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1.
J Biol Chem ; 300(1): 105574, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38110031

RESUMEN

The 70 kDa heat shock proteins (Hsp70s) play a pivotal role in many cellular functions using allosteric communication between their nucleotide-binding domain (NBD) and substrate-binding domain, mediated by an interdomain linker, to modulate their affinity for protein clients. Critical to modulation of the Hsp70 allosteric cycle, nucleotide-exchange factors (NEFs) act by a conserved mechanism involving binding to the ADP-bound NBD and opening of the nucleotide-binding cleft to accelerate the release of ADP and binding of ATP. The crystal structure of the complex between the NBD of the Escherichia coli Hsp70, DnaK, and its NEF, GrpE, was reported previously, but the GrpE in the complex carried a point mutation (G122D). Both the functional impact of this mutation and its location on the NEF led us to revisit the DnaK NBD/GrpE complex structurally using AlphaFold modeling and validation by solution methods that report on protein conformation and mutagenesis. This work resulted in a new model for the DnaK NBD in complex with GrpE in which subdomain IIB of the NBD rotates more than in the crystal structure, resulting in an open conformation of the nucleotide-binding cleft, which now resembles more closely what is seen in other Hsp/NEF complexes. Moreover, the new model is consistent with the increased ADP off-rate accompanying GrpE binding. Excitingly, our findings point to an interdomain allosteric signal in DnaK triggered by GrpE binding.


Asunto(s)
Proteínas de Escherichia coli , Escherichia coli , Proteínas HSP70 de Choque Térmico , Proteínas de Choque Térmico , Adenosina Difosfato/metabolismo , Adenosina Trifosfato/metabolismo , Regulación Alostérica , Cristalografía por Rayos X , Escherichia coli/química , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Proteínas HSP70 de Choque Térmico/química , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Mutagénesis , Mutación Puntual , Unión Proteica , Dominios Proteicos , Reproducibilidad de los Resultados , Rotación
2.
Pancreatology ; 24(3): 437-444, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38368219

RESUMEN

BACKGROUND: Objectives: To investigate communication clarity and understanding at the time of pancreatic adenocarcinoma (PDAC) diagnosis and whether they can influence patient engagement and compliance. METHODS: Consecutive PDAC patients were enrolled at the time of diagnosis after obtaining informed consent in a single-center study. The patients completed a validated scale (PHE-s®), and the understanding rate was assessed using standardized tools. Patient compliance was evaluated, and the correlation between the PHE-s®, understanding, and compliance was calculated. RESULTS: Thirty patients were enrolled (15 female) with a mean age 64.4, 13 were metastatic. The mean visit time was 31 min, being longer if visiting doctor was an oncologist (p = 0.002). The engagement level was high in 70% of the patients, and all but one were compliant. The analysis of doctor-patient interactions showed a median of 121 conversational turns for doctors, 75 for patients, and 20 for caregivers (p < 0.0001), and the median percentage of speaking time was 77% for doctors, 13% for patients, and 2% for caregivers (p < 0.0001). Female caregivers spent more time speaking than did male caregivers (median 11.6% vs. 1.3%; p = 0.06). There were 290 instances of problematic understanding, most of which occurred during the taking of patients' personal medical history for doctors, while for patients and caregivers, these occurred mainly during the discussion of diagnosis/treatment (p < 0.0001). In a multivariable analysis, only origin from central or southern Italy was associated with high engagement (p = 0.0087). CONCLUSION: In this first attempt to measure clarity of communication and engagement in patients with PDAC, typical features of conversation and problematic understanding emerged, which deserves further investigation.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Masculino , Femenino , Comunicación , Cooperación del Paciente , Italia
3.
Diabetes Obes Metab ; 26(9): 3576-3586, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38853712

RESUMEN

AIM: To compare the effectiveness of different basal insulins (BI) prescribed as an add-on to or switch from glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy. MATERIALS AND METHODS: Retrospective, real-world data from electronic medical records of 32 Italian diabetes clinics were used, after propensity score adjustment, to compare effectiveness after 6 months of treatment with second- versus first-generation BI (2BI vs. 1BI) or glargine 300 U/ml versus degludec 100 U/ml (Gla-300 vs. Deg-100), when added to (ADD-ON) or in substitution of (SWITCH) GLP-1 RA. Only comparisons, including a minimum of 100 patients per group, were performed to ensure adequate robustness of the analyses. RESULTS: In the ADD-ON cohort (N = 700), greater benefits of 2BI versus 1BI were found in glycated haemoglobin {HbA1c; estimated mean difference: -0.32% [95% confidence interval (CI) -0.62; -0.02]; p = .04} and fasting blood glucose [FBG; -20.73 mg/dl (95% CI -35.62; -5.84); p = .007]. In the SWITCH cohort (N = 2097), greater benefits of 2BI versus 1BI were found in HbA1c [-0.22% (95% CI -0.42; -0.02); p = .03], FBG [-10.15 mg/dl (95% CI -19.04; -1.26); p = .03], and body weight [-0.67 kg (95% CI -1.30; -0.04); p = .04]. In the SWITCH cohort starting 2BI (N = 688), marked differences in favour of Gla-300 versus Deg-100 were documented in HbA1c [-0.89% (95% CI -1.26; -0.52); p < .001] and FBG [-17.89 mg/dl (95% CI -32.45; -3.33); p = .02]. Using propensity score matching as a sensitivity analysis, the benefit on HbA1c was confirmed [-0.55% (95% CI -1.02; -0.08); p = .02]. BI titration was suboptimal in all examined cohorts. CONCLUSIONS: 2BI are a valuable option to intensify GLP-1 RA therapy. Switching to Gla-300 versus Deg-100 was associated with greater HbA1c improvement.


Asunto(s)
Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Hemoglobina Glucada , Hipoglucemiantes , Insulina Glargina , Insulina de Acción Prolongada , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Femenino , Masculino , Estudios Retrospectivos , Hipoglucemiantes/uso terapéutico , Persona de Mediana Edad , Hemoglobina Glucada/análisis , Hemoglobina Glucada/efectos de los fármacos , Receptor del Péptido 1 Similar al Glucagón/agonistas , Anciano , Insulina Glargina/uso terapéutico , Insulina Glargina/administración & dosificación , Insulina de Acción Prolongada/uso terapéutico , Glucemia/efectos de los fármacos , Quimioterapia Combinada , Italia/epidemiología , Resultado del Tratamiento , Investigación sobre la Eficacia Comparativa , Sustitución de Medicamentos , Hipoglucemia/inducido químicamente , Agonistas Receptor de Péptidos Similares al Glucagón
4.
Nutr Metab Cardiovasc Dis ; 34(8): 1846-1853, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38693036

RESUMEN

BACKGROUND AND AIMS: Add-on of basal insulin (BI) to intensify the ongoing therapy with glucagon-like peptide 1 receptor agonist (GLP-1 RA) is recommended, but it is unclear if free or fixed combination of BI and GLP-1 RA produce similar outcomes. A retrospective comparative effectiveness analysis of the add-on of glargine 300 U/mL (Gla-300) to ongoing GLP-1 RA vs. switch to fixed ratio combination of degludec and liraglutide (iDegLira) was performed. METHODS AND RESULTS: Real-world data collected in electronic medical records by 32 Italian diabetes clinics. Propensity score (PS) adjustment was applied to assess changes in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), body weight, and BI dose after 6 months from Gla-300 or iDegLira initiation. Compared to iDegLira group (N = 260), Gla-300+GLP-1 RA group (N = 255) had older age and higher levels of HbA1c (9.1 vs. 8.9%). After 6 months, statistically significant greater FBG improvement [estimated mean difference and 95% confidence intervals: -24.05 mg/dl (-37.04; -11.06; p = 0.0003) and BI dose increase [+0.03 U/kg (95%CI 0.00; 0.06); p = 0.009] were found in the free vs. fixed combination group, although low doses of BI (0.2 U/kg) were reached in both groups. Trends of larger HbA1c and body weight reductions with the free combination were also found, without reaching the statistical significance. CONCLUSION: Although inertia in insulin initiation and titration was documented in both groups, higher benefit on FBG control was obtained with free vs. fixed combination, likely due to a better titration of BI and GLP-1 RA.


Asunto(s)
Biomarcadores , Glucemia , Investigación sobre la Eficacia Comparativa , Diabetes Mellitus Tipo 2 , Combinación de Medicamentos , Receptor del Péptido 1 Similar al Glucagón , Hemoglobina Glucada , Control Glucémico , Hipoglucemiantes , Incretinas , Insulina Glargina , Insulina de Acción Prolongada , Liraglutida , Humanos , Masculino , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/administración & dosificación , Hemoglobina Glucada/metabolismo , Resultado del Tratamiento , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Anciano , Insulina Glargina/efectos adversos , Insulina Glargina/uso terapéutico , Insulina Glargina/administración & dosificación , Liraglutida/efectos adversos , Liraglutida/uso terapéutico , Insulina de Acción Prolongada/uso terapéutico , Insulina de Acción Prolongada/efectos adversos , Insulina de Acción Prolongada/administración & dosificación , Incretinas/efectos adversos , Incretinas/uso terapéutico , Control Glucémico/efectos adversos , Biomarcadores/sangre , Factores de Tiempo , Italia , Registros Electrónicos de Salud , Sustitución de Medicamentos
5.
BMC Health Serv Res ; 24(1): 826, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39033270

RESUMEN

BACKGROUND: Access to mental and physical healthcare in rural areas is challenging for Veterans and their families but essential for good health. Even though recent research has revealed some of the challenges rural Veterans face accessing healthcare, a complete understanding of the gap in access is still unclear. METHODS: This qualitative study aimed to explore participants' perceptions of healthcare access. Structured interviews were conducted with 124 Veterans and spouses of Veterans from rural qualifying counties in South Carolina and Florida. RESULTS: The study's results revealed five main dimensions of access: geographic proximity, transportation, communication, cultural competence, and resources. Distance to service needed can negatively impact access for Veterans and their families in general, especially for those whose health is declining or who cannot drive because of their age. Lack of transportation, problems with transportation services, and lack of public transportation can lead to delays in care. Additionally, the lack of communication with the Veterans Affairs (VA) Health System and with the healthcare team, as well as inefficient communication among the healthcare team, lack of coordination of care between the VA health system and community providers, and the lack of cultural competence of healthcare providers and contracted personnel made access to services even more challenging. CONCLUSIONS: Improving communication can help to develop a sense of trust between Veterans and the VA, and between Veterans and spouses with the healthcare team. It can also lead to increased patient satisfaction. Ensuring healthcare providers and contracted personnel are culturally competent to talk and treat Veterans can improve patient trust and adherence to treatment. Lastly, resource-related challenges included financial problems, lack of prompt access to appointments, lack of providers, limited access to local clinics and hospitals, limited local programs available, and reimbursement issues.


Asunto(s)
Accesibilidad a los Servicios de Salud , Investigación Cualitativa , Población Rural , Veteranos , Humanos , Masculino , South Carolina , Femenino , Persona de Mediana Edad , Veteranos/psicología , Veteranos/estadística & datos numéricos , Florida , Anciano , Entrevistas como Asunto , Adulto , Estados Unidos , Competencia Cultural
6.
Molecules ; 29(4)2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38398549

RESUMEN

The iminosugar 1-deoxynojirimicyn (DNJ) contained in mulberry leaves has displayed systemic beneficial effects against disorders of carbohydrate metabolism. Nevertheless, its effect is impaired by the short half-life. Alginate-based carriers were developed to encapsulate a DNJ-rich mulberry extract: Ca-alginate beads, obtained by external gelation, and spray-dried alginate microparticles (SDMs). Mean size and distribution, morphology, drug loading, encapsulation efficiency, experimental yield, and release characteristics were determined for the two formulations. Ca-alginate beads and SDMs exhibited an encapsulation efficiency of about 54% and 98%, respectively, and a DNJ loading in the range of 0.43-0.63 µg/mg. The in vitro release study demonstrated the carriers' capability in controlling the DNJ release in acid and basic conditions (<50% in 5 h), due to electrostatic interactions, which were demonstrated by 1H-NMR relaxometry studies. Thus, alginate-based particles proved to be promising strategies for producing food supplements containing mulberry leaf extracts for the management of hyperglycemic state.


Asunto(s)
Alginatos , Morus , Alginatos/metabolismo , 1-Desoxinojirimicina/química , Morus/química , Suplementos Dietéticos , Extractos Vegetales/química , Hojas de la Planta/metabolismo
7.
Acta Diabetol ; 61(5): 599-607, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38332378

RESUMEN

AIM: In Italy, the ISPED CARD initiative was launched to measure and improve quality of care in children and adolescents with type 1 diabetes. METHODS: Process and outcome indicators and the related information derived from electronic medical records were identified. A network of pediatric diabetes centers was created on a voluntary basis. RESULTS: Overall, 20 centers provided data on 3284 patients aged < = 18 years. HbA1c was monitored ≥ 2/year in 81.2% of the cases. BMI was monitored ≥ 1/year in 99.0%, lipid profile in 45.3%, and blood pressure in 91.7%. Pubertal status, albuminuria, eye examination, and screening of celiac disease and thyroiditis were underreported. From 2017 to 2021, average HbA1c levels decreased from 7.8 ± 1.2 to 7.6 ± 1.3%, while patients with LDL cholesterol > 100 mg/dl increased from 18.9 to 36.7%. Prevalence of patients with elevated blood pressure and BMI/SDS values also increased. In 2021, 44.7% of patients were treated with the newest basal insulins, while use of regular human insulin had dropped to 7.7%. Use of insulin pump remained stable (37.9%). CONCLUSIONS: This report documents the feasibility of the ISPED CARD initiative and shows lights and shadows in the care provided. Improving care, increasing number of centers, and ameliorating data recording represent future challenges.


Asunto(s)
Diabetes Mellitus Tipo 1 , Mejoramiento de la Calidad , Sistema de Registros , Humanos , Niño , Adolescente , Masculino , Femenino , Sistema de Registros/estadística & datos numéricos , Diabetes Mellitus Tipo 1/terapia , Italia/epidemiología , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Preescolar , Calidad de la Atención de Salud/normas , Lactante
8.
Phys Imaging Radiat Oncol ; 29: 100538, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38317851

RESUMEN

Accurate dosimetry of ultra-high dose-rate beams using diamond detectors remains challenging, primarily due to the elevated photocurrent peaks exceeding the input dynamics of precision electrometers. This work aimed at demonstrating the effectiveness of compact gated-integration electronics in conditioning the current peaks (>20 mA) generated by a highly sensitive (S ≃ 26 nC/Gy) custom-made diamond photoconductor under electron FLASH irradiation, as well as in real-time monitoring of beam dose and dose-rate. For the emerging FLASH technology, this study provided a new perspective on using commercially available diamond dosimeters with high sensitivity, currently employed in conventional radiotherapy.

9.
Artículo en Inglés | MEDLINE | ID: mdl-38512345

RESUMEN

BACKGROUND: According to scientific literature, burnout can be described as a multidimensional syndrome with three fundamental dimensions: emotional exhaustion, depersonalization and reduced personal accomplishment. Every day, clown-doctors, play therapists, teachers and volunteers, such as ceramic art therapists, work in pediatric cancer wards to improve the quality of life of hospitalized children and activate positive resources during their therapeutic journey. METHODS: This study investigated burnout levels and the relationship between work-related stress and resilience in a total of 36 operators (clown-doctors, in-hospital teachers, play therapists, and ceramic art therapists), working at the Unit of Pediatric Oncology of IRCCS A. Gemelli University Polyclinic Foundation in Rome, Italy. All participants completed a battery of questionnaires to evaluate burnout (Maslach Burnout Inventory) and resilience (Connor-Davidson Resilience Scale). RESULTS: The results of this study show that these workers are exposed to work-related stress and that the burnout levels are not homogeneous across the various groups considered. The results also show the need to provide non-health hospital workers with a psychological support service or ensure the presence of a mental health professional to help them avoid the risk of burnout. CONCLUSIONS: The heavy emotional burden endured by these operators makes them vulnerable and exposes them to burnout.

10.
Acta Diabetol ; 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38789610

RESUMEN

AIMS: Glargine 300 U/mL (Gla-300) has been recently approved for use in children and adolescents with type 1 diabetes (T1D). However, real-world effectiveness data are scarce, and aim of this analysis was to assess clinical outcomes in young patients with T1D switching from 1st generation basal insulin (1BI) to Gla-300. METHODS: ISPED CARD is a retrospective, multicenter study, based on data anonymously extracted from Electronic Medical Records. The study involved a network of 20 pediatric diabetes centers. Data on all patients aged < 18 years with T1D switching from 1BI to Gla-300 were analyzed to assess clinical characteristics at the switch and changes after 6 and 12 months in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and standardized body mass index (BMI/SDS). Titration of basal and short-acting insulin doses was also evaluated. RESULTS: Overall, 200 patients were identified. The mean age at the switch to Gla-300 was 13 years, and mean duration of diabetes was 3.9 years. Average HbA1c levels at switch were 8.8%. After 6 months, HbA1c levels decreased by - 0.88% (95% CI - 1.28; - 0.48; p < 0.0001). The benefit was maintained after 12 months from the switch (mean reduction of HbA1c levels - 0.80%, 95% CI - 1.25; - 0.35, p = 0.0006). Trends of reduction in FBG levels were also evidenced both at 6 months and 12 months. No significant changes in short-acting and basal insulin doses were documented. CONCLUSIONS: The study provides the first real-world evidence of the effectiveness of Gla-300 in children and adolescents with T1D previously treated with 1BI. The benefits in terms of HbA1c levels reduction were substantial, and sustained after 12 months. Additional benefits can be expected by improving the titration of insulin doses.

11.
Vaccine ; 42(4): 930-936, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38246845

RESUMEN

BACKGROUND: Students in medicine and other health professions are exposed to numerous occupational hazards, primarily biological hazards, during their academic careers at university. The aim of the present study was to investigate the seroprevalence characteristics of anti-HBsAg, anti-Measles, anti-Mumps, anti-Rubella and anti-Varicella IgG antibodies in healthcare students of a large teaching hospital in Rome. METHODS: To accomplish the study's aims, antibody serology data were gathered from students of Medicine and Surgery, Dentistry, and Health Professions at the Catholic University of the Sacred Heart (Rome Campus) during their first Health Surveillance visit, that took place from 2013 to 2023. RESULTS: Our study sample included 2523 students, 44.4 % were protected against Hepatitis B, 87.3 % against measles, 85.5 % against mumps, 94.6 % rubella and 95.2 % against varicella. Differences in antibody coverage between age groups were statistically significant (p < 0.001), except for mumps. It found a lower probability of having seronegative anti-HBVs with an older date since the presumed primary vaccination. CONCLUSION: In our sample, seropositivity rate against vaccine-preventable diseases, especially for Hepatitis B, was often inadequate to prevent possible biological risks connected with the activities carried out on the ward.


Asunto(s)
Varicela , Hepatitis B , Sarampión , Paperas , Rubéola (Sarampión Alemán) , Enfermedades Prevenibles por Vacunación , Humanos , Paperas/epidemiología , Paperas/prevención & control , Estudios Seroepidemiológicos , Sarampión/epidemiología , Sarampión/prevención & control , Rubéola (Sarampión Alemán)/epidemiología , Rubéola (Sarampión Alemán)/prevención & control , Varicela/epidemiología , Varicela/prevención & control , Estudiantes , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Vacuna contra el Sarampión-Parotiditis-Rubéola , Anticuerpos Antivirales , Inmunidad , Atención a la Salud , Vacunación
12.
Syst Rev ; 13(1): 84, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38461297

RESUMEN

OBJECTIVE: Sudden cardiac death (SCD) is a rare and yet unexplained condition. The most frequent cause is myocardial infarction, while a small proportion is due to arrhythmogenic syndromes (e.g., channelopathies). This systematic review and meta-analysis aimed to provide a comprehensive overview of the prevalence and risk factors associated with SCD in workers. MATERIAL AND METHODS: A search for eligible studies was performed utilizing three databases (PubMed, ISI Web of Knowledge, and Scopus). The inclusion criteria were fulfilled if sudden cardiac death due to channelopathy in workers was mentioned. RESULTS: Out of the 1408 articles found across three databases, 6 articles were included in the systematic review but the meta-analysis was conducted on 3 studies The total sample included was 23,450 participants. The pooled prevalence of channelopathies in employees was 0.3% (95% CI 0.07-0.43%), of sudden cardiac death in employees was 2.8% (95% CI 0.37-5.20%), and of sudden cardiac death in employees with a diagnosis of cardiac channelopathies was 0.2% (95% CI 0.02- 0.30%). CONCLUSIONS: SCD is a serious and potentially preventable condition that can occur among workers. By identifying and addressing work-related risk factors, providing appropriate screening and interventions, and promoting healthy lifestyle behaviors, we can work to reduce the incidence of SCD and improve the cardiovascular health and well-being of workers.


Asunto(s)
Canalopatías , Infarto del Miocardio , Humanos , Canalopatías/complicaciones , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Factores de Riesgo , Infarto del Miocardio/complicaciones , Incidencia
13.
J Med Chem ; 67(5): 3795-3812, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38373290

RESUMEN

Antimicrobial resistance is a global public health threat. Metallo-ß-lactamases (MBLs) inactivate ß-lactam antibiotics, including carbapenems, are disseminating among Gram-negative bacteria, and lack clinically useful inhibitors. The evolving bisthiazolidine (BTZ) scaffold inhibits all three MBL subclasses (B1-B3). We report design, synthesis, and evaluation of BTZ analogues. Structure-activity relationships identified the BTZ thiol as essential, while carboxylate is replaceable, with its removal enhancing potency by facilitating hydrophobic interactions within the MBL active site. While the introduction of a flexible aromatic ring is neutral or detrimental for inhibition, a rigid (fused) ring generated nM benzobisheterocycle (BBH) inhibitors that potentiated carbapenems against MBL-producing strains. Crystallography of BBH:MBL complexes identified hydrophobic interactions as the basis of potency toward B1 MBLs. These data underscore BTZs as versatile, potent broad-spectrum MBL inhibitors (with activity extending to enzymes refractory to other inhibitors) and provide a rational approach to further improve the tricyclic BBH scaffold.


Asunto(s)
Antibacterianos , Inhibidores de beta-Lactamasas , Inhibidores de beta-Lactamasas/farmacología , Inhibidores de beta-Lactamasas/química , Antibacterianos/farmacología , Antibacterianos/química , beta-Lactamasas/química , Carbapenémicos , Bacterias Gramnegativas
14.
Dermatol Ther (Heidelb) ; 14(4): 919-932, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38509380

RESUMEN

INTRODUCTION: Several systemic therapies have been approved for the treatment of severe AD. In particular, Janus kinase inhibitors (JAKi), including abrocitinib, baricitinib, and upadacitinib, recently received approval for the treatment of patients with severe AD after being evaluated in several clinical trials. However, a few concerns have been raised regarding their long-term safety and the management of these drugs in real-world clinical practice. In this article we described the results of a Delphi consensus aimed at describing the knowledge on JAKi and focusing, in particular, on providing clinical recommendations for dermatologists in daily practice regarding the use of these drugs. METHODS: Twelve Italian dermatologists reviewed the most recent literature regarding the efficacy and safety profiles of JAKi and proposed 24 statements. RESULTS: Agreement was reached for statements focusing on three main topics: (1) place in therapy of JAKi in patients with moderate-to-severe AD; (2) effectiveness and safety of JAK inhibitors in different phenotypes; (3) different approaches to the management of patients treated with JAKi in clinical practice. The panel proposed several recommendations regarding all the statements. CONCLUSION: Given the wide use of JAKi in clinical practice, it is crucial to establish a specific follow-up for each patient's phenotype in order to achieve the best possible clinical outcome and minimize potential adverse events.

15.
Eur J Intern Med ; 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39129121

RESUMEN

BACKGROUND: Diabetic kidney disease is the most common cause of end-stage kidney disease (ESKD) in the western world. Rapid estimated glomerular filtration rate (eGFR) decline is an independent predictor of ESKD and death in the general population and in subjects with type 2 diabetes mellitus (T2D). AIM: We investigated in a large sample of subjects with newly diagnosed T2D the prevalence and clinical determinants of fast eGFR decline, taking advantage from the dataset of the Associazione Medici Diabetologi (AMD) Annals initiative. METHODS: The eGFR trajectories were evaluated by applying a linear mixed model for repeated measures (LMMRM) and rapid eGFR decline defined as an eGFR decline greater than 5 mL/min/1.73 m2 per year at 3 years. RESULTS: Among 105,163 (57.7% M) subjects with newly diagnosed T2D, 13,587 (12.9 %) subjects showed a rapid eGFR loss. The independent significant predictors were age, female gender, HbA1c, smoking, high baseline eGFR, albuminuria and retinopathy. CONCLUSION: Our study demonstrates that a significant percentage of newly diagnosed T2D subjects have a rapid eGFR decline. Given the association between dynamic changes in eGFR and the risk of ESKD or death, we suggest to include this variable in the definition of CKD.

16.
Artículo en Inglés | MEDLINE | ID: mdl-39088376

RESUMEN

Background: Familial chylomicronemia syndrome (FCS) is a rare inherited condition due to lipoprotein lipase deficiency, characterized by hyperchylomicronemia and severe hypertriglyceridemia. Diagnosis is often delayed, thus increasing the risk of acute pancreatitis and hospitalization. Hypertriglyceridemia is a common finding in patients with type 2 diabetes (T2D), who may harbor FCS among the most severe forms. Aim of the Study: We investigated the prevalence and clinical characteristics associated with severe hypertriglyceridemia in a range indicative of FCS, in a large population of subjects with T2D. Methods: Within the large population of the AMD Annals Initiative, patients with T2D with a lipid profile suggestive of FCS [triglycerides >880 mg/dL and/or high-density lipoprotein (HDL)-cholesterol <22 mg/dL or non-HDL-cholesterol ≤70 mg/dL] and their clinical features have been identified. Results: Overall, 8592 patients had triglyceride values >880 mg/dL in a single examination, 613 in two examinations, and 34 in three or more measurements. Patients with high triglyceride levels were mostly male (80%), with a relatively young age (54 years), short duration of diabetes (6.3 years), and elevated hemoglobin A1c (HbA1c) levels (9.4%). By stratifying this group of patients according to the severity of hypertriglyceridemia, more severe hypertriglyceridemia (triglyceride levels ≥2000 mg/dL) was associated with an even younger age (52 vs. 54 years), even higher mean HbA1c values (10.0% vs. 9.4%), and significantly higher HDL-cholesterol levels (37.9 vs. 32.4 mg/dL; P < 0.0001). Patients with persistently elevated triglyceride levels (n = 34), on three measurements, had a younger age; lower body mass index, HbA1c, and HDL-cholesterol levels; more frequent use of fibrates and insulin; and a higher prevalence of major cardiovascular events. Conclusions: Severe hypertriglyceridemia is a frequent condition in outpatients with T2D participating in the AMD Annals Initiative, and it is associated with male sex, young age, short disease duration, and a worse glycemic profile. Among patients with persistent severe hypertriglyceridemia, hidden FCS may be present.

17.
BMJ Open ; 14(1): e078670, 2024 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-38238053

RESUMEN

INTRODUCTION: Pain is a multidimensional experience that varies among individuals and has a significant impact on their health. A biopsychosocial approach is recommended for effective pain management; however, health professionals' education is weak on this issue. Patient involvement is a promising didactic methodology in developing a more holistic perspective, however there is a lack of reliable evidence on this topic. The aim of the present study is to evaluate the effectiveness of patient involvement in pain education in undergraduate medicine and nursing students. METHODS AND ANALYSIS: An open-label randomised controlled trial including qualitative data will be conducted. After an introductory lesson, each student will be randomly assigned to the intervention group, which includes an educational session conducted by a patient-partner along with an educator, or to the control group in which the session is exclusively conducted by an educator. Both sessions will be carried out according to the Case-Based Learning approach. Primary outcomes will be students' knowledge, attitudes, opinions and beliefs about pain management, whereas the secondary outcome will be students' satisfaction. The Pain Knowledge and Attitudes (PAK) and Chronic Pain Myth Scale (CPMS) will be administered preintervention and postintervention to measure primary outcomes. Students' satisfaction will be measured by a questionnaire at the end of the session. Two focus groups will be conducted to evaluate non-quantifiable aspects of learning. ETHICS AND DISSEMINATION: The protocol of this study was approved by the independent Area Vasta Emilia Nord ethics committee.Adherence to The Declaration of Helsinki and Good Clinical Practice will ensure that the rights, safety and well-being of the participants in the study are safeguarded, as well as data reliability. The results will be disseminated through scientific publications and used to improve the educational offer. A version of the anonymised data set will be released for public access. TRIAL REGISTRATION: Trial was not registered on ClinicalTrials.gov as the interventions being compared only concern educational programmes and the outcomes considered do not refer to any clinical dimension.


Asunto(s)
Dolor Crónico , Educación en Enfermería , Humanos , Participación del Paciente , Reproducibilidad de los Resultados , Manejo del Dolor , Ensayos Clínicos Controlados Aleatorios como Asunto
18.
Rev. argent. cir. plást ; 30(1): 85-89, 20240000. fig
Artículo en Español | LILACS, BINACIS | ID: biblio-1551535

RESUMEN

La rinoplastia es una de las intervenciones más comunes en cirugía plástica. Se opera aquí una rinoplastia secundaria por vía abierta injertando los alares y la punta con cartílagos auriculares, mientras el tabique cartilaginoso fue usado para los spreader grafts. Se describe aquí una infección posoperatoria de su punta nasal. Al 9no día de su posoperatorio comienza con la punta nasal congestiva y levemente inflamada. Se medica con una crema con antibióticos, pero el día 14 aparece con la punta nasal muy inflamada y con colección. Cuando en el consultorio el cirujano la ve, como cualquier absceso, decide realizarle drenaje con un trocar 18G, 3 miniincisiones en la piel debajo de la punta nasal, de la que drena un líquido amarronado. Luego con el mismo trocar se realiza un lavado dentro de la cavidad con rifampicina solución. Se medica con trimetoprima-sulfametoxazol (Bactrimforte®) 2 comp/día. Al otro día se observa una notable mejoría. Se continuó con lavado diario durante 4 días con el mismo antibiótico evolucionando rápidamente bien. El Bactrim se lo continúa por 20 días. Al mes la punta nasal está muy bien, deshinchada con cicatrices apenas visibles. A los cuatro meses, la punta está muy blanda, las alas nasales y las narinas normales, la punta con buena proyección igual que el dorso con los spreader graft.


Rhinoplasty is one of the most common interventions in plastic surgery. A secondary open rhinoplasty was carried out grafting the allae and the tip of the nose with conchae cartilage, while the septum was used for spreader grafts. We are here describing this post operatory with a tip of the nose infection.In the control, at the 9th postoperative day, the nasal tip began to be congested and at the 14th post op day the patient showed a clear inflammatory collection. In the office, the surgeon decided to evacuate it with three punctureslike little incisions at the inferior part of the skin tip with a trocar 18G. Through them, drained brownish purulent secretion. With the same trocar, rifampicin solution was injected through these little incisions, like washing the subdermal area. It was medicated with trimethoprim-sulfamethoxazole (Bactrim forte®) 2 tablets/day. The following day, there was a clear improvement in the congestion and erythema of the nose. This procedure of washing was repeated for four days. There was a quick evolution of the inflammatory process and 20 more days, there was no sign of the infection. Four months later, the tip of the nose was soft and the result was considered optimal by the patient and doctors.


Asunto(s)
Humanos , Femenino , Adulto , Complicaciones Posoperatorias/terapia , Rinoplastia/métodos , Trasplantes/cirugía , Infecciones/terapia
20.
Actual. nutr ; 24(3): 194-199, Jul-Sept 2023. tab
Artículo en Español | LILACS, ARGMSAL, BINACIS | ID: biblio-1511518

RESUMEN

Introducción: El tratamiento mediante los distintos tipos de dietas cetogénicas ha demostrado en diversos trabajos efectividad en la reducción de las crisis convulsivas, de manera total o parcial. Sin embargo, se reportan tasas de deserción en la realización a largo plazo. Objetivo: Este trabajo tiene como objetivo identificar beneficios y dificultades que perciben las familias de niños en el tratamiento de Epilepsia resistente a fármacos que lleven a cabo la dieta cetogénica y que podrían influir en la adherencia o deserción. Materiales y métodos: Se realizó un estudio descriptivo transversal retrospectivo, en el Servicio de Neurología Infantil del HIBA, sección Dieta Cetogénica. Para el estudio, se realizó una encuesta para recabar características sociodemográficas de la población bajo estudio y también sobre dificultades y beneficios hallados en la terapia cetogénica. Se analizaron frecuencias, medias y chi cuadrado para establecer diferencias significativas con intervalo de confianza de 95%. Resultados: La muestra estuvo compuesta por 51 participantes, de 0 a 18 años. Al indagar sobre si percibían mejoras tras realizar terapia cetogénica, el 81% respondió que sí, el 11% no percibió mejoras y el 8% no sabía. Acerca de la presencia de dificultades para llevar a cabo el tratamiento, el 71% respondió que se encontraba con dificultades, el 23% no registró dificultades y el 6% manifestó que a veces. Al relacionar la presencia de dificultades con el nivel socioeconómico, se observaron diferencias significativas entre los grupos, siendo de mayor incidencia en familias de ingresos más bajos. Respecto de la variable edad, no se encontraron diferencias significativas en relación con las dificultades percibidas. Conclusiones: Es importante continuar trabajando con las familias en las dificultades que presentan para evitar deserción del tratamiento. Asimismo, resulta indispensable destacar el alto porcentaje de mejorías que perciben sus padres para lograr mayor adherencia


Introduction: Treatment using the different types of ketogenic diets has been shown in various studies to be effective in reducing seizures, which can be total or partial. However, dropout rates are reported in the long-term completion of it. Objetive: The objective of this work is to identify the benefits and difficulties perceived by the families of children undergoing treatment for drug-resistant epilepsy who follow the ketogenic diet and that could influence adherence or desertion. Materials and methods: A retrospective cross-sectional descriptive study was carried out at the HIBA Child Neurology Service, Ketogenic Diet section. For the study, a survey was carried out to collect sociodemographic characteristics of the population under study and also about difficulties and benefits found in ketogenic therapy. Frequencies, measures and chi square were analyzed to establish significant differences with a 95% confidence interval. Results: The sample consisted of 51 participants, from 0 to 18 years old. When asked if they perceived improvements after performing ketogenic therapy, 81% answered yes, 11% did not perceive improvements and 8% did not know. About the presence of difficulties to carry out the treatment, 71% answered that they had difficulties, 23% did not have them and 6% sometimes.When relating the presence of difficulties with the socioeconomic level, significant differences were observed between the groups, with a higher incidence in lower-income families. Regarding the age variable, no significant differences were found in relation to the perceived difficulties. Conclusion: It is important to continue working with families on the difficulties they present to avoid dropping out of treatment. Likewise, it is essential to highlight the high percentage of improvements that their parents perceive to achieve greater adherence


Asunto(s)
Dieta Cetogénica , Epilepsia Refractaria , Calidad de Vida , Niño
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