutamate release at the onset of critical phases of SZ may prevent or slow down the clinical deterioration of the disease.

Anatomy and Design of Musculocutaneous Flaps in Nasal Reconstruction. / Anatomía y diseño de colgajos musculocutáneos en reconstrucción nasal.

The nose is a common site for skin tumors. The main arteries that supply the nose extend through the subcutaneous tissue. Submuscular dissection facilitates the design of safe, reliable musculocutaneous flaps that adapt well to the morphology of nasal defects. The diversity of these flaps makes them the first choice for reconstructing defects in more complex regions, such as the inner canthus of the eye and the nasal ala. We describe the surgical design of the procerus, V-Y nasalis, and lateral wall nasalis musculocutaneous flaps used to repair defects following tumor excision. The descriptions are illustrated by photographs taken by the authors during procedures and in cadaveric dissections.

Quality of life and persistent symptoms after hospitalization for COVID-19. A prospective observational study comparing ICU with non-ICU patients.

BACKGROUND: Hospitalized COVID-19 patients are prone to develop persistent symptoms and to show reduced quality of life following hospital admission. METHODS: Prospective cohort study of COVID-19 patients admitted to a hospital from March 1 to April 30, 2020. The primary outcome was to compare health related quality of life and persistent symptoms six months after hospital admission, of COVID-19 patients who required ICU admission with those who did not. RESULTS: Among the 242 patients hospitalized during the defined period of time, 44 (18.2%) needed ICU admission. Forty (16.5%) patients died during hospital admission. Two hundred and two (83.5%) patients were discharged alive from the hospital. At six months, 183 (75.6%) patients completed the questionnaires (32 ICU patients and 151 non ICU patients). Ninety-six (52.4%) reported decreased quality of life and 143 (78.1%) described persistent symptoms. More ICU patients showed worsening of their quality of life (71.9% vs 43.7%, P=0.004). There were no differences in the proportion of patients with persistent symptoms between ICU and non ICU patients (87.5% vs 76.2%, P=0.159). ICU patients showed more frequently dyspnea on exertion (78.1% vs 47.7%, P=0.02), dyspnea on light exertion (37.5% vs 4.6%, P<0.001), and asthenia (56.3 vs 29.1, P=0.003). CONCLUSIONS: Survivors of COVID-19 needing hospitalization had persistent symptoms and a decline in the quality of life. ICU patients referred a large decrease of their quality of life compared with non ICU patients.

Acute isolated dislocation of the distal radial ulnar joint - ulnar volar with no other associated lesion: Case report and review of the literature.

Isolated dislocation of the distal radioulnar joint is a rare phenomenon with few described cases in the literature for which the management is not well established. We report here a case of distal radioulnar joint dislocation - ulnar volar. The patient is a 58-year-old woman who fell on an extended upper extremity with forced supination. The patient was treated non-surgically with closed reduction and immobilization followed by physical and ergonomic therapy. During treatment MRI imaging was performed which showed no lesion to the TFCC. Following immobilization, the patient had good mobility of the forearm and the wrist. Early diagnosis, treatment, and imaging allowed for excellent functional recovery without surgical treatment.

Autophagy mediates ER stress and inflammation in Helicobacter pylori-related gastric cancer.

Autophagy is a cellular degradation mechanism, which is triggered by the bacterium Helicobacter pylori. A single nucleotide polymorphism (SNP) in the autophagy gene ATG16L1 (rs2241880, G-allele) has been shown to dysregulate autophagy and increase intestinal endoplasmic reticulum (ER) stress. Here, we investigate the role of this SNP in H.pylori-mediated gastric carcinogenesis and its molecular pathways. ATG16L1 rs2241880 was genotyped in subjects from different ethnic cohorts (Dutch and Australian) presenting with gastric (pre)malignant lesions of various severity. Expression of GRP78 (a marker for ER stress) was assessed in gastric tissues. The effect of ATG16L1 rs2241880 on H.pylori-mediated ER stress and pro-inflammatory cytokine induction was investigated in organoids and CRISPR/Cas9 modified cell lines. Development of gastric cancer was associated with the ATG16L1 rs2241880 G-allele. Intestinal metaplastic cells in gastric tissue of patients showed increased levels of ER-stress. In vitro models showed that H.pylori increases autophagy while reducing ER stress, which appeared partly mediated by the ATG16L1 rs2241880 genotype. H.pylori-induced IL-8 production was increased while TNF-α production was decreased, in cells homozygous for the G-allele. The ATG16L1 rs2241880 G-allele is associated with progression of gastric premalignant lesions and cancer. Modulation of H.pylori-induced ER stress pathways and pro-inflammatory mediators by ATG16L1 rs2441880 may underlie this increased risk.

Type 2 Diabetes and all-cause mortality among Spanish women with breast cancer.

PURPOSE: To explore the effect of type 2 diabetes mellitus (T2DM) on the risk of death among women with breast cancer (BC). METHODS: A survival analysis was conducted among a cohort of women diagnosed with BC between 2006 and 2012 in Spain (n = 4,493). Biopsy or surgery confirmed BC cases were identified through the state population-based cancer registry with information on patients' characteristics and vital status. Physician-diagnosed T2DM was confirmed based on primary health care clinical history. Cox regression analyses were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for all-cause death. Analyses were adjusted for age, hospital size, several clinical characteristics (including BC stage and histology, among others) and treatment modalities. RESULTS: Among the 4,493 BC women, 388 (8.6%) had coexisting T2DM. Overall, 1,299 (28.9%) BC women died during the completion of the follow-up and 785 (17.5%) did so during the first five years after BC diagnosis, resulting in a five-year survival rate of 82.5%. The death rate was higher in women with T2DM (43.8% died during whole period and 26.0% during the first five years) when compared with women without T2DM (27.5% and 16.7%, respectively). Accordingly, all-cause mortality was higher in women with T2DM (aHR: 1.22; 95% CI 1.03-1.44), especially if T2DM was diagnosed before BC (aHR:1.24; 95% CI 1.03-1.50) and in women with BC diagnosed before 50 years (aHR: 2.38; 95% CI 1.04-5.48). CONCLUSIONS: T2DM was associated with higher all-cause mortality among Spanish women with BC, particularly when the T2DM diagnosis was prior to the BC.

[Quality of life and persistent symptoms after hospitalization for COVID-19. A prospective observational study comparing ICU with non-ICU patients]. / Calidad de vida y síntomas persistentes tras hospitalización por COVID-19. Estudio observacional prospectivo comparando pacientes con o sin ingreso en UCI.

Background: Hospitalized COVID-19 patients are prone to develop persistent symptoms and to show reduced quality of life following hospital admission. Methods: Prospective cohort study of COVID-19 patients admitted to a hospital from March 1 to April 30, 2020. The primary outcome was to compare health related quality of life and persistent symptoms six months after hospital admission, of COVID-19 patients who required ICU admission with those who did not. Results: Among the 242 patients hospitalized during the defined period of time, 44 (18.2%) needed ICU admission. Forty (16.5%) patients died during hospital admission. Two hundred and two (83.5%) patients were discharged alive from the hospital. At six months, 183 (75.6%) patients completed the questionnaires (32 ICU patients and 151 non ICU patients). Ninety-six (52.4%) reported decreased quality of life and 143 (78.1%) described persistent symptoms. More ICU patients showed worsening of their quality of life (71.9 vs. 43.7%, P = 0.004). There were no differences in the proportion of patients with persistent symptoms between ICU and non ICU patients (87.5 vs. 76.2%, P = 0.159). ICU patients showed more frequently dyspnea on exertion (78.1 vs. 47.7%, P = 0.02), dyspnea on light exertion (37.5 vs. 4.6%, P < 0.001), and asthenia (56.3 vs. 29.1, P = 0.003). Conclusions: Survivors of COVID-19 needing hospitalization had persistent symptoms and a decline in the quality of life. ICU patients referred a large decrease of their quality of life compared with non ICU patients.

Intraoperative irradiation in breast cancer: preliminary results in 80 patients as partial breast irradiation or anticipated boost prior to hypo-fractionated whole breast irradiation.

PURPOSE: To present the first results of intraoperative irradiation (IORT) in breast cancer with a low-energy photon system used as partial breast irradiation (PBI) or as an anticipated boost before whole breast hypo-fractionated irradiation (IORT + WBI), concerning tolerance, side effects, quality of life, and patient-reported outcomes. MATERIALS AND METHODS: Eighty patients treated with an Intrabeam® system of 50 kV X-rays received a 20 Gy dose intraoperatively were included. Moderate daily hypofractionation of 2.7 Gy in 15 fractions up to 40.5 Gy was administered if high-risk factors were present. Acute post-operative toxicity, surgery complications, chronic toxicity, patient-reported cosmesis and Breast-Q questionnaire were performed at follow-up visits. RESULTS: Thirty-one patients were treated as PBI and the remaining 49 as IORT + WBI. Only the IORT + WBI group presented acute toxicity, mainly mild acute dermatitis (11 patients) and one subacute mastitis. A total of 20 patients presented fibrosis (18 patients grade I, 2 patients grade II), 15 (30.5%) patients in the IORT + WBI group and 3 (9.6%) patients in the group of PBI. The cosmesis evaluation in 73 patients resulted poor, fair, good or excellent in 2, 7, 38 and 26 patients, respectively. In PBI group Breast-Q scored higher, especially in terms of their psychosocial well-being (78 vs 65) and satisfaction with radiation-induced toxicity (77 vs 72, respectively) compared to IORT + WBI group. CONCLUSION: IORT is a well-tolerated procedure with low toxicity, good cosmesis and favorable patient-reported outcomes mainly when administered as PBI.