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1.
Int J Ophthalmol ; 17(6): 1042-1048, 2024.
Article in English | MEDLINE | ID: mdl-38895679

ABSTRACT

AIM: To compare the safety and effectiveness of eyelid treatment with the ILux®-MGD Treatment System in one session versus five sessions of mechanical meibomian gland expression (MMGE) in patients with moderate to severe meibomian gland dysfunction (MGD). METHODS: A prospective, randomized, open-label, and controlled clinical trial that compared one session of the ILux® MGD Treatment System versus five sessions of MMGE in both eyes of 130 patients aged ≥18y with Ocular Surface Disease Index (OSDI) scores ≥13, total meibomian gland scores (MGS) of <15 in the lower eyelid of each eye, and non-invasive tear break-up time (NI-TBUT) <10s, who were randomized 1:1 to ILux® or MMGE. RESULTS: The mean age was 58±17.49y. Baseline total MGS scores in both treatment groups were comparable. During follow-up, there were significant differences in total MGS and per sector with P<0.001. Multivariate analysis was performed using generalized estimating equations corresponding to the generalized linear model for repeated means to determine the treatment relationship with total MGS, NIBUT, and OSDI. There was a significant difference between ILux® and MMGE (P<0.001) at follow-up from the first to the twelfth month in MGS, NI-BUT, and OSDI scores. No adverse events were reported. CONCLUSION: ILux® treatment compared to MMGE significantly improves symptoms and signs in patients with moderate to severe MGD for one year without adverse events.

2.
Comput Biol Med ; 178: 108772, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38917532

ABSTRACT

BACKGROUND: Despite the recent advances in computational fluid dynamics (CFD) techniques applied to blood flow within the left atrium (LA), the relationship between atrial geometry, flow patterns, and blood stasis within the left atrial appendage (LAA) remains unclear. A better understanding of this relationship would have important clinical implications, as thrombi originating in the LAA are a common cause of stroke in patients with atrial fibrillation (AF). AIM: To identify the most representative atrial flow patterns on a patient-specific basis and study their influence on LAA blood stasis by varying the flow split ratio and some common atrial modeling assumptions. METHODS: Three recent techniques were applied to nine patient-specific computational fluid dynamics (CFD) models of patients with AF: a kinematic atrial model to isolate the influence of wall motion because of AF, projection on a universal LAA coordinate system, and quantification of stagnant blood volume (SBV). RESULTS: We identified three different atrial flow patterns based on the position of the center of the main circulatory flow. The results also illustrate how atrial flow patterns are highly affected by the flow split ratio, increasing the SBV within the LAA. As the flow split ratio is determined by the patient's lying position, the results suggest that the most frequent position adopted while sleeping may have implications for the medium- and long-term risks of stroke.

3.
RMD Open ; 10(2)2024 May 24.
Article in English | MEDLINE | ID: mdl-38796183

ABSTRACT

OBJECTIVE: This study aims to use a novel technology based on natural language processing (NLP) to extract clinical information from electronic health records (EHRs) to characterise the clinical profile of patients diagnosed with spondyloarthritis (SpA) at a large-scale hospital. METHODS: An observational, retrospective analysis was conducted on EHR data from all patients with SpA (including psoriatic arthritis (PsA)) at Hospital Universitario La Paz, between 2020 and 2022. Data were collected using Savana Manager, an NLP-based system, enabling the extraction of information from unstructured, free-text EHRs. Variables analysed included demographic data, SpA subtypes, comorbidities and treatments. The performance of the technology in detecting SpA clinical entities was evaluated through precision, recall and F-1 score metrics. RESULTS: From a hospital population of 639 474 patients, 4337 (0.7%) patients had a diagnosis of SpA or their subtypes in their EHR. The population predominantly comprised men (55.3%) with a mean age of 50.9 years. Peripheral SpA (including PsA) was reported in 31.6%, axial SpA in 20.9%, both axial and peripheral SpA in 3.7%, while 43.7% of patients did not have the SpA subtype reported. Common comorbidities included hypertension (25.0%), dyslipidaemia (22.2%) and diabetes mellitus (15.5%). The use of conventional disease-modifying antirheumatic drugs (csDMARDs) and biological DMARDs (bDMARDs) was documented, with methotrexate (25.3% of patients) being the most used csDMARDs and adalimumab (10.6% of patients) the most used bDMARD. The NLP technology demonstrated high precision and recall, with all the assessed F-1 score values over 0.80, indicating reliable data extraction. CONCLUSION: The application of NLP technology facilitated the characterisation of the SpA patient profile, including demographics, clinical features, comorbidities and treatments. This study supports the utility of NLP in enhancing the understanding of SpA and suggests its potential for improving patient management by extracting meaningful information from unstructured EHR data.


Subject(s)
Electronic Health Records , Natural Language Processing , Spondylarthritis , Humans , Male , Female , Middle Aged , Retrospective Studies , Spondylarthritis/diagnosis , Spondylarthritis/epidemiology , Spondylarthritis/drug therapy , Adult , Comorbidity , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/epidemiology , Antirheumatic Agents/therapeutic use
4.
J Am Med Dir Assoc ; 25(7): 105023, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38763163

ABSTRACT

OBJECTIVES: The prevalence of obstructive sleep apnea (OSA) escalates with advancing age. Although the apnea-hypopnea index (AHI) is the standard measure for assessing OSA severity, it does not account for additional oximetric parameters that may influence disease progression in older adults. This study aimed to evaluate disparities in respiratory polygraphy/polysomnography parameters among patients with OSA, stratified by age and sex. DESIGN: Retrospective propensity score-matched study. SETTING AND PARTICIPANTS: Sleep unit of a university hospital; 11,747 participants, 210 aged 80 years or older. METHODS: Propensity score matching was used to establish 4 age cohorts, with the 210 oldest adults serving as the reference group. Primary outcome variables included the total sleep time with oxygen saturation (SaO2) below 90% (T90), average SaO2, minimum SaO2, and AHI. The association between T90 and AHI, as well as the severity of OSA, was assessed across the 4 age categories. RESULTS: Despite comparable AHI scores, the oldest patients with OSA exhibited the highest T90 and the lowest SaO2 levels compared to younger counterparts. The proportion of patients with severe OSA and T90 in the highest quartile increased with age: 12.5% in young adults, 14.8% in adults, 21.7% in the old, and 34% in the very old participants (P < .001). old and very old patients had a greater likelihood of being in the most severe OSA category compared to the younger ones, with odds ratios (OR) 2.57 (95% CI 1.42-4.65) and 5.52 (95% CI 3.06-9.97), respectively. These patterns were more pronounced in women of advanced age, indicating a sex-specific variation in disease severity with increasing age. CONCLUSIONS AND IMPLICATIONS: Old patients with OSA, particularly women, demonstrate elevated T90 and reduced SaO2 levels, irrespective of AHI, indicating a hypoxemia increased risk. The diagnostic criteria, management, and outcomes for OSA may require adaptations to address the unique needs of very old populations.

5.
Article in English | MEDLINE | ID: mdl-38571333

ABSTRACT

BACKGROUND: Post-publication handling of integrity concerns in randomized clinical trials (RCTs) is a contentious matter. OBJECTIVES: We undertook a scoping systematic review to map the literature regarding post-publication integrity issues in RCTs. SEARCH STRATEGY AND SELECTION CRITERIA: Following prospective registration (https://osf.io/pgxd8) we initially searched PubMed and Scopus but subsequently extended it to include the Cochrane Library, and Google Scholar databases without language, article type or publication time restriction until November 2022. Reviewers independently selected published articles covering any aspect of post-publication research integrity concerns in RCTs. DATA COLLECTION AND ANALYSIS: The study findings grouped within domains relating to issues concerning post-publication integrity were extracted in duplicate, verified by a third reviewer, and then tabulated. MAIN RESULTS: The initial search captured 3159 citations, of which 89 studies were included in the review. Cross-sectional studies constituted the majority of included studies (n = 34, 38.2%), followed by systematic reviews (n = 10, 11.2%), methodology reviews/studies (n = 9, 10.1%) and other types of descriptive studies (n = 8, 9.0%). A total of 21 articles (23.6%) covered the domain on general issues, 25 (28.1%) in the journal's instructions and policies domain, eight (9.0%) in the editorial and peer review domain, one (1.1%) in the correspondence and complaints (post-publication peer review) domain, 12 (13.5%) in the investigation for concerns domain, six (6.7%) in the post-investigation decisions and sanctions domain, none in the critical appraisal guidance domain, five (5.6%) in the integrity assessment in systematic reviews domain, and 26 (29.2%) in the recommendations for future research domain. A total of 12 of the selected articles (13.5%) covered two (n = 9) or three (n = 3) different domains. CONCLUSIONS: Various research integrity domains and issues covering post-publication aspects of RCT integrity were captured and gaps were identified, mostly related with the necessary implications for all stakeholders to improve research transparency. There is an urgent need for a multistakeholder consensus towards creating specific statements for addressing post-publication integrity concerns in RCTs.

6.
Cureus ; 16(3): e55599, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38586726

ABSTRACT

Objectives An observational, retrospective, longitudinal, and analytical study aimed to evaluate the effectiveness of the erector spinae plane (ESP) block in managing pain in patients with vertebral fractures secondary to tumoral activity. This study included patients treated at the Pain Clinic who underwent ESP block. The objectives were to describe demographic characteristics, oncological diagnosis, vertebral fracture features, imaging techniques, medications used, and the level of ESP block. Additionally, pain levels were assessed using a numerical analog scale, and the consumption of opioid analgesic medications before and after the ESP block, during follow-up consultations, along with patient satisfaction. Methodology This retrospective, observational, and analytical study was conducted at the Pain Clinic of the National Cancer Institute of Mexico. Patients with vertebral fractures secondary to tumor activity were included, with data collected from March 2020 to September 2023. A consecutive non-probabilistic sampling method was employed, and specific inclusion and exclusion criteria were applied. Data were analyzed using descriptive statistics and the Wilcoxon signed-rank test for quantitative variables, with a significance level of p ≤ 0.05. IBM SPSS Statistics v. 26.0 (IBM Corp., Armonk, NY) software was utilized. Results A sample comprising 16 individuals was obtained, with an equal distribution between males and females. Fracture levels displayed variation, with L3 (12.5%) and T6 (12.5%) being the most prevalent. The ESP approach was primarily conducted using ultrasound (68.8%), while fluoroscopy and computed tomography were utilized in 25.0% and 6.3% of cases, respectively. Predominantly, methylprednisolone and ropivacaine (75.0%) were administered, with phenol used in 18.8% and a combination of methylprednisolone and bupivacaine in 6.3%. Patient satisfaction levels were reported at 81.3% (satisfied or very satisfied). Statistically significant disparities were noted between baseline and incidental pain reduction and oral opioid equivalent dosage in milligrams of morphine per day (MME/day) before and after ESP block (p ≤ 0.05). Conclusions This research provides promising preliminary evidence supporting the effectiveness of ESP block for pain management in vertebral fractures secondary to tumoral activity, enhancing the quality and safety of care for oncology patients. The absence of complications, significant improvement in pain, and reduction in opioid dependence underscore the clinical relevance of this therapeutic approach. An observational, retrospective, longitudinal, and analytical study aimed to evaluate the effectiveness of the ESP block in managing pain in patients with vertebral fractures secondary to tumoral activity. This study included patients treated at the Pain Clinic who underwent ESP block. The objectives were to describe demographic characteristics, oncological diagnosis, vertebral fracture features, imaging techniques, medications used, and the level of ESP block. Additionally, pain levels were assessed using a numerical analogue scale, and the consumption of opioid analgesic medications before and after the ESP block, during follow-up consultations, along with patient satisfaction.

7.
Med. clín (Ed. impr.) ; 162(8): 387-393, abr.-2024. graf, ilus
Article in English | IBECS | ID: ibc-232533

ABSTRACT

Technological advances imply an increase in artificially generating sources of electromagnetic fields (EMF), therefore, resulting in a permanent exposure of people and the environment (electromagnetic pollution). Inconsistent results have been published considering the evaluated health effects. The purpose of this study was to review scientific literature on EMF to provide a global and retrospective perspective, on the association between human exposure to non-ionizing radiation (NIR, mainly radiofrequency-EMF) and health and environmental effects. Studies on the health effects of 5G radiation exposure have not yet been performed with sufficient statistical power, as the exposure time is still relatively short and also the latency and intensity of exposure to 5G. The safety standards only consider thermal effects, do not contemplate non-thermal effects. We consider relevant to communicate this knowledge to the general public to improve education in this field, and to healthcare professionals to prevent diseases that may result from RF-EMF exposures. (AU)


Los avances tecnológicos implican un aumento de las fuentes artificiales que generan campos electromagnéticos (CEM), esto se traduce en una exposición permanente de las personas y el medio ambiente (contaminación electromagnética) a CEM. Se han publicado resultados contradictorios en cuanto a los efectos evaluados sobre la salud. El propósito de este estudio fue revisar la literatura científica sobre CEM para proporcionar una perspectiva global y retrospectiva, sobre la asociación entre la exposición humana a la radiación no ionizante (RNI, principalmente CEM en el rango de las radiofrecuencias) y los efectos sobre la salud y el medio ambiente. Aún no se han realizado estudios sobre los efectos en la salud de la exposición a la radiación 5G con suficiente potencia estadística, ya que el tiempo de exposición es todavía relativamente corto, igual que ocurre con la latencia y la intensidad de la exposición a la 5G. Las normas de seguridad solo consideran los efectos térmicos, no contemplan los efectos no térmicos. Consideramos relevante comunicar el conocimiento actual sobre este tema tanto al público en general para mejorar la educación en este campo, como a los profesionales sanitarios para prevenir las enfermedades que puedan derivarse de las exposiciones a RF-EMF. (AU)


Subject(s)
Humans , Electromagnetic Pollution , Technological Development , Environment , Occupational Exposure , Radiation, Nonionizing
8.
J Thromb Thrombolysis ; 57(4): 650-657, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38491266

ABSTRACT

BACKGROUND: The interrelation of cancer with venous thromboembolism is established, yet the specific impact on the incidence and progression of superficial vein thrombosis (SVT) remains unclear. OBJECTIVES: To investigate the association between SVT and malignancies, focusing on risk factors, presentation, course and complications. METHODS: A single-center prospective observational study of patients diagnosed with DVT or SVT referred to a venous thromboembolism clinic between January 2013 and April 2018. RESULTS: Of the 632 patients, 205 presented with SVT at referral, 16.6% having active cancer. Significant associations were found between active cancer and the risk of developing proximal SVT (RR 1.54 [1.18-2.03] p < 0.01), SVT within 3 cm from junction (RR 2.01 [1.13-3.72] p = 0.019), bilateral SVT (RR 8.38 [2.10-33.43] p < 0.01) and SVT affecting multiple veins (RR 2.42 [1.40-4.20] p < 0.01), with a higher risk of persistence (RR 1.51 [1.18-1.95] p < 0.01) and progression (RR 5.75 [2.23-14.79] p < 0.01) at initial assessment. Patients with SVT and no malignancy history demonstrated an elevated risk for new-onset cancer during follow-up (RR 1.43 [1.13-1.18] p = 0.022), especially in cases of proximal or bilateral SVT, initial progression or subsequent DVT or PE. No significant differences were observed in persistence, recurrence or complications during initial evaluation or follow-up across different pharmacological treatments. CONCLUSIONS: Research suggests a probable link between cancer history and the development of SVT. SVT presented more severely in cancer patients. SVT, especially in its more complex forms, could serve as a predictive marker for the future development of cancer. Treatment approaches varied, no significant differences in outcomes were noted.


Subject(s)
Neoplasms , Venous Thromboembolism , Venous Thrombosis , Humans , Venous Thromboembolism/drug therapy , Anticoagulants/therapeutic use , Venous Thrombosis/diagnosis , Risk Factors , Neoplasms/complications
9.
J Nurs Meas ; 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38519070

ABSTRACT

Background and Purpose: The aims of this study are as follows: to adapt and validate the psychometric properties of the Spanish version of the Practice Environment Scale of the Nursing Work Index (PES-NWI) adapted to the nursing home environment across seven Spanish-speaking countries and to cross-culturally adapt the Scale of the Nursing Work Index with nurses from seven countries. Methods: Adaptation process and psychometric validation of the instrument included translation and back-translation, content validity, test-retest reliability, internal consistency, and construct validity. Results: A total of 134 nursing homes belonging to the same religious order were randomly selected from seven Spanish-speaking countries with a sample of 378 nurses. The exploratory factor analysis explained a five-factor structure (56% of the explained variance) with adequate goodness-of-fit indices in the final factor solution. Conclusions: The validation process indicates that the Spanish language version of the PES-NWI with five factors and 31 items, for long-term care facilities for the elderly, is valid and reliable in its current version and can be used to measure the environment of nurses working in clinical practice in Spanish-speaking nursing homes.

10.
Clin Exp Dermatol ; 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38531692

ABSTRACT

BACKGROUND: Topical imiquimod has shown to be an effective treatment for EMPD, although available evidence supporting its use is based on case reports and small series of patients. OBJECTIVES: To investigate the therapeutic outcomes and analyze potential clinico-pathological factors associated with imiquimod response in a large cohort of EMPD patients. METHODS: Retrospective chart review of 125 EMPD patients treated with imiquimod at 20 Spanish tertiary-care hospitals. RESULTS: During the study period, patients received 134 treatment regimens with imiquimod, with 70 (52.2%) cases achieving complete response (CR), 41 (30.6%) partial response and 23 (17.2%) no response. The cumulative CR rates at 24 and 48 weeks of treatment were 46.3% and 71.8%, respectively, without significant differences between first-time and previously treated EMPD. Larger lesions (≥6 cm; p = 0.038) and EMPD affecting >1 anatomical site (p = 0.002) were significantly associated with a worse treatment response. However, the CR rate did not differ significantly by the number of treatment applications (≤4 vs. > 4 times/week; p = 0.112). Among patients who achieved CR, 30 (42.9%) developed local recurrences during a mean follow-up period of 36 months, with an estimated 3 and 5-year recurrence free-survival of 55.7% and 36.4%, respectively. CONCLUSIONS: Imiquimod appears as an effective therapeutic alternative for both first-line and previously treated EMPD lesions. However, a less favorable therapeutic response could be expected in larger lesions and those affecting >1 anatomical site. Based on our results, a 3-4 times weekly regimen of imiquimod with a treatment duration of at least 6 months could be considered an appropriate therapeutic strategy for EMPD patients.

11.
J Int Adv Otol ; 20(1): 19-25, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38454284

ABSTRACT

BACKGROUND: Objectives: (1) To determine whether the incidence of Bell's Palsy (BP) increased during the pandemic. (2) To investigate whether the outcomes of patients with BP and COVID-19 infection or vaccination differ from those in the pre-pandemic era. METHODS: Patients with BP were studied in 2 periods retrospectively (March 2021-March 2022 and August 2018-August 2019). A prospective study from March 2021 to March 2022 was also performed. Primary outcome was grade ≤Ⅱ in the House-Brackmann (HB) and/or >70 in the Sunnybrook facial grading system (SFGS) scales at the 12-week visit. Reverse transcriptase polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enzyme-linked immunosorbent assay-based SARS-CoV-2 immuonoglobulin G (IgG) test (blood) were measured. RESULTS: About 162 and 196 patients with BP were identified between March 2021 and March 2022 and August 2018 and August 2019, respectively. Forty-seven patients (29%) entered the prospective study; 85% had HB grades I or II, while 92% had an SFGS score of 71-100 at the last visit. Only 3 patients (6.5%) had a positive PCR during the initial episode, whereas 35 patients (77%) had positive IgG SARS-CoV-2. There was no association between positive PCR and facial function outcomes. Of the 162 patients, 105 (67%) had received COVID-19 vaccine. In 23 of them (22%), the paralysis appeared within the first 30 days after a vaccine dose. CONCLUSION: Coronavirus disease 2019 did not increase the incidence of BP. A direct association between the coronavirus and BP outcome cannot be established. The considerable number of patients developing BP within the first month suggests a possible association between COVID-19 vaccines and BP.


Subject(s)
Bell Palsy , COVID-19 , Facial Paralysis , Humans , Bell Palsy/epidemiology , COVID-19 Vaccines , Retrospective Studies , Prospective Studies , Incidence , COVID-19/epidemiology , SARS-CoV-2 , Immunoglobulin G
12.
J Endovasc Ther ; : 15266028241233994, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38385241

ABSTRACT

CLINICAL IMPACT: Mechanical thrombectomy using a thromboaspiration catheter can be an effective alternative in the treatment of subacute pulmonary embolism.

13.
Int J Mol Sci ; 25(4)2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38396997

ABSTRACT

This study explores the genetic factors associated with atypical femoral fractures (AFF), rare fractures associated with prolonged anti-resorptive therapy. AFF are fragility fractures that typically appear in the subtrochanteric or diaphyseal regions of the femur. While some cases resemble fractures in rare genetic bone disorders, the exact cause remains unclear. This study investigates 457 genes related to skeletal homeostasis in 13 AFF patients by exome sequencing, comparing the results with osteoporotic patients (n = 27) and Iberian samples from the 1000 Genomes Project (n = 107). Only one AFF case carried a pathogenic variant in the gene set, specifically in the ALPL gene. The study then examined variant accumulation in the gene set, revealing significantly more variants in AFF patients than in osteoporotic patients without AFF (p = 3.7 × 10-5), particularly in ACAN, AKAP13, ARHGEF3, P4HB, PITX2, and SUCO genes, all of them related to osteogenesis. This suggests that variant accumulation in bone-related genes may contribute to AFF risk. The polygenic nature of AFF implies that a complex interplay of genetic factors determines the susceptibility to AFF, with ACAN, SUCO, AKAP13, ARHGEF3, PITX2, and P4HB as potential genetic risk factors. Larger studies are needed to confirm the utility of gene set analysis in identifying patients at high risk of AFF during anti-resorptive therapy.


Subject(s)
Bone Density Conservation Agents , Bone Diseases , Femoral Fractures , Humans , Femoral Fractures/genetics , Femur/pathology , Diaphyses , Diphosphonates
14.
Microbiol Spectr ; 12(3): e0411123, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38319084

ABSTRACT

Ceftazidime-avibactam (CZA) therapy has significantly improved survival rates for patients infected by carbapenem-resistant bacteria, including KPC producers. However, resistance to CZA is a growing concern, attributed to multiple mechanisms. In this study, we characterized four clinical CZA-resistant Klebsiella pneumoniae isolates obtained between July 2019 and December 2020. These isolates expressed novel allelic variants of blaKPC-2 resulting from changes in hotspots of the mature protein, particularly in loops surrounding the active site of KPC. Notably, KPC-80 had an K269_D270insPNK mutation near the Lys270-loop, KPC-81 had a del_I173 mutation within the Ω-loop, KPC-96 showed a Y241N substitution within the Val240-loop and KPC-97 had an V277_I278insNSEAV mutation within the Lys270-loop. Three of the four isolates exhibited low-level resistance to imipenem (4 µg/mL), while all remained susceptible to meropenem. Avibactam and relebactam effectively restored carbapenem susceptibility in resistant isolates. Cloning mutant blaKPC genes into pMBLe increased imipenem MICs in recipient Escherichia coli TOP10 for blaKPC-80, blaKPC-96, and blaKPC-97 by two dilutions; again, these MICs were restored by avibactam and relebactam. Frameshift mutations disrupted ompK35 in three isolates. Additional resistance genes, including blaTEM-1, blaOXA-18 and blaOXA-1, were also identified. Interestingly, three isolates belonged to clonal complex 11 (ST258 and ST11) and one to ST629. This study highlights the emergence of CZA resistance including unique allelic variants of blaKPC-2 and impermeability. Comprehensive epidemiological surveillance and in-depth molecular studies are imperative for understanding and monitoring these complex resistance mechanisms, crucial for effective antimicrobial treatment strategies. IMPORTANCE: The emergence of ceftazidime-avibactam (CZA) resistance poses a significant threat to the efficacy of this life-saving therapy against carbapenem-resistant bacteria, particularly Klebsiella pneumoniae-producing KPC enzymes. This study investigates four clinical isolates exhibiting resistance to CZA, revealing novel allelic variants of the key resistance gene, blaKPC-2. The mutations identified in hotspots surrounding the active site of KPC, such as K269_D270insPNK, del_I173, Y241N and V277_I278insNSEAV, prove the adaptability of these pathogens. Intriguingly, low-level resistance to imipenem and disruptions in porin genes were observed, emphasizing the complexity of the resistance mechanisms. Interestingly, three of four isolates belonged to clonal complex 11. This research not only sheds light on the clinical significance of CZA resistance but also shows the urgency for comprehensive surveillance and molecular studies to inform effective antimicrobial treatment strategies in the face of evolving bacterial resistance.


Subject(s)
Anti-Bacterial Agents , Azabicyclo Compounds , Ceftazidime , Klebsiella Infections , Humans , Anti-Bacterial Agents/pharmacology , Klebsiella pneumoniae , Argentina , beta-Lactamases/genetics , Bacterial Proteins/genetics , Carbapenems , Microbial Sensitivity Tests , Imipenem , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Drug Combinations
15.
Nat Commun ; 15(1): 477, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38216572

ABSTRACT

Schwann cell tumors are the most common cancers of the peripheral nervous system and can arise in patients with neurofibromatosis type-1 (NF-1) or neurofibromatosis type-2 (NF-2). Functional interactions between NF1 and NF2 and broader mechanisms underlying malignant transformation of the Schwann lineage are unclear. Here we integrate bulk and single-cell genomics, biochemistry, and pharmacology across human samples, cell lines, and mouse allografts to identify cellular de-differentiation mechanisms driving malignant transformation and treatment resistance. We find DNA methylation groups of Schwann cell tumors can be distinguished by differentiation programs that correlate with response to the MEK inhibitor selumetinib. Functional genomic screening in NF1-mutant tumor cells reveals NF2 loss and PAK activation underlie selumetinib resistance, and we find that concurrent MEK and PAK inhibition is effective in vivo. These data support a de-differentiation paradigm underlying malignant transformation and treatment resistance of Schwann cell tumors and elucidate a functional link between NF1 and NF2.


Subject(s)
Neurilemmoma , Neurofibromatoses , Neurofibromatosis 1 , Neurofibromatosis 2 , Animals , Humans , Mice , Mitogen-Activated Protein Kinase Kinases/metabolism , Neurilemmoma/genetics , Neurilemmoma/pathology , Neurofibromatoses/metabolism , Neurofibromatoses/pathology , Neurofibromatosis 1/genetics , Neurofibromatosis 1/metabolism , Neurofibromatosis 2/genetics , Neurofibromatosis 2/pathology , Schwann Cells/metabolism , Drug Resistance, Neoplasm/genetics
16.
J Am Acad Dermatol ; 90(1): 66-73, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37704106

ABSTRACT

BACKGROUND: Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited. OBJECTIVES: To assess the DSS and outcomes of surgical and nonsurgical therapeutic modalities in a large cohort of EMPD patients. METHODS: Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals. RESULTS: Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5-, 10-, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1 mm) or metastatic disease (P < .05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively. LIMITATIONS: Retrospective design. CONCLUSIONS: EMPD is usually a chronic condition with favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to the ones observed in patients treated with topical agents.


Subject(s)
Paget Disease, Extramammary , Humans , Retrospective Studies , Paget Disease, Extramammary/surgery , Mohs Surgery , Survival Analysis , Margins of Excision , Treatment Outcome , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/therapy , Neoplasm Recurrence, Local/pathology
17.
Med Clin (Barc) ; 162(8): 387-393, 2024 04 26.
Article in English, Spanish | MEDLINE | ID: mdl-38151370

ABSTRACT

Technological advances imply an increase in artificially generating sources of electromagnetic fields (EMF), therefore, resulting in a permanent exposure of people and the environment (electromagnetic pollution). Inconsistent results have been published considering the evaluated health effects. The purpose of this study was to review scientific literature on EMF to provide a global and retrospective perspective, on the association between human exposure to non-ionizing radiation (NIR, mainly radiofrequency-EMF) and health and environmental effects. Studies on the health effects of 5G radiation exposure have not yet been performed with sufficient statistical power, as the exposure time is still relatively short and also the latency and intensity of exposure to 5G. The safety standards only consider thermal effects, do not contemplate non-thermal effects. We consider relevant to communicate this knowledge to the general public to improve education in this field, and to healthcare professionals to prevent diseases that may result from RF-EMF exposures.


Subject(s)
Electromagnetic Fields , Environmental Exposure , Humans , Environmental Exposure/adverse effects , Retrospective Studies , Electromagnetic Fields/adverse effects , Radio Waves/adverse effects
19.
Heart Lung Circ ; 33(1): 38-45, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38151398

ABSTRACT

INTRODUCTION: Cardiogenic shock is associated with high in-hospital morbidity and mortality. Improvements in this care process could lead to better outcomes. METHODS: This retrospective study of patients with cardiogenic shock compared two periods: no specific program to address cardiogenic shock and implementation of a cardiogenic shock program. This program included the establishment of a multidisciplinary team (shock team), early alert to the transplant hospital, initiation of a ventricular assist extracorporeal membrane oxygenation (ECMO) program, and extension of continuous care by acute cardiovascular care specialists. The primary objective was to analyse whether there were differences between in-hospital mortality and mortality during follow-up. Predictors of in-hospital mortality were examined as a secondary objective. RESULTS: A total of 139 patients were enrolled: 69 of them in the previous period and 70 in the cardiogenic shock program period. There was a significant reduction in in-hospital mortality (55.1% vs 37.1%; p=0.03) and mortality during follow-up (62.7% vs 44.6%; p=0.03) in the second period. Diabetes mellitus, ejection fraction, out-of-hospital cardiac arrest, and implementation of the cardiogenic shock program were independent predictors of in-hospital mortality. CONCLUSIONS: The implementation of a comprehensive cardiogenic shock program in a non-transplanting hospital improved in-hospital and follow-up mortality of patients in cardiogenic shock.


Subject(s)
Extracorporeal Membrane Oxygenation , Out-of-Hospital Cardiac Arrest , Humans , Shock, Cardiogenic , Retrospective Studies , Hospital Mortality , Extracorporeal Membrane Oxygenation/adverse effects
20.
J AIDS HIV Treat ; 5(1): 46-53, 2023.
Article in English | MEDLINE | ID: mdl-38075387

ABSTRACT

Objective: This retrospective chart review study aims to identify patients in an HIV clinical setting in an area of high HIV prevalence in Atlanta, Georgia, USA who have chronic pain, analgesic prescriptions, and/or mental health diagnoses. Design: People living with HIV (PLWH) are at higher risk for experiencing trauma, mental health conditions, and chronic pain than their HIV-negative counterparts. This study was designed to evaluate the intersection of these factors within an urban HIV clinic. Methods: Retrospective chart review study. Results: Of the adult patients enrolled at an HIV clinic in Atlanta, Georgia USA between 2011-2022 (n=15,970), 93.7% were prescribed analgesics, 40.5% had documented pain diagnoses, and 23.5% had documented mental health diagnoses. Additionally, 14.3% of all enrolled patients had all three factors concurrently. Conclusions: The complexity of HIV, chronic pain, mental health challenges, and analgesic use demand a patient-centered, collaborative approach including a multidisciplinary care team. Seeing persistent pain among PLWH with a trauma-informed approach to care within the lens of co-occurring mental health diagnoses will allow us to better understand, treat, and sustain patients in life-saving HIV care.

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