Epidemiology and Burden of Ventilator-Associated Pneumonia among Adult Intensive Care Unit Patients: A Portuguese, Multicenter, Retrospective Study (eVAP-PT Study).

Ventilator-associated pneumonia (VAP) is a prevailing nosocomial infection in critically ill patients requiring invasive mechanical ventilation (iMV). The impact of VAP is profound, adversely affecting patient outcomes and placing a significant burden on healthcare resources. This study assessed for the first time the contemporary VAP epidemiology in Portugal and its burden on the healthcare system and clinical outcomes. Additionally, resource consumption (duration of iMV, intensive care unit (ICU), hospital length of stay (LOS)) and empirical antimicrobial therapy were also evaluated. This multicenter, retrospective study included patients admitted to the hospital between July 2016 and December 2017 in a participating ICU, who underwent iMV for at least 48 h. Patients with a VAP diagnosis were segregated for further analysis (n = 197). Control patients, ventilated for >48 h but without a VAP diagnosis, were also included in a 1:1 ratio. Cumulative VAP incidence was computed. All-cause mortality was assessed at 28, 90, and 365 days after ICU admission. Cumulative VAP incidence was 9.2% (95% CI 8.0-10.5). The all-cause mortality rate in VAP patients was 24.9%, 34.0%, and 40.6%, respectively, and these values were similar to those observed in patients without VAP diagnosis. Further, patients with VAP had significantly longer ICU (27.5 vs. 11.0 days, p < 0.001) and hospital LOS (61 vs. 35.9 days, p < 0.001), more time under iMV (20.7 vs. 8.0 days, p < 0.001) and were more often subjected to tracheostomy (36.5 vs. 14.2%; p < 0.001). Patients with VAP who received inappropriate empirical antimicrobials had higher 28-day mortality, 34.3% vs. 19.5% (odds ratio 2.16, 95% CI 1.10-4.23), although the same was not independently associated with 1-year all-cause mortality (p = 0.107). This study described the VAP impact and burden on the Portuguese healthcare system, with approximately 9% of patients undergoing iMV for >48 h developing VAP, leading to increased resource consumption (longer ICU and hospital LOS). An unexpectedly high incidence of inappropriate, empirical antimicrobial therapy was also noted, being positively associated with a higher mortality risk of these patients. Knowledge of the Portuguese epidemiology characterization of VAP and its multidimensional impact is essential for efficient treatment and optimized long-term health outcomes of these patients.

Exploiting Co(III)-Cyclopentadienyl Complexes To Develop Anticancer Agents.

In recent years, organometallic complexes have attracted much attention as anticancer therapeutics aiming at overcoming the limitations of platinum drugs that are currently marketed. Still, the development of half-sandwich organometallic cobalt complexes remains scarcely explored. Four new cobalt(III)-cyclopentadienyl complexes containing N,N-heteroaromatic bidentate, and phosphane ligands were synthesized and fully characterized by elemental analysis, spectroscopic techniques, and DFT methods. The cytotoxicity of all complexes was determined in vitro by the MTS assay in colorectal (HCT116), ovarian (A2780), and breast (MDA-MB-231 and MCF-7) human cancer cell lines and in a healthy human cell line (fibroblasts). The complexes showed high cytotoxicity in cancer cell lines, mostly due to ROS production, apoptosis, autophagy induction, and disruption of the mitochondrial membrane. Also, these complexes were shown to be nontoxic in vivo in an ex ovo chick embryo yolk sac membrane (YSM) assay.

Access to psychological treatment for chronic cancer-related pain in Sweden.

OBJECTIVES: Cancer-related pain (CRP) is among the most frequent collateral effects of cancer, with chronic CRP, lasting at least 3 months, affecting >40% of cancer survivors. Evidence-based treatments, including pain-focused cognitive behavioral therapy (CBT), are available, but it appears that cancer patients/survivors are often poorly informed about CRP or the potential benefits of CBT for such pain. This study examined current experience of Swedish cancer patients/survivors in relation to CRP. METHODS: Participants (N = 276; 83% female; mean age = 55.5 years, SD = 11.9) were recruited to an online survey via cancer websites in Sweden, and they provided information about their history of chronic CRP and whether they received information about or treatment for CRP from a healthcare professional. RESULTS: Participants had a history of breast (36%), gynecological (12%), lung (10%), colon (8%), and other forms of cancer (36%). A majority (74%) reported a history of chronic CRP and being prescribed analgesic medications (70%). Less than half (47%) received information from their healthcare provider about the risk of CRP and only 13% with chronic CRP received psychological treatment, and of these, only 33% received CBT. Among those receiving psychological treatment for chronic CRP, satisfaction rates were moderate, reported as an average of 6 on a 0-10 scale (standard deviation 2.6). CONCLUSIONS: Greater efforts are needed to raise awareness among cancer patients/survivors and healthcare providers about the risk of CRP and evidence-based interventions, including CBT, the first-line intervention for chronic pain. These efforts will need to be matched with increases in treatment capacity, particularly pain-focused CBT.

Corrigendum: Efficacy of an ACT and compassion-based ehealth program for self-management of chronic pain (iACTwithPain): study protocol for a randomized controlled trial.

[This corrects the article DOI: 10.3389/fpsyg.2021.630766.].

Exploiting Pharma 4.0 Technologies in the Non-Biological Complex Drugs Manufacturing: Innovations and Implications.

The pharmaceutical industry has entered an era of transformation with the emergence of Pharma 4.0, which leverages cutting-edge technologies in manufacturing processes. These hold tremendous potential for enhancing the overall efficiency, safety, and quality of non-biological complex drugs (NBCDs), a category of pharmaceutical products that pose unique challenges due to their intricate composition and complex manufacturing requirements. This review attempts to provide insight into the application of select Pharma 4.0 technologies, namely machine learning, in silico modeling, and 3D printing, in the manufacturing process of NBCDs. Specifically, it reviews the impact of these tools on NBCDs such as liposomes, polymeric micelles, glatiramer acetate, iron carbohydrate complexes, and nanocrystals. It also addresses regulatory challenges associated with the implementation of these technologies and presents potential future perspectives, highlighting the incorporation of digital twins in this field of research as it seems to be a very promising approach, namely for the optimization of NBCDs manufacturing processes.

Agreement Between Epigastric Auscultation and pH Measurement in the Confirmation of Nasoenteral Tube Placement.

AIM: This study aimed to evaluate the agreement between epigastric auscultation and pH measurement in the confirmation of nasoenteral tube placement. METHOD: A cross-sectional study carried out in a medium-sized private hospital in the interior of the state of São Paulo. Forty-nine patients who were submitted to ninety insertion procedures and confirmation of tube placement. aimed at evaluating the agreement of clinical methods used by nurses to confirm the positioning of a nasoenteral tube inserted blindly at the bedside, by measuring the parameters of sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: The epigastric auscultation was the method that presented the highest sensitivity (100.0%), but lower specificity (2.0%). The measurement of the pH presented lower sensitivity (63.0%) than the auscultation, however, higher specificity (58%). Moreover, the positive predictive value of the pH measurement was 55% and the negative predictive value was 66%. There was no agreement between the epigastric auscultation and the pH measurement with the radiography. CONCLUSION: The pH measurement did not allow for distinguishing between gastric and enteric positioning, due to the similarity of the esophageal and pulmonary pH with the pH of the intestine. Furthermore, external factors such as the use of medication and reduced fasting time may interfere with the pH value.

Hepatic Encephalopathy in Cirrhotic Patients With Bacterial Infections: Frequency, Clinical Characteristics, and Prognostic Relevance.

Background/Objectives: Bacterial infections (BIs) are well-recognized precipitants of hepatic encephalopathy (HE). Nevertheless, there is a paucity of data in patients with HE associated with BI. Our aim was to describe clinical characteristics, recurrence, and prognosis of HE in patients with BI. Methods: A prospective study with inclusion of hospitalized cirrhotic patients with BI, followed until discharge, death, or liver transplantation. Results: 172 patients (age 57 ± 13, model of end-stage liver disease [MELD]-sodium 22 ± 8) were included. Infections were more commonly due to spontaneous bacterial peritonitis and cellulitis (22% and 23%), non-nosocomial (70%), and associated with systemic inflammatory response syndrome and septic shock in 40% and 9%, respectively. HE was diagnosed in 66 patients (grade ≥2 in 58%). In multivariate analysis, MELD-sodium, albumin, and prior HE were associated with HE at diagnosis of BI. Recurrence of HE was diagnosed in 30 patients (median 13 [interquartile range 5-22] days), more commonly manifested as overt HE (90% vs. 60% at first episode, P = 0.012) and more frequently in patients with hyponatremia (54% vs. 27% for patients without, P < 0.001). In-hospital mortality was 34% and was more common for patients with HE (51% vs. 22%, P < 0.001), irrespective of grade, and for those with recurrence (63% vs. 42%, P < 0.001). In multivariate analysis, HE at diagnosis of infection and MELD-sodium were predictors of mortality. Conclusions: HE is frequent in cirrhotic patients with BI and is associated with severity of liver disease, but not with infection. These patients are at increased risk of short-term HE recurrence, especially those with hyponatremia. The presence and recurrence of HE, independent of severity, are associated with in-hospital mortality.

Real-Life Data on Readmissions of Worsening Heart Failure Outpatients in a Heart Failure Clinic.

Introduction Recurrent hospitalizations for worsening heart failure (WHF) represent a major global public health concern, resulting in significant individual morbimortality and socioeconomic costs. This real-life study aimed to determine the rate and predictors of readmission for WHF in a cohort of outpatients with chronic heart failure (CHF) followed in a heart failure clinic (HFC) at a university hospital. Methods We conducted a longitudinal, observational, and retrospective study of all consecutive CHF patients seen at the HFC of the São Francisco Xavier Hospital, Lisbon, by a multidisciplinary team in 2019. The patients were followed for one year and were on optimized therapy. The inclusion criteria for the study were patients who had been hospitalized and subsequently discharged at least three months prior to their enrollment. Patient demographics, heart failure (HF) characterization, comorbidities, pharmacological treatment, treatments of decompensated HF in the day hospital (DH), hospitalizations for WHF, and death were recorded. We applied logistic regression analysis to assess predictors of hospital readmission for HF. Results A total of 351 patients were included: 90 patients (26%) had WHF requiring treatment with intravenous diuretics in the DH; 45 patients (mean age: 79.1 ± 9.0 years) were readmitted for decompensated HF within one year (12.8%) with no gender difference, while 87.2% of the patients (mean age: 74.9 ± 12.1 years) were never readmitted. Readmitted patients were significantly older than those who were not (p=0.031). Additionally, they had a higher New York Heart Association (NYHA) functional classification (p<.001), were on a higher daily dose of furosemide (p=0.008) at the time of the inclusion visit, were more frequently affected by the chronic obstructive pulmonary disease (COPD) (p=0.004); had been treated more often in the DH for WHF (p<.001) and had a higher mortality rate (p<.001) at one year. Conclusions This study aimed to determine WHF patient readmission rates and predictors. According to our results, a higher NYHA class, the need for treatment in the DH for WHF, a daily dose of furosemide equal to or greater than 80 mg, and COPD were predictors of readmission for WHF. CHF patients continue to experience WHF and recurrent hospitalizations despite therapeutic advances and close follow-up in the HFC with the multidisciplinary team. Besides COPD, the HF readmission risk factors found were mainly related to advanced disease. Furthermore, the structured and multidisciplinary approach of our disease management program likely contributed to our relatively low rate of readmissions.

Nanosystems for Brain Targeting of Antipsychotic Drugs: An Update on the Most Promising Nanocarriers for Increased Bioavailability and Therapeutic Efficacy.

Orally administered antipsychotic drugs are the first-line treatment for psychotic disorders, such as schizophrenia and bipolar disorder. Nevertheless, adverse drug reactions jeopardize clinical outcomes, resulting in patient non-compliance. The design formulation strategies for enhancing brain drug delivery has been a major challenge, mainly due to the restrictive properties of the blood-brain barrier. However, recent pharmacokinetic and pharmacodynamic in vivo assays confirmed the advantage of the intranasal route when compared to oral and intravenous administration, as it allows direct nose-to-brain drug transport via neuronal pathways, reducing systemic side effects and maximizing therapeutic outcomes. In addition, the incorporation of antipsychotic drugs into nanosystems such as polymeric nanoparticles, polymeric mixed micelles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, nanoemulgels, nanosuspensions, niosomes and spanlastics, has proven to be quite promising. The developed nanosystems, having a small and homogeneous particle size (ideal for nose-to-brain delivery), high encapsulation efficiency and good stability, resulted in improved brain bioavailability and therapeutic-like effects in animal models. Hence, although it is essential to continue research in this field, the intranasal delivery of nanosystems for the treatment of schizophrenia, bipolar disorder and other related disorders has proven to be quite promising, opening a path for future therapies with higher efficacy.

The contribution of psychological flexibility to functioning in people living with cancer-related pain.

BACKGROUND: Studies of individuals with non-cancer-related chronic pain find that higher levels of psychological flexibility (PF) are associated with less distress, better functioning, and a better response to treatment. People diagnosed with cancer are at a significantly increased risk of developing chronic cancer-related pain, the presence of which is associated with poorer health outcomes. Little is known about whether PF is applicable to cancer pain. The current study investigates the relationship between chronic cancer-related pain, distress and functioning, and three theoretical processes proposed by the PF model: pain acceptance, present-moment focus, and committed action. METHODS: Adults (n = 246) with a cancer diagnosis (current or previous), and living in Sweden, completed an online survey involving standardized measures of cancer-related pain (intensity and impairment), depression, fatigue, PF and social stigma. RESULTS: Moderate to strong correlations were found between PF and all variables. In regression analyses, PF, and particularly pain acceptance, accounted for a large and significant proportion of the observed variance in depression, pain-related and overall functioning, after controlling for cancer status, pain intensity and social stigma. CONCLUSION: Consistent with studies of non-cancer-related pain, higher levels of PF were strongly associated with lower levels of distress and better functioning in individuals with cancer-related pain. Further studies are needed to further explore these relationships and to determine whether psychosocial treatments targeting PF may be of benefit to people with chronic cancer-related pain. SIGNIFICANCE: This study explores the relationship between cancer-related pain (intensity and impairment), depression, fatigue, overall functioning, social stigma and PF. The findings suggest that higher levels of PF are associated with lower levels of distress and improved functioning in chronic cancer-related pain, after controlling for cancer status (current, in remission), pain intensity and social stigma.

Oxide-silicate petrology and geochemistry of subducted hydrous ultramafic rocks beyond antigorite dehydration (Central Alps, Switzerland).

Oxide minerals contained in ultramafic rocks are useful tools to assess the redox conditions of the rock and fluids liberated upon progressive serpentinite dehydration during subduction, as these minerals contain a relevant redox-sensitive element, iron. Previous studies have revealed that magnetite predominates across the antigorite-out reaction. However, the fate of magnetite and other oxides at higher pressure and temperature conditions has remained underexplored. We present a comprehensive petrological and geochemical study of oxide-sulfide-silicate mineral assemblages in metaperidotites beyond antigorite- and chlorite-out reactions (T = 650-850 °C and P = 1-3 GPa). Several ultramafic lenses, covering different bulk rock compositions and extents of oxidation upon oceanic serpentinization, were investigated from the Central Alps, Switzerland. Results point to two endmember scenarios: (i) Most frequently, metaperidotites have olivine with a Mg# of 89-91 (defined as molar Mg/(Mg + Fetot) × 100) and contain low oxide modes (0.06-1.41 vol.%), hematite is absent, and redox conditions are weakly oxidized and buffered by orthopyroxene-olivine-magnetite. (ii) Rare occurrence, high olivine Mg# > 94.5 metaperidotites display coexisting hematite and magnetite, high oxide modes (up to 4 vol.%), and redox conditions are hematite-magnetite (HM) buffered (Δlog10fO2,QFM of + 3 to + 4). Spinel displays evolving compositions from magnetite over chromite to Al-Cr-spinel, roughly correlating with increasing temperature. Most of the samples buffered by the olivine-orthopyroxene-magnetite assemblage contain coexisting pentlandite ± pyrrhotite, thus identifying stable sulfides beyond antigorite dehydration for these weakly oxidized samples (Δlog10fO2,QFM < 2.5). No sulfides were recognized in the highly oxidized sample. The transition of magnetite to chromite at around 700 °C goes along with a shift in fO2 to lower values. At the prevailing oxygen fugacity in the weakly oxidized metaperidotites sulfur in a coexisting fluid is always present in its reduced form. However, oxidized sulfur can be stable in the dehydration fluids released from highly oxidized serpentinites. Supplementary Information: The online version contains supplementary material available at 10.1007/s00410-023-02032-w.

Lower Limbs are the Most Difficult-to-Treat Body Region of Patients with Psoriasis: Pooled Analysis of CLEAR and CLARITY Studies of Secukinumab Versus Ustekinumab by Body Region.

BACKGROUND: The impact of psoriasis, response to treatment, and patients' perceptions of treatment satisfaction vary by body area. OBJECTIVES: We aimed to evaluate the level of response in lower limbs versus other body regions in patient with moderate to severe psoriasis treated with secukinumab and ustekinumab. METHODS: Data were pooled from CLEAR and CLARITY trials, which included patients with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] score of ≥ 12) aged ≥ 18 years and a diagnosis of ≥ 6 months before randomisation. Patients received either secukinumab 300 mg or ustekinumab 45/90 mg. The PASI 100 responders and mean PASI scores at weeks 4, 12, 16, 28, 40 and 52 in the head and neck, trunk, upper limbs and lower limbs were measured. RESULTS: At baseline, analysis of PASI scores for each body region revealed that the lower limbs were the most severely affected body region in both treatment arms (mean PASI scores: secukinumab 24.0; ustekinumab 24.4). For both drugs, the highest clearance rates at week 52 were achieved in the trunk (secukinumab 85.2% vs ustekinumab 68.7%) and head and neck (80.7% vs 68.9%), followed by the upper limbs (72.6% vs 61.9%) and lower limbs (68.1% vs 57.2%). At week 52, the mean PASI score was higher in the lower limbs in both treatment arms versus other body regions. CONCLUSIONS: Lower limbs were the most severely affected and most difficult-to-treat regions in patients with psoriasis. Consistent with the individual results of both studies, secukinumab demonstrated numerically faster and higher skin clearance than ustekinumab in all body regions. CLINICAL TRIAL REGISTRATION: CLEAR: NCT02074982; CLARITY: NCT02826603.

In vitro activity of imipenem/relebactam against Pseudomonas aeruginosa isolates recovered from ICU patients in Spain and Portugal (SUPERIOR and STEP studies).

OBJECTIVES: To study the in vitro activity of imipenem/relebactam and comparators and the imipenem/relebactam resistance mechanisms in a Pseudomonas aeruginosa collection from Portugal (STEP, 2017-18) and Spain (SUPERIOR, 2016-17) surveillance studies. METHODS: P. aeruginosa isolates (n = 474) were prospectively recovered from complicated urinary tract (cUTI), complicated intra-abdominal (cIAI) and lower respiratory tract (LRTI) infections in 11 Portuguese and 8 Spanish ICUs. MICs were determined (ISO broth microdilution). All imipenem/relebactam-resistant P. aeruginosa isolates (n = 30) and a subset of imipenem/relebactam-susceptible strains (n = 32) were characterized by WGS. RESULTS: Imipenem/relebactam (93.7% susceptible), ceftazidime/avibactam (93.5% susceptible) and ceftolozane/tazobactam (93.2% susceptible) displayed comparable activity. The imipenem/relebactam resistance rate was 6.3% (Portugal 5.8%; Spain 8.9%). Relebactam restored imipenem susceptibility to 76.9% (103/134) of imipenem-resistant isolates, including MDR (82.1%; 32/39), XDR (68.8%; 53/77) and difficult-to-treat (DTR) isolates (67.2%; 45/67). Among sequenced strains, differences in population structure were detected depending on the country: clonal complex (CC)175 and CC309 in Spain and CC235, CC244, CC348 and CC253 in Portugal. Different carbapenemase gene distributions were also found: VIM-20 (n = 3), VIM-1 (n = 2), VIM-2 (n = 1) and VIM-36 (n = 1) in Spain and GES-13 (n = 13), VIM-2 (n = 3) and KPC-3 (n = 2) in Portugal. GES-13-CC235 (n = 13) and VIM type-CC175 (n = 5) associations were predominant in Portugal and Spain, respectively. Imipenem/relebactam showed activity against KPC-3 strains (2/2), but was inactive against all GES-13 producers and most of the VIM producers (8/10). Mutations in genes affecting porin inactivation, efflux pump overexpression and LPS modification might also be involved in imipenem/relebactam resistance. CONCLUSIONS: Microbiological results reinforce imipenem/relebactam as a potential option to treat cUTI, cIAI and LRTI caused by MDR/XDR P. aeruginosa isolates, except for GES-13 and VIM producers.

Usability Study of the iACTwithPain Platform: An Online Acceptance and Commitment Therapy and Compassion-Based Intervention for Chronic Pain.

Background: This pilot study aims to test the usability of the iACTwithPain platform, an online ACT-based intervention for people with chronic pain, to obtain information on which intervention and usability aspects need improvement and on expected retention rates. Methods: Seventy-three Portuguese women with chronic pain were invited to complete the first three sessions of the iACTwithPain intervention assess their quality, usefulness and the platform's usability. Twenty-one accepted the invitation. Additionally, eight healthcare professionals working with chronic medical conditions assessed the platform and the intervention from a practitioner's point of view. Results: This study presented a considerable attrition rate (71.43%) among chronic pain participants, with six completers. There were no significant differences in demographic or clinical variables between dropouts and completers except for completed education (participants who dropped out presented less education than completers). Reasons for dropout were related to difficult personal events occurring during the time of the intervention, lack of time, or having forgotten. There seemed to be an overall satisfaction with both the intervention, its contents and form of presentation of information, and the platform, concerning its design, appearance, and usability. Real image videos were preferred over animations or audio by chronic pain participants. Healthcare professionals emphasized the appealing and dynamic aspects of the animation format. Conclusion: This study informs the ongoing improvement of the iACTwithPain platform and provides valuable information on aspects researchers should consider while developing online psychological interventions for chronic pain. Further implications are discussed.

Imipenem-Relebactam Susceptibility in Enterobacterales Isolates Recovered from ICU Patients from Spain and Portugal (SUPERIOR and STEP Studies).

Imipenem-relebactam is a novel ß-lactam-ß-lactamase inhibitor combination. We evaluated the in vitro activity of imipenem-relebactam and comparators against Enterobacterales clinical isolates recovered in 8 Spanish and 11 Portuguese intensive care units (ICUs) (SUPERIOR, 2016-2017; STEP, 2017-2018). Overall, 747 Enterobacterales isolates (378 Escherichia coli, 252 Klebsiella spp., 64 Enterobacter spp., and 53 other species) were prospectively collected from ICU patients with complicated intraabdominal (cIAI), complicated urinary tract (cUTI), and lower respiratory tract (LRTI) infections. MICs were determined (ISO-broth microdilution), and whole-genome sequencing (WGS) was performed in a subset of isolates displaying susceptible and resistant imipenem-relebactam MICs. Imipenem-relebactam (98.7% susceptible) showed similar activity to ceftazidime-avibactam (99.5% susceptible) and higher than ceftolozane-tazobactam (86.9% susceptible). Imipenem-relebactam was inactive against 1.3% (10/747) isolates, all of them due to carbapenemase production (9 K. pneumoniae and 1 E. cloacae). Imipenem-relebactam was active against 100% of extended-spectrum ß-lactamase (ESBL)-E. coli and ESBL-Klebsiella spp. isolates and 80.4% of carbapenemase-Klebsiella spp. producers. Carbapenemase genes were confirmed by WGS in 41 Klebsiella spp.: OXA-48 (20/41), KPC-3 (14/41), OXA-181 (4/41), NDM-1 (1/41), OXA-48 + VIM-2 (1/41), and KPC-3 + VIM-2 (1/41). In Klebsiella spp. isolates, relebactam restored imipenem susceptibility in all KPC-3 producers, and resistant isolates (7/41) were mostly OXA-48 + CTX-M-15-K. pneumoniae high-risk clones (7/9). Intercountry differences were detected as follows: OXA-48 (17/21) was dominant in Spain, unlike KPC-3 (14/15) in Portugal. Imipenem-relebactam was 100% active against CTX-M-15-ST131-H30Rx-E. coli high-risk clone, predominant in both countries. Our results depict the potential role of imipenem-relebactam in ICU patients with cIAIs, cUTIs, and LRTIs due to wild-type ESBL- and carbapenemase-producing Enterobacterales, particularly KPC producers. IMPORTANCE We comparatively evaluate the in vitro activity of a drug combination consisting of a carbapenem (imipenem) and a novel inhibitor of beta-lactamases (relebactam), a mechanism that destroys beta-lactam antibiotics. We assess the activity against a collection of Enterobacterales clinical isolates recovered from difficult-to-treat infections in patients admitted to different intensive care units in Portugal and Spain. Imipenem-relebactam shows excellent activity in avoiding common resistance mechanisms in this setting, such as extended-spectrum beta-lactamases and carbapenemases widely distributed, including KPCs. We show few resistant isolates (<2%). Molecular characterization by whole-genome sequencing shows that most of the resistant isolates produced specific carbapenemase, such as OXA-48 or metalo-betalactamases. Our study updates the activity of imipenem-relebactam in light of current epidemiology in a hospital setting in which the use of this combination is needed due to the presence of infections due to multidrug-resistant isolates.

Tuberculosis and Its "Troubled Relationship" With Other Diseases.

Tuberculosis (TB) is a multisystemic disease caused most frequently by Mycobacterium tuberculosis. Extrapulmonary TB has become more frequent with the advent of human immunodeficiency virus (HIV) as HIV can facilitate the infection with M. tuberculosis, especially during HIV seroconversion. Here, we present the case of a 22-year-old man, from Guinea-Bissau, with a history of untreated HIV who was admitted to the intensive care unit for respiratory failure needing mechanical ventilation. Pulmonary TB was diagnosed. His stay was complicated with a hemorrhagic shock due to traumatic urethral catheterization, which led to a perforation of the capsule of the prostate. A prostatectomy was needed for bleeding control. The anatomopathological examination confirmed the presence of acid-resistant bacilli, and an extensive caseous type necrosis of the whole tissue, thus diagnosing a prostatic tuberculosis. The patient recovered after a hemorrhagic shock, a urologic and radical intervention, and some severe infectious complications.

Patellofemoral Pain Syndrome Risk Associated with Squats: A Systematic Review.

Patellofemoral pain syndrome (PFPS) is highly prevalent; it can cause severe pain and evolve into progressive functional loss, leading to difficulties performing daily tasks such as climbing and descending stairs and squatting. This systematic review aimed to find evidence, in the literature, of squat movements that can cause or worsen PFPS. This work was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and its protocol was registered in PROSPERO (CRD42019128711). From the 6570 collected records, 37 were included. From these 37 articles, 27 present a causal relationship between knee flexion and PFPS, 8 describe a relationship, considering the greater existence of muscle contractions, and one article did not describe this relationship in its results. The main limitations stem from the fact that different studies used different evaluation parameters to compare the force exerted on the patellofemoral joint. Furthermore, most studies are focused on sports populations. After analysing the included works, it was concluded that all squat exercises can cause tension overload in the knee, especially with a knee flexion between 60° and 90° degrees. The main causal/worsening factors of PFPS symptoms are the knee translocation forward the toes (on the same body side) when flexing the knee, and the muscle imbalance between the thigh muscles.

Sensing Technology Applications in the Mining Industry-A Systematic Review.

Introduction Industry 4.0 has enhanced technological development in all fields. Currently, one can analyse, treat, and model completely different variables in real time; these include production, environmental, and occupational variables. Resultingly, there has been a significant improvement in the quality of life of workers, the environment, and in businesses in general, encouraging the implementation of continuous improvement measures. However, it is not entirely clear how the mining industry is evolving alongside this industrial evolution. With this in mind, this systematic review aimed to find sensing technology applications within this sector, in order to assist the mining industry in its goal to evolve digitally. METHODOLOGY: The research and reporting of this article were carried out by means of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS AND DISCUSSION: A total of 29 papers were included in the study, with sensors being applied in several fields, namely safety, management, and localisation. Three different implementation phases were identified regarding its execution: prototype, trial, and (already) implemented. The overall results highlighted that many mechanisms are in need of improvement in underground settings. This might be due to the fact that underground mining has particular safety challenges. CONCLUSIONS: Ventilation and mapping are primary issues to be solved in the underground setting. With regard to the surface setting, the focus is directed toward slope stability and ways of improving it regarding monitoring and prevention. The literature screening revealed a tendency in these systems to keep advancing in technologically, becoming increasingly more intelligent. In the near future, it is expected that a more technologically advanced mining industry will arise, and this will be created and sustained by the optimisation of processes, equipment, and work practices, in order to improve both the quality of life of people and the health of the environment.

Acute Lyme neuroborreliosis with transient aphasia - Case report and review of current knowledge.

Lyme borreliosis (LB) is a tick-borne infectious disease, endemic in the Northern hemisphere, with a polymorphic clinical spectrum (cutaneous, articular, and neurologic involvement). The variability of clinical manifestations poses LB as a diagnostic challenge. We describe a case of acute Lyme neuroborreliosis (LNB) in an adult female with a history of recent travel in Europe. There are few reports of acute LNB presenting as encephalitis in the literature. Suspicion for the diagnosis and prompt treatment seems to have a positive impact on patient outcomes.